Category Archives: Molecular Medicine

Medical researchers say within a few years major breakthroughs in blood testing technology that use immune system response and genetic analysis to identify disease quickly and cost-effectively will be on the market.

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One morning last May, Tayah Fernandes's mother Shannon realized her four-year-old daughter was seriously unwell, and rushed her to the nearest ER in the English city of Manchester. The coronavirus had crashed onto Britain's shores weeks earlier, and emergency doctors were initially uncertain how best to treat Tayah's constellation of symptoms, which included stomach pains and a bright red rash.

They gave her antibiotics for a suspected bacterial infection, but her condition only worsened, her fever spiking. For her parents, for any parents, this was the ultimate medical nightmare; doctors in the dark for days over the cause of their daughter's illness.

Eventually, after further blood tests, physicians decided Tayah was suffering from an unusual inflammatory syndrome that pediatric infectious disease specialists had only just started to see, but suspected had links to Sars-COV-2.

Young patients across the U.K. and U.S. were arriving in intensive care units with symptoms similar to another disease doctors already recognized, called Kawasaki. But they had no guarantee that the same course of treatment injecting a solution of donors' antibodies into the bloodstream would prove successful.

In Tayah's case the antibodies solution, known as immunoglobulin, worked, to her parents' relief. But at around that same time last May a team of researchers at Imperial College, London confirmed through complex analyses of blood samples, taken from patients like Tayah, that this was indeed a new disease, distinct from Kawasaki.

A related breakthrough in that same laboratory, focused specifically on the way individual genes behave, could have seismic implications for a multi-billion dollar diagnostics sector that has received unprecedented attention from patients, regulators and the business world over the course of this pandemic.

A new method for identifying a specific illness from blood samples relies on the correlation between the activity in small set of genes, which represents the immune response, and specific pathogens that cause a specific disease just as the poliovirus causes polio, the coronavirus (SARS-COV-2, a pathogen) causes Covid-19. Scientists believe that by studying a small number of genes, they can quickly discern which pathogen is in a patient's system, what disease they have, and so how best to treat them.

Companies from small research university spin-offs to industry giants like Abbott Laboratories and Danaher's Cepheid are looking to build on two decades of research into the way our own immune systems naturally respond to foreign substances in our bodies, including pathogens like bacteria or viruses. A current technology like Cepheid's GeneXpert technology is able to distinguish between the different RNA of various viruses, such as SARS-COV-2, or a particular influenza strain, but experts say it's become increasingly clear that our body's immune systems can be faster, more accurate detection systems.

Historically, doctors have had to rely on a patient's case history and symptoms to narrow down the cause of an illness and develop a treatment plan. More recently, laboratory inspections at the molecular level such as the Cepheid technology have allowed clinicians to identify specific pathogens in nasal mucus, throat swabs or blood samples that might have caused an illness. But hunting for bacteria or a virus in this way can be time-consuming, costly and sometimes simply ineffective. The specific RNA signature of a virus can be hard to detect.

Abbott and Cepheid did not respond to requests for comment.

The team at Imperial College, London, working separately but at the same time as several counterparts around the world, are now convinced that future diagnoses can soon be conducted using table-top tests that will take just a matter of minutes.

These tests would not explicitly screen for a specific pathogen, but instead, allow scientists and medical professionals to simply watch how specific genes in the body are behaving as an indication of how an immune system is already responding to a pathogen that may not be easily otherwise detectable.

Imperial College professor Mike Levin currently leads an ongoing European Union-funded study focused on this potential, called "Diamonds." In recent years he and other scientists have shown how the observed activity in a small number of our genes can work as a kind of shorthand for our body's immune response to a pathogen. If a handful of specific genes out of thousands in a blood sample are seen to be activated or the opposite, inhibited it can indicate that a person is preparing to fight off a specific pathogen.

We think this is a completely revolutionary way of doing medical diagnosis.

Imperial College professor Mike Levin

Levin and colleagues already have a proof of concept for this diagnostic approach after studies involving thousands of patients with fever caused by tuberculosis, and hundreds of Kawasaki patients. And his Imperial College team's work with the "Diamonds" study are starting to bear fruit and could helpidentify the distinct immunological markers of illnesses like the coronavirus-linked multi-system inflammatory syndrome in children like Tayah Fernandes, now commonly known as MIS-C.

When Covid-19 turned up in multiple locations, with MIS-C in its wake, it presented Levin and his researchers with an unprecedented opportunity to test this technique on an entirely new disease.

In the future, these tests by relying on huge amounts of data and machine learning should be able to produce multi-class rather than just binary results. This means they could confirm not only if a pathogen is bacterial or viral, or whether someone has a specific disease or not, but could distinguish which one of a multitude of illnesses is afflicting their patient.

In short, Levin expects that by examining the behavior of a relatively small number of genes, clinicians will be able to assign patients to all the major disease classes within an hour.

"We think this is a completely revolutionary way of doing medical diagnosis," Levin said. He expects the research will provide the basis for new technology, but has no financial interest in any business related to it.

Rather than what he calls the "stepwise process" of first eliminating bacterial infections, treating for the most common conditions, and then doing more investigation, "this idea is the very first blood test can tell you, has the patient got an infection or not an infection, and what group of infection that is, right down to the individual pathogens."

Purvesh Khatri, an associate professor at the Stanford Institute for Immunity, Transplantation and Infection and Department of Medicine, says our immune systems have been evolving for millennia to combat pathogens, and so it may prove more effective, and efficient, to examine the response of our bodies.

"We didn't have a technology, until now, that could measure a set of genes in a rapid point of care way," he said. "But in the last couple of years, there have been enough technologies available that now allow us to measure a few genes in a rapid multiplex point of care assay way."

While neither the FDA nor any European regulators have approved these kinds of gene-based pathogen detection systems, Khatri, who is helping launch a related commercial venture, says they're coming soon. "In the next year or two, there will be several that will be available on the market."

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Theranos is history, but big blood testing breakthroughs are coming post-Covid - CNBC

A team of researchers received a $1 million grant late last month to study how memory cells recall past events when responding to attacks on the immune system and injuries on the skin.

The projects lead researchers said the team is looking into how memory T cells can memorize certain events, like an attack from a virus, and recall that memory once those events appear a second time. Rong Li, the chair of the Department of Biochemistry and Molecular Medicine in the School of Medicine and Health Sciences and the lead researcher on the project, said the team hopes to learn the molecular process these memory cells use to recall past events and to eventually mimic this process in treatments like cancer therapies and inflammation care.

That phenomena has been around for quite some time, Li said. But really, at the molecular level, at the cellular level, you ask really the fundamental question, In that case, how did cells remember that? That is really what this grant is about.

Li said the three-year grant from the W.M. Keck Foundation is exclusively for pre-clinical work, meaning the funds will cover the investigation of animal models and molecular tools. But he said if his research team is successful at working with the animal models, their findings could be applied to humans.

It would be very interesting to, for example, take human memory T cells from cancer patients, culture them in a laboratory setting and then introduce this human version of that key molecule back into those memory T cells and then put them back in the same cancer patient and see whether that can boost the hosts immune system to fight tumors, Li said. We are very excited about the long-term potential.

Li said the key to this research is the different expertise of each member of the research team.

He said he comes from the molecular biology perspective, while Brett Shook, an assistant professor of biochemistry and molecular medicine, is looking at this research through a physiology lens, including the healing of skin cell wounds and inflammation. He said other contributing researchers are helping with the immunological side of the research.

Shook said the team is applying an irritant to mices skin and then will precisely manipulate one gene at a time to determine the effect it has on memory. He said they can use tools in their lab to express a gene at a higher level than its typically expressed to try to emphasize a memory in certain cells, or they can eliminate the gene of interest entirely, completely disrupting the cells ability to remember any previous events.

Shook said the researchers are using these mice models to observe skin inflammation to determine how the memory cells respond.

He said they first apply an irritant to mices skin, which will cause inflammation in the tissue and eventually a rash. The researchers then manipulate the specific gene in the mice, which they believe controls the skin cells memory of the inflammation, and then reapply the irritant to determine whether the memory cells can recall the event and eliminate the rash more quickly.

Anytime you have a rash, that area now has some memory of inflammation, Brett said. We are able to injure the same area, and what has been documented is that regions of skin that have previously experienced inflammation will heal faster.

Experts in medicine and infectious diseases said this research is a relatively unexplored area and the findings could pave the way for enhanced cancer treatments.

Joaquin Madrenas, a professor of medicine at UCLA, said the implications of this research are very important, especially in terms of immunological memory. He said vaccines give the immune system exposure to foreign antigens so that upon exposure, the immune system can mount a memory response.

If we know what is the mechanism to induce memory, you can make better vaccines that will ensure the development of long lasting memory, Madrenas said.

Madrenas said studying cellular memory may also help cancer patients, especially those with types of cancer associated with a lack in immune response.

If you know the mechanisms of memory, you can induce memory in the immune system of a patient that can then get rid of the cancer and keep the cancer from growing, Madrenas said.

He said laboratory mice are inbred animals that are kept under clean conditions and should have no history of exposure to infections, making the task of translating the research findings to humans complicated.

We live in a completely exposed and uncontrolled environment, Madrenas said. Each one of us has a completely different antigen history. Your exposure to different viruses and bacteria and other infectious diseases is very different from mine, so the ability to manipulate your memory pool may be very different from mice.

Girish Kirimanjeswara, a professor of immunology and infectious diseases at Pennsylvania State University, said studying memory cells allow researchers to understand how the body encounters and responds to infectious diseases. He said this area of research is relatively less explored and this project could pave the way for a deeper understanding of how immune cells can recall a past exposure to a virus or cancer.

While we know how memory T cells may recognize a second encounter of a foreign substance, we are still learning about how these cells may be regulated, how long can they last, how do they function at various times etc, he said in an email. This research will explore many of those areas and also study the inherent cellular memory.

This article appeared in the March 8, 2021 issue of the Hatchet.

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Medical school researchers receive grant to study cell memory - GW Hatchet

--(BUSINESS WIRE)--Leaps.org:

WHAT:

COVID Vaccines and the Return to Life: Part 1 First of four virtual symposiums reviewing the most pressing, timely questions around the COVID-19 vaccines. Featuring leading scientific and medical experts, marking the one-year anniversary of the global declaration of the COVID-19 pandemic.

Topics include: the effect of the new circulating variants on the vaccines, what we know so far about transmission dynamics post- vaccination, the myths of good and bad vaccines as more alternatives come on board, and more. Public Q&A will follow the expert discussion.

WHEN:

Thursday, March 11, 2021

12:30 1:45 pm EST / 9:30 10:45 am PST

WHO:

Co-Host: Kira Peikoff, Editor-in-Chief, Leaps.org

Monica Gandhi, M.D., MPH, Professor of Medicine and Associate Division Chief (Clinical Operations/ Education) of the Division of HIV, Infectious Diseases, and Global Medicine at UCSF/San Francisco General Hospital.

Paul Offit, M.D., Director of the Vaccine Education Center, attending physician in infectious diseases at the Childrens Hospital of Philadelphia, and advisor to CDC and FDA vaccine committees.

Onyema Ogbuagu, MBBCh, Associate Professor at Yale School of Medicine and Yale Medicine infectious disease specialist treating COVID-19 patients and leading Yales COVID-19 vaccine trials.

Eric Topol, M.D., cardiologist, scientist, professor of molecular medicine, and the director and founder of Scripps Research Translational Institute.

CO-HOSTS:

Aspen Institute Science & Society Program

SabinAspen Vaccine Science & Policy Group

With generous support from the Gordon and Betty Moore Foundation and the Howard Hughes Medical Institute.

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A new study has revealed that immunoglobulin-M antibodies recognise microvesicles, which are critical for the progression of thrombosis.

A new study has revealed the important role of immunoglobulin-M (IgM) antibodies in preventing thrombosis. The researchers, from the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences and the Medical University of Vienna, both Austria, say that these antibodies recognise microvesicles, which are membrane blebs shed by cells and recognised for their critical role in thrombosis, so therefore prevent pro-thrombotic effects.

According to the authors, earlier studies have demonstrated that people with a low number of IgM antibodies have an increased risk for thrombosis. The team also previously demonstrated that a high percentage of natural IgM antibodies bind oxidation-specific epitopes, molecular structures that are present on dying cells and serve as signals for the immune system.

In the new study, the researchers identified the mechanisms explaining the anti-thrombotic effects of natural IgM antibodies. They demonstrated that the antibodies that bind oxidation-specific epitopes can prevent coagulation and thrombosis induced by microvesicles. This provides a mechanistic explanation for the previously published observation that low levels of these antibodies are associated with an increased risk of thrombosis.

We assume that natural IgM antibodies recognise microvesicles that are particularly pro-inflammatory and pro-coagulant, say the scientists in their paper.

In experiments on a mouse model and directly on human blood samples, the scientists were able to show that the addition of IgM antibodies inhibited blood clotting caused by specific microvesicles and protected mice from lung thrombosis. Conversely, it was also shown that depletion of the IgM antibodies increased blood clotting.

The study for the first time provides an explanation why people with a low number of natural IgM antibodies have an increased risk of thrombosis, write the authors.

The results offer high potential for novel treatments to reduce the risk of thrombosis. Influencing IgM antibody levels in high-risk patients could be a viable addition to the previously established blood thinning treatment, as this is also known to be associated with side effects such as an increased tendency to bleed in the case of injuries, said principal investigator Professor Christoph Binder.Microvesicles are already recognised as an important component of blood coagulation. However, our study created a novel possibility of targeting them therapeutically for the first time.

The study was published in Blood.

See original here:
Study shows role IgM antibodies play in preventing thrombosis - Drug Target Review

From the start of the COVID-19 pandemic, diagnostic testing has been highlighted as a key part of global measures to contain the spread of SARS-CoV-2. In a media briefing on March 16, 2020, Dr Tedros Adhanom Ghebreyesus, WHO Director-General, remarked that testing, isolation and contact tracing were the backbone of the response and urged all countries to test, test, test.RT-qPCR testing, which detects SARS-CoV-2 genetic material present in a patient sample, quickly became the predominant method used to identify infected individuals. However, several claims and allegations about the capabilities and value of PCR have been circulated throughout the course of the pandemic, leading to questions about its use.

To address these misconceptions and communicate the true strengths and limitations of the technology, a group of PCR experts recently published a commentary in the International Journal of Molecular Sciences. Technology Networks had the pleasure of speaking to Professor Stephen Bustin, professor of molecular medicine at Anglia Ruskin University, and lead author of the commentary, to learn more about some of the facts and fallacies highlighted.

The views and opinions expressed below are those of Stephen Bustin and do not necessarily reflect the official policy or position of Anglia Ruskin University.

Anna MacDonald (AM): RT-qPCR was quickly adopted at the start of the pandemic as the predominant method of detecting SARS-CoV-2. Can you describe some of the key strengths of the technology that made it a suitable choice?Stephen Bustin (SB): Indeed, the first three PCR tests for SARS-CoV-2 were designed within a day of its genome sequence having been published by Chinese scientists. Such lightning speed is unthinkable with any antigen-based test, hence PCR being the predominant method. Furthermore, a properly designed, optimized and validated RT-qPCR test is the most sensitive, specific, reliable and robust method for detecting a pathogen. Current protocols are not as fast as antigen tests, but they will be so in the future (see below).

Crucially, RT-qPCR tests are also easily modified to accommodate the appearance of mutations and variants and so are characterized by exceptional flexibility, an important advantage when dealing with an RNA virus that, against initial expectation, continually and rapidly changes. Once genetic changes that characterize variants have been identified by sequencing, it is straightforward to design tests and, crucially, use them immediately. Again, this is unlike antigen tests, that require the development and production of new antibodies, a process that takes months and is very expensive. PCR tests can distinguish the original virus from the variant even if they differ by only a single nucleotide change (e.g., variant B.1.1.7 N501Y which has a nucleotide change of A to T within the sequence coding for the spike protein).

Although mainstream PCR instruments take between 30 minutes and 1.5 hours to complete a test, a combination of fast protocols and instruments can reduce that time to less than 15 minutes. Even that does not fully exploit the potential of this technology, with extreme PCR shown to complete a test in less than 20 seconds. I have no doubt that in a year or twos time such instruments will be available commercially. Furthermore, there will be inexpensive hand-held personal and point-of-care devices that will give rapid results when and where needed.

AM: Several claims have been made suggesting that PCR-based testing is not fit for purpose. What has led to these allegations and what effect is this misinformation having?SB: These sentiments arise from the deliberate spreading of false information, coupled with misleading quotes and incomplete reporting. They are made by people who have little knowledge and no understanding of the technology, but are articulate and rely on the general publics ignorance and lack of interest in scientific detail. The media also are at fault, because they have generally failed to distinguish between authoritative scientific conclusions based on data and facts versus false and unreliable opinions based on mendacity and sophistry.

The most common falsehood is that the inventor of PCR, Kary Mullis, claimed that PCR should not be used for diagnostics. He did make an unfortunate comment about the reliability of diagnostic testing, but this related specifically to the detection of HIV in AIDS patients, was aimed at conventional gel-based PCR and was made in 1993, before real-time (qPCR) was in use as a diagnostic tool. I knew Kary Mullis personally and I know for certain that this was not his opinion as we discussed, and he was interested, in the use of RT-qPCR as a prognostic tool for colorectal cancer patients.

Without a shadow of a doubt, qPCR is highly suitable for diagnostic testing for pathogens for at least three reasons: (1) it has two levels of specificity that minimize the risk of false positive results, (2) its sensitivity minimizes the risk of false negative results and (3) as a closed-tube procedure amplified DNA is never released into the environment, minimising the chances of contamination. In a way we are seeing the same dishonest campaign resurrected that caused so much unnecessary heart-ache in the late 1990s concerning the MMR vaccine and autism.

These operations are driven by callous individuals and groups with an agenda, and unfortunately are not open to persuasion of any kind. PCR testing is just another topic that has become entangled in todays doctrine that feelings and opinions matter as much or, indeed, more than facts, a phenomenon that has become familiar in politics, education as well as in a health-related environment. Whilst it is easy to come up with a simple slogan that denigrates something and reduces a complex issue to a single catch phrase, it takes much longer to explain that matter adequately and sensitively. Ultimately, there is an obnoxious fringe element in our society that is not interested in listening or learning and, sadly, there is neither vaccine nor cure for stupidity. A serious consequence of this trend is that the public is unable to distinguish genuine scholarship and balanced expert advice from snake oil peddled by fraudsters and charlatans.

AM: Can you explain the main causes of false-positive or false-negative results and what can be done to reduce the chances of them occurring?SB: False positive results in a properly validated and CE-marked PCR test are caused by contamination or by inappropriate interpretation of the results. Contamination can be introduced during the sampling procedure, the extraction process or the dispensing of reagents for the PCR test. This is routinely detected by including appropriate negative controls at every stage, i.e., samples that do not contain the target RNA or DNA. These controls must always be negative; if they are and a PCR result is positive, this means that whatever target was being amplified is present. This is especially important when there is very little target present and the analysis generates results near the tests limit of detection. The analytical sensitivity of a PCR test refers to the smallest amount of target in a sample that can be detected and in theory this is a single molecule. It goes hand in hand with its analytical specificity, which describes the ability of the test to detect one specific target, e.g., SARS-CoV-2, as distinct from, say SARS-CoV.

However, both are different from diagnostic sensitivity and specificity, the former referring to the ability of the test to identify individuals who are infectious and the latter to its ability to identify correctly those without the disease. Hence a true PCR positive may well not be detecting infectious virus, for example if the individual has been asymptomatic for a couple of weeks after coming down with a disease and, whilst a few virus particles or nucleic acid fragments are present, they are not clinically relevant. Hence the interpretation of the test was at fault, not the test itself. This is a real problem for two reasons (1) the infectious dose of SARS-CoV-2 is still unknown and (2) the qPCR result output is the quantification cycle (Cq), which is not an objective value but differs with instruments, reagents and operators. Monitoring a combination of parameters that include symptoms, probability of infection and PCR results is the best approach to minimize false clinical positives.

False negatives, on the other hand, can be caused by sample degradation during handling or storage, which can be especially problematic with RNA, the presence of inhibitors, poor testing protocols, inexperienced staff not following proper procedures and, least likely, reagent failure. It may also be that the sample taken from an individual did not contain any virus or so little that it got lost or excessively diluted during the extraction procedure. This is of course why a negative test result is really a presumptive negative and a second test a day or so later could well result in a positive result, if the individual is in the early stages of infection.

AM: In 2009, you published the MIQE guidelines, with the aim of encouraging better experimental practice and more reliable interpretation of qPCR results. Have COVID-19 tests been developed using these guidelines? How could the guidelines be applied to improve the use of qPCR testing?SB: The MIQE guidelines were aimed at the research community, where new tests targeting a multitude of targets are being constantly developed and where it is difficult to compare the results generated in one laboratory with those obtained in another one. Furthermore, they deal with quantitative testing, which is somewhat different from testing for SARS-CoV-2.

However, the guidelines are relevant as they call for transparency with regards to assay design, reporting of test performance and interpretation of results. Researchers and companies have done a sterling job in developing a range of tests that are sensitive and specific and continue to monitor the emergence of new strains to ensure that their tests continue to generate reliable results. There should be more openness with regards to sharing the sequence details of the various tests in use, but the information provided is generally sound and informative.

However, the main issue that has caused some problems with the reliability of testing is the sampling, transport and extraction workflow, which is far from optimal. There are numerous different reagents and protocols, variable skill levels of those taking the samples, different time lines within the transport practice and inconsistent storage conditions as well as different RNA extraction and concentration procedures that all combine to increase the variability of test results, especially when comparing different test centres within or between different countries. There is an urgent need to develop a clear set of guidelines for optimal sample collection, which should be from saliva for SARS-CoV-2 as well as for RNA extraction, which would help standardize and so make the whole process more reliable.

AM: The use of qPCR to quantitate viral load is a particular area of concern. What are the main challenges of using the technique for this purpose? Are there any steps that can be taken to reduce the ambiguity of results?SB: First of all it is important to distinguish between infectious dose and viral load. It is still unknown what the infectious dose is for SARS-CoV-2, i.e., the amount of virus required to make a person sick. Its ease of transmission suggests that it may be quite low, but this might be 100, 1,000 or 10,000 viral particles. A higher infectious dose could result in a higher viral load, which describes the amount of virus replicating within the cells of an infected individual. There is evidence that higher viral loads result in more severe symptoms and may be associated with a worse outcome as well as lead to more shedding of whole virus by the infected individual.

A standard qPCR test cannot record exact viral copy numbers, as the test result for a positive sample only records a PCR cycle number, e.g., 25.5. This means that the instrument first detected the presence of a target after 25.5 cycles, and whilst a lower Cq value suggests that there is more target present, without additional information it is impossible to tell how much more. This requires knowledge of the amplification efficiency, since it is obvious that a more efficient test will record a lower Cq earlier than a less efficient test.

Quantification also requires the addition of standards, ideally certified reference RNA of known copy number, that amplify at specific PCR cycle numbers. The cycle number of the virus can then be related directly to that standard and give a measure of quantity. Unfortunately, such standard still do not exist. There is a related technology, called digital PCR, which can provide absolute counts of viral copy number. However, this technology is not suited to mass testing and it is expensive. The best solution, for the time being is to record a test result as positive or negative and interpret that result within the individual clinical context and, if in doubt, repeat a day or so later.

AM: In what ways do you think the pandemic has shaped the future of PCR?SB: Undoubtedly there will be a huge demand for continued, rapid testing at hospitals, care homes, nurseries, airports, cruise liners etc, initially for SARS-CoV-2 but extending to other respiratory viruses as well as fungal and bacterial pathogens. This will drive the development of easy-to-use sampling, extraction and testing devices that can rapidly test multiple samples with little or no operator intervention.

At the same time there will be an increasing demand for more personal devices, such as hand-held microfluidics-based systems where you can add a small amount of saliva, blood, urine or faecal matter and get a rapid test result in the privacy of your own home, at the GPs surgery or even at the chemists. The speed potential of the PCR and its ability to detect numerous targets all at the same time are still largely unexplored and the focus on improving current protocols and introducing new instrumentation and improved reagents will only serve to make PCR even more ubiquitous than it is now.

Reference: Bustin S, Mueller R, Shipley G, Nolan T. COVID-19 and diagnostic testing for SARS-CoV-2 by RT-qPCRfacts and fallacies. Int J Mol Sci. 2021;22(5):2459. doi:10.3390/ijms22052459

Professor Stephen Bustin was speaking to Anna MacDonald, Science Writer for Technology Networks.

Continued here:
RT-qPCRFacts and Fallacies: An Interview With Professor Stephen Bustin - Technology Networks

Faculty of medicine researchers have attracted more than $21 million in funding from the Canadian Institutes of Health Research (CIHR).

In all, 354 research grants were funded for a total investment of approximately $274 million through the Project Grants: Fall 2020 competition. In addition, 97 priority announcement grants were funded to a total amount of $9,575,000 and 11 supplemental prizes were awarded for a total of $296,500.

UBC researchers attracted a total of $25.6 million for 41 projects. Thirty-three UBC-led projects received Project Grant funding totalling $24.8 million and eight UBC-led projects received priority announcement grants totalling $775,000.

Douglas Allan, department of cellular and physiological sciences

Project: Transcriptional programs of synapse maturation

CIHR Funding: $856,800 (5 years)

Ali Bashashati, School of Biomedical Engineering;Peter Black, department of urologic sciences;Larry Goldenberg, department of urologic sciences

Project: Prostate cancer risk stratification for active surveillance using computer-aided analysis of histopathology and transcriptomics

CIHR Funding: $906,525 (5 years)

Colin Collins, department of urologic sciences

Project: Uncovering early mediators of lineage plasticity and validation of a metabolic vulnerability in neuroendocrine prostate cancer

CIHR Funding: $1,147,500 (5 years)

Angela Devlin, department of pediatrics;Pascal Bernatchez,department of anesthesiology, pharmacology and therapeutics;Constadina Panagiotopoulos, department of pediatrics

Project: Correcting early vascular dysfunction to improve cardiovascular outcomes in type 1 diabetes

CIHR Funding: $841,500 (5 years)

Quynh Doan,department of pediatrics

Project: Evaluating the psychometric properties and help-seeking impact of HEARTSMAP-U: a digital psychosocial self-assessment and navigational support application for post-secondary students.

CIHR Funding: $554,624 (4 years)

Nichole Fairbrother, department of psychiatry

Project: Perinatal Anxiety Disorders Screening Study

CIHR Funding: $684,676 (4 years)

David Fedida, department of anesthesiology, pharmacology and therapeutics

Project: Mechanisms of potassium channel activator action on Kv7.1 ion channel complexes.

CIHR Funding: $971,550 (5 years)

Brian Grunau, department of emergency medicine;Jane Buxton, School of Population and Public Health;James Christenson, department of emergency medicine

Project: Opioid Overdose-Related Cardiac Arrest: What are the Best Interventions?

CIHR Funding: $283,051 (3 years)

Joerg Gsponer, department of biochemistry and molecular biology;Lawrence Mcintosh, department of biochemistry and molecular biology

Project: Protein phase separation: A new mechanism of protein function regulation in Mycobacterium tuberculosis

CIHR Funding: $887,400 (5 years)

Jaime Guzman, department of pediatrics

Project: Treating Children with Arthritis According to their Individual Probability of Outcomes and Response to Treatments The PERSON-JIA Trial

CIHR Funding: $455,175 (5 years)

Nicholas Bansback, School of Population and Public Health

Project: Evaluating the impact of a mandatory switching policy for biosimilars

CIHR Funding: $298,350 (3 years)

Rob Holt, department of medical genetics

Project: Lentiviral infusion as a universal approach for genetically modified immune effector cell therapies.

CIHR Funding: $642,600 (4 years)

Rosemin Kassam, School of Population and Public Health

Project: Women supporting women using local solutions to improve infant and young child feeding and care practices in Punjab, Pakistan

CIHR Funding: $799,425 (5 years)

Christian Kastrup, department of biochemistry and molecular biology

Project: Minimally-invasive device and bioabsorbable hemostatic powder for managing non-compressible torso hemorrhage

CIHR Funding: $455,176 (4 years)

Jayachandran Kizhakkedathu, pathology and laboratory medicine;Dirk Lange, department of urologic sciences

Project: Novel Infection Resistant Coating in an Era of Drug Resistant Bacteria for the Treatment and Prevention of Medical Device Infection

CIHR Funding: $520,199 (3 years)

Rodney Knight, department of medicine

Project: Identifying the impact of cannabis use on mental health outcomes among sexual and gender minority youth: A mixed-methods study

CIHR Funding: $478,126 (3 years)

Chinten James Lim, department of pathology and laboratory medicine

Project: Targeting CD47 in pediatric acute lymphoblastic leukemia.

CIHR Funding: $1,028,925 (5 years)

Teresa Liu-AmbroseandLinda Li, department of physical therapy

Project: SuPA Mobility: Supporting Physical Activity to Promote Mobility in Mobility-Limited Older Adults

CIHR Funding: $631,128 (6 years)

Martin Mckeown, department of medicine, division of neurology

Project: In silico Design of Precision Electrical Stimuli for Electrical Vestibular Stimulation in Parkinsons Disease.

CIHR Funding: $841,270 (5 years)

Robert Molday, department of biochemistry and molecular biology

Project: High Resolution Structure of Human ABCA4, an ATP-binding Cassette (ABC) Lipid Importer Associated with Inherited Retinal Degenerative Diseases

CIHR Funding: $918,000 (5 years)

Melanie Murray, department of medicine

Project: Role of Female Sex Hormones on Aging in Women Living with HIV.

CIHR Funding: $382,500 (5 years)

Ivan Nabi, department of cellular and physiological sciences

Project: Using super-resolution microscopy to define the role of caveolin-1 in cancer

CIHR Funding: $910,350 (5 years)

Nobuhiko Tokuriki, department of biochemistry and molecular biology

Project: Novel antibiotic therapies that target bacterial energetic systems

CIHR Funding: $956,250 (5 years)

Michael Underhill, department of cellular and physiological sciences

Project: Tissue-resident mesenchymal progenitors and aging

CIHR Funding: $971,550 (5 years)

Cheryl Wellington, department of pathology and laboratory medicine;Angela Brooks-Wilson, department of medical genetics);Ging-Yuek Robin Hsiung, department of medicine

Project: Evaluating the potential of blood biomarkers to improve Alzheimers Disease risk stratification

CIHR Funding: $1,503,224 (4 years)

Christian Steidl, department of pathology and laboratory medicine

Project: Somatic mutations in the JAK-STAT and IRF signaling pathways in Non-Hodgkin lymphoma

CIHR Funding: $1,120,725 (5 years)

Glen Tibbits, department of pathology and laboratory medicine

Project: Catecholaminergic polymorphic ventricular tachycardia (CPVT): arrhythmogenic mechanisms and personalized intervention

CIHR Funding: $924,120 (5 years)

Jan Dutz, department of dermatology and skin science

Project: Phototherapy to modulate regulatory T cells and prevent autoimmune disease

CIHR Funding: $382,499 (3 years)

Kendall Ho, department of emergency medicine

Project: Technologies for Home Medication Vigilance and Protection (TEC4Home MVP)

Priority Announcement: Health Services and Policy Research

CIHR Funding: $50,000 / Canadian Medical Association (Ottawa) Funding: $50,000

Brodie Sakakibara, department of occupational science and occupational therapy

Project: Advancing virtual care in stroke rehabilitation: TeleRehabilitation with Aims to Improve Lower Extremity Recovery Post-Stroke (TRAIL)

Priority Announcement: Health Services and Policy Research

CIHR Funding: $50,000 / Canadian Medical Association (Ottawa) Funding: $50,000

Wendy Norman, department of family practice

Project: The CART PREG-Epi Study: Pandemic Reproductive health and health Equity- Guidance from Epidemiology to improve reproductive, perinatal, and maternal mental health and substance use care

Priority Announcement: Population and Public Health Public Health Systems

CIHR Funding: $100,000

Patricia Janssen, School of Population and Public Health

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Faculty of medicine researchers attract more than $21M in CIHR Fall 2020 funding - UBC Faculty - UBC Faculty of Medicine

Just before the COVID-19 pandemic hit, medical technology company Lucira Health was starting to fine-tune its at-home flu test.

We found ourselves in January 2020 wondering, wow, we have this platform, should we be looking at COVID-19? Kelly Brezoczky, executive vice president at Lucira Health, told The Verge. Most of the technology would transfer; it was just a matter of swapping in the coronavirus for the influenza virus.

By November 2020, Lucira had the first US Food and Drug Administration (FDA) authorization for a fully at-home COVID-19 test. If the company had kept working on its flu test, Brezoczky says shes not sure if it would have been on the market by then. Our COVID-19 product leapfrogged our first product, she says.

Before the pandemic, small companies like Lucira and academic research labs were working on shrinking and speeding up tests that could diagnose someones viral infection by detecting a viruss genetic material in a swab from their nose or throat. They wanted to make it possible for these highly accurate tests to be done in a doctors office, at the patient bedside, or at home. But for the most part, those systems were in early stages of development. Most of this kind of testing, known as molecular testing, still had to be done in a lab.

Skyrocketing need for COVID-19 testing accelerated all of those nascent efforts. Suddenly, the federal government and private companies were investing millions, and the Food and Drug Administration was using emergency authorizations to get tests on the market. Experts long predicted that at-home testing could be the future, but the pandemic shortened the timeline to get there.

Overall, it was a very big opportunity, says Paul Yager, a professor in the department of bioengineering at the University of Washington who works on rapid test development. It sounds cynical, but a bad public health problem that gets everyones attention and certainly this got everyones attention pumps money into the field.

A year ago, just as the COVID-19 pandemic was starting to accelerate in the United States, it was hard if not impossible for most people in the US to track down a coronavirus test. The country relied on a type of test called a PCR. PCR is the gold standard approach to identifying a virus. It looks for a snippet of the viruss genetic material in a swab collected from a patient. Thats why its also called a molecular test: it searches out a genetic molecule.

Molecular tests are very different from another kind of viral test called an antigen test. Antigen tests look for a protein on the surface of the virus rather than the molecular code of the virus itself. They are cheap and fast, but they can be less accurate than molecular tests like PCR.

PCR is typically a good approach: its extremely accurate and easy to develop against new viruses. However, its finicky, takes training to handle the samples, and requires bulky, energy-sucking, expensive equipment. Its usually run in hospitals or centralized labs. It also takes a few hours to run. During a health emergency, a few hours is too slow. And when cases spike and labs get a flood of samples, people may have to wait days to get their results.

A faster test in those situations could make a huge difference in public health officials ability to track down infections and cut off the spread of disease. But until the pandemic hit, there hadnt been significant investment or focus on creating faster, simpler molecular tests. It didnt seem as necessary. [Rapid testing] was more on the fringes, because our normal laboratory setup in the United States was already robust, says Jacqueline Linnes, assistant professor of biomedical engineering at Purdue University.

Small companies and academic research labs were still interested in creating those types of systems and made significant progress on the science and technology behind them. They figured out how to make gene detection energy efficient and cut down the number of steps needed to get a result. They also worked to make them easier to use by people without specialized training. But they didnt attract interest from big companies that could push them to market at scale, Linnes says. It was an academic exercise.

Yager, for example, had a small molecular test that could be applied to multiple types of diseases ready in 2017. But he couldnt get a company to work with him to commercialize the product. It was the commercial market that actually caused the project which was technically successful to fail, he told The Verge last March.

The pandemic upended that pattern. Suddenly, there was funding for and commercial interest in rapid testing. The National Institutes of Health (NIH) launched the Rapid Acceleration of Diagnostics (RADx) initiative, which funded the development of new testing technologies for COVID-19. The pandemic was a public health emergency, so the FDA cleared tests under Emergency Use Authorizations (EUAs), which allows tests to be used after shorter examination periods than usual.

We found out that industry has all of the resources and all of the know-how to make this stuff happen if only they have the motivation, Linnes says.

Because researchers and small startups had already been working on rapid tests, some were able to take the same approach as Lucira and swap out their original target for the coronavirus. Visby Medical had originally developed a rapid sexually transmitted infection test, but it quickly started work on a rapid COVID-19 test that was funded through the NIHs program. It got point-of-care authorization in February 2021.

The FDA authorized the first rapid molecular tests, made by the medical technology companies Cepheid and Abbott, in March 2020. Both can be used in health centers, nursing homes, or urgent care clinics close to patients. They take a specialized machine, but samples dont have to be sent out to a lab. Many rapid tests use that approach: they have to be done by medical professionals but right at the location where patients get swabbed.

Visbys test falls into that category. It has a single-use cartridge that can be used in environments like nursing homes and some schools. Eventually, Visby hopes its tests can be used at home, says Adam de la Zerda, founder and CEO of Visby Medical. The FDA has already cleared a handful of at-home COVID-19 tests, including Luciras. Last week, the agency authorized another at-home molecular test from the medical technology company Cue. Unlike Lucira, Cues test doesnt require a prescription.

Yager thinks there will be more of a push for at-home testing. Theyre not all approved for home use yet, but thats generally the direction that the FDA went and I think its a trend, he says.

Rapid molecular tests are still only available in extremely limited quantities. Lucira is still scaling its production lines, and Cue hasnt announced when its COVID-19 test could be on shelves. But theyll be more and more available over the next year and could usher in a new approach to disease testing overall. Today the model is that you schlep your way over to a hospital, or stand in a long line in a waiting room, and it takes a day. Thats not the way we want to go forward, Yager says.

The increased interest and money in rapid molecular testing is already making a huge difference for smaller companies and academic labs. Lucira became a publicly traded company in February and is worth over $400 million. That raised a lot of eyebrows, Yager says. The fact that theres now a game for the investors to get into is a very exciting thing.

Moving disease testing out of the lab would make diagnoses for diseases other than COVID-19 easier. It would also help people start treatment early. There are treatments for the flu, for example, that work well but only if people start them within a day or two of feeling symptoms.

Normally, most people dont go to the doctor in that window, says Luciras Brezoczky. Thats what Luciras flu test which the company is still planning to launch aimed to help with, she says. If people could buy an accurate test when they went out to buy cough medicine, theyd be able to know if antivirals would help. Then, you actually have a chance to reduce both duration and severity of symptoms, she says.

Visby also hopes to get clearance for its sexually transmitted infection test this year. Like the flu, those types of conditions are easier to treat if theyre caught early.

Rapid molecular tests are still expensive, Linnes says. Luciras COVID-19 test is $50. Cue hasnt set a price for its newly authorized at-home molecular test. At this point, the price of these tests might be too high for regular cold and flu season use. But eventually, mass production and broader use could lower the price and help them become more commonplace, Linnes says.

Apart from price, a big advantage of scaling rapid molecular test manufacturing would be building a foundation for the next public health emergency. If the tests were in regular use for more ordinary viruses, it would be easier to adjust them to test for a pandemic virus, Linnes says. The US wouldnt be as reliant on the slower in-lab PCR.

That only happens, though, if the investment and interest in these systems continue. Sliding back into the status quo of lab-based testing after the COVID-19 pandemic fades, and not taking advantage of the momentum for at-home testing, would leave everyone in the same position they were in a year ago. We need to continue the investment, Linnes says.

The COVID-19 pandemic showed how important it is to be able to quickly and accurately diagnose diseases, de la Zerda says. He thinks there will be more focus on rapid molecular testing so that governments are prepared for new viral threats. They could have made a big difference at the start of this pandemic. If we had access to these tests in high volumes, we probably would be in a very different position right now, he says. We certainly would not be at the level of 500,000 deaths in this country.

Update March 10, 5:12 PM ET: Updated to clarify the timing of Visby Medicals FDA authorization.

Link:
COVID-19 took disease tests out of the lab and may keep them there - The Verge

Do you have a BMI of >25? Or perhaps >30? If so, you are in good company.

Obesity is a killer, especially in the face of infection with COVID-19. As BMI rises, so does your risk of severe COVID infection, and death.

Theres never been a better time to lose weight, once and for all. Being overweight has many physical and psychological consequences. Are you in denial about your weight? When did you last work out your BMI?

Read on and find out the reason why losing weight right now is so important.

In July 2020, Public Health England produced a detailed report on all the relevant, up-to-date information about obesity and COVID-19. Much of the information here derives from this report.

Obesity, even without COVID infection, has serious effects on your health

Obesity has now been classified by the American Medical Association as a disease, not just a lifestyle factor.

Being obese is not a question of being lazy and greedy. Its a real medical condition that deserves just as much attention, understanding, and support as any other medical condition.

Obesity increases the risk of high blood pressure, heart attack, stroke, heart failure, type-2 diabetes, non-alcoholic liver disease, and various types of cancer.

These medical conditions occur far more often in people hospitalized with severe COVID infection, leading experts to believe that obesity is a common underlying factor.

Lets consider the following statements

In a recent study, (Yates, 2020) using data from the UK Biobank, the authors demonstrated the risk of COVID-19 infection increased as both BMI and waist circumference increased. Being overweight, obese, or severely obese, increased the risk of COVID infection by 31%, 55%, and 57%, respectively.

Hamer 2020 also studied data from 387,019 members of the UK biobank and calculated that being overweight (BMI/25), or obese (BMI>30), increased the risk of being admitted to hospital from COVID infection by 32%, and 97%, respectively.

A recent (May 2020) New York study in the British Medical Journal (BMJ) reported that people with obesity (BMI of >30), and severe obesity (BMI >40), were 4, and 6 times respectively, more likely to be admitted to hospital with COVID infection, than those with a BMI <30.

A systematic review and meta-analysis (Yang 2020), published in the Journal of Virology, concluded obesity increased the risk of severe COVID infection by a factor of 2.5, and the risk of a poor outcome by a factor of 2.3.

A meta-analysis published in the journal Obesity, Research and Clinical Practice (Hussain 2020), including results from 14 studies of 403,535 patients, concluded that compared to those with a normal BMI, obesity (BMI >25) doubled the risk of being critically ill, almost quadrupled the risk of death, and the risk of needing respiratory support was increased almost 7 times.

Many studies have reported an increased risk of death from COVID with increasing BMI.

For example, in May 2020 the British Medical Journal published a study of 20,133 patients admitted to 208 UK hospitals with COVID-19. Obesity (BMI>30) increased the risk of death by 33%.

There are many possible reasons why obesity increases your risk from COVID-19. These reasons were described in the journal Molecular Medicine Reports Petrakis, (May 2020).

Here is an explanation of their key findings its a bit technical Im afraid, but Ive simplified it the best I can

Obesity is known to impair immunity to other respiratory viruses, such as influenza, and reduces the response to the influenza vaccine (Green, 2017).

High blood glucose, and diabetes, both associated with obesity, have also been linked to increased morbidity and mortality from infections with other coronaviruses, for example, those causing the Severe Acute Respiratory Syndrome (SARS) outbreak in 2003, and the Middle Eastern Respiratory Syndrome (MERS) outbreak in 2012.

Being obese results in impaired lung function. There is increased fat deposition in the chest wall, the chest cavity (thorax), and the abdominal cavity (under the diaphragm) meaning that that in those who are obese, the chest is relatively compressed. Even without COVID-19 infection, obese individuals are working harder to maintain normal breathing.

COVID-19 enters the body through ACE2 receptors, found predominantly in the lung, and kidney, but also in the heart, and blood vessel walls. Activation of these receptors is integral in the control of blood pressure, as well as many other functions including the immune response, and regulating the process of inflammation.

Obesity is associated with chronic inflammation. Indeed, those with higher BMI levels often have metabolic syndrome a medical condition in which various metabolic processes are deranged, and which further increase the risk of atherosclerosis, and systemic (whole-body) inflammation. When you are obese, if you become infected with COVID-19, at the point of infection, your immune system is already over-activated.

In an obese person, when COVID-19 blocks your ACE2 receptors, your ACE1 receptors become relatively over-stimulated. This results in an outpouring of inflammatory cytokines (cell-signalling molecules) as the immune system goes into overdrive known as a cytokine storm.

In a cytokine storm, your lungs are overwhelmed with these cytokines, whose job it is to kill infected cells. The huge number of cytokines is so great, that instead of helping defend your body from infection, they destroy lung tissue. The air sacs in the lungs become filled with fluid, fluid, meaning oxygen cannot pass freely not the bloodstream and carbon dioxide cannot easily be excreted. This condition is called Acute Respiratory Distress Syndrome (ARDS).

This means people who are overweight or obese, have a higher risk of severe lung disease, requiring hospital admission, critical care, and mechanical ventilation. The CDC reports that the risk of death is ten times higher from COVID-19 infection, in people with metabolic syndrome and type-2 diabetes.

ACE2 receptors are also found in the islet cells of the pancreas. It has been suggested that COVID-19 may enter these islet cells, temporarily preventing the production of insulin, raised blood sugar, and causing type-2 diabetes. This may explain why people who are already diabetic, are especially vulnerable to COVID-19 infection.

With increasing obesity, your body becomes less sensitive to the hormone insulin. This is known as insulin resistance. In fact, as glucose levels rise, more and more insulin is produced, but your cells have difficulty recognizing and responding. Eventually, blood glucose levels can no longer be kept under control this is prediabetes. In due course, if no steps are taken, full-blown diabetes sets in.

Insulin resistance is harmful as it underpins the development of many different medical conditions.

The exact reasons insulin resistance worsens the prognosis of COVID-19 infection are still not fully understood. However, activation of the ACE2 receptor is known to enhance insulin signalling and reduce insulin resistance. COVID-19 attaches to the same receptors and may blunt this activity. More research is needed.

Adipocytes (fat cells) produce a hormone called leptin. This is a hormone that regulates appetite. High leptin levels make you feel full and help to stop you from eating. It also increases your energy expenditure.

Strangely, obese people tend to have higher leptin levels, probably due to leptin resistance. As a result, even though leptin levels are high, they still have a large appetite. High leptin levels accelerate atherosclerosis, causing damage to endothelial cells and lowering HDL (good) cholesterol.

Leptin is a cell-signalling molecule, which itself triggers the production of inflammatory cytokines (interleukins 2 and 6, and tumour necrosis factor) and sets off the inflammation cascade.

The good news is that leptin levels fall with weight reduction.

Many studies have shown that people who are obese tend to have an unhealthy diet eating large amounts of fast food and processed food. These are often high-fat, high-protein, high-salt, low- fibre, low in complex carbohydrates (carbs which release energy slowly), and low in vitamin D. These foods may also be contaminated with pesticides.

This diet causes changes to the gut microbiome, increasing the leakiness of the gut wall. This means the junctions between intestinal cells are weakened, such that bacteria, viruses, and toxins can pass from the gut contents into the bloodstream. These effects then further exacerbate systemic inflammation.

There is also a link between the unhealthy Western diet and autoimmune diseases. High-salt increases the risk of high blood pressure, cardiovascular disease, and stroke.

Fat is not an inactive tissue. In fact, visceral fat produces large numbers of cytokines, such as Interleukin 6 (IL-6), and tumour necrosis factor- (TNF-). IL-6 has several important roles, for example in the regulation of B and T lymphocytes. TNF- regulates many aspects of immune function, for example, to cause cell death and destruction.

In addition, eating a high-fat diet has been shown to increase the production of these cytokines.

Too much dietary fat can literally poison your organs. Lipotoxicity occurs when there is so much dietary fat, that adipocytes (fat cells) cannot store any more, and the excess fat spills over into the bloodstream. Free fatty acids are then stored in other tissues such as the liver, heart, and kidneys. These fats are toxic and cause organ damage, for example, non-alcoholic liver disease, heart failure, and kidney failure.

Lipotoxicity is also associated with insulin and leptin resistance.

Oxidative stress is another type of metabolic derangement, in which electrically charged particles called reactive oxygen species (ROS), cause tissue destruction.

Obesity increases oxidative stress. As a result, there is an increased breakdown of lipids in the walls of red blood cells, meaning these red cells, carrying vital haemoglobin, are less able to squeeze through microcapillaries, and release oxygen as they should.

Increased oxidative stress seems also to increase damage to the air sacs in the lungs, the alveoli, and to stimulates coagulation, leading to an increase in microvascular thrombosis.

Obesity seems to increase general susceptibility to infection. Some have suggested that COVID-19 may even use excess adipose tissue as a reservoir where it can replicate, and to facilitate viral shedding, and enhance transmission of infection.

There is some evidence that people living with obesity have worse COVID symptoms than those with a normal BMI.

In obesity, there is increased fat deposition in the heart muscle, but the effects on the heart are further compounded as obesity is also associated with high blood pressure, metabolic syndrome, and diabetes.

In the heart, obesity results in obesity-related cardiomyopathy, with enlargement and fat deposition in cardiac muscle cells. Obesity is liked to sleep apnoea, meaning the heart is relatively under-perfused with oxygen during sleep.

If you are obese, there are numerous biochemical and metabolic reasons why COVID-19 infection is more likely to be severe and have a poor outcome. This is due to a combination of factors.

Are you convinced? Its all pretty scary. But heres the good news losing weight will reverse many of these parameters and help keep you well. Whats stopping you? The time is now.

You dont need to have unrealistic targets. Just losing 5% of your body weight will reduce insulin resistance and relieve oxidative stress. Even a mere 5% weight loss has major health benefits.

For example, if you weigh 100kg, 5% is 5kg (11 lb).

If you lose 2lb a week you can lose this in just 5-6 weeks.

And there are so many benefits of losing weight quite apart from improving your chances from COVID.

Obesity and COVID-19 are a double pandemic. Its a frightening reality.

However, now you know the facts, you can make up your mind right now, to change things for the better. Dont let the virus win!

Why not see your GP and discuss ways you can lose weight, and what support is available? There are many different weight-losing diets, but if you have a lot of weight to lose, you can take weight loss medication, or be referred for bariatric surgery. Why not find out what you can do and get started right away?

For more information

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What do we know about obesity and COVID-19? - Open Access Government

CAMBRIDGE, Mass. and NEW YORK, March 10, 2021 (GLOBE NEWSWIRE) -- Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a precision oncology medicine company pioneering the discovery and development of small molecule, tumor-agnostic therapies, today announced that pre-clinical data on BDTX-189 and BDTX-1535 will be presented as late-breaking poster presentations at the American Association for Cancer Research (AACR) Virtual Annual Meeting, taking place April 10-15, 2021.

Presentation details are as follows:

Title: Prospective pre-clinical modeling to estimate clinical pharmacokinetics and doses of BDTX-189, an inhibitor of allosteric ErbB mutations in advanced solid malignancies Session Type: E-Poster Session Session Category: Experimental and Molecular TherapeuticsSession Title: Pharmacology, Pharmacogenetics, and PharmacogenomicsDate and Time: Saturday, April 10, 8:30 AM ETAbstract Number: LB127

Title: CNS penetrant, irreversible inhibitors potently inhibit the family of allosteric oncogenic EGFR mutants expressed in GBM and demonstrate efficacy in patient-derived xenograft models Session Type: E-Poster Session Session Category: Experimental and Molecular TherapeuticsSession Title: Tyrosine Kinase and Phosphatase Inhibitors Date and Time: Saturday, April 10, 8:30 AM ETAbstract Number: LB140

Full abstracts will be published online at 12:01 AM ET on April 9, 2021 on the AACR website at http://www.aacr.org. Both presentations will also be available online on the Companys website at https://www.blackdiamondtherapeutics.com/technology/presentations-publications/.

About BDTX-189BDTX-189 is an orally available, irreversible small molecule inhibitor that blocks the function of an undrugged family of oncogenic proteins defined by driver mutations across a range of tumor types, and which affect both of the epidermal growth factor receptor (EGFR) and the tyrosine-protein kinase, ErbB-2, or human epidermal growth factor receptor 2 (HER2). These mutations include extracellular domain allosteric mutations of HER2, as well as EGFR and HER2 kinase domain exon 20 insertions, and additional activating oncogenic drivers of ErbB. The ErbB receptors are a group of receptor tyrosine kinases involved in key cellular functions, including cell growth and survival. BDTX-189 is also designed to spare normal, or wild type EGFR, which we believe will improve upon the toxicity profiles of current ErbB kinase inhibitors.

Currently, there are no medicines approved by the U.S. Food and Drug Administration to target all of these oncogenic mutations with a single therapy.

About Black DiamondBlack Diamond Therapeutics is a precision oncology medicine company pioneering the discovery of small molecule, tumor-agnostic therapies. Black Diamond targets undrugged mutations in patients with genetically defined cancers. Black Diamond is built upon a deep understanding of cancer genetics, protein structure and function, and medicinal chemistry. The Companys proprietary technology platform, Mutation-Allostery-Pharmacology, or MAP, platform, is designed to allow Black Diamond to analyze population-level genetic sequencing data to identify oncogenic mutations that promote cancer across tumor types, group these mutations into families, and develop a single small molecule therapy in a tumor-agnostic manner that targets a specific family of mutations. Black Diamond was founded by David M. Epstein, Ph.D., and Elizabeth Buck, Ph.D., and, beginning in 2017, together with Versant Ventures, began building the MAP platform and chemistry discovery engine. For more information, please visit http://www.blackdiamondtherapeutics.com.

Contacts:

For Investors:Natalie Wildenradtinvestors@bdtx.com

For Media:Kathy Vincent(310) 403-8951media@bdtx.com

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Black Diamond Therapeutics to Present Pre-Clinical Data on BDTX-189 and BDTX-1535 at American Association for Cancer Research Annual Meeting -...

Two new second-generation COVID-19 vaccines are being rapidly tested at McMaster University in Hamilton, one of which is designed to be inhaled rather thaninjected.

Its the first vaccine in Canada being developed that would deliver COVID-19 vaccines by inhalation through themouth.

The 30-member team of investigators and researchers is led by Zhou Xing, a professor in the department of medicine and McMaster Immunology ResearchCentre.

He is also an expert on respiratory mucosal immunity, infectious diseases, and tuberculosis vaccinedevelopment.

In an interview with McMaster Universitys communications manager, Michelle Donovan, Xing said his team was able to move quickly on their COVID-19 vaccine research because the foundation had already beenlaid.

We have been pursuing tuberculosis mucosal immunity research, said Xing. that line of work has been ongoing for the past 20 years. That tells you, conventionally, how long that journey has been compared to work on the COVID-19vaccine.

We have built up a very strong bench-to-human translational pipeline, which is where our strength lies. So we could easily apply all the knowledge, experiences and expertise to developing COVID-19 vaccines strategies, continuedXing.

We were ready to jump in as soon as we received our [Canadian Institutes of Health Research] funding in June2020.

(McMaster Faculty of HealthSciences)

The McMaster research team refers to it as a second or next-generation COVID-19 vaccine strategy because it differs from the current-market vaccines in that it was bioengineered to express three select SARS-CoV-2antigens.

The current front-running vaccines target only one, the spikeprotein.

The major difference is that the McMaster vaccine will be delivered via the respiratory mucosal route, rather than being injected into the muscle through theskin.

We believe our vaccines will engage what we call an all-around, or holistic protective mucosal immunity, Xing told Michelle Donovan. We aim to release or induce the broadest possible protective immunity, right at the site of viral entry. The different vaccine design and different route of administration lead to what we believe to be much better protectiveimmunity.

The vaccines being worked on by Xings team arent only a boost in the fight againstCOVID-19.

The team believes their vaccines will also help fight the growing list of variants and future viruses, aswell.

All the current-generation vaccines are being given to the masses, and that is where we think our vaccine strategies come into play, working as immunity boosters, saidXing.

It works by not only boosting the immune response to the early vaccine shots but by inducing a new layer of immune protection mediated by broadened T cell immunity. Thus, it will help fight the current and the next pandemics caused by coronaviruses. That is how we envision it will playout.

Xing leads McMaster's efforts alongside Brian Lichty, an associate professor in the department of medicine and director of the Robert E. Fitzhenry Vector Laboratory; Fiona Smaill, professor of pathology & molecular medicine; Matthew Miller, associate professor of biochemistry & biomedical sciences; and a large team of experts, who are part of Canada's Global Nexus for Pandemics and BiologicalThreats.

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Hamilton's McMaster research team developing COVID-19 vaccine that can be inhaled - insauga.com