Immunology

Therapeutic Hopes: Meet the Minds Behind Trinity’s COVID-19 Research Hub – The University Times

When the coronavirus pandemic struck Ireland and the world, it sent most people into a panic. But not the immunology researchers at the Trinity Biomedical Sciences Institute (TBSI) and Trinity Translational Medicine Institute (TTMI).

Once coronavirus reached Ireland, TBSI Director Prof Kingston Mills along with TTMI Director Prof Aideen Long gathered 14 of Trinitys top scientists to form the COVID-19 Research Hub. Their goal is to leverage Trinitys expertise in immunology and infectious disease to answer the big immunological questions surrounding the virus and contribute to the global efforts developing treatments and vaccines.

There are not too many experts around the world on SARS viruses, but everybody has suddenly become an expert in COVID-19, remarked Mills. None of us obviously worked on SARS viruses before, so were adapting our expertise to cope with that.

Under the groups main 4.8 million grant from Science Foundation Ireland (SFI), individual researchers are exploring a number of areas, from anti-inflammatories to vaccine efficacy. Were bringing our own strengths, our own specific areas of interest to bear on COVID, says Prof Luke ONeill, the chair of Trinitys School of Biochemistry and Immunology.

None of us obviously worked on SARS viruses before, so were adapting our expertise to cope with that

ONeills current area of interest is on the role of inflammation in disease. Inflammation is part of the bodys natural response to clear an infection but can cause severe damage if it gets out of control. In coronavirus patients, overactive production of immune molecules called cytokines can produce a cytokine storm, overstimulating the inflammatory response and damaging the lungs and other tissues.

But most of the time, the immune system naturally regulates levels of inflammation. In 2018, ONeills lab published in Nature that a molecule called itaconate, produced as part of the bodys natural metabolism, creates some of these natural anti-inflammatory effects.

Although the discovery of the anti-inflammatory role of itaconate is exciting on its own, in 2019, a lab unrelated to ONeills group published in Immunity that itaconate also has antiviral effects against Zika virus in brain cells. Following those findings, ONeill was approached by a SARS virus expert to collaborate on testing itaconate against the coronavirus, with promising early results.

What were showing is that itaconate can block the virus, says ONeill. It could be antiviral directly in some way, and secondly, the anti-inflammatory bit might help because obviously it will limit inflammation when this becomes a severe disease.

ONeill explains that the coronavirus uses a spike protein to enter human cells, binding to a receptor called ACE2 found on many cell types including lung and heart cells. Itaconate appears to lower ACE2 expression, thus preventing the virus from entering cells. If this molecule can block ACE2 and be anti-inflammatory double whammy. Youre going to have a very interesting prospect there, says ONeill.

Although the initial data is intriguing, ONeill is quick to point out that it is early days, both in terms of how recently itaconate was discovered and in testing its effects against the coronavirus. ONeills lab has several parallel projects also focused on anti-inflammatory therapies, and he says: Any one of our projects could be made relevant and have an impact on COVID. So whatever we do is going to feed in ultimately. The whole lab is kind of working on COVID with some directly, some indirectly.

If this molecule can block ACE2 and be anti-inflammatory double whammy, youre going to have a very interesting prospect there

ONeills research covers just one of the four main areas being explored by the COVID-19 Research Hub. Mills and his lab are focusing on vaccines, but not in the way you might think.

We wont be developing a vaccine on our own, but weve been working with pharmaceutical companies to help them to improve the way that the vaccines work, explains Mills, and how they can induce more sustained immune responses. This is frequently done by testing different adjuvants, which are additions to a vaccine that help stimulate a stronger immune response.

Its still unclear exactly how long immunity to the coronavirus lasts after an infection or administration of the vaccine, but ONeill says the goal of a vaccination programme is to ideally create herd immunity and in the process, prevent fatal cases of the disease.

What has become increasingly clear about the coronavirus, however, is that people vary widely in their immune response to the infection. A further research area is examining why some people who are exposed to the virus do not get infected, and why some people who do get infected go on to develop a severe disease.

[We are] looking at patients that have been exposed, and yet, spontaneously clear the virus, says Long. What is it about their innate immune system that helps them to do that?, she asks, citing examples of partners of coronavirus patients who did not become sick after exposure to the virus.

We wont be developing a vaccine on our own, but weve been working with pharmaceutical companies to help them to improve the way that the vaccines work and how they can induce more sustained immune responses

Long theorises that these patients innate immune systems (the non-specific first line of defense of our immune systems) may have some unique features that make them especially effective. Determining what those features are could lead to a better understanding of how to protect people from the virus.

Around 15 per cent of coronavirus cases globally are classified as severe, and a further five per cent are classified as critical, according to the World Health Organisation, but scientists still dont know why some people are more susceptible to serious illness than others. Long says the group is exploring the effects of diabetes, obesity and age, factors which have already been shown to potentially link to coronavirus susceptibility. But the group is going beyond these factors, also looking at differences in infection between genders as well as socioeconomic status.

Long says she brings the patient-focused angle to the research hub via TTMI which is based in St Jamess Hospital, allowing for a close collaboration between the lab-based scientists of the TBSI and the clinicians based in St Jamess.

Its nice to have a situation where you have clinicians that are dealing with the patients, that are making clinical observations that we dont see that form scientific questions that then we can try and answer in the lab, says Long. I think thats a really nice dimension.

Underpinning all the work being done in the COVID-19 Research Hub is a continued focus on testing, an area that has improved dramatically since March and April when the research hub was formed but can be improved even further.

Its nice to have a situation where you have clinicians that are dealing with the patients, that are making clinical observations that we dont see that form scientific questions that then we can try and answer in the lab

What were developing is a high throughput assay that will be completed in two hours and doesnt require a swab, you only need saliva, says Mills. A faster, less invasive test like this could significantly improve testing capacity and shorten the current wait time to receive test results which is currently around two to three days, according to the HSE.

Antibody tests are also being developed, which can identify what percentage of the population has been exposed to and produced an immune response to the virus. Those who have antibodies against the coronavirus are less likely to become reinfected, says Mills.

All of these research areas complement the existing vaccine clinical trials that have resulted in the first non-trial patient in the UK receiving the Pfizer-BioNTech vaccine this past week. Pfizer and their competitor Moderna are both using mRNA-based vaccines, a technology never before approved for use as a drug.

The RNA vaccines are pretty interesting because they were seen as fringe in the vaccine world for a long time, commented ONeill. He said he and the whole scientific community are waiting to see more hard data as the vaccines are rolled out but there is no reason not to trust the results coming out so far.

As enthusiastic as these researchers are about the progress being made, Long acknowledges that these things dont happen overnight. These things are slow, and things are moving relatively quickly. Theyre not as quick as we would like, she says. But these are unprecedented times. I am optimistic. ONeill agrees: Ive no doubt at all, if we fast forward even three months from now, therell be progress thatll give us hope.

ONeill thinks one of the most critical parts of making progress over the next few months will be an effective information campaign from the government about what to expect from a coronavirus vaccination. He thinks letting people know that there may be mild side effects that can be managed with paracetamol, releasing all the efficacy data about the vaccines to the public and ensuring that taking the vaccine is voluntary will be essential.

The RNA vaccines are pretty interesting because they were seen as fringe in the vaccine world for a long time

You say look, if you take this vaccine, youre protecting the community its not about you, he said. Because remember, 97, 98 per cent of people get over this virus and wouldnt need a vaccine anyway. Its the three per cent you want to protect with the vaccination program. He hopes that this approach will inspire people to respond to the greater good and get vaccinated for the benefit of the community.

Buoyed by the SFI grant after an initial investment of 2.4 million from Allied Irish Banks, the COVID-19 Research Hub scientists are also involved in several international collaborations with labs in the US, the UK, the Netherlands and Hong Kong.

Ultimately, these researchers hope that the establishment of the COVID-19 Research Hub will not just help fight the current pandemic, but future diseases as well. Thats sort of the long-term aim: to be ready to deal with the next pandemic, which may not be a SARS virus. It could be something else we dont know thats coming down the line, says Mills.

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Immunology

How does the COVID-19 vaccine work and how safe is it? CBC Asks an infectious disease specialist – CBC.ca

Live at noon on Thursday,CBC asks Matthew Miller, an associate professor of infectious diseases and immunology at McMaster University in Hamilton, all about the COVID-19 vaccine.

Miller says the vaccine teaches human cells how to make one of the proteins of SARS-CoV-2 (the one it uses to attach to and enter our cells). After making that protein which Miller said isn't dangerous or toxic to humans the body learns what the virus does, which can prevent our cells from getting infected.

What are the long-term safety concerns? If we get the vaccine do we still have to socially distance and wear masks? What percentage of the population needs to be vaccinated in order for there to be herd immunity to protect those who can't get vaccinated?

We'll ask these questions and more during Miller's live interview with the CBC's Conrad Collaco.

What do you want to know about the vaccine? Let us know and we'll ask the expert.

Be a part of our live chat. Send your questions and comments to us by email at Hamilton@cbc.ca or on Twitter, Facebook or Instagram.

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How does the COVID-19 vaccine work and how safe is it? CBC Asks an infectious disease specialist - CBC.ca

Immunology

Trixeo Aerosphere approved in the EU for maintenance treatment of COPD | Small Molecules | News Channels – PipelineReview.com

DetailsCategory: Small MoleculesPublished on Monday, 14 December 2020 13:46Hits: 493

Fourth major approval for AstraZenecas triple-combination therapy which is marketed as Breztri Aerosphere in the US, China and Japan

LONDON, UK I December 14, 2020 I AstraZenecas Trixeo Aerosphere (formoterol fumarate/glycopyrronium bromide/budesonide) has been approved in the European Union (EU) for maintenance treatment in adult patients with moderate to severe chronic obstructive pulmonary disease (COPD) who are not adequately treated by a combination of an inhaled corticosteroid (ICS) and a long-acting beta2-agonist (LABA), or a combination of a LABA and a long-acting muscarinic antagonist (LAMA).

The approval by the European Commission was based on positive results from the ETHOS Phase III trial in which Trixeo Aerosphere, a triple-combination therapy, showed a statistically significant reduction in the rate of moderate or severe exacerbations compared with dual-combination therapies Bevespi Aerosphere (glycopyrronium/formoterol fumarate) and PT009 (budesonide/formoterol fumarate) over 52 weeks.1 The approval was also supported by efficacy and safety data from the KRONOS Phase III trial.2

Trixeo Aerosphere was recommended for marketing authorisation by the Committee for Medicinal Products for Human Use of the European Medicines Agency in October 2020.

COPD is a progressive disease, which can cause obstruction of airflow in the lungs resulting in debilitating bouts of breathlessness and is the third leading cause of death globally.3-6

Klaus Rabe, Professor of Pulmonary Medicine at the University of Kiel, Director of the Department of Pneumology at Clinic Grosshansdorf, Germany, and lead investigator of the ETHOS Phase III trial, said: Chronic obstructive pulmonary disease significantly contributes to morbidity and healthcare resource utilisation in Europe. Even a single exacerbation can cause further deterioration of a patients lung function and increase the risk of hospitalisation, so preventing exacerbations is a clinical priority. Trixeo Aerosphere has demonstrated significant benefits in reducing exacerbations in patients with moderate to severe disease, and triple-combination therapy will play an increasingly important clinical role in treating these patients.

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: Trixeo Aerosphere has a strong clinical profile compared with dual-combination therapies and offers an important new treatment option for patients with chronic obstructive pulmonary disease. In Europe, about one in 10 adults over the age of 40 has chronic obstructive pulmonary disease, with prevalence increasing. We look forward to discussing all-cause mortality data from the ETHOS Phase III trial with health authorities.

Results from the ETHOS Phase III trial were published in The New England Journal of Medicinein June 20201 and results from the KRONOS Phase III trial were published in The Lancet Respiratory Medicine in September 2018.2 In both trials, the safety and tolerability of Trixeo Aerosphere were consistent with the profiles of the dual comparators.1,2

COPD

COPD is a progressive disease which can cause obstruction of airflow in the lungs resulting in debilitating bouts of breathlessness.3,4,5 It affects an estimated 384 million people7 and is the third leading cause of death globally.6 In Europe, approximately 10% of adults over the age of 40 have COPD, with prevalence set to increase,8,9 significantly contributing to morbidity3 and healthcare resource utilisation.10 Improving lung function, reducing exacerbations and managing daily symptoms such as breathlessness are important treatment goals in the management of COPD.3 A single COPD exacerbation can have a negative impact on lung function,11,12 quality of life13 and increase the risk of hospitalisation.14 Additionally, even one COPD exacerbation that results in hospitalisation increases the risk of death.15,16

ATHENA clinical trial programme

The ETHOS and KRONOS Phase III trials are part of AstraZenecas ATHENA Phase III clinical trial programme for Trixeo Aerosphere, which included more than 15,500 patients globally across 11 trials.

ETHOS is a randomised, double-blinded, multi-centre, parallel-group, 52-week Phase III trial to assess the efficacy and safety of Trixeo Aerosphere in symptomatic patients with moderate to very severe COPD and a history of exacerbation(s) in the previous year. The primary endpoint was the rate of moderate or severe exacerbations.1 Results were published in The New England Journal of Medicine.1

KRONOS is a randomised, double-blinded, parallel-group, 24-week, chronic-dosing, multi-centre Phase III trial to assess the efficacy and safety of Trixeo Aerosphere in patients with moderate to very severe COPD regardless of whether or not they had an exacerbation in the previous year. The primary endpoints were lung function parameters.2 Results were published in The Lancet Respiratory Medicine.2

Trixeo Aerosphere

Trixeo Aerosphere (formoterol fumarate/glycopyrronium bromide/budesonide) is a single-inhaler, fixed-dose triple-combination of formoterol fumarate, a LABA, glycopyrronium bromide, a LAMA, with budesonide, an ICS, and delivered in a pressurised metered-dose inhaler.

Trixeo Aerosphere is approved under the brand name Breztri Aerosphere in Japan, China and the US for patients with COPD.

AstraZeneca in Respiratory & Immunology

Respiratory & Immunology is one of AstraZenecas three therapy areas and is a key growth driver for the Company.

Building on a 50-year heritage,AstraZeneca is an established leader in respiratory care, across inhaled and biologic medicines. AstraZeneca aims to transform the treatment of asthma and COPD by eliminating preventable asthma attacks across all severities and removing COPD as a leading cause of death through earlier biology-led treatment.The Companys early respiratory research is focused on emerging science involving immune mechanisms, lung damage and abnormal cell-repair processes in disease and neuronal dysfunction.

With common pathways and underlying disease drivers across respiratory and immunology, AstraZeneca is following the science from chronic lung diseases to immunology-driven disease areas. The Companys growing presence in immunology is focused on five mid- to late-stage franchises with multi-disease potential in rheumatology (including systemic lupus erythematosus), dermatology, gastroenterology, and systemic eosinophilic-driven diseases. AstraZenecas ambition in immunology is to achieve disease control and ultimately clinical remission in targeted immune-driven diseases.

AstraZeneca

AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visitastrazeneca.comand follow the Company on Twitter@AstraZeneca.

Contacts

For details on how to contact the Investor Relations Team, please clickhere. For Media contacts, clickhere.

References

1. Rabe KF, Martinez FJ, Ferguson GT, et al. Inhaled Triple Therapy at Two Glucocorticoid Doses in Moderate-to-Very Severe COPD. N Engl J Med 2020; 383: 35-48.

2. Ferguson GT, Rabe KF, Martinez FJ, et al. Triple combination of budesonide/glycopyrrolate /formoterol fumarate using co-suspension delivery technology versus dual therapies in chronic obstructive pulmonary disease (KRONOS): a double-blind, parallel-group, randomised controlled trial. Lancet Respir Med. 2018; 6: 747758.

3. GOLD. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2020. [Online]. Available at: http://goldcopd.org. [Last accessed: October 2020].

4. Laviolette L, Laveneziana P; ERS Research Seminar Faculty. Dyspnoea: a multidimensional and multidisciplinary approach.Eur Respir J. 2014; 43 (6): 1750-1762.

5. May SM, Li JT. Burden of chronic obstructive pulmonary disease: healthcare costs and beyond.Allergy Asthma Proc. 2015; 36 (1): 4-10.

6. World Health Organization. The top 10 causes of death. 24 May 2018. Available at: https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death [Last accessed: December 2020].

7. Adeloye D, Chua S, Lee C,et al. Global Health Epidemiology Reference Group (GHERG). Global and regional estimates of COPD prevalence: Systematic review and meta-analysis.J Glob Health. 2015; 5 (2): 020415.

8. European lung white book. 2013. Chapter 13 Chronic obstructive pulmonary disease. Available at: https://www.erswhitebook.org/chapters/chronic-obstructive-pulmonary-disease/ [Last accessed: September 2020].

9. Rehman A, Hassali, MAA, Muhammad SA, et al. The economic burden of chronic obstructive pulmonary disease (COPD) in Europe: results from a systematic review of the literature. Eur J Health Econ 2020; 21: 181194.

10. European lung white book. 2013 publication. Chapter 2 The Economic Burden of Lung Disease. Available at: https://www.erswhitebook.org/chapters/the-economic-burden-of-lung-disease/ [Last accessed: October 2020].

11. Kerkhof M, Voorham J, Dorinsky P, et al. Association between COPD exacerbations and lung function decline during maintenance therapy.Thorax. 2020; 75 (9): 744-753.

12. Halpin DMG, Decramer M, Celli BR, et al. Effect of a single exacerbation on decline in lung function in COPD. Respiratory Medicine 2017; 128: 85-91.

13. Roche N, Wedzicha JA, Patalano F, et al. COPD exacerbations significantly impact quality of life as measured by SGRQ-C total score: results from the FLAME study.Eur Resp J.2017; 50 (Suppl 61): OA1487.

14. Rothnie KJ, Mllerov H, Smeeth L, et al. Natural History of Chronic Obstructive Pulmonary Disease Exacerbations in a General Practice-based Population with Chronic Obstructive Pulmonary Disease. Am Jour of Resp Crit Care Med. 2018; 198 (4): 464-471.

15. Ho TW, Tsai YJ, Ruan SY, et al. In-Hospital and One-Year Mortality and Their Predictors in Patients Hospitalized for First-Ever Chronic Obstructive Pulmonary Disease Exacerbations: A Nationwide Population-Based Study. PLOS ONE. 2014; 9 (12): e114866.

16. Suissa S, DellAniello S, Ernst P. Long-term natural history of chronic obstructive pulmonary disease: severe exacerbations and mortality. Thorax. 2012; 67 (11): 957-63.

SOURCE: AstraZeneca

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Trixeo Aerosphere approved in the EU for maintenance treatment of COPD | Small Molecules | News Channels - PipelineReview.com

Immunology

Vaccines Against SARS-CoV-2 Will Have Side Effects Thats a Good Thing – Brooklyn Reader

By: Matthew Woodruff, Emory University

Takeaways

Temporary side effects from vaccines are a normal sign of a developing immune response.

Vaccines work by training your immune system to recognize and remember a pathogen in a safe way.

Expected side effects from a COVID-19 vaccine include redness and swelling at the injection site and stiffness and soreness in the muscle.

A potent vaccine may even cause fever. It does not mean that the vaccine gave you COVID-19.

In 2021 hundreds of millions of people will be vaccinated against SARS-CoV-2. The success of that COVID-19 vaccination campaign will heavily depend on public trust that the vaccines are not only effective, but also safe. To build that trust, the medical and scientific communities have a responsibility to engage in difficult discussions with the public about the significant fraction of people who will experience temporary side effects from these vaccines.

I am an immunologist who studies the fundamentals of immune responses to vaccination, so part of that responsibility falls on me.

Simply put, receiving these vaccines will likely make a whole lot of people feel crappy for a few days. Thats probably a good thing, and its a far better prospect than long-term illness or death.

In 1989, immunologist Charles Janeway published an article summarizing the state of the field of immunology. Until that point, immunologists had accepted that immune responses were initiated when encountering something foreign bacteria, viruses, and parasites that was non-self.

Janeway suspected that there was more to the story, and famously laid out what he referred to as the immunologists dirty little secret: Your immune system doesnt just respond just to foreign things. It responds to foreign things that it perceives to be dangerous.

Now, 30 years later, immunologists know that your immune system uses a complex set of sensors to understand not only whether or not something is foreign, but also what kind of threat, if any, a microbe might pose. It can tell the difference between viruses like SARS-CoV-2 and parasites, like tapeworms, and activate specialized arms of your immune system to deal with those specific threats accordingly. It can even monitor the level of tissue damage caused by an invader, and ramp up your immune response to match.

Sensing the type of threat posed by a microbe, and the level of intensity of that threat, allows your immune system to select the right set of responses, wield them precisely, and avoid the very real danger of immune overreaction.

Vaccines work by introducing a safe version of a pathogen to a patients immune system. Your immune system remembers its past encounters and responds more efficiently if it sees the same pathogen again. However, it generates memory only if the vaccine packs enough danger signals to kick off a solid immune response.

As a result, your immune systems need to sense danger before responding is at once extremely important (imagine if it started attacking the thousands of species of friendly bacteria in your gut!) and highly problematic. The requirement for danger means that your immune system is programmed not to respond unless a clear threat is identified. It also means that if Im developing a vaccine, I have to convince your immune system that the vaccine itself is a threat worth taking seriously.

This can be accomplished in a number of ways. One is to inject a weakened what immunologists call attenuated or even killed version of a pathogen. This approach has the benefit of looking almost identical to the real pathogen, triggering many of the same danger signals and often resulting in strong, long-term immunity, as is seen in polio vaccination. It can also be risky if you havent weakened the pathogen enough and roll out the vaccine too fast, there is a possibility of unintentionally infecting a large number of vaccine recipients. In addition to this unacceptable human cost, the resulting loss of trust in vaccines could lead to additional suffering as fewer people take other, safer vaccines.

A safer approach is to use individual components of the pathogen, harmless by themselves but capable of training your immune system to recognize the real thing. However, these pieces of the pathogen dont often contain the danger signals necessary to stimulate a strong memory response. As a result, they need to be supplemented with synthetic danger signals, which immunologists refer to as adjuvants.

To make vaccines more effective, whole labs have been dedicated to the testing and development of new adjuvants. All are designed with the same basic purpose to kick the immune system into action in a way that maximizes the effectiveness and longevity of the response. In doing so, we maximize the number of people that will benefit from the vaccine and the length of time those people are protected.

To do this, we take advantage of the same sensors that your immune system uses to sense damage in an active infection. That means that while they will stimulate an effective immune response, they will do so by producing temporary inflammatory effects. At a cellular level, the vaccine triggers inflammation at the injection site. Blood vessels in the area become a little more leaky to help recruit immune cells into the muscle tissue, causing the area to become red and swell. All of this kicks off a full-blown immune response in a lymph node somewhere nearby that will play out over the course of weeks.

In terms of symptoms, this can result in redness and swelling at the injection site, stiffness and soreness in the muscle, tenderness and swelling of the local lymph nodes and, if the vaccine is potent enough, even fever (and that associated generally crappy feeling).

This is the balance of vaccine design maximizing protection and benefits while minimizing their uncomfortable, but necessary, side effects. Thats not to say that serious side effects dont occur they do but they are exceedingly rare. Two of the most discussed serious side effects, anaphalaxis (a severe allergic reaction) and Guillain-Barr Syndrome (nerve damage due to inflammation), occur at a frequency of less than 1 in 500,000 doses.

Early data suggest that the mRNA vaccines in development against SARS-CoV-2 are highly effective upwards of 90%. That means they are capable of stimulating robust immune responses, complete with sufficient danger signaling, in greater than nine out of 10 patients. Thats a high number under any circumstances, and suggests that these vaccines are potent.

So lets be clear here. You should expect to feel sore at the injection site the day after you get vaccinated. You should expect some redness and swelling, and you might even expect to feel generally run down for a day or two post-vaccination. All of these things are normal, anticipated and even intended.

While the data arent finalized, more than 2% of the Moderna vaccine recipients experienced what they categorized as severe temporary side effects such as fatigue and headache. The percentage of people who experience any side effects will be higher. These are signs that the vaccine is doing what it was designed to do train your immune system to respond against something it might otherwise ignore so that youll be protected later. It does not mean that the vaccine gave you COVID-19.

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It all comes down to this: Some time in the coming months, you will be given a simple choice to protect yourself, your loved ones and your community from a highly transmissible and deadly disease that results in long-term health consequences for a significant number of otherwise healthy people. It may cost you a few days of feeling sick.

Please choose wisely.

Matthew Woodruff, Instructor, Lowance Center for Human Immunology, Emory University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

This coverage of coronavirus is a special to BK Reader. We are asking for your help in keeping our coverage and database current with any helpful references and news tips. Please send all tips to [emailprotected]. With your help, Brooklyn will emerge stronger and more unified as a borough. Thank you.

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Physiology

The Ramayana As The Expression of Human Physiology – http://www.newsgram.com/

Dr. Tony Nader received his MD degree from the American University of Beirut, where he also studied internal medicine and psychiatry. He in his second book talks about how human physiology is associated with the Ramayana.

The book takes one of the most purely subjective and spiritual records of knowledge in our mythological references, the Ramayana, and compares it to one of the most objectively-studied and scientifically-described aspects of life, that is human physiology.

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Maharishi Mahesh Yogi was an Indian guru born in 1918, who was also a disciple of Swami Brahmananda Saraswati and the Shankaracharya in the Himalayas. He was the person who introduced Transcendental Meditation in the west.

Ramayana is for full enlightenment; Ramayana is for perfection in every profession; Ramayana is for mastery over Natural Law; Ramayana is for the fulfillment of any desire, one may have. Ramayana is to create a perfect man, a perfect society, and a perfect world.

Maharishi Mahesh Yogi

Here, in this book, the Ramayana is not considered to be any kind of mythological text belonging to any particular religion, race, or belief. It is considered as a Natural Law having events and characters present in it revealing a story of every individuals physiology. The Ramayana is a part of veda, term Veda in Sanskrit refer to knowledge. Vedic literature is considered to be an understanding of life and creating passed on to people from ancient vedic families in India.

The Ramayana revolves around Lord Rama who was an incarnation of lord Vishnu to kill the evil Ravana. Rama belonged to Ikshvaku race of slar dynasty and his parents were Dasharath and Kaushalya. Throughtout the story of Ramayana, Rama performed great deed of destroying negativity and following ethics. Maharishi explains that the story isa description of total Natural Lawits characters and their actions and interactions unfold the story of Natural Law as it expresses itself into all aspects of creation.

Ram Avatar corresponds to the somato-sensory and supplementary sensory-motor cortex in the brain. Unsplash

Ramas arrows always returned to his quiver, which which interprets the mechanism to inform the central nervous system about specific activities that take place around us. There are special sensory spindle fibres that enable information to be sent back to the brain describing how far the muscle has been stretched. On a cellular level, the return of Ramas arrows demonstrates that the nerve cell is capable of renewing itself so that impulses can go out again and again.

Want to read more in Hindi? Checkout: ,

In the ventral view of the brain we see the clear correspondence between Ganesh and the pons, medulla, and cerebellum. The face of Ganesha corresponds to the pons, eyes correspond to the roots of the trigeminal nerves, ears correspond to the cerebellum, trunk corresponds to the medulla, tusks correspond to the nerves at the base of the pons.

ALSO READ:Rudraksh- Setting Up World-Class Convention Centre in Varanasi

The 4 arms of Saraswat correspond to the 4 lobes of the brain. The 4 hands of Lakshm correspond to the4 chambers of the heart. The 8 arms of Durga correspond to the 8 nerves that emanate from the sacral bone.

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The Ramayana As The Expression of Human Physiology - http://www.newsgram.com/

Physiology

Flavours added to vaping devices can damage the heart: Study – The Statesman

Researchers have revealed the appealing array of fruit and candy flavours that entice millions of young people to take up vaping are cardiotoxic and disrupt the hearts normal electrical activity.

Mounting studies indicate that the nicotine and other chemicals delivered by vaping, while generally less toxic than conventional cigarettes, can damage the lungs and heart.

But so far there has been no clear understanding about what happens when the vaporized flavouring molecules in flavoured vaping products, after being inhaled, enter the bloodstream and reach the heart, said study author Sami Noujaim from the University of South Florida in the US.

In the study, published in the American Journal of Physiology-Heart and Circulatory Physiology, the research team reported on a series of experiments assessing the toxicity of vape flavourings in cardiac cells and in young mice.

The flavoured electronic nicotine delivery systems widely popular among teens and young adults are not harm-free.

Altogether, our findings in the cells and mice indicate that vaping does interfere with the normal functioning of the heart and can potentially lead to cardiac rhythm disturbances, Noujaim said.

In mouse cardiac muscle cells (HL-1 cells), the researchers tested the toxicity of three different popular flavours of e-liquid: fruit flavour, cinnamon, and vanilla custard.

All three were toxic to HL-1 cells exposed to e-vapour bubbled into the laboratory dish where the cells were cultured.

Cardiac cells derived from human pluripotent stem cells were exposed to three distinct e-vapours.

The first e-vapour containing the only solvent interfered with the electrical activity and beating rate of cardiac cells in the dish. A second e-vapour with nicotine added to the solvent increased the toxic effects on these cells.

The third e-vapour comprised of nicotine, solvent, and vanilla custard flavouring (the flavour previously identified as most toxic) augmented damage to the spontaneously beating cells even more.

This experiment told us that the flavouring chemicals added to vaping devices can increase harm beyond what the nicotine alone can do, Noujaim said.

The findings showed that mice exposed to vaping were more prone to an abnormal and dangerous heart rhythm disturbance known as ventricular tachycardia compared to control mice.

Our research matters because regulation of the vaping industry is a work in progress, Noujaim noted.

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Flavours added to vaping devices can damage the heart: Study - The Statesman

Physiology

Uncovering the Mind-Body Connection of Touch – Signals AZ

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Humans are born with the language of touch, and physical connection is essential to our development, growth, and survival throughout life.

An infant requires the protective embrace of a parent or caretaker to fully develop, learn trust, and make connections. University of Arizona researcher Dr.Katalin Gothard, born and trained as a medical doctor in Romania, interacted with infants who lacked that physical connection while training at an orphanage during her pediatric clerkship. Due to dictatorial policies in Romania, many orphanages were bursting with unwanted babies while suffering from lack of funds and staff. Because of scarce resources and the goal to keep the children alive, workers prioritized medical needs like preventing malnutrition and infection.

Though she and the staff did their best to keep the children physically healthy, Gothard didnt fully understand the impact that the lack of touch would have on the orphans until she began to study the mind-body connection as a scientist in the United States.

All those antibiotics and all that nutrition did not make them happier adults, said Gothard, a UArizona professor of physiology and member of the universitysBIO5 Institute. Picking them up, holding them and tickling them would have been much more important.

Though initially educated as a medical doctor, Gothard was also trained as a neuroscientist. Observing the toll of mental and emotional hardships caused in part by the oppressive regime in Romania inspired her to change career paths from medicine to science.

I strongly believe that theres no human suffering that compares to the suffering that our own mind can inflict on us, she said. Theres no physical disease that compares to the pain and misery

Dr. Katalin Gothard

and hopelessness of a mental disease.

Gothard now dedicates herself to understanding how physical sensations and experiences affect our emotions. For more than 20 years, the physician-turned-scientist has focused on the amygdala, the almond-shaped mass within the brain, as the critical center of this mind-body dialogue.

In 2019, she and colleaguesdiscovered cells in the amygdalathat responded not just to sights and sounds, but also touch something that had never before been shown.

In the moment of the discovery, Gothard felt a strong pull from her earlier days at the orphanage to investigate those touch-responsive brain cells.

One day we found cells that respond to touch, and it was irresistible. I thought, Does that mean that I could work on something that takes me back to those years at the orphanage when I was ignorant, and I didnt know what these babies really needed?' she said. It was one of those things in life that you cannot say no to. It walks into your life and you know that from that day on your life will change.

Physical Versus Emotional Responses to Touch

Though we know that a handshake forms a connection, a hug brings comfort and a touch from a stranger feels uncomfortable, scientists and physicians have yet to determine the neural mechanisms behind these mind-body processes. With a $2.1 million grant from National Institutes of Health, a team of trainees led by Gothard and her co-investigatorAndrew Fuglevand, a professor of neuroscience and physiology, is seeking to understand how the brain interprets the social, emotional, and physical determinants of touch.

Gothards lab examines the differences in brain activity between gentle grooming on the cheek and a pesky puff of air on the forehead. The researchers observed that the response to the physical aspects of touch when and where occurs much faster than the response to the emotional and social components, like whether the touch was pleasant or from a familiar person.

They also compared the influences of the various touch parameters on emotional state and found that although the objective parameters of touch are processed first, the social aspects were more important in influencing amygdala activity and resulting emotional states.

If you receive a gentle caress from a person that is not welcome even though the pressure on your skin, the sweep speed, the temperature of the hand might be exactly the same as a welcomed touch your amygdala will say, I dont like this,' Gothard said.

With these findings, Gothard realized the emotional and social consequences of touch, combined with our expectations, outrank the physical.

She and her team found that recipient heart rate at the time of touch correlated with emotional response: When the touch was a positive experience, both the heart rate and amygdala activity slowed, but when the touch was negative, heart rate and amygdala activity both increased. She now aims to find the link between touch and changes to markers in the body, including heart rate, as this causal factor might also be the direct link between touch and changes to amygdala circuitry.

The more we understand about the brain, the more humble we become about how little insight we have on whats happening inside that dark cranial box, she said.

COVID-19 Causing Touch Deprivation

Gothard hopes her work will one day inform not only the ways humans normally process touch, but also how these circuits can go awry in people with mental illnesses such as social anxiety or schizophrenia, in which the response to touch is more complex. The research may also help to explain how a lack of touch during infancy such as that experienced by orphans leads to attachment disorders later in life.

Implications for Gothards work further extend to the deprivation of touch during the COVID-19 pandemic. While Gothard stands by the recommendations of social distancing to mitigate the spread of disease, she believes that social isolation during the pandemic will have major, lasting mental health ramifications.

We are in the middle of uncertainty. What you want in the middle of uncertainty is a hug, but you cant do that right now, she said.

Since physical touch is currently scarce, especially for the elderly and for those who live alone, its important to find ways to pacify the brains craving for touch, Gothard said.

She recommends massaging the scalp during hair washing or stimulating the body through physical movement and exercise with the sunshine and breeze. Mind-body scans, such as those often used in yoga and other mindfulness practices, can also help substitute physical touch.

Although these substitutes help to meet the need for physical connection, Gothard said, they cannot fully replace the language of touch we were born to give and receive.

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Uncovering the Mind-Body Connection of Touch - Signals AZ

Physiology

PSC: Focus should be on health, safety – Malaya

RATHER than banning athletes aged 17 and below in combat sports, Philippine Sports Commission chairman Butch Ramirezsaid the countrys sports leaders should instead focus on the strict enforcement of health and safety guidelines in all competitions, particularly in age group play.

In basketball, if a child falls you could suffer a head injury, in baseball you could get hit by a ball in the head. Gymnastics, you could also get hurt playing, Ramirez noted in a wide-ranging virtual press conference last Friday.

This is why my position as a member of the Philippine Sports Commission is that our interest is not in winning buton the safety of our children athletes from injuries, said the PSC chief, who conveyed his stand during the hearing on House Bill 1526 last Wednesday.

TheAct Banning Minors from Full-Contact Competitive Sports is authored by Ako party-list Representatives Alfredo Garbin Jr. and Elizaldy Co. The bill has been opposed by13 National Sports Associations, claiming it could be detrimental to their grassroots programs.

This is why I recommended to the authors of the bill that they amend it to focus on the protocols of play, whether it be combat sports or team sports, Ramirez said. What I am after is the safety conditions of theequipment andvenue and the technical knowledge of those running the event.

When we were the athletic director of a school in the south we all had that, said Ramirez, who was the former athletic director of Ateneo de Davao.

He also shared his thoughts on the qualifications of sports coaches and safety guidelines of sports events.

He pointed out that being a former national athlete is not an assurancethat you will be a good coach. That is why I believe that a coach should have a bachelors degree in physical education so he will have a better understanding of human physiology, the muscle development of a child athlete.

Ramirez stressed that technical knowledge is essential as a coach because if you have achild who should only have 10 hours of training weekly and you have him doing 20 hours this will lead to burnout and he might get injured.

Kung wala kang alam sa human physiology and technical knowledge, you might destroy the child. So the qualifications of coaches are important.

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PSC: Focus should be on health, safety - Malaya

Cell Biology

Special Genes Behind the Pressure Sensor of the Venus Flytrap – SciTechDaily

Open trap of Dionaea muscipula with potential prey. Middle: basal part of a trigger hair, where action potentials are elicited in the sensory cells upon touch stimulation. During the late phase of the action potential, potassium ions need to be reimported into the sensory cells via KDM1 to enable the generation of consecutive action potentials. Credit: Ines Kreuzer, Soenke Scherzer / University of Wuerzburg

The display of a smartphone reacts to finger pressure. The carnivorous Venus flytrap, on the other hand, even notices when a lightweight like a fly lands on it. Special genes make this possible.

All plant cells can be made to react by touch or injury. The carnivorous Venus flytrap (Dionaea muscipula) has highly sensitive organs for this purpose: sensory hairs that register even the weakest mechanical stimuli, amplify them, and convert them into electrical signals that then spread quickly through the plant tissue.

Researchers from Julius-Maximilians-Universitt (JMU) Wrzburg in Bavaria, Germany, have isolated individual sensory hairs and analyzed the gene pool that is active in catching insects. In the process, we found for the first time the genes that presumably serve throughout the plant kingdom to convert local mechanical stimuli into systemic signals, says JMU plant researcher Professor Rainer Hedrich.

Thats a fine thing, because virtually nothing was known about mechano-receptors in plants until now. Hedrichs team presents the results in the open-access journal PLOS Biology.

The hinged trap of Dionaea consists of two halves, each carrying three sensory hairs. When a hair is bent by touch, an electrical signal, an action potential, is generated at its base. At the base of the hair are cells in which ion channels burst open due to a stretching of their envelope membrane and become electrically conductive. The upper part of the sensory hair acts as a lever that amplifies the stimulus triggered by even the lightest prey.

These micro-force-touch sensors thus transform the mechanical stimulus into an electrical signal that spreads from the hair over the entire flap trap. After two action potentials, the trap snaps shut. Based on the number of action potentials triggered by the prey animal during its attempts to free itself, the carnivorous plant estimates whether the prey is big enough whether it is worth setting the elaborate digestion in motion.

To investigate the molecular basis for this unique function, Hedrichs team harvested about 1000 sensory hairs. Together with JMU bioinformatician Professor Jrg Schultz, they set out to identify the genes in the hairs.

In the process, we noticed that the fingerprint of the genes active in the hair differs from that of the other cell types in the trap, says Schulz. How is the mechanical stimulus converted into electricity? To answer this, we focused on the ion channels that are expressed in the sensory hair or are found exclusively there, says Hedrich.

The sensory hair-specific potassium channel KDM1 stood out. Newly developed electrophysiological methods showed that without this channel, the electrical excitability of the sensory hairs is lost, i.e. they can no longer fire action potentials. Now we need to identify and characterize the ion channels that play an important role in the early phases of the action potential, Hedrich said.

Reference: The Venus flytrap trigger hairspecific potassium channel KDM1 can reestablish the K+ gradient required for hapto-electric signaling by Anda L. Iosip, Jennifer Bhm, Snke Scherzer, Khaled A. S. Al-Rasheid, Ingo Dreyer, Jrg Schultz, Dirk Becker, Ines Kreuzer and Rainer Hedrich, 9 December 2020, PLOS Biology.DOI: 10.1371/journal.pbio.3000964

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Special Genes Behind the Pressure Sensor of the Venus Flytrap - SciTechDaily

Cell Biology

6 scientists in Singapore who have pivoted to Covid-19 related work – The Straits Times

SINGAPORE -Meet six scientists in Singaporewho have pivoted away from their areas of expertiseto Covid-19 related work.

PHOTO:NTU SINGAPORE

Professor Stephan Schuster is an environmental detective. Like his crime-solving counterparts, the professor at the Nanyang Technological University's (NTU) School of Biological Sciences looks for what is unseen to the naked eye.

This has come in useful during the Covid-19 pandemic, as humanity battles an invisible foe.

His work involves taking samples from the air and surfaces, and analysing them to find traces of genetic material of organisms like viruses. Both environments are ultra-low biomass environments, meaning each sample might have only a few micrograms of genetic material, said Prof Schuster, who is also deputy centre director for facilities and capacities at NTU's Singapore Centre for Environmental Life Sciences Engineering.

"Nevertheless, the (genetic material) recovered from these samples is very complex, as they originate from many different microbial organisms," he said.

Prof Schuster and his colleagues got cracking. They found in a study pending publication that air pollution could result in negative outcomes for respiratory illnesses, including those with Covid-19.

The Straits Times had earlier reported that microorganisms in the air measure between 0.5 and 10 microns and are likely to reach deep inside the lung tissue. Those with pulmonary diseases may be unable to expel them.

Prof Schuster said they could pivot during the outbreak because of the completion of a five-year research programme on the air microbiome, his skilled co-workers and the availability of tools like air samplers.

"This crisis has proven that scientists all over the world are able and willing to swiftly move to new fields and to apply their knowledge," he said.

ST PHOTO: ARIFFIN JAMAR

At the start of the Covid-19 outbreak, healthcare professionals and policymakers were stumped on many fronts. A key question was how the coronavirus spread from human to human.

Researchers like National University of Singapore (NUS) Associate Professor Tham Kwok Wai leapt into action, tapping their previous work.

Prof Tham, who had studied the spread of viruses such as influenza in an indoor setting, found that the indoor environment was also a primary domain for transmission of the virus that causes Covid-19.

Because of his previous research, he knew there were measures that could control its spread indoors. For instance, increasing ventilation of a room will help to dilute the concentration of the virus in the air, reducing transmission risk. Safe distancing also works, as the viral load diminishes with distance from the infected person, he said.

Passing re-circulating air through high efficiency filters can help to remove viruses that usually "clump" together, said the professor from the NUS School of Design and Environment.

Before Covid-19, Prof Tham's research had focused on the impact of the indoor environment on humans, and on cooling and ventilation technologies for indoor environmental control.

"I began to see how I could apply my research on environmental intervention to Covid-19 at the onset of the pandemic, around December 2019," he said.

Prof Tham said tackling the outbreak requires researchers with various expertise.

Other than virology, for instance, knowledge in aerosol science or fluid mechanics could also help with better understanding of how expelled droplets could spread.

Prof Tham said: "This demonstrates how a trans-disciplinary approach is essential in tackling the Covid-19 challenge holistically. And this constitutes the basis for policy formulation."

ST PHOTO: DESMOND WEE

Professor Lim Chwee Teck has spent the bulk of his career developing microfluidic biomedical devices, which analyse tiny amounts of fluids to detect diseases such as cancer. But when the Covid-19 crisis was rapidly worsening early this year, he switched to Covid-19 diagnostics.

"We felt we had to do something despite the fact that we had not worked on flu viruses previously," said Prof Lim, director of the National University of Singapore's Institute for Health Innovation & Technology.

Since March, he and his team have developed a portable polymerase chain reaction (PCR) diagnostic system that can produce test results within an hour, and he is currently developing a rapid antigen test kit that can detect Covid-19 within 15 minutes.

The portable PCR kit, called Epidax, uses a specially designed microfluidic chip to process a smaller amount of a nasal swab sample to detect Covid-19 faster.

The portable PCR kit, called Epidax, can produce test results within an hour. ST PHOTO: DESMOND WEE

A reagent is used to extract the RNA and amplify it on the chip, so the PCR test can be done.

"All these features significantly minimise sample handling and shorten the test and waiting time, so patients can get their test results in about an hour or less," said Prof Lim.

In conventional PCR tests, the nasal swabs are sent to a lab to extract the RNA before the test can be done. Those taking a conventional PCR test usually have to wait a day or two for their results.

So far, clinical tests with Epidax have shown 100 per cent accuracy in detecting Covid-19.

Prof Lim hopes that his faster and portable PCR system can be used for rapid screening and mass testing in places such as clinics, schools and offices.

The team has filed a patent for Epidax, and has licensed the technology to a local medical technology company.

ST PHOTO: JASON QUAH

At the onset of the pandemic, Professor Marcus Ong realised that the unprecedented outbreak would not just impact infected patients and front-line healthcare workers.

The virus could put the whole healthcare system, hospitals and all patients under pressure, either directly or indirectly.

To help cushion the impact of the relatively unknown virus on the healthcare system, Prof Ong - senior consultant at Singapore General Hospital's Department of Emergency Medicine - turned towards his research interests in data science and simulation modelling.

Said Prof Ong: "We saw an urgent need to use data to support our health system's response to Covid-19, in order to protect our patients and our healthcare system."

He is speaking from experience, having lost some of his friends and colleagues to severe acute respiratory syndrome in 2003.

"We realised how important a comprehensive, whole-system response was in order to protect the health system from being overwhelmed and to save lives."

Since February, his team has been building computer simulation models based on the pandemic to improve healthcare policies in areas such as resource allocation and business disruptions.

"The virtual outbreak model can be further developed to address different disease outbreak scenarios in the future, and will also enhance our national response to future epidemics," said Prof Ong.

A recent study published by his team found that Covid-19 medical literature written in the early days of the outbreak was focused mainly on clinical elements and diagnosis.

Big-picture issues such as the outbreak's effect on the mental health of healthcare workers and how it affected the care of non-Covid-19 patients, as well as the use of novel technologies, were initially under-explored.

ST PHOTO:TIMOTHY DAVID

Using his expertise in malaria research, Professor Peter Preiser of Nanyang Technological University (NTU) developed a paper test to detect viral proteins produced by the Sars-CoV-2 virus.

The professor of Molecular Genetics & Cell Biology did this by adapting technology he had created to differentiate between types of malaria parasites, knowing there would be a need for reliable diagnostics and a rapid response in a crisis like Covid-19.

The result is a cellulose-based paper test which is able to recognise Sars-CoV-2 proteins in a patients blood sample. If the viral proteins are present, the paper strip changes from white to blue in 10 minutes.

Prof Preiser produced two versions: a serology test which is able to recognise antibodies from past Covid-19 infections; and a rapid antigen test, which is able to detect antigens to identify those who are infected with Covid-19.

Prof Preiser, who is also the Associate Vice-President for biomedical and life sciences at NTU, said that the tests would only cost a few dollars and are able to yield fast results, making them suitable for mass roll-outs.

For instance, the serology test could potentially be used for pre and post vaccinations, to ensure that priority is given to those who have not been infected before, and also ensure that the administered vaccine has been effective.

Conventional serology tests can take between two and 24 hours when performed in a lab, he noted.

The team is now looking at the possibility of using a finger prick method for blood collection, and the possibility of a saliva test for comfort and convenience.

The success of the Covid-19 tests has given us a lot of confidence in (our) technology and provided us with a lot of information on how we can use the same approach to detect other bio markers (for other) infectious diseases, said Prof Preiser.

PHOTO: A*STAR

Social technologist Dr Yang Yinping has a passion for building and applying technology to advance human communications.

She has conducted research in areas like sentiment analysis and emotion recognition, which have useful implications for public health.

For instance, in 2013, she co-led a project to examine social network activities during the H7N9 bird flu outbreak, in collaboration with the Ministry of Health.

Most recently, the principal investigator and group manager at the Agency for Science, Technology and Researchs (A*Star) Institute of High Performance Computing started examining peoples sentiments during the Covid-19 pandemic, using an algorithm system which examines social media posts on Twitter.

To date, more than 124 million worldwide tweets have been collected and processed. They are analysed according to four emotions fear, anger, sadness, and joy, along with the course of events contextualising these feelings.

For instance, fear was the overriding global sentiment when the virus first surfaced, followed by anger, which peaked on March 12, a day after the World Health Organisation declared the Covid-19 virus as a pandemic.

She said these feelings should be monitored closely, as they offer insights into concerns faced by the community.

But sentiments often vary across countries, perhaps owing to each governments response to the pandemic, among other factors, added Dr Yang.

In Singapore, for instance, joy and other positive emotions overtook initial feelings of fear from March 30 onwards, suggesting a sense of pride, gratitude and relief, she noted.

In the coming days, Dr Yang anticipates stronger sentiments of joy, in response to positive news of a vaccine and other treatment developments.

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6 scientists in Singapore who have pivoted to Covid-19 related work - The Straits Times