Podcasts about Neutrophil

Immune 90: Immunology of Injury March 25, 2025 From the 2024 Society for Leukocyte Biology meeting at Michigan State University, home of the Spartans, Immune's Cindy and Brianne talk with Liz Kovacs and Jim Lederer about their careers, dirty mice, old mice, and immunity during trauma. Hosts: Cindy Leifer and Brianne Barker Guests: James Lederer and Elizabeth Kovacs Subscribe (free): Apple Podcasts, RSS, email Become a patron of Immune! Links for this episode MicrobeTV Discord Server Jim Lederer's Neutrophil trained immunity and Trauma effects on immune cells Liz Kovacs's Aging and lung inflammation and Alcohol effects on burn patients Paper on use of “dirty mice” also known as natural immune mice Society for Leukocyte Biology Time stamps by Jolene Ramsey. Thanks! Music by Tatami. Immune logo image by Blausen Medical Send your immunology questions and comments to immune@microbe.tv Information on this podcast should not be construed as medical advice.

In this week's episode we'll learn more about the significance of hypercalcemia in monoclonal gammopathy of undetermined significance, the role of neutrophil gelatinase-associated lipocalin in hemostasis, and the feasibility of combining CD19-targeted NK- or T-cell therapy with anti-CD19 monoclonal antibodies.Featured Articles:Approaching Hypercalcemia in Gammopathy of Undetermined Significance: Insights from the iStopMM study Deficiency of neutrophil gelatinase-associated lipocalin elicits Hemophilia-like bleeding and clotting disorder Anti-CD19 antibody cotreatment enhances serial killing activity of anti-CD19 CAR-T/-NK cells and reduces trogocytosis 

Darshan H. Brahmbhatt, Podcast Editor of JACC: Advances discusses a recently published original research paper on neutrophil extracellular traps in ST-Segment elevation myocardial infarction.

Immune discusses two stories of immune cells eating other cells: microglia engulfing brain neurons to shape cortical development and behavior, and mast cells trapping neutrophils to increase their functional and metabolic fitness. Hosts: Vincent Racaniello, Cindy Leifer, and Brianne Barker Subscribe (free): Apple Podcasts, RSS, email Become a patron of Immune! Links for this episode MicrobeTV Discord Server Microglia shape cortical development and behavior (Cell) Neutrophil trapping by mast cells (Cell) Time stamps by Jolene. Thanks! Music by Steve Neal. Immune logo image by Blausen Medical Send your immunology questions and comments to immune@microbe.tv

Join Professor Iain McInnes and Professors Hideto Kameda and Peter Nash for the latest episode on The Immune-Mediated Inflammatory Disease Forum, where they discuss the latest information and data in RA. In this episode, they discuss a paper that investigated whether the baseline neutrophil-to-lymphocyte ratio had an effect on the treatment response to filgotinib.

When you visit your doctor for a routine physical, the protocol often includes ordering blood work. Why? What can the results indicate?Your doctor looks at your lab results to help diagnose and monitor treatment for many conditions. However, many patients, probably even you, have experienced being told that their labs are normal, but they feel awful. What if you could read your blood work and determine what's going on inside your body? Today, I'll walk you through reading blood work, but instead of looking at the normal ranges, we will look at the functional ranges and understand what the numbers mean. Specifically, we will look at the five markers inside your CBC with differential. This episode is the first part of a 3-hour Blood Work and Business Intensive session. Watch out for Parts 2 and 3.Have you ever wished you had a step-by-step process to create a treatment plan for any client seeking your help? One you felt confident with and only needed their regular blood work to create? That's what we are doing during the one-day event: Functional Medicine Made Easy. Get the details and register at drkylieburton.com/fm"Today's episode is brought to you by StarWalker Organic Farms. We're a third-generation family-run farm deeply committed to producing the highest quality organic beef, pork, and artisanal jerky. With a strong belief in the power of regenerative farming, we aim to produce not only richer, more nutritious products but also to nurture the land for generations to come. Our dedication to organic and humane practices means every cut of meat supports wellness, the environment, and the well-being of our animals. And the best part? We ship nationwide, bringing the StarWalker difference directly to your door. Elevate your health with sustainably sourced meats. Visit us at starwalkerorganicfarms.com to discover more."My favorite place for ordering labs is virtualclinic.MD. Make your account and order functional medicine labs and regular blood work at any Labcorp facility across the country. Yes, you can order labs as a health coach through this platform. As long as you have a healthcare business, you can order labs. Make your account and start ordering today - tell them Dr. Kylie Burton sent you.Leave a review, share it with your colleagues, and let people on social media know you love what you're hearing. Spread the message, and I'll be very grateful for it!“We're not reading the labs to diagnose. We're reading them to figure out what the heck is wrong with our patient.”- Dr. Kylie Burton In This Episode:Do you need a license to read blood work?What is the purpose of reading a patient's blood work?Normal range vs. Functional rangeThe CBC with differentialWBC and what the range meanWhat does the Neutrophil count indicate?What does the Lymphocyte count indicate?What does the Monocyte count indicate?What do the Eosinophil and Basophil ranges indicate?WBC breakdown and what the numbers mean Practical application (let's read some blood work)Resources:Build Your Virtual Platform in 90 Days - https://drkylieburton.com/business/Join the 90-day...

Immune reviews research showing that the migration of neutrophils between endothelial cells activates bactericidal function via mechanosensing. Hosts: Vincent Racaniello, Steph Langel, Cynthia Leifer, and Brianne Barker Subscribe (free): Apple Podcasts, Google Podcasts. RSS, email Become a patron of Immune! Links for this episode MicrobeTV Discord Server Trans endothelial migration activates neutrophil killing (Immunity) Time stamps by Jolene. Thanks! Music by Steve Neal. Immune logo image by Blausen Medical Send your immunology questions and comments to immune@microbe.tv

References Cell 2021. 184, 1–15 ⁠J Zhejiang Univ Sci B.⁠ 2022 Jul 15; 23(7): 607–612. --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

While it's true that the majority of people will have a run-in with some kind of cancer in their lifetime, we need to remember that no 2 cancers are the same, and your overall metabolic health has a huge impact on how your body will manage the cancer and what your survival rates will be, plus which treatment path you should go down. To test your body's current metabolic health status when dealing with cancer, there's a number of simple blood tests you can run that will show how well (or poorly) your body is handling the tumor load.  You'll want to run the following tests: CBC and specifically look at WBC, Platelets, and the Neutrophil to Lymphocyte ratio Comprehensive Metabolic Panel - Creatinine, Liver enzymes, Alkaline Phosphatase Inflammatory markers - LDH, ESR, hs-CRP

References Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids2014.Volume 1841, Issue 9, Pages 1241-1246 Guerra-graduate lipid lectures --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

BUFFALO, NY- October 30, 2023 – A new editorial paper was published in Oncotarget's Volume 14 on March 24, 2023, entitled, “Neutrophil PAD4: how does it function in cancer beyond promoting NETosis?” Expansion of pathologically activated immune suppressive myeloid cells called myeloid-derived suppressor cells (MDSC) is one of the hallmarks of cancer. In most tumor types, MDSC are represented primarily by pathologically activated neutrophils (PMN-MDSC). In this new editorial, researchers Laura Garcia-Gerique and Yulia Nefedova from the Wistar Institute discussed their team's recent study identifying a novel mechanism by which neutrophil PAD4 promotes cancer progression. “Using several transplantable and genetically engineered mouse models, we demonstrated that tumor growth was accompanied by significantly elevated enzymatic activity of neutrophil PAD4 [10]. To further clarify the role of PAD4 in tumor progression, we utilized PAD4fl/fl MRP8Cre mice with targeted deletion of PAD4 in myeloid cells, primarily neutrophils.” PMN-MDSC originate in the bone marrow and migrate to various sites including tumor tissues and premetastatic niches. These cells have a relatively short lifespan (less than 48 hours) and, therefore, are continually replaced from the bone marrow. Tumor-infiltrating PMN-MDSC possess a potent suppressive activity as they are able to inhibit both antigen-specific immune responses of T cells and non-specific anti-CD3/CD28-stimulated responses. As a result, a highly immunosuppressive environment is created in tumors, which prevents their rejection via immunological mechanisms. In addition, PMN-MDSC employ non-immunological mechanisms to facilitate tumor progression, including angiogenesis, remodeling of extracellular matrix, and production of cytokines. In patients with solid tumors, levels of MDSC in circulation and tumor tissues have been positively associated with a poor response to the therapy in many types of cancer and represent an independent indicator of poor outcomes. However, many of the details about how PMN-MDSC support cancer progression, and thus approaches for therapeutically targeting these cells, remain enigmatic. “Taken together, our study identified a new mechanism responsible for transcriptional regulation of neutrophil migration and a new mechanism by which neutrophil PAD4 is contributing to tumor progression. PAD4 inhibitors are in development and may enter early phase clinical trials in the future.” DOI - https://doi.org/10.18632/oncotarget.28369 Correspondence to - Yulia Nefedova - ynefedova@wistar.org Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28369 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, PAD4, PMN-MDSC, neutrophils, neutrophil migration About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

References Oral Microbiol Immunol. 2006 April 21 (2):84-92 1647-6017 Gut Microbes. 2022; 14(1): 2073785. Adv Exp Med Biol. 2020:1263:13-23 Bredon, Anne. 1950. Led Zepplin. 1969. https://youtu.be/dZitPJMh60A?si=MnEpM-iemNFWEKE7 --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

In this week's episode, we discuss the findings from a phase 2 study of lenalinomide plus rituximab in elderly frail patients with DLBCL, learn more about platelet GP6-mediated neutrophil recruitment in early stages of acute lung injury, and discuss a newly identified isoform of the tyrosine kinase AXL, termed AXL3, in mantle cell lymphoma.

References Cell. 2021 Aug 19;184(17):4480-4494.e15 Sci Rep. 2019 Mar 5;9(1):3433 Med Hypotheses. 2021 Jan:146:110466. Hayward, J. 1967. Moody Blues. "Tuesday Afternoon" https://youtu.be/jmMPBQ4kYKk?si=X0UyZJFq2AAnKSvJ --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

Blood associate editors Jeanne Hendrickson and Thomas Ortel edited a How I Treat series on inpatient consultative hematology. In this timely series of articles, the authors present an approach to bleeding, thrombosis, anemia, and quantitative neutrophil abnormalities.

In this week's episode, we'll learn more about what whole genome sequencing reveals about genetic subtypes of follicular lymphoma and risk of transformation, discuss the role of the lipid mediator, resolvin D4, in infectious neutrophil deployment and emergency granulopoiesis, and learn more about Hodgkin lymphoma-directed therapy and the role of PET in early-stage nodular lymphocyte-predominant Hodgkin lymphoma. 

In this podcast Heather Cameron-Whytock discusses risk factors for cross-country horse falls at British Eventing competition and Sanni Hansen discusses neutrophil gelatinase-associated lipocalin as a potential biomarker for equine asthma.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.27.546744v1?rss=1 Authors: Strickland, J., Pan, D., Godfrey, C., Kim, J. S., Hopke, A., Degrange, M., Villavicencio, B., Mansour, M. K., Zerbe, C. S., Irimia, D., Amir, A., Weiner, O. D. Abstract: Neutrophils exhibit self-amplified swarming to sites of injury and infection. How swarming is controlled to ensure the proper level of neutrophil recruitment is unknown. Using an ex vivo model of infection, we find that human neutrophils use active relay to generate multiple pulsatile waves of swarming signals. Unlike classic active relay systems such as action potentials, neutrophil swarming relay waves are self-extinguishing, limiting the spatial range of cell recruitment. We identify an NADPH-oxidase-based negative feedback loop that is needed for this self-extinguishing behavior. Through this circuit, neutrophils adjust the number and size of swarming waves for homeostatic levels of cell recruitment over a wide range of initial cell densities. We link a broken homeostat to neutrophil over-recruitment in the context of human chronic granulomatous disease. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

CME credits: 1.25 Valid until: 15-06-2024 Claim your CME credit at https://reachmd.com/programs/cme/the-neutrophil-and-neutrophil-serine-proteases-nsps-in-non-cf-bronchiectasis-ncfbe/15620/ An estimated 350,000-500,000 adults are affected by bronchiectasis in the United States, and up to 90% of patients with bronchiectasis present with chronic cough. This educational activity provides a framework of treatment options for NCFBE, empowering medical practitioners to work collaboratively with pulmonary specialists and confidently proceed with a sustainable treatment plan that is evidence-based and makes sense for both practitioner and patient.

CME credits: 1.25 Valid until: 15-06-2024 Claim your CME credit at https://reachmd.com/programs/cme/the-when-and-how-of-implementing-new-anti-neutrophil-therapies-into-standard-clinical-practice/15625/ An estimated 350,000-500,000 adults are affected by bronchiectasis in the United States, and up to 90% of patients with bronchiectasis present with chronic cough. This educational activity provides a framework of treatment options for NCFBE, empowering medical practitioners to work collaboratively with pulmonary specialists and confidently proceed with a sustainable treatment plan that is evidence-based and makes sense for both practitioner and patient.

Listen to a soundcast of the April 17, 2023, FDA approval of Omisirge (omidubicel-onlv) to reduce time to neutrophil recovery and infection in patients with hematologic malignancies.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.19.529165v1?rss=1 Authors: Zhu, Y., Wang, T., Wang, Z., Chen, X., Wang, L., Niu, R., Sun, Z., Zhang, C., Luo, Y., Hu, Y., Gu, W. Abstract: Background: Atherosclerosis is a chronic lipid-driven inflammatory disease, largely influenced by hemodynamics. Neutrophil extracellular traps (NETs)-mediated inflammation plays an important role in atherosclerosis. However, little is known about the mechanism of the generation of NETs under different shear stress and subsequent damage to endothelial cells. We sought to identify a novel mechanical signal provokes NETs generation and to investigate its potential role in atherosclerosis. Methods: ApoE-/- mice were fed with high-fat diet (HFD) to induce atherosclerosis. The model of lower shear stress (LSS) with a partial ligation of the left carotid artery was established to assess the role of LSS in NETs generation and atherosclerotic lesions development. Furthermore, the underlying mechanism of LSS promoting NETs generation and injuring endothelial cells was deciphered in neutrophil-like human promyelocytic leukemia (HL-60) cells in parallel-plate flow chamber. Results: We found that LSS correlated spatially with both NETs and atherosclerosis, while inhibition of NETosis could significantly reduce plaque formation in ApoE-/- mice. In vitro, LSS could promote NETs generation directly through down-regulation of Piezo1, a mechanosensitive ion channel. downexpression of Piezol could activate neutrophils and promote NETosis in static. Conversely, Yoda1-evoked activation of Piezo1 attenuated LSS-induced NETosis. Mechanistically, the downexpression of Piezo1 resulted in decreased Ca2+ influx and increased histone deacetylase 2 (HDAC2), which increase reactive oxygen species levels, then led to NETosis. LSS-induced NETs generation promoted the apoptosis and adherence of endothelial cells. Conclusions: LSS directly promotes NETosis through piezo1-HDAC2 axis in atherosclerosis progression. This study uncovers the essential role of Piezo1-mediated mechanical signaling in NETs generation and plaque formation, which provides a promising therapeutic strategy for atherosclerosis. 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/2023.02.15.528710v1?rss=1 Authors: Ruiz-Uribe, N. E., Bracko, O., Swallow, M., Omurzakov, A., Dash, S., Uchida, H., Xiang, D., Haft-Javaherian, M., Falkenhain, K., Lamont, M. E., Ali, M., Njiru, B. N., Chang, H.-Y., Tan, A. Y., Xiang, J. Z., Iadecola, C., Park, L., Sanchez, T., Nishimura, N., Schaffer, C. B. Abstract: INTRODUCTIONIn this study, we explore the role of oxidative stress produced by NOX2-containing NADPH oxidase as a molecular mechanism causing capillary stalling and cerebral blood flow deficits in the APP/PS1 mouse model of AD. METHODSWe inhibited NOX2 in APP/PS1 mice by administering a 10 mg/kg dose of the peptide inhibitor gp91-ds-tat i.p., for two weeks. We used in vivo two-photon imaging to measure capillary stalling, penetrating arteriole flow, and vascular inflammation. We also characterized short-term memory function and gene expression changes in cerebral microvessels. RESULTSWe found that after NOX2 inhibition capillary stalling, as well as parenchymal and vascular inflammation, were significantly reduced. In addition, we found a significant increase in penetrating arteriole flow, followed by an improvement in short-term memory, and downregulation of inflammatory gene expression pathways. DISCUSSIONOxidative stress is a major mechanism leading to microvascular dysfunction in AD, and represents an important therapeutic target. 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/2023.01.09.522931v1?rss=1 Authors: Ngo, A. T., Sarkar, A., Yarovoi, I., Levine, N., Bochenek, V., Zhao, G., Rauova, L., Kowalska, M. A., Eckart, K., Mangalmurti, N., Rux, A., Cines, D. B., Poncz, M., Gollomp, K. Abstract: Neutrophil extracellular traps (NETs) are abundant in sepsis, and proposed NET-directed therapies in sepsis prevent their formation or accelerate degradation. Yet NETs are important for microbial entrapment, as NET digestion liberates pathogens and NET degradation products (NDPs) that deleteriously promote thrombosis and endothelial cell injury. We proposed an alternative strategy of NET-stabilization with the chemokine, platelet factor 4 (PF4, CXCL4), which we have shown enhances NET-mediated microbial entrapment. We now show that NET compaction by PF4 reduces their thrombogenicity. In vitro, we quantified plasma thrombin and fibrin generation by intact or degraded NETs and cell-free (cf) DNA fragments, and found that digested NETs and short DNA fragments were more thrombogenic than intact NETs and high molecular weight genomic DNA, respectively. PF4 reduced the thrombogenicity of digested NETs and DNA by interfering, in part, with contact pathway activation. In endothelial cell culture studies, short DNA fragments promoted von Willebrand factor release and tissue factor expression via a toll-like receptor 9-dependent mechanism. PF4 blocked these effects. Cxcl4-/- mice infused with cfDNA exhibited higher plasma thrombin anti-thrombin (TAT) levels compared to wild-type controls. Following challenge with bacterial lipopolysaccharide, Cxcl4-/- mice had similar elevations in plasma TAT and cfDNA, effects prevented by PF4 infusion. Thus, NET-stabilization by PF4 prevents the release of short fragments of cfDNA, limiting the activation of the contact coagulation pathway and reducing endothelial injury. These results support our hypothesis that NET-stabilization reduces pathologic sequelae in sepsis, an observation of potential clinical benefit. 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/2022.12.30.521706v1?rss=1 Authors: Town, J. P., Weiner, O. P. Abstract: To migrate efficiently, neutrophils must polarize their cytoskeletal regulators along a single axis of motion. This polarization process is thought to be mediated through local positive feedback that amplifies leading edge signals and global negative feedback that enables sites of positive feedback to compete for dominance. Though this two-component model efficiently establishes cell polarity, it has potential limitations, including a tendency to "lock" onto a particular direction, limiting the ability of cells to reorient. We use spatially-defined optogenetic control of a leading edge organizer (PI3K) to probe how cells balance "decisiveness" needed to polarize in a single direction with the flexibility needed to respond to new cues. Underlying this balancing act is a local Rac inhibitor that destabilizes the leading edge to promote exploration. We show that this local inhibitor enables cells to process input signal dynamics, linking front stability and orientation to local temporal increases in input signals. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Systemic lupus erythematosus (SLE) causes significant long-term morbidity and mortality, particularly in children. There is some evidence that the innate immune system, in particular neutrophil activity, can be compromised in adult-onset lupus. Yet there is a paucity of data on neutrophil activity in pediatric SLE. This month on Pediapod, we join Early Career Investigator, Rakesh Kumar Pilania, an assistant professor at the postgraduate Institute of Medical Education and Research in Chandigarh, India to discuss his study of neutrophil activity in patients with pediatric SLE and what it reveals about the etiology of this condition.Read the full study here. Pediatric systemic lupus erythematosus: phagocytic defect and oxidase activity of neutrophils | Pediatric Research (nature.com) Hosted on Acast. See acast.com/privacy for more information.

A rare donor program is a collaborative effort of many blood centers and/or hospitals to combine their rare donor resources to supply what they have to patients in need. These centers work to identify rare donors by screening methods and inclusion in database systems. Learn in this episode what resources are available to the medical community to ensure availability for patients in need of blood and why it is critical to national and international collaboration through joint programs.   About our Speaker:  Sandra Nance has provided leadership to the American Rare Donor Program, American Red Cross Histocompatibility and Immunogenetics laboratories, the National Reference Laboratories for Blood Group Serology, Molecular Testing, Neutrophil and Specialized Testing. She engineered the nationalized American Red Cross SBB Program. She is now a volunteer for the American Red Cross and Emeritus Adjunct Assistant Professor at the University of Pennsylvania in the Department of Pathology and Laboratory Medicine. She earned her Master in Pathology from the University of Maryland and her SBB from The Johns Hopkins Medical Institutions.   Ms. Nance held leadership positions in the AABB, ASCP, ICII, and ISBT. She chaired the ISBT Working Party on Rare Donors and conceptualized the ISBT Working Party on Immunohematology, and as the past Chair, managed the Case Studies. She has been inducted into the ASCP and the National Blood Foundation Halls of Fame and has received the AABB's Sally Frank, John Elliott and President's Awards, AIMS John Moulds, CBBS Suzanne Ledin, MAABB Kay Beattie, New York Supervisors Ron Dubin, and UTMB Jean Stubbins awards. She is the past Editor in Chief of Immunohematology Journal of Blood Group Serology and Molecular Genetics, is a member of Transfusion's Editorial Board and reviews for several journals. She developed the polyethylene glycol method for serologic testing and the monocyte monolayer assay (MMA) to predict in vivo survival of transfused incompatible red cells. She initiated the International MMA Training classes so other countries can implement the MMA to assist with patients requiring rare blood. Ms. Nance has been invited to present over 250 lectures and has been a frequent contributor to the scientific literature.

Dr. Mandy Rounds, a Research Fellow at MedStar National Rehabilitation Hospital, interviews Dr. Katie Forster, a pediatric hospitalist and researcher at University of Pittsburgh School of Medicine about the findings of the article, “The association between urine neutrophil gelatinase-associated lipocalin (urine NGAL) and UTI in people with neurogenic lower urinary tract dysfunction”. They discuss the importance of this new type of biomarker (uNGAL) and the implications it has for UTIs in those with neurogenic bladder. To access this journal article, click here:https://www.nature.com/articles/s41393-020-00552-x

Hosts Katherine Raspovic and Jacob Wynes have discussions with award winning Scientific Format poster authors:    Scientific Choice Award: Poster SCI-314: Predictive Value of Neutrophil to Lymphocyte Ratio in Wound Healing Among Patients Undergoing Transmetatarsal Amputations: A Retrospective Cohort Study, discussion with poster author Jonathan D. Furmanek, DPM.   1st Place – Poster No. SCI-319: Calcaneocuboid Joint Preparation in Charcot Reconstruction and its Effect on Postoperative Outcomes, discussion with poster author Taylor J. Bunka, DPM 2nd Place – Poster No. SCI-305: Risk Factors and Surgical Outcomes in Patients With Positive Soft Tissue Cultures at Time of Closure, discussion with poster author Robert Sheckler, DPM 3rd Place – Poster No. SCI-320: Outcomes in Drainage Ankle Disarticulation versus Guillotine Transtibial Amputation in the Staged Approach to Below Knee Amputation, discussion with poster author Nicole K. Cates, DPM, AACFAS For more educational resources, visit: https://www.acfas.org/  Release Date: April 22, 2022 Run Time: 11min 14sec

All of your most burning questions on candida and diet answered by New Zealand Naturopath of 30 + years! In each bite-size episode, you'll get practical tips you can follow right away to improve your health and lifestyle. So go ahead and binge listen. --- Full video of this episode: https://youtu.be/BehpVp0ZW04 --- Download My Candida Diet & Cleanse Guide Free Mobile App: IOS: https://apps.apple.com/ca/app/candida-diet-cleanse-guide/id1553653763 Android: https://play.google.com/store/apps/details?id=com.candida.crusher *New* Candida Diet Cleanse and Detox Planner Planner: https://amzn.to/3C9lH7u --- Subscribe to Eric Bakker - The Naturopath All of your most burning questions on candida and diet answered by New Zealand Naturopath of 30 + years! In each bite-size episode, you'll get practical tips you can follow right away to improve your health and lifestyle. So go ahead and binge listen. --- FOLLOW Eric Bakker - The Naturopath: YouTube: https://www.youtube.com/user/CandidaCrusher Twitter: https://twitter.com/ericbakker Facebook: https://www.facebook.com/ericbakker.ND?ref=tn_tnmn

Join us this week for another congress highlights episode covering the recent European Society of Cardiology congress, held virtually from 27-30 August 2021. Listen for commentary on the key highlights, including: - Professor Subodh Verma on EMPEROR-Preserved, EMPEROR-Pooled, and a post hoc analysis of SUSTAIN 6 and PIONEER 6 - Professor Darren McGuire on FIGARO-DKD, and new guidelines for heart failure and cardiovascular disease prevention Disclosures: Prof. Darren McGuire declares the following: Clinical trial leadership: AstraZeneca, Boehringer Ingelheim, Eisai Esperion, GlaxoSmithKline, Janssen, Lexicon, Merck & Co. Inc, Novo Nordisk, Sanofi, CSL Behring, Lilly Consultancy: Affimune, Applied Therapeautics, AstraZeneca, Boehringer Ingelheim, Lilly, Merck & Co. Inc, Pfizer Inc, Novo Nordisk, Metavant, Sanofi, Bayer Prof. Subodh Verma declares the following: Research Grants: AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk Speaker Honoraria: AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk, Sanofi, Sun Pharma Consultancy: AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk All conflicts of interest have been mitigated prior to this activity. Funding statement: This independent educational activity is supported by an educational grant from Novo Nordisk A/S. The educational content has been developed by Liberum IME in conjunction with an independent steering committee; Novo Nordisk A/S has had no influence on the content of this education. References Packer M, et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021 Aug 27. doi: 10.1056/NEJMoa2107038. Online ahead of print. [EMPEROR-Preserved] Packer M, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020 Oct 8;383(15):1413-1424. [EMPEROR-Reduced] Packer M, et al. Empagliflozin and Major Renal Outcomes in Heart Failure. N Engl J Med. 2021 Aug 27. doi: 10.1056/NEJMc2112411. Online ahead of print. [EMPEROR-Pooled] Verma S, et al. Neutrophil-to-lymphocyte ratio predicts cardiovascular events in patients with type 2 diabetes: post hoc analysis of SUSTAIN 6 and PIONEER 6. Eur Heart J 2021. In press Pitt B, et al. Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes. N Engl J Med. 2021 Aug 28. doi: 10.1056/NEJMoa2110956. Epub ahead of print. [FIGARO-DKD] Bakris GL, et al. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med. 2020 Dec 3;383(23):2219-2229. doi: 10.1056/NEJMoa2025845. [FIDELIO-DKD] FIDELITY analysis: Presented by Dr. Gerasimos Filippatos at the European Society of Cardiology Virtual Congress, August 28, 2021. McDonagh TA, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Aug 27:ehab368. doi: 10.1093/eurheartj/ehab368. Epub ahead of print.

In this week's episode, we will review a study that shows that BCL11B is an important oncogene in acute leukemias with myeloid and T-lymphoid features, learn more about antibody responses to SARS-CoV-2 vaccination in lymphoma patients receiving B-cell directed therapies, and examine the role of programmed death ligand 1 (or PD-L1) and the PI 3 kinase-AKT survival pathway in delayed neutrophil apoptosis at sites of tissue inflammation.

There are approximately 37 trillion cells in a human body. Enter the world of Cells At Work as we cross the first season of this anime off of Roni's list. We talk about our favourite characters, the educational aspect of the show, and why we have a crush on Neutrophil. Yup, he's hot. Listen to the Cells At Work Theme Song -> Mission! Health Comes First Check out Dr. Ed Hope's review of Cells At Work -> Doctor reacts to Cells at Work! (Hataraku Saibou) ----- Want more from us, be sure to follow us, we're @nerdycurious all over the damn place! And we're also LIVE on Twitch Mondays, Thursdays, & Saturdays @ 5PM Pacific! Come hang out and chat with us in our attempt to make fandom a better place -> twitch.tv/nerdycurious --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app Support this podcast: https://anchor.fm/nerdycurious/support

Neste episódio, contamos com a participação das reumatologistas Dra. Joana Starling, mestre em ciências aplicadas a saúde do adulto pela UFMG, e Dra. Gilda Ferreira, coordenadora do serviço de reumatologia do hospital das clinicas da UFMG, para falar sobre uma das principais causas de mortalidade no Lupus Eritematoso Sistêmico: as infecções. Referências: 1)Estudos sobre pro calcitonina: -Serio I, Arnaud L, Mathian A, et al. Can procalcitonin be used to distinguish between disease flare and infection in patients with systemic lupus erythematosus: a systematic literature review. Clin Rheumatol. 2014;33(9):1209-15. - Liu LN, Wang P, Guan SY, et al. Comparison of plasma/serum levels of procalcitonin between infection and febrile disease flare in patients with systemic lupus erythematosus: a metaanalysis. Rheumatol Int. 2017;37(12):1991-8. 2) Ospina FE, Echeverri A, Zambrano D, et al. Distinguishing infections vs flares in patients with systemic lupus erythematosus. Rheumatology (Oxford). 2017;56(suppl_1):i46-i54. 3) Estudos sobre razoes neutrofilo/linfocito e plaqueta/linfocito: - Qin B, Ma N, Tang Q, et al. Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) were useful markers in assessment of inflammatory response and disease activity in SLE patients. Mod Rheumatol. 2016;26(3):372-6. 36. -Kim HA, Jung JY, Suh CH. Usefulness of neutrophil-tolymphocyte ratio as a biomarker for diagnosing infections in patients with systemic lupus erythematosus. Clin Rheumatol. 2017;36(11):2479-85.

Could a CBC w/diff tell us who's going to do poorly with COVID? Using the neutrophil to lymphocyte ratio could be quite helpful. Show Notes: www.eddyjoemd.com/NLR Receive a FREE audiobook (TWO for Amazon Prime members) with your FREE 30-day trial by using my link for Audible: CLICK HERE! You will be reminded when your trial is ending, by the way.

There’s a common misconception that you need to run expensive advanced biomedical tests to fix your health. Over the years we’ve found just the opposite, that you can learn much of what you need to know from basic blood chemistry. Perhaps the best example is the information gained from a Complete Blood Count (CBC) with Differential. As the most common blood test, it is widely used to assess general health status, screen for disorders, and to evaluate nutritional status. On this podcast, NBT Scientific Director Megan Hall and I are talking about leukocytes, also known as white blood cells (WBCs), as critical elements of the CBC blood test. Megan discusses the various types of leukocytes and what it means when your count is outside the reference range. We talk about what leukocytes tell you about your nutritional status, why some people “never get sick” as well as signs you’ve got chronic inflammation or physiological stress. Megan also discusses how to use this information to determine the next steps in your health journey. Here’s the outline of this interview with Megan Hall: [00:01:04] Forum post: Chronically Low White Blood Cell Count. Get access when you support us on Patreon. [00:01:45] Leukocytes = White Blood Cells (WBCs) found on CBC with differential blood test. [00:02:58] Different types of white blood cells. [00:04:18] Phagocytosis video. [00:06:10] Absolute vs relative counts of WBCs. [00:09:15] Optimal range of WBCs in relation to all-cause mortality. [00:11:25] Baltimore Longitudinal Study on Aging: Ruggiero, Carmelinda, et al. "White blood cell count and mortality in the Baltimore Longitudinal Study of Aging." Journal of the American College of Cardiology 49.18 (2007): 1841-1850.  [00:12:57] Study: Shah, Anoop Dinesh, et al. "White cell count in the normal range and short-term and long-term mortality: international comparisons of electronic health record cohorts in England and New Zealand." BMJ open 7.2 (2017): e013100.  [00:15:30] bloodsmart.ai. [00:18:00] Why WBCs might be high: Leukocytosis. [00:18:45] Paper: WBCs are predictive of all cause mortality: Crowell, Richard J., and Jonathan M. Samet. "Invited commentary: why does the white blood cell count predict mortality?." American Journal of Epidemiology 142.5 (1995): 499-501.  [00:20:00] Podcast: Air Pollution Is a Cause of Endothelial Injury, Systemic Inflammation and Cardiovascular Disease, with Arden Pope, PhD. [00:21:57] Association of leukocytosis with metabolic syndrome; Study: Babio, Nancy, et al. "White blood cell counts as risk markers of developing metabolic syndrome and its components in the PREDIMED study." PloS one 8.3 (2013): e58354. [00:22:15] Megan's outline for this podcast. [00:22:41] What to do if you have elevated WBC counts. [00:22:54] Impact of stress; Studies: 1. Nishitani, Naoko, and Hisataka Sakakibara. "Association of psychological stress response of fatigue with white blood cell count in male daytime workers." Industrial health 52.6 (2014): 531-534. and 2. Jasinska, Anna J., et al. "Immunosuppressive effect and global dysregulation of blood transcriptome in response to psychosocial stress in vervet monkeys (Chlorocebus sabaeus)." Scientific reports 10.1 (2020): 1-12.  [00:23:32] Dr. Simon Marshall and Lesley Paterson; Podcast: How to Manage Stress, with Simon Marshall, PhD. [00:24:08] Reasons WBC counts might be low; Leukopenia. [00:27:57] "I never get sick". [00:30:40] What to do if your WBCs are low. [00:30:56] Effects of low energy availability: Studies: 1. Johannsen, Neil M., et al. "Effect of different doses of aerobic exercise on total white blood cell (WBC) and WBC subfraction number in postmenopausal women: results from DREW." PloS one 7.2 (2012): e31319. and 2. Sarin, Heikki V., et al. "Molecular pathways mediating immunosuppression in response to prolonged intensive physical training, low-energy availability, and intensive weight loss." Frontiers in immunology 10 (2019): 907.  [00:31:44] Articles by Megan on energy availability and underfueling: 1. Why Your Ketogenic Diet Isn’t Working Part One: Underfueling and Overtraining; 2. How to Prevent Weight Loss (or Gain Muscle) on a Therapeutic Ketogenic Diet; 3. What We Eat and How We Train Part 1: Coach and Ketogenic Diet Researcher, Megan Roberts; 4. How to Carbo Load the Right Way [00:31:52] Podcast: How to Identify and Treat Relative Energy Deficiency in Sport (RED-S), with Nicky Keay. [00:33:03] Ranges may slightly differ by ethnicity; 1. Haddy, Theresa B., Sohail R. Rana, and Oswaldo Castro. "Benign ethnic neutropenia: what is a normal absolute neutrophil count?." Journal of Laboratory and Clinical Medicine 133.1 (1999): 15-22; 2. Palmblad, Jan, and Petter Höglund. "Ethnic benign neutropenia: a phenomenon finds an explanation." Pediatric blood & cancer 65.12 (2018): e27361; 3. Grann, Victor R., et al. "Neutropenia in 6 ethnic groups from the Caribbean and the US." Cancer: Interdisciplinary International Journal of the American Cancer Society 113.4 (2008): 854-860.  [00:34:39] Absolute Neutrophil to absolute Lymphocyte Ratio (NLR) as indicator of systemic inflammation; Studies: 1. Gürağaç, Ali, and Zafer Demirer. "The neutrophil-to-lymphocyte ratio in clinical practice." Canadian Urological Association Journal 10.3-4 (2016): 141-2; 2. Fest, Jesse, et al. "The neutrophil-to-lymphocyte ratio is associated with mortality in the general population: The Rotterdam Study." European journal of epidemiology 34.5 (2019): 463-470.  [00:36:19] Elevated NLR associated with poor outcomes in COVID-19 patients. Studies: 1. Yang, Ai-Ping, et al. "The diagnostic and predictive role of NLR, d-NLR and PLR in COVID-19 patients." International immunopharmacology (2020): 106504; 2. Ciccullo, Arturo, et al. "Neutrophil-to-lymphocyte ratio and clinical outcome in COVID-19: a report from the Italian front line." International Journal of Antimicrobial Agents (2020); 3. Liu, Jingyuan, et al. "Neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage." Journal of Translational Medicine 18 (2020): 1-12.  [00:37:41] NLR predicts mortality in medical inpatients: Isaac, Vivian, et al. "Elevated neutrophil to lymphocyte ratio predicts mortality in medical inpatients with multiple chronic conditions." Medicine 95.23 (2016).  [00:38:21] What to do if NLR is out of range. [00:39:23] NLR on bloodsmart.ai (found on the Marker Detail View page). [00:40:01] NLR as a marker of physiological stress: 1. Onsrud, M., and E. Thorsby. "Influence of in vivo hydrocortisone on some human blood lymphocyte subpopulations: I. Effect on natural killer cell activity." Scandinavian journal of immunology 13.6 (1981): 573-579; 2. PulmCrit: Neutrophil-Lymphocyte Ratio (NLR): Free upgrade to your WBC. [00:41:59] Schedule a 15-minute Starter Session.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.02.868505v1?rss=1 Authors: Francois, J., Kandasamy, A., Yeh, Y.-T., Ayala, C., Meili, R., Chien, S., Lasheras, J. C., del Alamo, J. C. Abstract: Three-dimensional (3-D) neutrophil migration is essential for immune surveillance and inflammatory responses. During 3-D migration, especially through extravascular spaces, neutrophils rely on frontal protrusions and rear contractions to squeeze and maneuver through extracellular matrices containing narrow pores. However, the role of matrix density and the cells' ability to probe and remodel matrix pores during 3-D chemotaxis are far from being understood. We investigated these processes by tracking the trajectories of over 20,000 neutrophils in a 3-D migration device containing collagen matrices of varying concentrations and analyzing the shape of these trajectories at multiple scales. Additionally, we quantified the transient 3-D matrix deformations caused by the migrating cells. The mean pore size of our reconstituted collagen matrices decreased when the collagen concentration ([col]) was increased. In low-[col] matrices, neutrophils exerted large transient deformations and migrated in relatively straight trajectories. In contrast, they were not able to appreciably deform high-[col] matrices and adapted to this inability by turning more often to circumvent these narrow matrix pores. While this adaptation resulted in slower migration, the cells were able to balance the more frequent turning with the long-range directional bias necessary for chemotaxis. Based on our statistical analysis of cell trajectories, we postulate that neutrophils achieve this balance by using matrix obstacles as pivoting points to steer their motion towards the chemoattractant. Inhibiting myosin-II contractility or Arp2/3-mediated pseudopod protrusions not only compromised the cells' ability to deform the matrix, but also made them switch to increased turning in more restrictive matrices when compared to untreated control cells. Both myosin-II contractility and Arp2/3-mediated branched polymerization of actin played a role in fast migration, but Arp2/3 was also crucial for neutrophils when coordinating the orientations of successive turns to prevent veering away from the chemotactic path. These results may contribute to an improved understanding of the mechanisms employed by migrating neutrophils in confined 3-D environments, as well as the molecular and environmental regulators for maintaining persistent motion. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.27.223008v1?rss=1 Authors: Wang, Y., Hsu, A. Y., Walton, E. M., Syahirah, R., Wang, T., Zhou, W., Ding, C., Lemke, A. P., Tobin, D. M., Deng, Q. Abstract: Tissue-specific knockout techniques are widely applied in biological studies to probe the tissue-specific roles of specific genes in physiology, development, and disease. CRISPR/Cas9 is a widely used technology to perform fast and efficient genome editing in vitro and in vivo. Here, we report a robust CRISPR-based gateway system for tissue-specific gene inactivation in zebrafish. A transgenic fish line expressing Cas9 under the control of a neutrophil-restricted promoter was constructed. As proof of principle, we transiently disrupted rac2 or cdk2 in neutrophils using plasmids driving the expression of sgRNAs from U6 promoters. Loss of the rac2 or cdk2 gene in neutrophils resulted in significantly decreased cell motility, which could be restored by re-expressing Rac2 or Cdk2 in neutrophils in the corresponding knockout background. The subcellular location of Rac activation and actin structure and stress in the context of neutrophil migration was determined in both the wild-type and rac2 knockout neutrophils in vivo. In addition, we evaluated an alternative approach where the Cas9 protein is ubiquitously expressed while the sgRNA is processed by ribozymes and expressed in a neutrophil-restricted manner. Cell motility was also reduced upon rac2 sgRNA expression. Together, our work provides a potent tool that can be used to advance the utility of zebrafish in identification and characterization of gene functions in neutrophils. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.24.219956v1?rss=1 Authors: Tjondro, H. C., Ugonotti, J., Kawahara, R., Chatterjee, S., Loke, I., Chen, S., Soltermann, F., Hinneburg, H., Parker, B. L., Venkatakrishnan, V., Dieckmann, R., Grant, O. C., Bylund, J., Rodger, A., Woods, R. J., Struwe, W. B., Karlsson-Bengtsson, A., Thaysen-Andersen, M. Abstract: Myeloperoxidase (MPO), an important glycoprotein in neutrophil-mediated immunity, produces microbicidal hypohalous acids, but the underpinning glycobiology remains elusive. Deep characterisation of neutrophil-derived MPO (nMPO) using advanced mass spectrometry demonstrated that under-processed oligomannosidic-, truncated paucimannosidic- and hyper-truncated N-acetyl-{beta}-D-glucosamine (GlcNAc) core-type asparagine-linked glycans decorate the protein. Occlusion of Asn355 and Asn391 and sterical hindrance of Asn323- and Asn483-glycans located in the MPO dimerisation zone were found to shape the local glycan processing thereby providing a molecular basis for the site-specific nMPO glycosylation. Native mass spectrometry, mass photometry, and glycopeptide profiling revealed extreme molecular complexity of dimeric nMPO arising from heterogeneous glycosylation, oxidation, chlorination and polypeptide truncation variants, and a lower-abundance monomer. Longitudinal profiling of maturing, mature, granule-separated, and pathogen-activated neutrophils demonstrated that MPO is dynamically expressed during granulopoiesis, unevenly distributed across granules and rapidly degranulated, but surprisingly carries uniform glycosylation across conditions. Complete proMPO-to-MPO maturation evidently occur during early/mid-stage granulopoiesis. The conserved Asn355- and Asn391-sequons displayed elevated GlcNAc signatures and higher oxidation and chlorination activity of the secretory vesicle/plasma membrane-resident MPO relative to MPO from other granules. Endoglycosidase H-treated nMPO displaying Asn355-/Asn391-GlcNAcylation recapitulated the activity gain and showed increased thermal stability and enhanced polypeptide flexibility relative to untreated nMPO as measured by activity assays, circular dichroism and molecular dynamics. Endoglycosidase H-treated nMPO also demonstrated an elevated ceruloplasmin-mediated inhibition relative to nMPO. Modelling revealed that hyper-truncated Asn355-glycans positioned in the MPO:ceruloplasmin interface are critical for contact-free inhibition. We report on novel roles of the peculiar MPO glycosylation providing new insight into neutrophil glycobiology. Copy rights belong to original authors. Visit the link for more info

The synthesis of protease-mediated hyper inflammation in pre-morbid respiratory distress pathobiochemical states linked to coronavirus transmission . How COPD and ARDS in association with cardiovascular disease, diabetes and lung dysfunction pre-dispose to viral infection and illness. Published 11 July 2020. --- Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Airway passage disease has been well characterized in cystic fibrosis and this research which involves both clinical and animal model systems can inform general respiratory distress syndrome and viral pneumonia as that ascribed to the coronavirus 19. Published 10 July 2020 --- Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Dr Guerra recaps protease mechanisms and zymogen activation ultimately linking serpin mediation of neutrophil elastase during coronavirus infection. Published 08 July 2020 --- Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Finally, a way to read comics in class without your teacher complaining! Real life scientists are producing educational comics to teach cool science stuff. And they're FREE! Check them out, they have some pretty good explanations for a bunch of different topics.The FDA has recognised the ability of video games to help with therapy and greenlit a game for treating ADHD suffers. I can't wait for a game to help you deal with idiots, but we'll get there one day.Where did Matt Mercer's Vox Machina come from? Now you can read both of the first two seasons of the Critical Role prequels in a hardback omnibus. Wait, didn't we already do comics this week? Oops. Anyway, watch Critical Role. It's really good.This week, Professor took to the skies in Sky Rogue and DJ set us up the bomb in Valorant.Real Life Scientists making comics- https://www.sciencenews.org/article/real-life-scientists-inspire-comic-book-superheroes-science-literacy- https://www.jkxcomics.com/- https://static1.squarespace.com/static/59ab7c15e4fcb5c602a09465/t/5a08e052e2c483d6cb8cf769/1510531187492/JKXComics_EBV+and+the+Replication+Dance.pdfA video game for kids with ADHD is greenlit by the FDA- https://www.statnews.com/2020/06/15/fda-akili-adhd-endeavorrx/Dark Horse to Release 'Critical Role' Hardcover Omnibus- https://www.hollywoodreporter.com/heat-vision/dark-horse-release-critical-role-hardcover-omnibus-1296484Games PlayedProfessor– Sky Rogue - https://store.steampowered.com/app/381020/Sky_Rogue/Rating: 3.5/5DJ– Valorant – https://playvalorant.com/en-us/Rating: 3/5Other topics discussedThe Last of Us Part 2 game review : Not as Good as It Thinks It Is- https://www.thewrap.com/the-last-of-us-part-2-review-not-as-good-as-it-thinks-it-is-ellie-naughty-dog/Naughty Dog's Neil Druckmann calls out journalist Jason Schreier for Anne Frank joke- https://www.ginx.tv/en/video-games/naughty-dog-s-neil-druckmann-calls-out-journalist-jason-schrier-for-anne-frank-jokeG.I. Joe - Give Him The Stick : Parody of G.I. Joe's Public Service Announcements created by Fensler films- https://www.youtube.com/watch?v=DXFdPTaCtkcVictoria's sudden spike in coronavirus cases could result in localised lockdowns- https://7news.com.au/lifestyle/health-wellbeing/victorias-sudden-spike-in-coronavirus-cases-could-result-in-localised-lockdowns-c-1113679Epstein–Barr virus (EBV) (formally called Human gammaherpesvirus 4, is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans.)- https://en.wikipedia.org/wiki/Epstein%E2%80%93Barr_virusOnce Upon a Time….Life (French animated series which tells the story of the human body for children.)- https://en.wikipedia.org/wiki/Once_Upon_a_Time..._LifeCells at Work! (Japanese manga series written and illustrated by Akane Shimizu. It features the anthropomorphized cells of a human body, with the two main protagonists being a red blood cell and a white blood cell she frequently encounters.)- https://en.wikipedia.org/wiki/Cells_at_Work!Cells at Work! CODE BLACK (spin-off written by Shigemitsu Harada, illustrated by Ikuta Hatsuya, and supervised by the author of the original, Akane Shimizu. Similar to the original, the series is set in a world of anthropomorphic cells working in a body. It follows a the life of a rookie Erythrocyte, AA2153, and a Neutrophil, U-1196, as they work in a poorly maintained, middle-aged body burdened by issues such as stress, smoking, drinking and the like, causing complications in the cells' work and living environment.)- https://cellsatwork.fandom.com/wiki/Cells_at_Work!_CODE_BLACKInside Ralphie (Magic School Bus episode) (Third episode of Season 1 of the animated children's series The Magic School Bus. While Ralphie hosts a TV broadcast from his sickbed, his classmates seek to discover the cause of his illness.)- https://magicschoolbus.fandom.com/wiki/Inside_RalphieFor Lunch (Magic School Bus episode) (Second episode of season one of the animated children's series The Magic School Bus. Ms. Frizzle's students explore Arnold's digestive system after he accidentally swallows his miniaturized classmates.)- https://magicschoolbus.fandom.com/wiki/For_LunchFood and Drug Administration ((FDA or USFDA) is a federal agency of the United States Department of Health and Human Services, one of the United States federal executive departments. The FDA is responsible for protecting and promoting public health through the control and supervision of food safety, tobacco products, dietary supplements, prescription and over-the-counterpharmaceutical drugs (medications), vaccines,biopharmaceuticals,blood transfusions, medical devices, electromagnetic radiation emitting devices (ERED), cosmetics, animal foods & feed and veterinary products.)- https://en.wikipedia.org/wiki/Food_and_Drug_AdministrationRitalin (Methylphenidate, sold under the trade name Ritalin among others, is a stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is a first line medication for ADHD. It may be taken by mouth or applied to the skin.)- https://en.wikipedia.org/wiki/MethylphenidateTali Health (Tali Health creates game based programs to improve attention in children. TALi TRAIN is a clinically validated digital training and treatment program that addresses the world’s leading reported early childhood issue-attention difficulties, a key feature in conditions including ADHD and ASD (Autism Spectrum Disorder).)- https://talihealth.com.au/Michele Assarasakorn (comic artist | colorist on ISOLA / Gotham Academy/ Critical Role)Twitter : https://twitter.com/msassykInstagram : https://www.instagram.com/msassyk/Critical Role Wiki (A Place Documenting the Current History of Exandria)- https://criticalrole.fandom.com/wiki/Critical_Role_WikiThe World of RWBY: The Official Companion (RWBY lore book)- https://www.amazon.com/World-RWBY-Official-Companion/dp/1974704386Critical Role: Vox Machina Origins Library Edition: Series I & II Collection at Amazon-https://www.amazon.com/Critical-Role-Machina-Origins-Collection/dp/1506721737Ace Combat (Ace Combat is a hybrid arcade-style flight action video game franchise mainly developed by Bandai Namco Studios and published by Bandai Namco Entertainment.)- https://en.wikipedia.org/wiki/Ace_CombatLUFTRAUSERS (shoot 'em up video game developed by Netherlands-based indie developer studio Vlambeer and published by Devolver Digital for Microsoft Windows, OS X,Linux, PlayStation 3 and PlayStation Vita.)- https://store.steampowered.com/app/233150/LUFTRAUSERS/Guns of Icarus (Guns of Icarus Online is the original PvP steampunk airship combat game that laid the groundwork for the expanded Guns of Icarus experience, Guns of Icarus Alliance.)- https://store.steampowered.com/app/209080/Guns_of_Icarus_Online/PS5 Reveal Event & Every Next Gen Game announced- https://www.gamespot.com/articles/ps5-reveal-event-every-nextgen-game-announced-by-s/1100-6478266/Space Shuttle Challenger disaster (The Space Shuttle Challenger disaster was a fatal incident in the United States space program that occurred on Tuesday, January 28, 1986, when the Space Shuttle Challenger (OV-099) broke apart 73 seconds into its flight, killing all seven crew members aboard. The failure was caused by the failure of O-ring seals used in the joint that were not designed to handle the unusually cold conditions that existed at this launch.)- https://en.wikipedia.org/wiki/Space_Shuttle_Challenger_disasterSpace Shuttle Columbia disaster (The Space Shuttle Columbia disaster was a fatal incident in the United States space program that occurred on February 1, 2003, when the Space Shuttle Columbia (OV-102) disintegrated as it reentered the atmosphere, killing all seven crew members. During the launch of STS-107,Columbia's 28th mission, a piece of foam insulation broke off from the Space Shuttle external tank and struck the left wing of the orbiter.)- https://en.wikipedia.org/wiki/Space_Shuttle_Columbia_disasterThe Slo Mo Guys - How a TV Works in Slow Motion- https://www.youtube.com/watch?v=3BJU2drrtCMWinnie the Pooh could be banned from Shanghai Disneyland as a result of an ongoing meme used to criticize China's leader-https://www.businessinsider.com/winnie-the-pooh-shanghai-disneyland-meme-2018-11?r=AU&IR=TObama & Xi Jinping as Tigger & Winnie The Pooh- https://pbs.twimg.com/media/DsXrZ-6UwAUHGRx?format=jpg&name=900x900Shout Outs11 June 2020 – Playstation 5 reveal - https://deadline.com/2020/06/sony-playstation-5-revealed-videogames-1202957140/Sony lifted the veil to reveal the PlayStation 5, the video game console it hopes will be a significant lure for consumers this holiday season. In a live-streamed video presentation lasting more than an hour, Sony Interactive Entertainment revealed new details for the PS5, including its design and lineup of new games. Rockstar Games’ Grand Theft Auto will be included for free, and there are two dozen other games heading to the platform. The unit’s two-tone design is a shift from previous versions and gives off distinct imperial stormtrooper vibes. PS5 will be available in both a standard model with an Ultra HD Blu-ray disc drive, and a digital model without a disc drive. One of the biggest series of all time, Grand Theft Auto, will be coming to PS5, with enhanced and expanded versions of Grand Theft Auto V and Grand Theft Auto Online to launch on PS5 in the second half of 2021.15 June 2020 – Rare stone ginger beer bottle from 1930s-era sells for record price - https://www.abc.net.au/news/2020-06-15/ginger-beer-bottle-sells-for-huge-price/12353574A rare ginger beer bottle from the 1930s, made for a Warwick soft drink company, has sold for a record price in Toowoomba. It has collectors encouraging people to check their sheds and old farm dumps for possible 'buried treasure'. The hammer fell at $17,500 for the stoneware Doneley and Butler bottle. The little green lip at the top is what set it apart from bottles worth a fraction of that price."These bottles are extremely rare, there have only been two or three found in perfect condition," said auctioneer Graham Lancaster."That colour combination of glazes makes it unique worldwide."He said the Warwick bottle set a record price locally, and quite possible a world-record, for an antique crown-seal soft drink bottle of its type.16 June 2020 – Christopher Nolan’s Batman Begins turns 15 - https://comicbook.com/movies/news/batman-begins-anniversary-the-dark-knight-christopher-nolan-christian-bale/As the '90s progressed, the image of Batman on the big screen began to descend into the realm of campiness previously seen in Adam West's take on the character back in the '60s TV series and movie, which started to sour audiences on the character entirely. After a variety of reports emerged about a new take on the character in the early '00s, fans were given Christopher Nolan's gritty and grounded origin story for the character in 2005, debuting Christian Bale as the Dark Knight. This new take on the character harkened back to some of the more grounded interpretations of the character, while adding just enough whimsy to remind audiences that this was still a comic book movie. Batman Begins went on to take in $371 million worldwide, a fraction of the figures that subsequent superhero movies would go on to earn, That film's success might not have been groundbreaking, but it set the stage for The Dark Knight and The Dark Knight Rises, with some audiences considering those films to be the best comic book films of all time, both of which earned major box office hauls and the former earning Heath Ledger a posthumous Oscar for his performance as the Joker.18 June 2020 – Dame Vera Lynn passes away at 103 - https://www.bbc.com/news/uk-53091856The singer was best known for performing hits such as We'll Meet Again to troops on the front line in countries including India and Egypt. Six weeks ago, ahead of the 75th anniversary of VE Day and during the height of the coronavirus pandemic, Dame Vera said simple acts of bravery and sacrifice still define our nation. A week later, she became the oldest artist to get a top 40 album in the UK, beating her own record when her greatest hits album re-entered the charts at number 30. Born in London's East Ham in 1917, Dame Vera's singing talent was discovered at a young age and by age 11 she had left school to pursue a full-time career as a dancer and singer. Lynn devoted much time and energy to charity work connected with ex-servicemen, disabled children and breast cancer. She was held in great affection by Second World War veterans and in 2000 was named the Briton who best exemplified the spirit of the 20th century. Paying tribute, Prime Minister Boris Johnson said the singer's "charm and magical voice entranced and uplifted our country in some of our darkest hours". "Her voice will live on to lift the hearts of generations to come," he said. She died at the age of 103 in Ditchling,East Sussex.19 June 2020 – Sir Ian Holm passes away at 88 - https://www.theguardian.com/film/2020/jun/19/ian-holm-dies-alien-chariots-of-fire-bilbo-bagginsSir Ian Holm, an acclaimed British actor whose long career included roles in Chariots of Fire and The Lord of the Rings has died. A star of stage and screen, Sir Ian won a Tony Award for best featured actor as Lenny in Harold Pinter's play The Homecoming in 1967. He won a British Academy Film Award and gained a supporting-actor Oscar nomination for portraying pioneering athletics coach Sam Mussabini in the hit 1982 film Chariots of Fire. His other well-known film roles include Ash in Alien, Father Vito Cornelius in The Fifth Element, Chef Skinner in Ratatouille, and Bilbo Baggins in The Lord of the Rings and The Hobbit film series. Sir Ian was knighted in 1998 for his services to drama. He died from Parkinson’s disease in London.Remembrances16 June 1804 – Johann Adam Hiller - https://en.wikipedia.org/wiki/Johann_Adam_HillerGerman composer,conductor and writer on music, regarded as the creator of the Singspiel, an early form of German opera. It is a form of German-language music drama, now regarded as a genre of opera. It is characterized by spoken dialogue, which is alternated with ensembles,songs, ballads, and arias which were often strophic, or folk-like. Singspiel plots are generally comic or romantic in nature, and frequently include elements of magic, fantastical creatures, and comically exaggerated characterizations of good and evil. In many of these operas he collaborated with the poet Christian Felix Weiße. Furthermore, Hiller was a teacher who encouraged musical education for women, his pupils including Elisabeth Mara and Corona Schröter. He was Kapellmeister of Abel Seyler's theatrical company, and became the first Kapellmeister of Leipzig Gewandhaus. To Hiller has been given the credit of being the originator of the Singspiel, the beginning of German comedy opera as distinct from the French and Italian developments. The most important of his operas were: Lottchen am Hofe (Lottie at court, 1760),Der Teufel ist los (The devil is loose, 1768), and Poltis, oder Das gerettete Troja (Poltis, or Troy rescued, 1782). The lyrics of all his Singspiele were of considerable musical value, and were long popular. Among his sacred compositions are: A Passion Cantata, Funeral Music in Honor of Hasse, a setting of the one hundredth Psalm; and a few symphonies. He died at the age of 76 in Leipzig.16 June 1858 – John Snow - https://en.wikipedia.org/wiki/John_SnowEnglish physician and a leader in the development of anaesthesia and medical hygiene. He is considered one of the founders of modern epidemiology, in part because of his work in tracing the source of a cholera outbreak in Soho, London, in 1854, which he curtailed by removing the handle of a water pump. Snow's findings inspired the adoption of anaesthesia as well as fundamental changes in the water and waste systems of London, which led to similar changes in other cities, and a significant improvement in general public health around the world. John Snow was one of the first physicians to study and calculate dosages for the use of ether and chloroform as surgical anaesthetics, allowing patients to undergo surgical and obstetric procedures without the distress and pain they would otherwise experience. He designed the apparatus to safely administer ether to the patients and also designed a mask to administer chloroform. He personally administered chloroform to Queen Victoria when she gave birth to the last two of her nine children, Leopold in 1853 and Beatrice in 1857 and was still not yet knighted, leading to wider public acceptance of obstetric anaesthesia. John Snow studied chloroform as much as he studied ether, which was introduced in 1847 by James Young Simpson, a Scottish obstetrician. He realised that chloroform was much more potent and required more attention and precision when administering it. Snow first realised this with Hannah Greener, a 15-year-old patient who died on 28 January 1848 after a surgical procedure that required the cutting of her toenail. She was administered chloroform by covering her face with a cloth dipped in the substance. However, she quickly lost pulse and died. After investigating her death and a couple of deaths that followed, he realized that chloroform had to be administered carefully and published his findings in a letter to The Lancet. Snow was a skeptic of the then-dominant miasma theory that stated that diseases such as cholera and bubonic plague were caused by pollution or a noxious form of "bad air". The germ theory of disease had not yet been developed, so Snow did not understand the mechanism by which the disease was transmitted. His observation of the evidence led him to discount the theory of foul air. He first published his theory in an 1849 essay, On the Mode of Communication of Cholera, followed by a more detailed treatise in 1855 incorporating the results of his investigation of the role of the water supply in the Soho epidemic of 1854. By talking to local residents (with the help of Reverend Henry Whitehead), he identified the source of the outbreak as the public water pump on Broad Street (now Broadwick Street). Although Snow's chemical and microscope examination of a water sample from the Broad Street pump did not conclusively prove its danger, his studies of the pattern of the disease were convincing enough to persuade the local council to disable the well pump by removing its handle (force rod). Snow later used a dot map to illustrate the cluster of cholera cases around the pump. He also used statistics to illustrate the connection between the quality of the water source and cholera cases. He showed that homes supplied by the Southwark and Vauxhall Waterworks Company, which was taking water from sewage-polluted sections of the Thames, had a cholera rate fourteen times that of those supplied by Lambeth Waterworks Company, which obtained water from the upriver, cleaner Seething Wells. Snow's study was a major event in the history of public health and geography. It is regarded as the founding event of the science of epidemiology. He died from stroke at the age of 45 in London.16 June 1869 – Charles Sturt - https://en.wikipedia.org/wiki/Charles_SturtCharles Napier Sturt, British officer and explorer of Australia, and part of the European exploration of Australia. He led several expeditions into the interior of the continent, starting from Sydney and later from Adelaide. His expeditions traced several of the westward-flowing rivers, establishing that they all merged into the Murray River, which flows into the Southern Ocean. He was searching to prove his own passionately held belief that an "inland sea" was located at the centre of the continent. Sturt found the conditions and climate in New South Wales much better than he expected, and he developed a great interest in the country. Sturt received approval from Governor Darling on 4 November 1828 to explore the area of the Macquarie River in western New South Wales. The party faced the ordeal of rowing back upriver on the Murray and Murrumbidgee, against the current, in the heat of an Australian summer. Their supplies ran out and, when they reached the site of Narrandera in April, they were unable to go any further. Sturt sent two men overland in search of supplies and they returned in time to save the party from starvation. But Sturt went blind for some months and never fully recovered his health. By the time they reached Sydney again, they had rowed and sailed nearly 2,900 kilometres of the river system. Sturt believed that it was his destiny to discover a great salt water lake, known as 'the inland sea', in the middle of Australia. At very least, he wanted to be the first explorer to plant his foot in 'the centre' of Australia. In August 1844, he set out with a party of 15 men, 200 sheep, six drays, and a boat to explore north-western New South Wales and to advance into central Australia. They travelled along the Murray and Darling rivers before passing the future site of Broken Hill. They were stranded for months by the extreme summer conditions near the present site of Milparinka. When the rains eventually came, Sturt moved north and established a depot at Fort Grey (today this site is within Sturt National Park). With a small group of men, including explorer John McDouall Stuart as his draughtsman, Sturt pressed on across what is now known as Sturt's Stony Desert and into the Simpson Desert. Unable to go further, he turned back to the depot. Sturt made a second attempt to reach the centre of Australia, but he developed scurvy in the extreme conditions. His health broke down and he was forced to abandon the attempt. John Harris Browne, surgeon on the expedition, assisted Sturt, took over leadership of the party and, after travelling a total of 3,000 miles (4,800 km), brought it back to safety. He died from heart failure at the age of 74 in Cheltenham, Gloucestershire.16 June 1977 – Wernher von Braun - https://en.wikipedia.org/wiki/Wernher_von_BraunGerman and later American aerospace engineer and space architect. He was the leading figure in the development of rocket technology in Nazi Germany and a pioneer of rocket and space technology in the United States. While in his twenties and early thirties, von Braun worked in Nazi Germany's rocket development program. He helped design and develop the V-2 rocket at Peenemünde during World War II. Though a member of the SS, following the war he was secretly moved to the United States, along with about 1,600 other German scientists, engineers, and technicians, as part of Operation Paperclip. He worked for the United States Army on an intermediate-range ballistic missile program, and he developed the rockets that launched the United States' first space satellite Explorer 1. In 1960, his group was assimilated into NASA, where he served as director of the newly formed Marshall Space Flight Center and as the chief architect of the Saturn V super heavy-lift launch vehicle that propelled the Apollo spacecraft to the Moon. In 1967, von Braun was inducted into the National Academy of Engineering, and in 1975, he received the National Medal of Science. He advocated a human mission to Mars. Von Braun also developed the idea of a Space Camp that would train children in fields of science and space technologies, as well as help their mental development much the same way sports camps aim at improving physical development. Von Braun took a very conservative approach to engineering, designing with ample safety factors and redundant structure. This became a point of contention with other engineers, who struggled to keep vehicle weight down so that payload could be maximized. As noted above, his excessive caution likely led to the U.S. losing the race to put a man into space with the Soviets. He died from pancreatic cancer at the age of 65 in Alexandria, Virginia.Famous Birthdays16 June 1801 – Julius Plücker - https://en.wikipedia.org/wiki/Julius_Pl%C3%BCckerGerman mathematician and physicist. He made fundamental contributions to the field of analytical geometry and was a pioneer in the investigations of cathode rays that led eventually to the discovery of the electron. He also vastly extended the study of Lamé curves. In 1836, Plücker was made professor of physics at University of Bonn. In 1858, after a year of working with vacuum tubes of his Bonn colleague Heinrich Geißler, he published his first classical researches on the action of the magnet on the electric discharge in rarefied gases. He found that the discharge caused a fluorescent glow to form on the glass walls of the vacuum tube, and that the glow could be made to shift by applying an electromagnet to the tube, thus creating a magnetic field. It was later shown that the glow was produced by cathode rays. Plücker, first by himself and afterwards in conjunction with Johann Hittorf, made many important discoveries in the spectroscopy of gases. He was the first to use the vacuum tube with the capillary part now called a Geissler tube, by means of which the luminous intensity of feeble electric discharges was raised sufficiently to allow of spectroscopic investigation. He anticipated Robert Wilhelm Bunsen and Gustav Kirchhoff in announcing that the lines of the spectrum were characteristic of the chemical substance which emitted them, and in indicating the value of this discovery in chemical analysis. According to Hittorf, he was the first who saw the three lines of the hydrogen spectrum, which a few months after his death, were recognized in the spectrum of the solar protuberances. In 1865, Plücker returned to the field of geometry and invented what was known as line geometry in the nineteenth century. In projective geometry, Plücker coordinates refer to a set of homogeneous co-ordinates introduced initially to embed the set of lines in three dimensions as a quadric in five dimensions. The construction uses 2×2 minor determinants, or equivalently the second exterior power of the underlying vector space of dimension 4. It is now part of the theory of Grassmannians, to which these co-ordinates apply in generality (k-dimensional subspaces of n-dimensional space). He was born in Elberfeld,Duchy of Berg,Holy Roman Empire.16 June 1915 – John Tukey - https://en.wikipedia.org/wiki/John_TukeyJohn Wilder Tukey, American mathematician best known for development of the Fast Fourier Transform (FFT) algorithm and box plot. The Tukey range test, the Tukey lambda distribution, the Tukey test of additivity, and the Teichmüller–Tukey lemma all bear his name. He is also credited with coining the term 'bit'. Early in his career Tukey worked on developing statistical methods for computers at Bell Labs where he invented the term "bit" in 1947. n 1970, he contributed significantly to what is today known as the jackknife estimation—also termed Quenouille–Tukey jackknife. He introduced the box plot in his 1977 book, "Exploratory Data Analysis". He is also the creator of several little-known methods such as the trimean and median-median line, an easier alternative to linear regression. He also contributed to statistical practice and articulated the important distinction between exploratory data analysis and confirmatory data analysis, believing that much statistical methodology placed too great an emphasis on the latter. Though he believed in the utility of separating the two types of analysis, he pointed out that sometimes, especially in natural science, this was problematic and termed such situations uncomfortable science. Tukey coined many statistical terms that have become part of common usage, but the two most famous coinages attributed to him were related to computer science. While working with John von Neumann on early computer designs, Tukey introduced the word "bit" as a contraction of "binary digit" The term "bit" was first used in an article by Claude Shannon in 1948. In 2000, Fred Shapiro, a librarian at the Yale Law School, published a letter revealing that Tukey's 1958 paper "The Teaching of Concrete Mathematics" contained the earliest known usage of the term "software" found in a search of JSTOR's electronic archives, predating the OED's citation by two years. This led many to credit Tukey with coining the term, particularly in obituaries published that same year, although Tukey never claimed credit for any such coinage. In 1995, Paul Niquette claimed he had originally coined the term in October 1953, although he could not find any documents supporting his claim.The earliest known publication of the term "software" in an engineering context was in August 1953 by Richard R. Carhart, in a RAND Corporation research memorandum. He was born in New Bedford, Massachusetts.16 June 1909 – Archie Carr - https://en.wikipedia.org/wiki/Archie_CarrArchie Fairly Carr, Jr., American herpetologist,ecologist and a pioneering conservationist. He was a Professor of Zoology at the University of Florida. In 1987 he was awarded the Eminent Ecologist Award by the Ecological Society of America. He made extraordinary contribution to sea turtle conservation by way of bringing attention to the world's declining turtle populations due to over-exploitation and loss of safe habitat. He started out as a high school science teacher before becoming a college professor. He published numerous books and articles, including Ulendo: Travels of a Naturalist in and out of Africa, High Jungles and Low, So Excellent a Fishe (about his green turtles), The Windward Road and several Time-Life books such as The Everglades and The Reptiles. He was also the author of the Handbook of Turtles, and with Coleman J. Goin, Guide to the Reptiles, Amphibians and Freshwater Fishes of Florida. While a serious scientific and nature writer, he also had a remarkable sense of humor, which led him to publish the parody of scientific taxonomic keys - his A Subjective Key to the Fishes of Alachua County, Florida, affectionately known as the "Carr Key". Carr was also known for his efforts in conservation, especially for sea turtles, helping convince Costa Rica to establish Tortuguero National Park in 1975. He was a co-founder of the Caribbean Conservation Corporation, which helps to save and monitor sea turtles in Tortuguero,Costa Rica. He was often joined in his conservation work by his wife Marjorie Carr, who was a major advocate for conservation in her own right. In 1952 Carr was awarded the Daniel Giraud Elliot Medal from the National Academy of Sciences. He was born in Mobile, Alabama.Events of Interest16 June 1884 – The first purpose-built roller coaster, LaMarcus Adna Thompson's "Switchback Railway", opens in New York's Coney Island amusement park. - https://www.history.com/this-day-in-history/first-roller-coaster-in-america-opensKnown as a switchback railway, it was the brainchild of LaMarcus Thompson, traveled approximately six miles per hour and cost a nickel to ride. The new entertainment was an instant success and by the turn of the century there were hundreds of roller coasters around the country. For five cents, riders would climb a tower to board the large bench-like car and were pushed off to coast 600 ft (183 m) down the track to another tower. The car went just over 6 mph (9.7 km/h). At the top of the other tower the vehicle was switched to a return track or "switched back" (hence the name). The new entertainment was an instant success and by the turn of the century there were hundreds of roller coasters around the country.16 June 1911 – IBM founded as the Computing-Tabulating-Recording Company in Endicott, New York. - http://www.techgetz.com/history-of-ibm/In 1911 the company that leased Unit record equipment, especially Hollerith punched cards and card readers to government bureaus and insurance agencies, became the Computing-Tabulating-Recording Company (CTR). Thomas J. Watson (1874-1956) took over in 1924, using the name “International Business Machines.” IBM expanded into electric typewriters and other office machines. Watson was a salesman and concentrated on building a highly motivated, very well paid sales force that could craft solutions for clients unfamiliar with the latest technology. His motto was “THINK”; customers were advised to not “fold, spindle or mutilate” the delicate cardboard cards.16 June 2012 – The United States Air Force's robotic Boeing X-37B spaceplane returns to Earth after a classified 469-day orbital mission. - https://www.space.com/16110-secret-x37b-space-plane-landing.htmlThe unmanned X-37B spacecraft, also known as Orbital Test Vehicle-2 (OTV-2), glided back to Earth on autopilot, touching down at California's Vandenberg Air Force Base at 5:48 a.m. PDT (8:48 a.m. EDT, 1248 GMT). The landing brought to an end the X-37B program's second-ever spaceflight, a mission that lasted more than 15 months with objectives that remain shrouded in secrecy. The X-37B stayed in orbit for 469 days this time, more than doubling the 225 days its sister ship, OTV-1, spent in space last year on the program's maiden flight. Officials at Vandenberg said the spacecraft conducted "on-orbit experiments" during its mission. Exactly what the spacecraft, which is built by Boeing, was doing up there for so long is a secret. The details of the X-37B's mission, which is overseen by the Air Force's Rapid Capabilities Office, are classified, as is its payload. This secrecy has led to some speculation, especially online and abroad, that the X-37B could be a space weapon of some sort — perhaps a sophisticated satellite-killer. Some experts also suspect that the vehicle may be an orbital spy platform. "This is a test vehicle to prove the materials and capabilities, to put experiments in space and bring them back and check out the technologies," Richard McKinney, the Air Force's deputy undersecretary for space programs.16 June 2016 – Shanghai Disneyland Park, the first Disney Park in Mainland China, opens to the public - https://www.dw.com/en/distinctly-chinese-disneyland-opens-in-shanghai/a-19332984Shanghai Disney Resort, the first Disney resort in Mainland China and the sixth worldwide, celebrated its historic Grand Opening today, culminating one of Disney's most ambitious projects ever. The wonder and imagination of Disney greeted the people of China in magical new ways as the gates opened to Shanghai Disneyland, a theme park like no other with the biggest, tallest castle in any Disney park, the first pirate-themed land and Disney's most technologically advanced park to date. Walt Disney Co. CEO Bob Iger and Chinese Vice Premier Wang Yang cut a red ribbon together, signaling the Communist Party's endorsement of the $5.5 billion (4.87 billion euro) resort - one of the largest foreign investments in China. The lavish ceremony featured a children's choir singing "When You Wish Upon a Star," as well as actors dressed as Sleeping Beauty, Donald Duck, and other Disney characters dancing on stage. The entrance of the park is called "Mickey Avenue" instead of "Main Street USA." Stores feature Minnie Mouse in traditional quipau dresses and the Wandering Moon Teahouse is modeled after a building in eastern China. Shanghai Disney Resort is filled with immersive Disney storytelling, thrilling attractions, spectacular live entertainment and memory-making experiences designed to inspire and delight Chinese guests. The world-class vacation destination includes a magical theme park with six themed lands, two imaginatively designed hotels, a Disneytown shopping and dining district, and Wishing Star Park recreational area.IntroArtist – Goblins from MarsSong Title – Super Mario - Overworld Theme (GFM Trap Remix)Song Link -https://www.youtube.com/watch?v=-GNMe6kF0j0&index=4&list=PLHmTsVREU3Ar1AJWkimkl6Pux3R5PB-QJFollow us onFacebook- Page - https://www.facebook.com/NerdsAmalgamated/- Group - https://www.facebook.com/groups/440485136816406/Twitter - https://twitter.com/NAmalgamatedSpotify - https://open.spotify.com/show/6Nux69rftdBeeEXwD8GXrSiTunes -https://itunes.apple.com/au/podcast/top-shelf-nerds/id1347661094RSS -http://www.thatsnotcanonproductions.com/topshelfnerdspodcast?format=rssInstagram - https://www.instagram.com/nerds_amalgamated/Email - Nerds.Amalgamated@gmail.comSupport via Podhero- https://podhero.com/podcast/449127/nerds-amalgamatedRate & Review us on Podchaser - https://www.podchaser.com/podcasts/nerds-amalgamated-623195

Neutrophil Extracellular Traps (NETs) as Biomarkers and Therapeutic Targets? Dr RR Baliga's 'Got Knowledge Doc' PodKasts for Physicians References Yang L, Liu Q, Zhang X, et al. DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25 [published online ahead of print, 2020 Jun 11]. Nature. 2020 Thålin C, et al. Neutrophil Extracellular Traps: Villains and Targets in Arterial, Venous, and Cancer-Associated Thrombosis. Arterioscler Thromb Vasc Biol. 2019;39(9):1724-1738. Döring Y, Libby P, Soehnlein O. Neutrophil Extracellular Traps Participate in Cardiovascular Diseases: Recent Experimental and Clinical Insights. Circ Res. 2020;126(9):1228-1241.

Audio abstract for the published article: Neutrophil Extracellular Traps Profiles in Patients with Incident Systemic Lupus Erythematosus and Lupus Nephritis by Maurizio Bruschi, Alice Bonanni, Andrea Petretto, Augusto Vaglio, Federico Pratesi, Laura Santucci, Paola Migliorini, Roberta Bertelli, Maricla Galetti, Silvana Belletti, Lorenzo Cavagna, Gabriella Moroni, Franco Franceschini, Micaela Fredi, Giulia Pazzola, Landino Allegri, Renato Alberto Sinico, Giampaola Pesce, Marcello Bagnasco, Angelo Manfredi, Giuseppe A. Ramirez, Paola Ramoino, Paolo Bianchini, Francesco Puppo, Francesca Pupo, Simone Negrini, Federico Mattana, Giacomo Emmi, Giacomo Garibotto, Domenico Santoro, Francesco Scolari, Angelo Ravelli, Angela Tincani, Paolo Cravedi, Stefano Volpi, Giovanni Candiano and Gian Marco Ghiggeri The Journal of Rheumatology March 2020, 47 (3) 377-386; DOI: https://doi.org/10.3899/jrheum.181232

When it comes to testing, you can always count on a lively debate about how to best identify food sensitivity and intolerance. In this interview we review recent clinical and mechanistic research on the ALCAT test, including studies conducted by Yale School of Medicine and other institutions. In addition, general advice will be given about how food testing can help integrative practitioners create personalized diets for health and performance for their patients. About the Expert Roger Deutsch is the CEO of Cell Science Systems, where he oversees research and general management. He has been involved with all aspects of the development of ALCAT technology for 34 years. He previously studied psychology at the State University of New York, Purchase and Chinese medicine at the International College of Oriental Medicine in the United Kingdom. He is coauthor of the book, Your Hidden Food Allergies Are Making You Fat, and has lectured in more than 25 countries on the topics of food, inflammation, and the aging process. He is deeply involved in supporting free education for impoverished girls and free healthcare in rural India. About the Sponsor Cell Science Systems, Corp (CSS) is a CLIA licensed lab and an FDA registered medical device establishment that has developed the ALCAT test for food and chemical sensitivities, as well as GI function assays, telomere length assessments, molecular diagnostics, and this month will also be launching cellular tests for the assessment of functional micronutrient deficiencies and antioxidant status. CSS received the company of the year award in 2016 for Food Intolerance Testing, North America, by Frost & Sullivan. The ALCAT test has been clinically validated in research at the Yale School of Medicine, where mechanistic studies were also conducted. Those studies have led to new discoveries regarding the pathogenic mechanisms underlying food sensitivities. CSS will continue to participate in industry grant–funded, cross-border, translational research that focuses on the role of food-induced release of DNA and its role in pathology. CSS is located in Deerfield Beach, FL, and also operates a wholly owned subsidiary lab in Potsdam, Germany. Transcript Karolyn Gazella: Hello. I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today, our topic is Identifying Food Sensitivity and Intolerance. I'd like to thank Cell Science Systems, who is the sponsor of this topic. My guest is Roger Deutsch, who is one of the pioneers in the field of food and chemical sensitivity testing. Roger, thank you so much for joining me. Roger Deutsch: Thank you, Karolyn. Pleasure to be here. Gazella: Well, historically, it's been kind of challenging to identify food sensitivities and intolerances in patients. Generally speaking, I'm just wondering, why is that? Does the research you've participated in offer any new understandings? Deutsch: Yeah, the research that I've been involved in certainly does offer a lot of new understandings. Just to put this in context, and just to repeat, I'm sure most people are very clear on this distinction between allergy and intolerance. Just for sake of brief review, the term allergy was coined by a physician named von Pirquet in 1906 to denote an altered reaction. Then there was quite a bit of debate amongst allergists in Europe during the '20s and '30s as to what should be included in that definition of an altered reaction. At the end of the day, they settled on including only those types of reactions that induced an immediate symptom onset, because those are more definable. Just through some research in the '30s where they transferred serum from an allergic patient to a non-allergic patient and then scratch test the area where the serum transfer took place, and they would induce the wheal-and-flare. They knew that there was some factor in the serum that caused allergy. They didn't know what it was. They called it reagent. Then, years later, in 1969, they found out reagent was IgE. Then they found out all the events that were preceding the IgE molecule and then how the IgE molecule bound to mast cells and then cross linked, which caused degranulation and release of histamine and medium symptoms and so forth. Later, interestingly, they found out that's the same pathway the body uses to protect against infections with worms. So they called that allergen. Of course, worms are large compared to a cell, so when the immune system has to combat such a big pathogen, it's a very dramatic reaction, so there's a very dramatic release of histamine. The symptom onset, then, is very dramatic and very rapid. Then that being as clear as it was, by contrast, intolerances or sensitivities due to an enzyme deficiency or some other part of the immune system, the innate immune system underlining a sensitivity was more difficult because the symptom onset wasn't immediate. The linkage between cause and effect was ambiguous, obscure, and the pathway was unknown, so what do you look for? A lot of different things were proposed. Before too long, people proposed looking at the white blood cell. In the 1950s, an allergist in El Paso named Black reported his usage of looking at white blood cells through a microscope, being challenged with an allergen and seeing morphological changes that then were correlated with clinical symptoms. Then that work got picked by some researchers from Washington University named, gosh. I forgot what their name is. I don't know. It will come to me later, but anyway, they gave it the name cytotoxic test. They published about three or four papers, and it became very popular and broadly used. There was a lot of political upheaval because it's something that came on that proposed a solution to a lot of problems. People don't like huge paradigm shifts, so it fell a little bit by the wayside. We knew that there was a white blood cell component to the thing, which is logical. The immune system would underline an immune reaction. It's no mystery. When we came along, we thought, "Look. The allergists don't like the cytotoxic test." Bryan was the name, William and Marian Bryan brought out the cytotoxic testing. Allergists get upset about it, because it maybe changes the paradigm in ways they were afraid of. It was subjective, because it required a technician to look at cells under a microscope and make a judgment call as to whether or not there was a reaction. We came along in that period of time, in the mid-'80s and applied electronic instrumentation to the measurement of the cells and introduced some other standards, better controls over the allergen presentation and used the computer to interpret the degree of change in the white blood cells. We went along quite a long time observing and making the clear association that when the white blood cells would expand or degranulate or didn't become [inaudible 00:05:48], now we know undergo apoptosis or necrosis or pyroptosis, there was good clinical correlation. We did studies in the late '80s with people who were pioneers, and had backgrounds in research and drug companies even that were interested in this field. We found that when you had an ALCAT, the name of our technology was ALCAT. When you had an ALCAT positive and if you challenged the person with the food that was positive under double blind conditions, you would get correlation about 80% of the time. When there was an ALCAT negative, you would get correlation, in other words, no clinical response from a double blind challenge, about 85% of the time. That was good clinical validation. It was building the mechanism. If you fast forward to earlier this year and last year, there had been a number of clinical studies in between, of course, but we gave the technology to be investigated to some very smart people at Yale School of Medicine. They did a clinical study that they know how to do, a randomized, controlled, double blind, placebo-controlled trial, feeding patients either a diet that was based on the ALCAT test, eliminating positive foods or placebo group, and nobody knew who was in what group except the one coordinator who didn't tell until the end, a placebo diet based on an ALCAT test where they kept the positive foods in. They just looked at change in symptom scores over time. They saw a huge difference between the people following the true experimental diet versus the ones following the placebo. Then they looked at some chemistries. They actually banked serum at the beginning of the study, knowing that retrospectively, they'd see who had done well. Then they could go and evaluate what might have happened amongst that population that had a strong response. They did find that, out of about 1,200 or so peptides and proteins that they assayed, that neutrophil elastase would drip precipitously in those people. Clearly, the neutrophil seemed to have some effect. They went on and did some look into what's happening inside the cell, and which subtypes of leukocytes were most involved. They did immunological studies using flow psychometry and they found that eosinophils were activated most of the time. Neutrophil elastase was being released, so obviously, there was some orchestration between these two classes of granulocytes, but the other thing they found, which is very interesting, is that there was greater release of DNA from the cells that had reacted in a positive way than there were, excuse me, reacted to a food that was tested as positive versus when there was no food in that sample or an ALCAT-negative food. Somehow, the positive reaction would induce the peripheral leukocytes to undergo some sort of process that would result in the release of toxic mediums like neutrophil elastase and others, but would also cause a release of cellular DNA. That's an interesting finding, because over the last few years, most people are not familiar with this yet, but common sense tells you DNA doesn't belong outside the cells. It belongs either nicely tucked away in a eukaryotic cell in the nuclei or in the mitochondria. When it gets out, it can cause problems. We could talk all day about how it gets out, but there's some very smart research from Max Planck Institute, which shows that these neutrophils and macrophages and other granulocytes use, as a strategy to kill pathogens, something called ETosis. When it applied to neutrophils, it's called NETosis. Even after this cell has released free radicals, then it's to try and defend against invaders. Even though the cell is dead, a lot of the nuclear material, the histones, the DNA, merge with granules and the toxic mediators inside and the plasma membranes and the internal membranes and strip out, form these nets. That can trap pathogens, and the DNA is toxic, and kills them. That's occurring, but if too much of this goes on and the body's mechanism for cleaning up the mess, which is mostly DNA's want, and you have the persistence of this toxic DNA in the circulation, excuse me. It causes all sorts of problems, like metabolic problems, like lupus, like arthritis, and even cancer. It's a new area of medicine, so it's interesting. We've found that the ALCAT predicts the foods that trigger the release of DNA. Now we have the next step ahead of us, using a grant that we received from one of the larger industry players, we're going to characterize the nature of the DNA that's released, because the nuance here is that if the DNA is methylated, it's not toxic. If the DNA is unmethylated, it is very toxic. We want to look at that. The expectation is that we'll find that it is mostly unmethylated, because the release of DNA is kind of chaotic and not controlled. Gazella: That is fascinating. I have you tell you, you're talking about the 2018 study that was published in Alternative and Complementary Therapies? Deutsch: No, this study was, it came out Yale. Gazella: It was earlier this year? Deutsch: Yeah, I can't remember the actual name of the journal right off the top of my head. Gazella: Okay. Deutsch: If people go on to CellScienceSystems.com, there are a couple of papers from Yale. The first one I spoke of was a clinical paper. That was published in EMJ Gastroenterology. The other one was another nice, international journal. Gazella: Great. I do want to talk about the study that was published in Alternative and Complementary Therapies, but I want to stay on this topic that you just introduced, because honestly, it's fascinating to me. I think our readers will find it fascinating as well. Right now, can we draw clinical conclusions that ALCAT can be used to predict which foods might increase the release of potential unmethylated DNA, or is that down the road? Is that a clinical application right now, or is that something that is down the road? Deutsch: I think the clinical utility has been established a long time ago from the studies from back in the late '80s where they did these double blind and placebo-controlled oral challenges very carefully and found overall efficacy of the test at 84-plus percent. There's been other studies, one that you just mentioned that also came out in last month's Complementary and Alternative Medicine with some work done at University of Northern Illinois. There, of course, they found some other pathways and some other mechanisms. They found that Serum Amyloid A, which is reflective of overall body inflammation, also drops precipitously in people who have clinical improvement when they alter diet based on ALCAT, much more so than control groups, where you have blinded sham diets being implemented. Another validation just came out last week. This was on European Society of Clinical Nutrition and Metabolism. There was a group from the University of Pavia, which is northern Italy. The University itself was established in the 900s or the 800s. It's a very old institution, very well-respected in Europe. They found that with respect to gluten, isolated gluten, the 33-mer peptide that you can buy from chemical companies that are used in a lot of tests, some tests, and gluten-containing grains, wheat, oats, barley and rye, that the ALCAT test and double blinded placebo-controlled oral challenges with gluten and grains was also very highly correlated. They proposed, at the University, that ALCAT actually be used as a new diagnostic criterion for non-celiac gluten sensitivity. Gazella: Yeah. There's a lot of solid research showing the clinical efficacy of using the ALCAT test. That's what I'm hearing from you regarding the research that's been done up to this point. Deutsch: Yep. It's pretty clear. Gazella: Great. Good. I want to step back a little bit. How common are sensitivities and intolerances to specific foods? Deutsch: That's always a challenging question, because we don't have a clear-cut definition. Intolerances are generally induced by a lack of an enzyme to break down some component of a food, and we have an adverse reaction that may not be that severe, so lactase deficiency can induce lactose intolerance. If you bring those in, but then you get into the more nuanced types of intolerances where there's a chemical that is naturally occurring in a food or could be added in processing where the person lacks the enzyme to break down that toxin. Again, keeping in mind that all plants produce natural toxins in order to defend against pests. Nowadays, I think we see the inability of individuals to break down some of those toxins and the innate immune system comes into play, because we're increasingly depleting and compromising our ability to detoxify. Again, because of some overall changes in diet and how food is produced, the industrialization of farming and so forth. You might find that because the body is not as efficient as it should be, breaking down a toxin the food with which the person has not had, through his ancestry, the development of those detoxification pathways, that if they have a little bit, it's okay. If they have too much, it becomes a problem or if it's the wrong time of year and there's too many other co-factors or they visited Mexico and have a disruption in their diet, then they have more of an issue with it. It's not as clear-cut as, say, an allergy where just a few molecules of the offending substance can trigger a very dramatic response. It actually gets amplified by things like Substance P in the body and spreads out, because it's a whole different pathway and a whole different animal entirely. It depends how you want to try and define these intolerances and sensitivities. People fluctuate, depending on season, detoxification pathways, intestinal permeability, overall level of health, cofactors and so forth. If you are comfortable with a generalization, I'd say that it's very rare. We have found some, but we've had to look hard. It's very rare to find a person who doesn't have any sensitivities or intolerances. In how many? Again, it depends how you operationally define them, but it's highly relevant. It underlies a lot of inflammatory problems, metabolic syndrome and all the health issues that can come from that. It's extremely common, but I don't want to put a number on it, because we're all guessing. Gazella: Yeah. That's interesting. It's rare to find someone who doesn't have a sensitivity or an intolerances. That's a pretty big statement. I'd like to talk specifically about celiac disease and non-celiac gluten sensitivity. Tell us about testing regarding those issues. Deutsch: Celiac disease is an autoimmune disorder where cytotoxic T lymphocytes attack the enterocytes in the small intestine. In order for that to happen, the T lymphocytes have to recognize the allergen or trigger. The trigger, it's not really an allergen. The trigger is gluten. It's presented to the T lymphocyte by an antigen-presenting cell, mostly dendritic cells, which absorb the trigger, break down the peptides internally and lysosomes, transport it by an MHCT molecule to the surface where if there are T cells that recognize that complex, will become activated and may lead to celiac. Celiac depends upon the ability of the T lymphocytes to recognize the combination of that MHCT molecule with the gluten and gliadin peptides. If you're not genetically, if you don't have the genes to produce that specific variation of an MHCT molecule, you can not get celiac disease, so the tests for those genes, which are human leukocyte antigen GA DQ2.5 and H. They're very easy to test through PCR. We also do that testing. That test has phenomenal negative predictability. If you don't have those genes, you cannot get celiac. However, you could still have an adverse reaction to gluten, which is not mediated by the T lymphocytes and that pathway, but it is a function of the innate immune system, which means neutrophils, eosinophils, mostly neutrophils. That's what we call non-celiac gluten sensitivity. That's what they studied in Pavia and found that the ALCAT test is measuring the activation of the granulocytes, which are mostly peripheral granulocytes, mostly neutrophils. The same thing was seen years ago with Fezzano and Stroup, working with the people at NIH in leukocyte biology labs where they challenged with gluten in experimental animals in transgenic mice whose neutrophils would glow when they became activated. They saw all this activation. It's the same pathway, but it goes further in those people who are genetically predisposed. If you go past the first lines of defense of the innate immune system and reach into the specific immune systems, T lymphocyte population becoming active, that causes the real problem. Gazella: I see. ALCAT is actually effective for both food sensitivity and food allergy. Deutsch: I wouldn't say it's effective for food allergy, because I wouldn't call celiac disease really a food allergy, because there's no IBE molecule. Again, the allergists only like to use the word allergy when there's IgE involved or there's an immediate symptom onset. Here, you do have other immunological reactions, more like a Type 4 reaction, whereas an allergy, in the Gell and Coombs system, is a Type 1 reaction. ALCAT will let you know whether you're going to have a problem with gluten. Exactly how that problem will manifest will depend upon many factors, your genetics and also your microenvironment, your ecology in your gut. The ALCAT will tell you both those issues, but not what we call a true food allergy with a Type 1 type of reaction. Gazella: Right, okay. Good point. Good clarification. Let's dig into that 2018 study that was published in the Journal of Alternative and Complementary Therapies. Can you describe the objective, the method, and the outcomes of that study? Deutsch: Going from memory, I don't have that in front of me. It was basically, again, a double-blinded, randomized trial looking for improvement in symptoms that are typically related to sensitivities, food sensitivities. We were looking at various inflammatory conditions where the control diet was, again, a sham diet where foods were taken out, but they were not ALCAT test positive foods. The test subject didn't know that their new diet instructions were excluding ALCAT test positive foods or ALCAT negative things. Then just looking at the outcomes and some biomarkers, and specifically Serum Amyloid A and body composition. There were differences seen that were pretty distinct between the two groups. There was a much greater improvement in the symptoms in the report, which is also on our website. It was, again, the University of Northern Illinois. Dr Lukaszuk led the research project, showed that there was much greater reduction in symptoms amongst the people who were following the ALCAT test and the significance was significantly high. It wasn't something that could have happened as a function of [inaudible 00:26:01]. There was a very sharp drop in Serum Amyloid A, which a lot of people are beginning to look at more than high-sensitivity C-reactive proteins as an indicator of total body inflammation. It puts together a nice picture of that. Biochemistry is changing. The new system is less reactive and people are improving body composition and reducing their symptoms. Gazella: Yeah. It sounds like you've got some great research going on, but I'd like to talk a little bit about the future. Can you tell us about cellular technology for identification of functional nutritional deficiencies? Deutsch: One of my favorite topics. I used to live in Austin for 14 years. During that time, there was a lab. There was a charitable organization named the Clayton Foundation that backed a researcher of Experimental Biology Department, University of Texas in Austin named William Shive. William Shive was a protégé of a gentleman who wrote the book in the 1950s called Biochemical Individuality. That book basically explained that we're all quite different, and his experience was that he went in. Prior to the 1950s, he went in for a surgery the night before. They gave him morphine to help him sleep, and it kept him awake all night. That kind of reaction caused him to think over about how we're all a little bit different. A paradoxical reaction like that was quite pronounced. He did a lot of research just in animals and humans, looking at how we're different, and extended that concept to the idea that nutritional needs are also unique. In the 1970s, a group basically challenged, recognized that we needed, as a profession, to have a test for nutritional deficiencies that took into account individuality. William Shive was proposed as the person to help develop it because of his knowledge in the field. He got backing from the Clayton Foundation. The Clayton Foundation, by the way, was a gentleman named Clayton who was in partnership with MD Anderson there in New Orleans. They would support research in nutrition and cancer. One of the things they did was to try and recycle the funding. As soon as something was developed, they would try and commercialize and monetize it, license it out, and recycle those funds for new things, because philanthropists want to see more and more benefit happen. I got to know Dr Shive, and he was doing his evaluations in using the classical way of looking at lymphocyte proliferation, using incorporation of radioactive [inaudible 00:29:27] into the DNA and then extracting that after five days and measuring radioactivity and therefore inferring how much new DNA there was, what DNA synthesis levels occurred and being able to infer growth of lymphocytes, which we spoke about before. When they were stimulated by a mitogen, where a mitogen could be a plant lectin like phytohemagglutinin, which would universally induced EMD cells to multiply. Remembering here what I was speaking to you about the difference between gluten sensitivity and celiac disease. Celiac disease is, again, involving T lymphocytes, meaning it's a function of the specific immune system, so only certain T lymphocytes will recognize a pathogen's peptides being presented to it, and others won't, which is why it's not really a great test for looking at particular allergies because there's too much background noise. 99% of lymphocytes don't react to a pathogen, but 1% of them do. After an infection or during an infection, a small number of lymphocytes that recognize the pathogen will divide in the circulation and in the lymphatics and multiply themselves, which is obviously not something that granulocytes to. He's stimulating lymphocytes with a mitogen. You want them to divide, because the ability of these cells to divide and clone rapidly enables you to produce the antibodies and the lymphocytes that will kill the pathogens. What they need to divide are nutrients. If you stimulate them, and they divide very slowly, you might look at adding nutrients into the culture. There was research done on that in the 1930s where people would take mold spores and radiate them and see that they no longer would divide. Then they one by one added back specific nutrients to see what would restore metabolic machinery. In fact, a group from the University of Chicago got a Nobel prize for that in 1958, so the idea was out there that lymphocyte proliferation could be a good marker for measuring a functional response to changing nutrients in a culture. My early discussions with Dr Shive were, "Dr Shive, the concept is great, but why are you using this old-fashioned method that involves radioactivity if you want to count cells?" Use a cell counter. He agreed. We started to do some work together. Unfortunately, Dr. Shive passed away, but I always was fascinated by that area, and continued to work on it for maybe 15 or 20 years, looking at using cell counters to measure lymphocyte response when stimulated with a mitogen when you alter the culture medium to add another nutrient, one by one. If you found that the adding of the nutrient induced a more robust lymphocyte proliferative response, you can infer that for whatever reason functionally, that nutrient was not at optimal levels, and there should be repletion of that nutrient through foods that contain it or even supplementation. After many years, we kind of looked at that, but we thought that even a cell counter, we're in the cell counter manufacturing business. Some people don't know it, but we're a CLIA lab, and we do these tests, but we also build cell counters and sizers that are used in our tests, because we want them to do very specific things. We found that there were other methods that we looked at that could be done more rapidly and more simply, and correlated with the cell counts. We've been validating that over the last couple of years, and we're actually going to release that testing this month, in January, to look at the levels of improvement of specific immune function when you add specific micronutrients to cell cultures. We're also looking at doing the same kind of testing under conditions of oxidative stress to see which antioxidants improve the survival of the cells when there is an oxidative stress situation going on. Gazella: That's awesome. There's a lot of integrative practitioners who are interested in that type of personalized medicine. When you say it's available in January, is it clinically available to practitioners in January? Deutsch: Yes. Gazella: Awesome. That's great. Deutsch: Yeah, we're making it available. Gazella: I have one final question. I've been researching Cell Science Systems, and it seems like it's not just about delivering a test for your company. It's about helping clinicians personalize the diet for their patients, but then providing support regarding compliance and sustainability. Why is that so important to your company? Deutsch: Our company is here to help. I've done this for coming on 34 years now, and I had health problems in my earlier years. I worked through it. I was an athlete as a kid and all that, played on teams and all that, but I had bad allergies. Finally, when I was in my 20s, with the help of some naturopaths in Australia, figured out that my issues were basically diet-driven. I got interested in this field. I know how, from firsthand experience, what a problem it can be if you don't know that you're eating something which causes your eczema, your respiratory problems, your fatigue, your arthritis, your migraines, so on and so forth. I want to do everything possible to have an impact. I know that's the way most people in the naturopathic community are as well. We've created some tools to help educate patients, to help them comply, to help them understand how to substitute certain things, to be able to take an ALCAT test result and have it reflect into a several-hundred-page personalized book of recipes, and then just make this all available. We created an educational course, which actually, we'll have to go to the Naturopathic Societies and see if they'll accredit it, but we have accreditation for this from the dietitians and nurse practitioners, so it's a course that we offer. Again, we're going to present this to the naturopaths. It costs $199. Then when people go through that, then they can purchase from us these meal planning tools and other things for their patients. We're going to put a lot of this online, so it'll be very convenient, at our website for this purpose, called GutHealthPartners.org, and just make compliance a lot easier so people stick with it and get the benefits. That's what we're doing. Gazella: That's great. We also have a lot of dietitian and nurse practitioners who are readers of the Natural Medicine Journal, so I'm sure that they'll appreciate that. That sounds like a wonderful mission for your company. This has been very interesting. Thank you again, Roger, for joining me today. Once again, I'd also like to thank our sponsor, of course, Cell Science Systems. Have a great day, Roger. Deutsch: Thanks. Thanks for having me, Karolyn.

Stephanie takes the Immune team on a tour of neutrophils, the most abundant leukocytes in mammals, including tethers and slings, neutrophil rolling, and neutrophil nets. Hosts: Vincent Racaniello, Stephanie Langel, and Cynthia Leifer Subscribe (free): iTunes, Google Podcasts. RSS, email Become a patron of Immune! Links for this episode Slings enable neutrophil rolling (Nature) Sling video (La Jolla Inst Allergy Immunol) Neutrophil extracellular traps kill bacteria (Science) Neutrophil review (Sci Immunol) Image credit Time stamps by Jolene. Thanks! Weekly Science Picks Steph- Should reviewers remain anonymous? Cindy- Breast Cancer Research Foundation Vincent- Initiative to End Paywalls (The Scientist) Music by Steve Neal. Immune logo image by Blausen Medical. Send your immunology questions and comments to immune@microbe.tv

Vincent and Daniel solve the case of the Panamanian Farmer with Three Weeks of Diarrhea, and discuss how microbes egested during bites of sand flies exacerbate the severity of leishmaniasis. Hosts: Vincent Racanielloand Daniel Griffin Become a patron of TWiP. Links for this episode: Sand fly microbesand leishmaniasis severity (Cell Host Micr) Letters read on TWiP 153 Case Study for TWiP 153 Man in clinic, in city recently, developed rash in groin area, concerned about this. Lives in open relationship with male partner, had sexual encounter with another male. Few weeks. Rash is in the pubic hair, is very itchy. Mostly around umbilicus, can see blue spots in this area. These are skin changes. Buys magnifying glass to look and describes seeing things which we see as well. No notable medical history. Send your case diagnosis, questions and comments to twip@microbe.tv Music by Ronald Jenkees

Neutrophil grabbing Staph. From Wikipedia No, your eyes aren't deceiving you, and yes, we know how to count... Episode 29 is still in limbo as Camilla valiantly attempts to re-record just her portion. In this episode, Kevin and Camilla discuss Salmonella virulence, and how different strains alter the immunogenicity of pathogens. Oh, and Kate's here too... KATE'S BACK!! WOO!! Dr. Franz has a new job, but is just as snarky and ill-prepared as ever. Plus she refuses to drink on the job.Donate to us on Patreon!Like us on Facebook!And don't forget to share us with your friends so we can grow!EDIT: Sorry if this showed up in your feed late - there was a mistake in formatting :-(LinksThe Paper: Strains of bacterial species induce a greatly varied acute adaptive immune response: the contribution of the accessory genomeShort Path DistilleryOrgan Preservation Alliance (where Kate works now)

 Asthma is a chronic inflammatory lung disease that affects an estimated 300 million people worldwide, including 25 million in the United States. There are currently no definitive diagnostic tests for asthma. Diagnosis is based on history and tests of respiratory function.

Commentary by Dr. Valentin Fuster

Them TWiM team discusses the importance of neutrophils in microbial infections, and evidence that ancient bacteria had two cell walls. Hosts: Vincent Racaniello, Elio Schaechter, Michael Schmidt, and Michele Swanson. Subscribe to TWiM (free) on iTunes, Stitcher, RSS, or by email. You can also listen on your mobile device with the Microbeworld app. Links for this episode Conquering neutrophils (PLoS Path) Ancestral outer membrane in firmicutes (eLife ) Were gram positive rods the first bacteria? (Cell) Image credit Letters read on TWiM 136 This episode is brought to you by CuriosityStream, a subscription streaming service that offers over 1,400 documentaries and non­fiction series from the world's best filmmakers. Get unlimited access starting at just $2.99 a month, and for our audience, the first two months are completely free if you sign up at curiositystream.com/m​icrobe ​and use the promo code MICROBE​. This episode is also brought to you by Drobo, a family of safe, expandable, yet simple to use storage arrays. Drobos are designed to protect your important data forever. Visit www.drobo.com to learn more. Listeners can save $100 on a Drobo system at drobostore.com by using the discount code Microbe100. Send your microbiology questions and comments (email or mp3 file) to twim@microbe.tv 

Hosts: Vincent Racaniello, Michele Swanson, and Michael Schmidt. Vincent, Michael, and Michele reveal how a fungal protease blunts the innate immune response and promotes pathogenicity. Subscribe to TWiM (free) on iTunes, Stitcher, RSS, or by email. You can also listen on your mobile device with the Microbeworld app. Links for this episode Michele on Flint Legionella outbreak (Detroit News) Fungal mimicry of a mammalian aminopeptidase (Cell Host Micr)   This episode is sponsored by ASM Agar Art Contest and ASM Microbe 2016 Send your microbiology questions and comments (email or mp3 file) to twim@twiv.tv, or call them in to 908-312-0760. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twim.

Alan Smrcka explains the distinct contributions that different heterotrimeric G protein subunits make to neutrophil migration.

Sat, 6 Feb 2016 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/19413/ https://edoc.ub.uni-muenchen.de/19413/1/Philippi_Vanessa.pdf Philippi, Vanessa ddc:590, ddc:500, Tierärztli

Inflammation is at the very heart of many disease processes, from infection and trauma to ageing and cancer. Split across 4 episodes, David Semeraro talks to Jon Lund about acute inflammation, covering definitions, mechanisms and progress with many examples from clinical cases, histopathological and macroscopic inflamed organ specimens. Listening to this series of podcasts will tell you all you need to know about the basics of acute inflammation, a thorough knowledge of which is essential for pre-clinical and clinical medical students and doctors in training in all specialities and at all levels. David Semeraro is a Consultant Histopathologist at the Royal Derby Hospital, UK and Jon Lund is Associate Professor of Surgery at the University of Nottingham, UK.

Immune dysregulation influences outcome following acute ischemic stroke (AIS). Admission white blood cell counts are routinely obtained, making the neutrophil–lymphocyte ratio (NLR) a readily available biomarker of the immune response to stroke. With colleagues Taura Barr, WVU Prevention Research Center, One Medical Center Drive, sought to identify the relationship between NLR and 90 day AIS outcome. Rob Tarr asks her what they found. Read the full paper: http://goo.gl/nGXmYO

Vincent, Michele, and Michael discuss how a gene from bacteria protects a tick from plant cyanide poisoning, and enhanced transmission of Streptococcus pneumoniae by influenza virus co-infection in mice.

Fri, 6 Jun 2014 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/18577/ https://edoc.ub.uni-muenchen.de/18577/1/Dau_Therese_Thuy_Dung.pdf Dau, Thérèse Thuy Dung ddc:570, dd

Serine proteases in cytoplasmic granules of neutrophils (NSPs), namely neutrophil elastase, cathepsin G (CG) and proteinase 3, have been under intense investigation for several decades. They are mainly known for their role in intracellular killing of pathogens and are also increasingly recognized as key regulators of innate immune responses. In 2009, I identified a fourth serine protease in neutrophils that has been completely overlooked and neglected so far. The aim of this thesis was an in-depth biochemical and functional characterization of this novel serine protease 4 (NSP4) of human neutrophils. Using monoclonal antibodies to NSP4, the distribution of NSP4 in normal human tissues was studied. NSP4 was observed only in neutrophils and neutrophil precursors of the bone marrow. The content of NSP4 in neutrophil lysates was about 20-fold lower compared to CG. Nevertheless, NSP4 was found to be released into the supernatant upon neutrophil activation. NSP4 could be further identified as a novel azurophil granule protein of neutrophils by Western blot analyses of subcellular fractions. For the functional analysis, the production and yield of recombinant NSP4 was clearly improved using different expression systems and DNA construct modifications. The proteolytic specificity was analyzed using E. coli peptide libraries, mass spectrometry and several synthetic peptide libraries. All these analyses clearly revealed an arginine specificity for NSP4. Consistent with this, NSP4 was strongly inhibited by heparin-accelerated antithrombin and C1 inhibitor and, with lower efficacy, by α1-proteinase inhibitor (α1PI). The data allowed me to generate an NSP4-specific α1PI variant that was shown to form covalent complexes with all NSP4 of neutrophil lysates and supernatants of activated neutrophils. This finding strongly indicated that NSP4 is fully processed and stored as an already activated enzyme in azurophil granules. In addition, dipeptidyl peptidase I (DPPI) was identified as the activator of NSP4 in vivo, as DPPI deficiency resulted in complete absence of NSP4 in a Papillon-Lefèvre patient. Analysis of cell-based calcium assays revealed that proteinase-activated receptor-2 may represent a potential natural substrate of NSP4. So far, NSP4-deficient mice did not show an abnormal phenotype under clean housing conditions. Activation of isolated neutrophils by phorbol esters or immune complexes was also not impaired. This study establishes NSP4 as the only arginine-specific pre-activated serine protease stored in azurophil granules of neutrophils that may fullfil a quite distinct, supportive role in neutrophil responses to tissue damage and bacterial infections.

Aspergillus fumigatus is a saprophytic mold that naturally inhabits the soil. Asexual reproduction yields hardy conidia that circulate in the air and are inhaled daily by humans. The fungus seems not to have evolved distinct mechanisms of pathogenicity, but is capable of responding to many stressful environmental cues present in its naturally harsh niche. The robust conidia present no problem to a fully functioning immune system, but if the innate immune system is compromised, the conidia can become activated and differentiate within the lung tissue to form invasive and disseminating hyphae. The resulting disease is called aspergillosis and is difficult to detect and to treat. To date, scientists have yet to find the factor(s) missing during immunosuppression that allow a healthy patient to easily dispose of A. fumigatus. We explored two possibilities: the production of neutrophil extracellular traps (NETs) and the release of IFN-γ by natural killer (NK) cells. We report here that NETs alone cannot kill the fungus, but do inhibit polar growth. Elongation of hyphal tips is abrogated due to zinc starvation, likely a consequence of the zinc-chelating, NETs-associated protein calprotectin. NK cells alone are also incapable of fungicidal activity, but their release of IFN-γ upon contact with A. fumigatus abrogates hyphal growth by a yet unknown mechanism. In vitro studies of the innate immune response, though helpful, are far from representative of the in vivo response. Neither NETs nor IFN-γ alone can manage Aspergillus infection, but in combination, these and other immune assaults certainly can. The difficulty lies in identifying the precise combination of immune cells and cytokine milieu that in a healthy individual prevent infection. Additionally, we explored mechanisms by which the fungus responds to stress, namely the HOG MAPK pathway, historically involved in osmotic stress response. In filamentous fungi, certain stress signals are sensed by a cytoplasmic hybrid histidine kinase sensor and then passed through the HOG system via phosphorylation. We identified the putative hybrid sensor kinase in A. fumigatus, and generated a corresponding knockout mutant. The ΔtcsC mutant was indeed sensitive to osmotic stress, and resistant to the phenolpyrrole fungicide fludioxonil. In the wild type the addition of either osmotic stress or fludioxonil resulted in SakA phosphorylation and translocation to the nucleus. SakA, the Hog1 homolog in A. fumigatus, is located at the end of the HOG pathway, confirming the role of TcsC as the cytoplasmic sensor upstream of SakA. In hypoxia, on farnesol, and in high concentrations of divalent cations the ΔtcsC mutant exhibited a striking “fluffy” phenotype characterized by the production of tremendous aerial hyphae and little or no differentiation, i.e., no conidiation. Though the ΔtcsC mutant showed no change in virulence compared to wild type, components of the TcsC signalling pathway remain promising targets for antifungal agents.

Sat, 21 Jul 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/14818/ https://edoc.ub.uni-muenchen.de/14818/1/Chandraratne_Sue.pdf Chandraratne, Sue ddc:590, ddc:500, Tie

Treatment of acute lung injury (ALI) remains an unsolved problem in intensive care medicine. As simvastatin exerts protective effects in inflammatory diseases we explored its effects on development of ALI and due to the importance of neutrophils in ALI also on neutrophil effector functions. C57Bl/6 mice were exposed to aerosolized LPS (500 µg/ml) for 30 min. The count of alveolar, interstitial, and intravasal neutrophils were assessed 4 h later by flow cytometry. Lung permeability changes were assessed by FITC-dextran clearance and albumin content in the BAL fluid. In vitro, we analyzed the effect of simvastatin on neutrophil adhesion, degranulation, apoptosis, and formation of reactive oxygen species. To monitor effects of simvastatin on bacterial clearance we performed phagocytosis and bacterial killing studies in vitro as well as sepsis experiments in mice. Simvastatin treatment before and after onset of ALI reduces neutrophil influx into the lung as well as lung permeability indicating the protective role of simvastatin in ALI. Moreover, simvastatin reduces the formation of ROS species and adhesion of neutrophils without affecting apoptosis, bacterial phagocytosis and bacterial clearance. Simvastatin reduces recruitment and activation of neutrophils hereby protecting from LPS-induced ALI. Our results imply a potential role for statins in the management of ALI.

Marina De Bernard, Venetian Institute of Molecular Medicine, University of Padua, ITALY speaks on "Modulation of the host immune response by Helicobacter pylori Neutrophil Activating Protein and its possible applications in therapy". This seminar has been recorded by ICGEB Trieste

Sat, 1 Jan 2011 12:00:00 +0100 https://epub.ub.uni-muenchen.de/16835/1/10_1159_000324881.pdf Moller, S.; Bendtsen, F.; Krag, A.; Vogeser, M.; Benesic, A.; Gerbes, Alexander L.

Background. Inhaled antibiotics are commonly used in the treatment of cystic fibrosis lung disease. A previous study suggested neutrophil elastase activation by colistin in vitro. Here, we investigated direct effects of the commonly used antibiotics colistin and tobramycin on neutrophil elastase activity. Methods. Neutrophil elastase was measured spectrophotometrically. The antibiotics colistin and tobramycin were added in different concentrations with or without the addition of albumin. Results. Generally, neutrophil elastase activity was lower in the absence of albumin compared to its presence. Both antibiotics, colistin and tobramycin, had inhibitory effects on neutrophil elastase activity except for high concentrations of colistin when albumin was absent. Conclusions. Our results suggest inhibitory effects of colistin and tobramycin in vitro. There was a clear dependency of neutrophil elastase measurements on the presence of albumin. Clinical studies are needed to investigate potential direct effects of inhaled antibiotics on neutrophil elastase activity in cystic fibrosis airways.

During acute bacterial infections such as meningitis, neutrophils enter the tissue where they combat the infection before they undergo apoptosis and are taken up by macrophages. Neutrophils show pro-inflammatory activity and may contribute to tissue damage. In pneumococcal meningitis, neuronal damage despite adequate chemotherapy is a frequent clinical finding. This damage may be due to excessive neutrophil activity. We here show that transgenic expression of Bcl-2 in haematopoietic cells blocks the resolution of inflammation following antibiotic therapy in a mouse model of pneumococcal meningitis. The persistence of neutrophil brain infiltrates was accompanied by high levels of IL-1beta and G-CSF as well as reduced levels of anti-inflammatory TGF-beta. Significantly, Bcl-2-transgenic mice developed more severe disease that was dependent on neutrophils, characterized by pronounced vasogenic edema, vasculitis, brain haemorrhages and higher clinical scores. In vitro analysis of neutrophils demonstrated that apoptosis inhibition completely preserves neutrophil effector function and prevents internalization by macrophages. The inhibitor of cyclin-dependent kinases, roscovitine induced apoptosis in neutrophils in vitro and in vivo. In wild type mice treated with antibiotics, roscovitine significantly improved the resolution of the inflammation after pneumococcal infection and accelerated recovery. These results indicate that apoptosis is essential to turn off activated neutrophils and show that inflammatory activity and disease severity in a pyogenic infection can be modulated by targeting the apoptotic pathway in neutrophils.

Wed, 7 Jan 2009 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/9518/ https://edoc.ub.uni-muenchen.de/9518/1/Kessenbrock_Kai.pdf Kessenbrock, Kai ddc:570, ddc:500, Fakultä

Objective—To purify neutrophil elastase (NE) from dog blood and develop and validate an ELISA for the measurement of canine NE (cNE) in canine serum as a marker for gastrointestinal tract inflammation. Sample Population—Neutrophils from 6 euthanized dogs and serum from 54 healthy dogs. Procedures—cNE was purified from dog blood by use of dextran sedimentation, repeated cycles of freezing-thawing and sonication, cation-exchange chromatography, and continuous elution electrophoresis. Antibodies against cNE were generated in rabbits, and an ELISA was developed and validated by determination of sensitivity, dilutional parallelism, spiking recovery, intra-assay variability, and interassay variability. A reference range was established by assaying serum samples from the 54 healthy dogs and use of the lower 97.5th percentile. Results—cNE was successfully purified from blood, and antibodies were successfully generated in rabbits. An ELISA was developed with a sensitivity of 1,100 g/L. The reference range was established as < 2,239 g/L. Ratios of observed-to-expected results for dilutional parallelism for 4 serum samples ranged from 85.4% to 123.1%. Accuracy, as determined by spiking recovery, ranged from 27.1% to 114.0%. The coefficient of variation for 4 serum samples was 14.2%, 16.0%, 16.8%, and 13.4%, respectively, for intra-assay variability and 15.4%, 15.0%, 10.5%, and 14.6%, respectively, for interassay variability. Conclusions and Clinical Relevance—The purification protocol used here resulted in rapid and reproducible purification of cNE with a high yield. The ELISA developed yielded linear results and was accurate and precise. Additional studies are needed to evaluate the clinical usefulness of this assay.

Hemodialysis treatment is associated with activation of neutrophil granulocytes. Pentoxifylline has been shown to inhibit neutrophil activation in vitro and in vivo. We investigated the effect of pentoxifylline on leukocyte and platelet counts and on plasma levels of extracellularly released neutrophil elastase and lactoferrin during a four-hour hemodialysis treatment. Eight patients received 400 mg of pentoxifylline or placebo orally twice a day over 14 days and an additional dose of 400 mg of pentoxifylline intravenously during hemodialysis. Each subject served as his own control in a randomized, double-blind, cross-over study. Combined oral and intravenous treatment with pentoxifylline prevented neither leukopenia nor neutrophil degranulation during the time interval studied. Elastase plasma levels paralleled the drop in leucocyte counts and thereafter increased similarly in both groups. Lactoferrin plasma levels exhibited less increase in the treated group; however, this effect was not statistically significant. This may be due to the small number of cases studied and to difficulties in reaching effective plasma levels without side effects.

Sat, 1 Jan 1983 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9216/1/9216.pdf Fritz, Hans; Hiller, E.; Duswald, Karl-Heimo; Jochum, Marianne