Physiology

Thomas Jefferson University-led group creates first 3D map of heart neurons – Optics.org

02Jun2020

New imaging technique Knife-Edge Scanning Microscopy gives insight into neurons' role in heart attacks and other conditions.

As an added layer of control, the heart has its own little brain, called the intracardiac nervous system (ICN), which monitors and corrects any local disturbances in communication. The ICN can even protect cardiac muscle during a heart attack.

How the ICN carries out these roles has not been well understood because the organization and location of neurons was not known. But now, in a study published in iScience, researchers at Thomas Jefferson University, Philadelphia, PA, and collaborators have been able to answer these questions in significant detail.

The ICN represents a big void in our understanding that falls between neurology and cardiology, said co-senior author James Schwaber, PhD, director of the Daniel Baugh Institute for Functional Genomics and Computational Biology (DBI) and co-senior author of the study.

The only other organ for which such a detailed high-resolution 3D map exists is the brain, commented co-senior author Raj Vadigepalli, PhD, Professor of Pathology, Cell Biology and Anatomy. What we have created is the first comprehensive roadmap of the hearts nervous system that can be referenced by other researchers for a range of questions about the function, physiology, and connectivity of different neurons in the ICN.

The study drew on technologies and expertise from different research groups (from Jefferson and University of Central Florida) and industry partners Strateos and MBF Bioscience, eventually creating a dual-approach pipeline.

Novel imaging technique

One approach involved a novel imaging technique called Knife-Edge Scanning Microscopy (KSEM) that allowed the researchers to build a precise 3D model of the entire rodent heart; it is the first use of this technology for cardiac research.

The second approach used a technique called laser capture microdissection to sample single neurons for gene expression analysis, as well as to precisely map their individual positions within the 3D structure of the heart.

The 3D map revealed hitherto unknown complexity of the ICN. The researchers found that the neurons that make up the ICN are found in a coherent band of clusters on the base (top) of the heart, where the hearts veins and arteries enter and leave, but also extend down the length of the left atrium on the back of the heart.

The gene expression analysis of individual neurons also pointed to previously unknown diversity of molecular identities or phenotypes. We found that there are several different types of neuromodulators and receptors present, said Dr. Vadigepalli. This means that we dont just have neurons in the heart that shut on and off activity, but also those that can fine-tune ICN activity.

Sex-specific differences

When comparing male and female rat hearts, the researchers also found sex-specific differences in the way neurons were organized. Co-authors Alison Moss, PhD Candidate in Biochemistry and Molecular Pharmacology, and Shaina Robbins, a senior research assistant, are pursuing further analyses based on these findings.

It could help us explain some of the differences in heart disease in men and women, says Moss. Were now trying to create a 3D model of the intrinsic nervous system of the pig heart, which is even more anatomically comparable to the human heart, to explore those questions further.

This project is part of a NIH research program called Stimulating Peripheral Activity to Relieve Conditions, or SPARC, which aims to promote development of therapeutic devices that modulate electrical activity in nerves to improve organ function. Eventually the hope is to create a 3D map for the human heart, both in health and disease, concluded Dr. Schwaber. Weve created the foundation for an endless possibility of future studies.

View post:
Thomas Jefferson University-led group creates first 3D map of heart neurons - Optics.org

Immunology

Experts Urge Caution in Interpreting COVID-19 Antibody Tests – Technology Networks

As stay-at-home orders are lifted around the country and public life begins to return, health experts continue to emphasize the importance of testing for COVID-19 to prevent a second and potentially worse wave of infections.

There are two kinds of COVID-19 tests, and both are critical to controlling this pandemic. Molecular diagnostic tests, first developed in January, detect parts of the COVID-19-causing virus on swabs from peoples noses or throats. Such tests can identify people with active infections, even when they have no symptoms. With widespread and rapid diagnostic testing, people with the virus can be identified quickly and isolated, and anyone who came into contact with them quarantined and tested. Such surveillance and isolation measures can prevent a few cases from mushrooming into an outbreak.

Antibody, or serology, tests became available in April. They are performed on a blood sample and detect antibodies produced by the body in response to the virus. A positive test indicates that a person was infected at some time in the past. In a paper published recently in the journal Clinical Chemistry, Neil Anderson, MD, an assistant professor of pathology and immunology at Washington University School of Medicine in St. Louis and the assistant medical director of the Clinical Microbiology Laboratory at Barnes-Jewish Hospital, and Christopher Farnsworth, PhD, an instructor of pathology and immunology at the School of Medicine, emphasized the importance of ensuring that antibody tests are used appropriately. Here, they discuss further how such tests should and should not be used.

Why are antibody tests for COVID-19 important?

Farnsworth: Antibody testing is really helpful in monitoring how widely a virus has spread within a community. Such testing could help determine how many people have recovered from the virus, even if they never had symptoms. For many viruses, once about 70% of the population is immune either because they have had a natural infection or, better yet, received a vaccination infected people are less likely to encounter a susceptible person and give them the virus, so transmission goes down and the epidemic ends. Thats called herd immunity. Now, estimates suggest about 1% to 2% of people in the U.S. have been infected with the virus that causes COVID-19, so we are nowhere close to achieving herd immunity.

If my antibody test is positive, does that mean Ive had COVID-19 and wont get it again?

Anderson: A positive test just means your body has produced antibodies in response to a past infection; it doesnt tell us whether those antibodies will protect you from getting re-infected. The only way wed know for sure is if we followed patients who are antibody-positive for months or years to see whether they get re-infected. Those studies are underway by scientists at other institutions, but there is no answer yet.

Can antibody tests decide who can safely go back to work?

Farnsworth: Many people are anxious to get people back to work, but antibody tests may give some people a false sense of security. The problem is that even a highly accurate antibody test like the one we use in our laboratory has false positives and false negatives. When the true rate of infection in a community is very low, you will have more false positives than true positives, no matter how good the test is. In Missouri, we think that fewer than 1% of the population has been infected. In our research, we estimated that if we screened asymptomatic individuals, only one out of seven positive antibody tests in Missouri would be true positives, even with a highly accurate test. So, the other six people may think theyre protected and let their guard down, and then they could get infected and spread the disease. Widespread antibody testing could do more harm than good if people do not understand the limitations of such testing.

How should antibody tests be used?

Anderson: There have not been formal guidelines at the national or local levels regarding how exactly these tests should be used. And, in the absence of such guidelines, many people are anxious to get antibody testing. The way I look at such tests is that theyre a tool. People develop antibodies a week to two weeks into an infection, so antibody tests can support diagnostic tests in identifying current infections. They also can be used for screening or public health surveillance. But, for all these purposes, antibody tests should not be the sole source of information for decision-making. As we learn more about the tests and what theyre capable of, I think well be able to make some evidence-based guidelines to indicate who should be tested and what we should do with the results.

Reference:Farnsworth, C. W., & Anderson, N. W. (2020). SARS-CoV-2 Serology: Much Hype, Little Data. Clinical Chemistry. doi:10.1093/clinchem/hvaa107

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

Read the original:
Experts Urge Caution in Interpreting COVID-19 Antibody Tests - Technology Networks

Immunology

Observations on Safety Procedures to Combat Covid-19 by Former CEO of British Society for Immunology – Euro Weekly News

The following was posted as a comment by Dr Marcus Stephan who now lives on the Costa del Sol but was considered interesting and important enough to publish on this website.

NO-ONE can possibly disagree with the fact that Spain has suffered very badly as a result of Covid-19.

The lockdown measures have been, using any measure, largely successful and the government should be commended as should the vast majority of the population for adhering to the rules.

However, as a former CEO of the British Society for Immunology, I am increasingly becoming frustrated by the over importance being given to what we refer to as fomite transmission. This virus spreads in droplet form from one person to another, there is no doubt about that and so keeping your distance is not only a good idea but the science tells us to do this.

Fomite transmission is what happens when an infected person coughs or sneezes on their hands and they then touch a surface. You then come along and touch the contaminated surface and manage to pick up enough viable virus and then you rub that into your eyes, mouth, or nose. If you do that well enough you may become infected.

There are a lot of ifs to consider, but yes, it is just possible. However, bear all this in mind, first of course viruses are not living things, just tiny specks of stuff and they dont remain viable outside their preferred host for very long.

So, to put it delicately a droplet of human nasal fluid containing virus particles that lands on a hard surface needs to get picked up by you fairly quickly if it is going to do its business and make you sick.

If the droplet dries out, Im afraid the virus particles have had it, likewise if the droplet gets exposed to sunlight, heat, or any well-known cleaning fluid same thing goes. So, you have to be fairly quick off the mark to scrape the virus particles up and make sure they get into you if you want to stand any chance of getting sick.

Im not making light of the fact that if you are in a particular category and you do pick up this virus the consequences can be severe, but I also think it is important we alter our behaviour based on the science.

All this talk of disinfecting sunbeds and disposable menus in restaurants is too much icing on the cake in my view, not just that but for some people this is increasing their anxiety about going out and that can lead to all sorts of other undesirable complications.

If you add a dose of common sense and good manners to the science, we have a near perfect solution until a vaccine arrives. By far and away the most important thing any of us can do is to wash our hands before we fiddle with our faces and that is extremely difficult to do, but if we can do it so much the better.

So even if you did manage to get someone elses infected secretions all over your hand so long as you dont touch your face until you have washed your hands all is OK. The virus doesnt get absorbed through your skin by the way.

The wearing of masks is something you wont get scientists or medics necessarily in agreement when it comes to using them in general. Lets be 100 per cent clear, they do not protect you in any way shape or form of breathing in someone elses sneeze or cough, you need a very special mask for that and these are not generally available.

As a means of cutting down what you might spread if you are infected, so long as you keep it on, they are probably a good idea. Going for a walk in the fresh air or sitting on one of our lovely beaches presents no risk.

The risk only really becomes a reality if you are in a closed in space and you have someone coughing or sneezing all over the place and the air starts to fill with microscopic droplets that dont get blown away and diluted.

Its rather what happened sadly on the cruise ships where people were confined to cabins and the efficient air conditioning system managed to pipe contaminated air from cabin to cabin.

So back to contaminated surfaces, there is a lot of scientific data that shows you need to literally pick up lots, possibly millions, of virus particles for the hand to nose route to be effective, but we believe you need far less if you manage to breath in a someones sneeze and that gets directly to your lungs.

So there really is no need to be over concerned about touching a supermarket trolley and why your payment card might require a touch pad to be sanitised Im afraid I cannot explain except to say that this is an example of science taking a back seat and paranoia muscling in.

One thing Spain hasnt ruled against, and I certainly would, is to stop anyone smoking in public, because you see this virus attacks the respiratory system and exhaled smoke will contain virus particles so if you can smell someone elses smoke then you might be breathing in virus.

The rules being put in place on our beaches for example have very good intentions, but they are a mess. Not only are they a mess but they will add further damage to our much-needed tourism economy, lets not forget that the vast majority of coastal towns in Spain depend on tourism.

Show me a peer-reviewed scientific article that indicates the use of a Lilo in the water presents a real risk of infection. If fomite transmission was a good as we are being led to believe then all the filthy coins and bank notes we pass around between us would be infecting us like wildfire.

Use a tissue when you sneeze and then throw it away, wash your hands before you touch your face. If you think you are infected then do the decent thing and stay at home alone. But dont be afraid to go out and enjoy this lovely part of Spain, all of us just need to take sensible personal responsibility.

Original post:
Observations on Safety Procedures to Combat Covid-19 by Former CEO of British Society for Immunology - Euro Weekly News

Immunology

New PALFORZIA Data on Long-Term Safety, Efficacy and Immunomodulation and New Data on Patient Satisfaction with PALFORZIA Treatment to be Presented at…

BRISBANE, Calif.--(BUSINESS WIRE)--Aimmune Therapeutics, Inc. (Nasdaq: AIMT), a biopharmaceutical company developing and commercializing treatments for life-threatening food allergies, today announced it will present important new long-term safety, efficacy and immunological data from ARC004, an open-label, rollover study of the landmark pivotal PALISADE trial of PALFORZIA [Peanut (Arachis hypogaea) Allergen Powder-dnfp] and data on patient-reported treatment satisfaction from the European phase 3 ARTEMIS trial of PALFORZIA. In addition, insights from the PAPRIQUA study about the psychosocial burden of peanut allergy on children and their caregivers will be presented. These data will be presented at the European Academy of Allergy and Clinical Immunology (EAACI) Digital Congress to be held from June 6-8.

We are presenting the longest follow-up data on the safety, efficacy and immunomodulation associated with daily dosing of PALFORZIA, as well as insights into patient satisfaction with PALFORZIA treatment, the first peanut allergy treatment approved by the U.S. Food and Drug Administration, said Daniel Adelman, M.D., Chief Medical Officer of Aimmune. Additionally, new insights about the daily burden of living with peanut allergy will be presented to highlight the need for an approved treatment for peanut allergy. To that end, we take great pride in our leadership and dedication to improving the lives of those affected by peanut allergy.

The following abstracts will be available , for on-demand viewing on the EAACI scientific programme website starting at 9:00am CEST / 3:00am EDT on Saturday, June 6, 2020

PALFORZIA Clinical Trial Data

Peanut Allergy Data

Additional Data Involving PALFORZIA

PALFORZIA (previously known as AR101) is an oral immunotherapy indicated for the mitigation of allergic reactions, including anaphylaxis, that may occur with accidental exposure to peanut. PALFORZIA is approved for use in the United States in patients with a confirmed diagnosis of peanut allergy. In Europe, Aimmune has a marketing authorization application for AR101 (PALFORZIA) under review with the European Medicines Agency (EMA).

INDICATION

PALFORZIA is an oral immunotherapy indicated for the mitigation of allergic reactions, including anaphylaxis, that may occur with accidental exposure to peanut. PALFORZIA is approved for use in patients with a confirmed diagnosis of peanut allergy. Initial Dose Escalation may be administered to patients aged 4 through 17 years. Up-Dosing and Maintenance may be continued in patients 4 years of age and older.

PALFORZIA is to be used in conjunction with a peanut-avoidant diet.

Limitations of Use: Not indicated for the emergency treatment of allergic reactions, including anaphylaxis.

IMPORTANT SAFETY INFORMATION

Boxed WARNING:

PALFORZIA can cause anaphylaxis, which may be life threatening and can occur at any time during PALFORZIA therapy.

Prescribe injectable epinephrine, instruct and train patients on its appropriate use, and instruct patients to seek immediate medical care upon its use.

Do not administer PALFORZIA to patients with uncontrolled asthma.

Dose modifications may be necessary following an anaphylactic reaction.

Observe patients during and after administration of the Initial Dose Escalation and the first dose of each Up-Dosing level, for at least 60 minutes.

PALFORZIA is available only through a restricted program called the PALFORZIA REMS.

CONTRAINDICATIONS

PALFORZIA is contraindicated in patients with uncontrolled asthma, or with a history of eosinophilic esophagitis and other eosinophilic gastrointestinal disease

WARNINGS AND PRECAUTIONS

Anaphylaxis

PALFORZIA can cause anaphylaxis, which may be life threatening. PALFORZIA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the PALFORZIA REMS because of the risk of anaphylaxis. Only prescribers, healthcare settings, pharmacies, and patients certified and enrolled in the REMS Program can prescribe, receive, dispense or administer PALFORZIA.

Anaphylaxis has been reported during all phases of PALFORZIA dosing, including Maintenance and in subjects who have undergone recommended Up-Dosing and dose modification procedures.

Do not initiate PALFORZIA treatment in a patient who has had severe or life-threatening anaphylaxis within the previous 60 days. PALFORZIA may not be suitable for patients with certain medical conditions that may reduce the ability to survive anaphylaxis, including but not limited to markedly compromised lung function, severe mast cell disorder, or cardiovascular disease. In addition, PALFORZIA may not be suitable for patients taking medications that can inhibit or potentiate the effects of epinephrine.

All Initial Dose Escalation doses and the first dose of each Up-Dosing level must be administered in a certified health care setting.

Patients may be more likely to experience allergic reactions following PALFORZIA administration in the presence of cofactors such as exercise, hot water exposure, intercurrent illness (e.g., viral infection), or fasting. Other potential cofactors may include menstruation, sleep deprivation, nonsteroidal anti-inflammatory drug use, or uncontrolled asthma. Patients should be proactively counseled about the potential for the increased risk of anaphylaxis in the presence of these cofactors. If possible, adjust the time of dosing to avoid these cofactors. If it is not possible to avoid these cofactors, consider withholding PALFORZIA temporarily.

Asthma

Uncontrolled asthma is a risk factor for a serious outcome, including death, in anaphylaxis. Ensure patients with asthma have their asthma under control prior to initiation of PALFORZIA.

PALFORZIA should be temporarily withheld if the patient is experiencing an acute asthma exacerbation. Following resolution of the exacerbation, resumption of PALFORZIA should be undertaken cautiously. Re-evaluate patients who have recurrent asthma exacerbations and consider discontinuation of PALFORZIA.

Eosinophilic Gastrointestinal Disease

Discontinue PALFORZIA and consider a diagnosis of eosinophilic esophagitis in patients who experience severe or persistent gastrointestinal symptoms, including dysphagia, vomiting, nausea, gastroesophageal reflux, chest pain, or abdominal pain.

Gastrointestinal Adverse Reactions

Gastrointestinal adverse reactions were commonly reported in PALFORZIA-treated subjects, and dose modification should be considered for patients who report these reactions. For severe or persistent gastrointestinal symptoms consider a diagnosis of eosinophilic esophagitis.

ADVERSE REACTIONS

The most common adverse events reported in subjects treated with PALFORZIA (incidence 5% and 5% than placebo) are abdominal pain, vomiting, nausea, oral pruritus, oral paresthesia, throat irritation, cough, rhinorrhea, sneezing, throat tightness, wheezing, dyspnea, pruritus, urticaria, anaphylactic reaction, and ear pruritus.

Please see full Prescribing Information, including Boxed WARNING, and Medication Guide at http://www.PALFORZIA.com.

For more information about PALFORZIA, please call 1-844-PALFORZ (1-844-725-3679) or visit http://www.PALFORZIA.com.

About Aimmune Therapeutics

Aimmune Therapeutics, Inc. is a biopharmaceutical company developing and commercializing treatments for potentially life-threatening food allergies. With a mission to improve the lives of people with food allergies, Aimmune is developing and commercializing oral treatments for potentially life-threatening food allergies. The Companys Characterized Oral Desensitization ImmunoTherapy (CODIT) approach is intended to provide meaningful levels of protection against allergic reactions resulting from accidental exposure to food allergens by desensitizing patients with defined, precise amounts of key allergens. Aimmune has one FDA-approved medicine for peanut allergy, a marketing authorization application under review with the European Medicines Agency (EMA) for its investigational medicine for peanut allergy, and other investigational therapies in development to treat other food allergies. For more information, please visit http://www.aimmune.com.

Forward-Looking Statements

Statements contained in this press release regarding matters that are not historical facts are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding: Aimmunes expectations regarding the upcoming presentation of data at the EAACI Digital Congress, including data regarding safety, efficacy, patient and caregiver experience of living with peanut allergy, and patient satisfaction with PALFORZIA treatment; and Aimmunes expectations regarding potential applications of the CODIT approach to treating life-threatening food allergies. Risks and uncertainties that contribute to the uncertain nature of the forward-looking statements include the risk that the COVID-19 worldwide pandemic may continue to negatively impact the business, research and clinical operations of Aimmune or its partners; Aimmunes or any of its collaborative partners ability to initiate and/or complete clinical trials; the unpredictability of the regulatory process; the possibility that Aimmunes or any of its collaborative partners clinical trials will not be successful; Aimmunes dependence on the success of PALFORZIA; Aimmunes reliance on third parties for the manufacture of Aimmunes products and product candidates; possible regulatory developments in the United States and foreign countries; and Aimmunes ability to attract and retain senior management personnel. These and other risks and uncertainties are described more fully in Aimmune's most recent filings with the Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the quarter ended March 31, 2020. All forward-looking statements contained in this press release speak only as of the date on which they were made. Aimmune undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

This press release concerns PALFORZIA (AR101), which has been approved for marketing by the FDA in the United States and has not been approved for marketing by the EMA or Swissmedic. AR101 in Europe is currently limited to investigational use, and no representation is made as to its safety or effectiveness for the purposes for which it is being investigated.

PALFORZIA, AIMMUNE, AIMMUNE THERAPEUTICS and CODIT are trademarks of Aimmune Therapeutics, Inc.

Original post:
New PALFORZIA Data on Long-Term Safety, Efficacy and Immunomodulation and New Data on Patient Satisfaction with PALFORZIA Treatment to be Presented at...

Immunology

Postdoctoral Fellow in Metabolic Medicine and Immunometabolism job with THE UNIVERSITY OF HONG KONG | 208675 – Times Higher Education (THE)

Work type: Full-timeDepartment: Department of Medicine (20600)Categories: Academic-related Staff

Applications are invited for appointment as Post-doctoral Fellow in Metabolic Medicine and Immunometabolism in the Department of Medicine and the State Key Laboratory of Pharmaceutical Biotechnology (2 posts) (Ref.: 500221), to commence as soon as possible for two to three years, with the possibility of renewal subject to satisfactory performance.

Applicants should have a Ph.D. degree, preferably with experience in adipose biology, immunology, multi-omics and/or manipulation of genetically-modified mice. The appointees will work on a research project to characterize heterogeneity of adipose tissues and to identify secretory factors involved in conversion of white adipocytes to brown adipocytes. Details of our research program can be found at http://www.sklpb.hku.hk and https://medic.hku.hk/staff_detail.php?id=19. Enquiries about the posts can be sent to Miss Lily Li at lily46@hku.hk. Those who have responded to the previous advertisement (Ref.: 499656) need not re-apply.

A highly competitive salary commensurate with qualifications and experience will be offered, in addition to annual leave and medical benefits.

The University only accepts online application for the above posts. Applicants should apply online and upload an up-to-date C.V. Review of applications will start from June 15, 2020 and continue until July 31, 2020, or until the posts are filled, whichever is earlier.

Read the rest here:
Postdoctoral Fellow in Metabolic Medicine and Immunometabolism job with THE UNIVERSITY OF HONG KONG | 208675 - Times Higher Education (THE)

Immunology

Lilly starts COVID-19 antibody trial, expanding on earlier efforts – BioWorld Online

Eli Lilly and Co. said June 1 the first patients have been dosed in a phase I test of LY-CoV555, a potential antibody treatment for COVID-19, with results expected by June 30. Should it prove safe, the candidate could quickly move into a phase II trial to assess its efficacy, Ajay Nirula, vice president of immunology at Lilly, told BioWorld. The news follows Lilly's May 4 announcement of efforts to co-develop antibodies for the prevention and treatment of the infection with Shanghai Junshi Biosciences Ltd. and testing of its already-marketed small-molecule JAK inhibitor, Olumiant (baricitinib), as part of the NIH-led adaptive COVID-19 treatment trial.

The new candidate, a neutralizing IgG1 monoclonal antibody directed against the spike protein of SARS-CoV-2, is the first to emerge from Lilly's collaboration with Abcellera Biologics Inc., a deal that itself was just signed in early March. Under the terms of the agreement, Abcellera and Lilly committed to equally share initial development costs toward a product, after which Lilly will be responsible for all further development, manufacturing and distribution work and costs.

Lilly's work joins significant efforts underway at Regeneron Pharmaceuticals Inc., Roche Holding AG, Vir Biotechnology Inc., Celltrion Inc. and academic institutions such as the University of Toronto, all of which are pursuing the development of antibody therapeutics for the virus. Though the Regeneron and Roche programs have already entered the clinic, clinical testing of LY-CoV555 appears to be the first clinical effort to evaluate an antibody specifically designed to block SARS-CoV-2's attachment and entry into human cells.

The candidate was generated in just three months after Abcellera and the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases identified it from a blood sample taken from one of the first U.S. patients who recovered from COVID-19.

Vancouver, British Columbia-based Abcellera's high-throughput microfluidics platform, adapted through the Defense Advanced Research Projects Agency's Pandemic Prevention Program for rapid response to pandemics, employs machine vision and artificial intelligence to identify immune cells and the exact sequences of antibodies they create. In this case, Lilly analyzed antibodies from the recovered patient, characterizing close to 500 of them to understand which ones were most potent at blocking SARS-CoV-2. In vitro and other testing helped narrow the scope even further before the company moved to generate a version of the most promising one for testing in the new phase I study.

The placebo-controlled trial, called J2W-MC-PYAA, is likely to enroll about 30 hospitalized COVID-19 patients. The key goals are to understand the safety and tolerability of the antibody, the pharmacokinetics that can guide dosing. But investigators, who started dosing patients Friday at the NYU Grossman School of Medicine and Cedars-Sinai in Los Angeles, will also help Lilly look at exploratory efficacy endpoints, such as measures of patient viral loads.

While Lilly is initially focused on testing LY-CoV555 in hospitalized patients, "ultimately, we want to branch out the program into different patient populations," Nirula said. The team is also interested in moving into other trials where they would study patients before they're hospitalized to see if administration of a therapeutic antibody earlier in the course of the disease could prevent progression to hospitalization or even play a prophylactic role. Such studies could be underway "in the relatively near future," he said.

Further potential studies could explore whether an antibody might be effective in combination with other medicines, such as Gilead Sciences Inc.'s remdesivir.

Later this month, Lilly's team will review the results of the phase I study of LY-CoV555 before potentially starting broader efficacy trials. But, in an illustration of the substantial urgency Lilly and other drugmakers see in the market, the Indianapolis company is also starting large-scale manufacturing of the potential therapy, it said.

"If LY-CoV555 becomes part of the near-term solution for COVID-19, we want to be ready to deliver it to patients as quickly as possible, with the goal of having several hundred thousand doses available by the end of the year," said Daniel Skovronsky, Lilly's chief scientific officer and president of Lilly Research Laboratories.

Meanwhile, together with Junshi Biosciences, Lilly is expected to file an IND and initiate clinical trials in the U.S. and China in the second quarter. That program, recently documented in an article in Nature, is also employing antibodies isolated from a recovered COVID-19 patient.

Lilly shares (NYSE:LLY) moved little on June 1, losing 50 cents to close at $152.45.

Read more from the original source:
Lilly starts COVID-19 antibody trial, expanding on earlier efforts - BioWorld Online

Immunology

Coronavirus weekly: recovery efforts happening in fits and starts – The Conversation UK

The world is moving slowly and carefully to reopen businesses, get people back to work and jump-start moribund economies amid the COVID-19 pandemic.

Some initial attempts have been characterized by stops and starts as new clusters of the disease emerge. In Toronto, Canada, young people recently gathered en masse in a city park, fuelling outrage and sparking fears of more sudden and unexpected spikes in COVID-19 cases.

In this weeks roundup of coronavirus stories from scholars across the globe, we explore how our post-pandemic lives will be different, the latest medical developments and how to keep spirits up as lockdowns endure.

This is our weekly roundup of expert info about the coronavirus.The Conversation, a not-for-profit group, works with a wide range of academics across its global network. Together we produce evidence-based analysis and insights. The articles are free to read there is no paywall and to republish. Keep up to date with the latest research by reading our free newsletter.

As businesses reopen and employees begin to return to work, nothing is truly going back to normal. In fact, the post-pandemic world will require a vastly new normal until theres a COVID-19 vaccine. And that means rethinking and reimagining how weve always done things.

Getting out and about. Were all experiencing a bit of cabin fever, and some people are having trouble respecting social distancing rules when they are venturing out into the world. William Petri, a professor of medicine at the University of Virginia who specializes in immunology, outlines the seven factors hell assess to determine when its safe enough to spend time away from home. He writes: I am going to wear a mask to help prevent my giving the infection to others, avoid touching surfaces such as handrails, try not to touch my eyes or nose or mouth with my hands and wash my hands frequently.

Public transit. Hopping on a bus or subway during rush hour to get to work is a longtime urban ritual. But COVID-19 has likely changed how we do it so were no longer squeezed in like sardines. But Hussein Dia of Australias Swinburne University of Technology says that public transit is here to stay; not everyone can walk or ride bikes to their destination, and so public transit will remain at the heart of urban mobility. Dia advocates rethinking public transit design to enable physical distancing, even though it reduces capacity.

Air travel. The same goes for air travel, write Kacey Ernst and Paloma Beamer, epidemiologist and exposure scientist, respectively. They have some tips for air travel and masks are, once again, a central recommendation, along with hand sanitizer.

Doing business differently. For businesses opening their doors to customers once again, its a brave new world one that will require them to take into account the fears and anxieties their employees and customers are feeling right now. According to M. Tina Dacin and Laura Reese, organizational behaviour experts at Queens University in Canada, businesses will have to win the hearts and minds of their customers and employees like never before.

African trade. African countries may benefit from this new normal. Faizel Ismail, director of the Nelson Mandela School of Public Governance at the University of Cape Town, writes that pandemic could be an opportunity to advance free trade via the African Continental Free Trade Area in a more developmental, inclusive and mutually beneficial way for African countries.

Tourism. Could a four-day work week help the struggling tourism industry post-pandemic? Jarrod Haar of Auckland University of Technology makes the case after New Zealand Prime Minister Jacinda Ardern floated the idea of shortening the traditional work week following COVID-19. Healthier, happier and more productive workers helping other businesses stay viable? That sounds like a win-win for all, he writes.

What about the animals? Kendra Coulter, an animal ethics expert at Canadas Brock University, makes a passionate case to promote the well-being of animals post-pandemic, arguing that COVID-19 has illuminated how terribly we treat them. She points to a coronavirus outbreak among low-income workers at a Canadian meat-packing plant, writing that contemporary slaughterhouses have proven to be dangerous for workers in addition to being fatal horror shows for animals.

And speaking of animals, llamas yes, llamas are among the bright spots in efforts to find a cure for COVID-19.

Whats the latest with tests? Shayan Sharif and Byram W. Bridle of the University of Guelph in Canada, meanwhile, explain the pitfalls and promises when it comes to antibody tests. According to the immunology experts: Can we conceivably use antibody testing as a measure of immunity? The answer is maybe!

A US state is getting it right. Since South Carolinas first COVID-19 case surfaced, trained case investigators have traced the contacts of every person who tested positive. Jenny Meredith, a pathology professor at the University of South Carolina School of Medicine, outlines what else the state got right, noting that contact tracing is critical to reopening the economy without triggering a spike in coronavirus cases and overwhelming health-care systems.

Were all fed up, anxious and occasionally depressed by the COVID-19 shutdowns as we take tentative, cautious steps towards the new normal. Thankfully our global network has offered up some advice on how to tackle the impact on our mental health and well-being.

Therapy. Nicholas Joyce, a psychologist at the University of South Florida, points out that online therapy is having its moment in the sun and helping those struggling with mental health issues during the pandemic. He argues that COVID-19 has made clear that telehealth is the way of the future.

Robust mental health. Simon Rosenbaum and Jill Newby of Australias UNSW outline the characteristics of strong mental health, and offer up some tips to keep the COVID-19 blues at bay.

Social enterprise. Anyone whos ever been lucky enough to spend time in the Canadian province of Newfoundland and Labrador knows the place itself can serve as a balm to frayed nerves. Natalie Slawinski of Memorial University and Wendy K. Smith of the University of Delaware explain how a social enterprise saved the remote fishing outpost of Fogo Island following the collapse of the cod industry and they can help local communities around the world recover from the COVID-19 pandemic.

Get the latest news and advice on COVID-19, direct from the experts in your inbox. Join hundreds of thousands who trust experts by subscribing to our newsletter.

Original post:
Coronavirus weekly: recovery efforts happening in fits and starts - The Conversation UK

Immunology

A new Benchmark in shrimp production – The Fish Site

As Benchmarks shrimp facility in Florida begins to gear up towards commercial production, Oscar Hennig, operations director of Benchmark Genetics shrimp-breeding programme who has been in the shrimp sector for nearly 30 years explains to The Fish Site what he hopes to achieve.

Benchmark Genetics

Ive been involved in the sector since 1991, starting off on farms in Australia. After finishing my masters in aquaculture in Florianpolis [in southern Brazil] I received a scholarship from the government of Japan for a two-year research project with shrimp immunology at the Shimonoseki National Fisheries University. From there I returned to Brazil for two years running a diagnostics lab for shrimp at the LABOMAR research institute. In the meantime, to make ends meet, I leased a growout farm. P. vannamei [whiteleg shrimp] farming was just starting in north-east Brazil and there was the need for expertise to help the transition from P. subtilis [southern brown shrimp].

At the end of 1999 I moved permanently to Hawaii, to manage a satellite facility of the Oceanic Institute, in Kona. I have been in Kona ever since, working as breeding-programme manager for different companies, with P. monodon [giant tiger prawn], P. stylirostris [blue shrimp] and mainly P. vannamei.

At the end of 2016 I was hired as a director for Benchmark Genetics, after Benchmark had bought CENIACUA, a P. vannamei breeding programme in Colombia. My role has been to bring this to the international arena.

Oscar Hennig

I was impressed by the CENIACUA facility, and the crew running it, in Cartagena we had as much space as we wanted and as many people as we needed, as the jobs were in the local community.

However, Cartagena doesnt have great logistics and we realised that we need a base in the US to improve our ability to export our stocks.

[The Central Florida town of] Fellsmere was suitable for a number of reasons, not least for being close to three international airports. It is also 30km from the coast, which helps with our biosecurity and also to protect us from the hurricanes that can devastate the Florida coast.

Back in 2017, when we selected the site, my only concern was that we were sourcing water from a well this can impact the fertilisation ratio but weve managed to produce steady numbers of nauplii.

Benchmark Genetics

The water comes from 750m deep, and the well brings a sterile (zero dissolved oxygen), ~32 ppt saline water that is second to none. Due to the inland location, discharging water is a challenge, so all our systems work on recirculation or on biofloc.

All activities are conducted indoors from maturation, to algae, to grow-out, to packing so the biosecurity is excellent.

Im proud of how its turned out and Im really happy with the team weve created. There are currently 15 people involved and theres plenty of space to expand. At the moment were operating at about one fifth of our capacity, as were conducting presale trials, in order to fine tune the lines of shrimp that are needed in our main markets China, Vietnam, Indonesia and Thailand and these are now being tested in a commercial environment.

Most shrimp producers only offer one product but there are so many production systems used by the global shrimp industry and we saw that one size does not fit all. As a result, we decided to cater for a range of options and have launched three lines commercially.

The first, which weve been developing since 2008, is resistant to whitespot, EMS and other diseases. Called BMK Protect this is mainly for customers in northern China, and other areas facing disease challenges. It shows its true potential in harsh/disease conditions.

The second line was bred specifically to improve performance in sites with low salinity: shrimp farming is becoming increasingly popular in water thats less than 5 ppt. It now accounts for roughly 60 percent of Indian shrimp production, 50 percent in China, 15 percent in Vietnam and 15 to 20 percent in Thailand.

The third line, called BMK Yield, balances growth rates with survival to ensure steady production. It produces a consistent yield and a high rate of survival, making it ideal for farms that are working with processing plants, as it allows the farmer to provide a steady supply of raw material.

Benchmark Genetics

At this moment we are using some of that capacity to produce PLs for farmers, in the US and abroad. The PPL will go to our partners multiplication centres worldwide. China has been the main market during this presale year, and BMK Protect has been the number one line. The other two are doing well in the presale, but their evaluation still ongoing.

Breeding without ablation is not a big deal for us; it takes more planning and a few adjustments but nothing major. It is not done at the commercial hatcheries [as opposed to broodstock production facilities] due to a ~30 percent reduction in nauplii production. This reduction off nauplii output is mainly due to the lower frequency of female spawning, not due to lower levels of nauplii per spawn.

We believe that PL produced by non-ablated females are stronger. We ran some trials to support this belief and found that the eggs were bigger in non-ablated females, which makes sense as they have more time to go through the maturation process. We have other trials in mind that we will pursue once we get back to a normal routine.

Consolidation of the industry at different levels and partnership with local companies. I see the industry moving in two extreme directions: high-density, enclosed, biosecure farming systems and extensive open ponds, with not much left in the middle.

There was a small decline in sales during February and it has been hard to get cargo space and to predict when flights would go logistics have been crazy and transport prices also increased. However, I am optimistic that, once Covid-19 is a thing of the past, people will be wanting to celebrate life and demand for shrimp will increase beyond levels prior to this pandemic. As a result, our plan to expand is still in place.

Here is the original post:
A new Benchmark in shrimp production - The Fish Site

Immunology

AbbVie Submits Regulatory Applications to FDA and EMA for RINVOQ (upadacitinib) for the Treatment of Adults with Active Psoriatic Arthritis | Small…

DetailsCategory: Small MoleculesPublished on Monday, 01 June 2020 18:15Hits: 277

- Submissions supported by two Phase 3 studies in which RINVOQ demonstrated improved joint outcomes, physical function and skin symptoms, with a greater proportion of patients achieving minimal disease activity versus placebo* [1,2] - Significantly more patients taking RINVOQ achieved an ACR20 response than patients receiving placebo[1,2]

NORTH CHICAGO, IL, USA I June 1, 2020 I AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced that it has submitted applications for a new indication to the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) for RINVOQ (upadacitinib; 15 mg, once daily), a selective and reversible JAK inhibitor, for the treatment of adult patients with active psoriatic arthritis.

"Psoriatic arthritis is a complex heterogeneous disease with manifestations across multiple domains, including joints and skin, causing daily pain, fatigue and stiffness," said Michael Severino, M.D., vice chairman and president, AbbVie. "We look forward to working with regulatory authorities and hope to bring RINVOQ to people living with this debilitating disease as quickly as possible."

The applications are supported by data from two Phase 3 studies across a broad range of more than 2,000 patients with active psoriatic arthritis.1,2 In both studies, RINVOQ met the primary endpoint of ACR20 response at week 12 versus placebo.1,2 RINVOQ 15 mg also achieved non-inferiority versus adalimumab in terms of ACR20 response at week 12.1 Patients receiving RINVOQ also experienced greater improvements in physical function (HAQ-DI) and skin symptoms (PASI 75), and a greater proportion achieved minimal disease activity.*,1,2 Overall, the safety profile of RINVOQ in psoriatic arthritis was consistent with previously reported results across the Phase 3 rheumatoid arthritis clinical trial program, with no new significant safety risks detected.1-3

*Physical function was measured by the Health Assessment Questionnaire Disability Index (HAQ-DI). Skin symptoms were measured by a 75 percent improvement in the Psoriasis Area Severity Index (PASI 75). Minimal disease activity is defined as the fulfillment of five of seven outcome measures: Tender joint count 1; swollen joint count 1; PASI 1 or body surface area-psoriasis 3 percent; Patient's Assessment of Pain Numerical Rating Scale (NRS) 1.5; Patient Global Assessment-Disease Activity NRS 2.0; HAQ-DI score 0.5; and Leeds Enthesitis Index 1.

About RINVOQ (upadacitinib)

Discovered and developed by AbbVie scientists, RINVOQ is a selective and reversible JAK inhibitor that is being studied in several immune-mediated inflammatory diseases.1,2,4-10 In August 2019, RINVOQ received U.S. FDA approval for adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. In December 2019, RINVOQ was approved by the European Commission for the treatment of adult patients with moderate to severe active rheumatoid arthritis who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs. The approved dose for RINVOQ in rheumatoid arthritis is 15 mg. Phase 3 trials of RINVOQ in psoriatic arthritis, rheumatoid arthritis, axial spondyloarthritis, Crohn's disease, atopic dermatitis, ulcerative colitis and giant cell arteritis are ongoing.1,2,4-10 Use of RINVOQ in psoriatic arthritis is not approved and its safety and efficacy have not been established by regulatory authorities.

About AbbVie in Rheumatology

For more than 20 years, AbbVie has been dedicated to improving care for people living with rheumatic diseases. Our longstanding commitment to discovering and delivering transformative therapies is underscored by our pursuit of cutting-edge science that improves our understanding of promising new pathways and targets in order to help more people living with rheumatic diseases reach their treatment goals. For more information on AbbVie in rheumatology, visit https://www.abbvie.com/our-science/therapeutic-focus-areas/immunology/immunology-focus-areas/rheumatology.html.

About AbbVie

AbbVie's mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women's health and gastroenterology, in addition to products and services across its Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at http://www.abbvie.com. Follow @abbvie on Twitter, Facebook, Instagram, YouTubeand LinkedIn.

References:

SOURCE: AbbVie

See the original post:
AbbVie Submits Regulatory Applications to FDA and EMA for RINVOQ (upadacitinib) for the Treatment of Adults with Active Psoriatic Arthritis | Small...

Physiology

Living on higher altitudes can reduce the risk of contracting COVID-19: Study – Northeast Now

Researchers have found that people living in higher altitudes, especially 3000 metres above sea level, reported a lower number of coronavirus cases than their lowland counterparts.

According to a study published in the journal Respiratory Physiology & Neurobiology on Monday, high-altitude environmental factors may contribute to reducing the virulence of novel coronavirus.

In order to carry out the study, the researchers examined the epidemiological data from Bolivia, Ecuador and Tibet.

According to the researchers, the Tibetan plateau region, comprising of Tibet, Qinghai and part of Sichuan, has a significantly lower number of cases in comparison to the rest of China.

The impact of COVID-19 on the plateau region (of 9,000,000 inhabitants) has been drastically low compared to the rest of China, the study stated.

Indeed, only 134 confirmed cases were reported for the plateau region, it added.

Examining the epidemiological data, the researchers also found that the number of COVID-19 cases was three times lower in the Bolivian Andes than in the rest of the country and four times lower in the Ecuadoran Andes.

The researchers claimed that the reason for the decreased severity of the global COVID-19 outbreak at high altitude could relate to both environmental and physiological factors.

A high-altitude environment is characterized by drastic changes in temperature between night and day, air dryness, and high levels of ultraviolet (UV) light radiation.

In particular UV light radiation A (UVA) and B (UVB) are well known to be capable of producing alterations in the molecular bonds of the DNA and RNA, and thus UV radiation at high-altitude may act as a natural sanitizer, the study said.

In relation to SARS-CoV-2, while complete disinfection cannot be achieved by UVA and UVB, these radiations should shorten the half-life of any given virus, it added.

According to a pulmonologist Clayton Cowl, prolonged exposure to altitude triggers a chain reaction in the lungs involving a protein known as ACE2 that might prevent pulmonary shunting, a problem common among COVID-19 patients.

Read more here:
Living on higher altitudes can reduce the risk of contracting COVID-19: Study - Northeast Now