A Single Drop of Blood Can Reveal Stress Hormones

A Rutgers-led team of researchers has developed a microchip that can measure stress hormones in real time from a drop of blood.

Cortisol and other stress hormones regulate many aspects of our physical and mental health, including sleep quality. High levels of cortisol can result in poor sleep, which increases stress that can contribute to panic attacks, heart attacks and other ailments.

Currently, measuring cortisol takes costly and cumbersome laboratory setups, so the Rutgers-led team looked for a way to monitor its natural fluctuations in daily life and provide patients with feedback that allows them to receive the right treatment at the right time.

The researchers used the same technologies used to fabricate computer chips to build sensors thinner than a human hair that can detect biomolecules at low levels. They validated the miniaturized device’s performance on 65 blood samples from patients with rheumatoid arthritis.

The use of nanosensors allowed us to detect cortisol molecules directly without the need for any other molecules or particles to act as labels,” said lead author Reza Mahmoodi, a postdoctoral scholar in the Department of Electrical and Computer Engineering at Rutgers University-New Brunswick.

With technologies like the team’s new microchip, patients can monitor their hormone levels and better manage chronic inflammation, stress and other conditions at a lower cost, said senior author Mehdi Javanmard, an associate professor in RutgersDepartment of Electrical and Computer Engineering.

Our new sensor produces an accurate and reliable response that allows a continuous readout of cortisol levels for real-time analysis,” he added. “It has great potential to be adapted to non-invasive cortisol measurement in other fluids such as saliva and urine. The fact that molecular labels are not required eliminates the need for large bulky instruments like optical microscopes and plate readers, making the readout instrumentation something you can measure ultimately in a small pocket-sized box or even fit onto a wristband one day.”

The study included Rutgers co-author Pengfei Xie, a Ph.D. student, and researchers from the University of Minnesota and University of Pennsylvania. The research was funded by the DARPA ElectRX program.

The study appears in the journal Science Advances.

Source: https://www.rutgers.edu/

Early Cancer Detection Test

Mayo Clinic today recognized the debut of a groundbreaking multi-cancer early detection (MCED) test called Galleri™ that can detect more than 50 types of cancers through a simple blood draw. The  Galleri test is intended  to complement U.S. guideline-recommended cancer screenings.

Mayo Clinic Oncologist Minetta Liu, M.D. was involved in the development of the new test. “Today, many cancers are found too late, leading to poor outcomes,” says Dr. Liu. “The ability to detect cancer early is critical to successful treatment.”

Cancer is expected to become the leading cause of death in the U.S. this year. Currently recommended cancer screening tests only cover five cancer types and screen for a single cancer at a time. In fact, there are no recommended early detection screening tests for other cancers, which account for 71% of cancer deaths.

Researchers used the Galleri test in the Circulating Cell-free Genome Atlas (CCGA) Study, a prospective, observational, longitudinal study designed to characterize the landscape of genomic cancer signals in the blood of people with and without cancer. In the study, the Galleri test demonstrated the ability to detect more than 50 types of cancers — over 45 of which have no recommended screening tests today — with a low false-positive rate of less than 1%.

According to Dr. Liu, when a cancer signal is detected, the Galleri test can identify where in the body the cancer is located with high accuracy — a critical component to help enable health care providers to direct diagnostic next steps and care.

We are grateful to Mayo Clinic for its dedication to advancing new technologies for early cancer detection and for playing a pivotal role in the development of Galleri,” says Dr. Josh Ofman, chief medical officer and head of external affairs at GRAIL.“A simple blood test capable of detecting more than 50 cancers is a ground-breaking advancement and could have a tremendous human and economic benefit.

Initial results from the interventional PATHFINDER Study, which involved the return of Galleri test results to providers to communicate to participants, were presented today at the 2021 American Society of Clinical Oncology Annual Meeting. They demonstrate Galleri’s performance in the clinical setting was consistent with findings from previous observational studies, underscoring the potential real-world ability of Galleri to find deadly cancers earlier.

Source: https://individualizedmedicineblog.mayoclinic.org/

Intravenous Immunoglobulins Could Stop Thrombosis after Astrazeneca Vaccination

Some people have developed dangerous blood clots in the brain after receiving the corona vaccination with the AstraZeneca preparation The University Medical Center Greifswald in Germany has now broken down the likely cause of the blood clots. According to Andreas Greinacher, he and his team found special antibodies in the blood of those affected, which are directed against the body’s own blood platelets. These cells play an important role in blood clotting. The antibodies activate the platelets: they clump together, as they normally do to close a wound, and thus form blood clots. The basic problem is therefore an autoimmune reaction.

In Germany, 13 cases of sinus vein thrombosis were reported shortly after an AstraZeneca vaccination, all of which were associated with a lack of blood platelets, i.e. a so-called thrombocytopenia. Around 1.6 million people in Germany were vaccinated. According to Greinacher, the problems that arose shortly after the vaccination are similar to a long-known complication with the administration of another agent, heparin-induced thrombocytopenia, or HIT for short. There, too, antibodies activate platelets so that clots form. In both cases the symptoms appear within 5 to 14 days after administration of the preparation. Greinacher therefore emphasized that the flu-like symptoms that often occur on the day after the vaccination are not a warning signal that a blood clot is developing. But anyone who has a painful leg about five days after the vaccination – as a sign of a deep vein thrombosis – or a severe headache should see a doctor immediately.

The Society for Thrombosis and Hemostasis Research has already published recommendations for doctors based on the Greifswald findings. She assumes that the formation of clots in people with sinus vein thrombosis and thrombocytopenia can be stopped by giving high doses of intravenous immunoglobulins. Greinacher could not answer how reliably this therapy helps those affected. That is not his area of expertise, he said.

Source: https://www.uni-greifswald.de/
AND
https://www.quora.com/

CRISPR Treatment Cuts Cholesterol by Up to 57% in a Single Shot

Scientists have improved upon a form of gene-editing therapy, creating an experimental treatment that looks to hold great promise for treating high cholesterol – a diagnosis affecting tens of millions of Americans, and linked to a number serious health complications. In new research conducted with mice, researchers used an injection of a newly-formulated lipid nanoparticle to deliver CRISPR-Cas9 genome editing components to living animals, with a single shot of the treatment reducing levels of low-density lipoprotein (LDL) cholesterol by up to 56.8 percent. In contrast, an existing FDA-approved lipid nanoparticle (or LNP; a tiny, biodegradable fat capsule) delivery system could only manage to reduce LDLs by 15.7 percent in testing. Of course, these results have so far only been demonstrated in mice, so the new therapy will take a lot of further testing before we know it’s both safe and equally effective in humans. But based on these results so far, signs are promising.

The way the treatment works relates to a gene in humans called Angiopoietin-like 3 (Angptl3), which produces proteins that inhibit the breakdown of certain fats in the bloodstream. People with a mutation in this gene tend to have lower amounts of fatty triglycerides and cholesterol in their blood – without showing other kinds of health complications – and for years scientists have been trying to recreate the process, with treatments that effectively mimic the effects of the mutation.

If we can replicate that condition by knocking out the Angptl3 gene in others, we have a good chance of having a safe and long term solution to high cholesterol,” says biomedical engineer Qiaobing Xu from Tufts University. “We just have to make sure we deliver the gene editing package specifically to the liver so as not to create unwanted side effects.

In the new research, Xu’s team developed a new formulation of LNPs called 306-O12B to target the gene, producing therapeutic effects in wild-type C57BL/6 mice that lasted at stable levels for 100 days after just a single injection of the treatment.

In addition to the cholesterol reduction, the experiment produced a 29.4 percent decrease in triglycerides in the animals’ blood, whereas the FDA-approved delivery method showed only a 16.3 percent reduction.

The findings are reported in PNAS.

New Blood Test Could Replace Biopsies

No one enjoys getting a biopsy, in which a tissue sample is surgically taken and analyzed in a lab for signs of disease, such as cancer. It’s not only unpleasant for the patient, but has clinical drawbacks: A biopsy doesn’t always extract the diseased tissue and isn’t helpful in detecting disease at early stages. These concerns have encouraged researchers to find less invasive and more accurate diagnostic methods. Prof. Nir Friedman and Ronen Sadeh of the Hebrew University of Jerusalem have developed a blood test that enables lab technicians to diagnose cancer and diseases of the heart and liver by identifying and determining the state of the dead cells throughout the body.

Millions of cells die every day and are replaced by new cells. When cells die, their DNA is fragmented. Some of these DNA fragments reach the blood and can be “read” by advanced DNA sequencing methods.

As a result of these scientific advancements, we understood that if this information is maintained within the DNA structure in the blood, we could use that data to determine the tissue source of dead cells and the genes that were active in those very cells. Based on those findings, we can uncover key details about the patient’s health,” Friedman said.

We are able to better understand why the cells died — whether it’s an infection or cancer — and based on that, be better positioned to determine how the disease is developing,” he said. Co-author Israa Sharkia added the simple blood test could “be administered often and quickly, allowing the medical staff involved to follow the presence or development of a disease more closely.”

A startup company, Senseera, has been established to pursue clinical testing of this innovative approach in partnership with major pharmaceutical companies.

The multi-author study published in Nature Biotechnology explains the test can even identify markers that may differentiate between patients with similar tumors, which could help physicians develop personalized treatments.

Source: https://www.zenger.news/

Diabetics die 3 times more of Covid-19

From the outset of the pandemic, data coming out of early coronavirus hot spots like China, Italy, and New York City foretold that certain groups of people would be more vulnerable to Covid-19. The disease hit older people and people with underlying medical conditions the hardest. As early as February, diabetes had emerged as one of the conditions associated with the highest risk. In one large study out of China, people with diabetes were more than three times as likely to die of Covid-19 than the overall population.

But that’s not what brought four diabetes experts from Australia and the United Kingdom onto a Zoom call back in April. They were supposed to just be catching up—a virtual tea among friends. But talk soon turned to something strange that they’d been seeing in their own hospitals and hearing about through the grapevine. The weird thing was that people were showing up in Covid-19 wards, after having tested positive for the virus, with lots of sugar in their blood. These were people with no known history of diabetes. But you wouldn’t know it from their lab results.

After that call, the experts reached out to colleagues in other countries to see if they’d seen or heard of similar cases. They had. Acute viral infections of all sorts can stress the body, causing blood sugar levels to rise. So that in itself wasn’t unusual, says Francesco Rubino, a bariatric surgeon and diabetes researcher at King’s College in London, who was on that first Zoom call. “What we were seeing and hearing was a little bit different.”

Doctors around the world had described to him strange situations in which Covid-19 patients were showing symptoms of diabetes that didn’t fit the typical two-flavor manifestation of the disease. In most people with type 1 diabetes, their immune cells suddenly turn traitorous, destroying the cells in the pancreas that produce insulin—the hormone that allows glucose to exit the bloodstream and enter cells. People with type 2 diabetes have a different problem; their body slowly becomes resistant to the insulin it does produce. Rubino and his colleagues were seeing blended features of both types showing up spontaneously in people who’d recently been diagnosed with Covid-19.

That was the first clinical puzzle,” he says. For clues to an explanation, Rubino and his colleagues looked to ACE2, the protein receptor that SARS-CoV-2 uses to invade human cells. It appears in the airways, yes, but also in other organs involved in controlling blood sugar, including the gut. Doctors in China discovered copies of the coronavirus in the poop of their Covid-19 patients. And a meta-analysis found that gastrointestinal symptoms plague one out of 10 Covid-19 sufferers.

In the last few decades, scientists have discovered that the gut is not the passive digestive organ once thought. It actually is a major endocrine player—responsible for producing hormone signals that talk to the pancreas, telling it to make more insulin, and to the brain, ordering it to make its owner stop eating. If the coronavirus is messing with these signals, that could provide a biological basis for why Covid-19 would be associated with different forms of diabetes, including hybrid and previously unknown manifestations of the disease. Rubino is one of a growing number of researchers who think that the relationship between the coronavirus and diabetes is actually a two-way street. Having diabetes doesn’t just tip the odds toward contracting a worse case of Covid-19. In some people, the virus might actually trigger the onset of diabetes, and the potential for a lifetime of having to manage it.

Source: https://www.wired.com/

NanoRobots Injected Into Human Bodies

In 1959, former Cornell physicist Richard Feynman delivered his famous lecture “There’s Plenty of Room at the Bottom,” in which he described the opportunity for shrinking technology, from machines to computer chips, to incredibly small sizes. Well, the bottom just got more crowded. A Cornell-led collaboration has created the first microscopic robots that incorporate semiconductor components, allowing them to be controlled – and made to walk – with standard electronic signals. These robots, roughly the size of paramecium, provide a template for building even more complex versions that utilize silicon-based intelligence, can be mass produced, and may someday travel through human tissue and blood.

The collaboration is led by Itai Cohen, professor of physics, Paul McEuen, the John A. Newman Professor of Physical Science – both in the College of Arts and Sciences – and their former postdoctoral researcher Marc Miskin, who is now an assistant professor at the University of Pennsylvania.

The walking robots are the latest iteration, and in many ways an evolution, of Cohen and McEuen’s previous nanoscale creations, from microscopic sensors to graphene-based origami machines. The new robots are about 5 microns thick (a micron is one-millionth of a meter), 40 microns wide and range from 40 to 70 microns in length. Each bot consists of a simple circuit made from silicon photovoltaics – which essentially functions as the torso and brain – and four electrochemical actuators that function as legs. As basic as the tiny machines may seem, creating the legs was an enormous feat.

In the context of the robot’s brains, there’s a sense in which we’re just taking existing semiconductor technology and making it small and releasable,” said McEuen, who co-chairs the Nanoscale Science and Microsystems Engineering (NEXT Nano) Task Force, part of the provost’s Radical Collaboration initiative, and directs the Kavli Institute at Cornell for Nanoscale Science.

But the legs did not exist before,” McEuen said. “There were no small, electrically activatable actuators that you could use. So we had to invent those and then combine them with the electronics.”

The team’s paper, “Electronically Integrated, Mass-Manufactured, Microscopic Robots,” has been published  in Nature.

Source: https://news.cornell.edu/
AND
https://thenextweb.com/

Can Plasma From Recovered Covid-19 Patients Cure Infected Others?

US Food and Drug Administration (FDA) officials announced today they have approved plans for nationwide trials of two treatments for Covid-19, the global pandemic disease caused by the new coronavirus—and for their simultaneous use in perhaps hundreds of hospitals.

The therapeutic agents—convalescent plasma and hyperimmune globulin—are both derived from the blood of people who have recovered from the disease, decoctions of the antibodies that the human immune system makes to fight off germs.

 

This is an important area of research—the use of products made from a recovered patient’s blood to potentially treat Covid-19,” said FDA commissioner Stephen Hahn in a release announcing the trials. “The FDA had played a key role in organizing a partnership between industry, academic institutions, and government agencies to facilitate expanded access to convalescent plasma. This is certainly a great example of how we can all come together to take swift action to help the American people during a crisis.”

Physicians are already using a somewhat haphazard collection of antiviral and other drugs for people critically ill with Covid-19, because they don’t have any other options. Nothing—no drug, no vaccine—is approved for use specifically against Covid-19 in the United States, so any new possibility is a hopeful one. Convalescent plasma and hyperimmune globulin join the rarified group of therapeutics that scientists are testing, including a trial of the Ebola drug remdesivir and the much-hyped antimalarial/immune suppressants chloroquine and hydroxychloroquine.

Using blood products from people who’ve already beaten a disease is a century-old approach, predating vaccines and antibiotics. Inspired by its use against polio, two physicians at a Naval hospital in Massachusetts tried it on people who had pneumonia as a result of influenza in 1918, with enough success to warrant more tests. The quality of actual studies of efficacy has varied over the decades, but health care workers used convalescent plasma against SARS, MERS, and Ebola. And a couple of studies—small and preliminary—have shown convalescent plasma having some promise against SARS-CoV-2 as well.

It was all promising enough that the FDA wanted to make sure current patients could have access to the plasma at the same time that researchers were starting a more rigorous investigation. “This seems like ancient history, but maybe it isn’t. There have been niche uses of it for a while,” says Michael Joyner, a physiologist at the Mayo Clinic who in March spearheaded the creation of an ad hoc coalition of researchers interested in pursuing the therapy. Joyner is facilitating the 40-center trial of the new therapies approved today by the FDA, with researchers at Johns Hopkins leading the science. (Joyner himself received gamma globulin, a variant of the treatment, as a preventative against hepatitis B in the 1980s, when he was a medical student.)

At Houston Methodist Hospital, James Musser, the chair of Pathology and Genome Medicine, is a friend of Arturo Casadevall, the Johns Hopkins University immunologist who proposed using convalescent serum early in the pandemic. Musser pushed to get his hospital involved, putting out a call for donors—people who had confirmed positive tests for the virus and had gone at least 14 days without symptoms. His hospital is already doing compassionate-use transfusions. “So far, as of yesterday, we’ve transfused four patients,” Musser said on Thursday. He expected a fifth to receive plasma today. And how’d it work?The truth is, it’s far too early,” Musser says. “We, nationally, need to do controlled trials and understand, first and foremost, is this a safe therapeutic? There’s lots of reasons to think it will be, but you never know.”

Source: https://www.wired.com/

Simple finger-prick tests Coronavirus

Millions of finger-prick coronavirus home-tests could be ready to order on Amazon or pick up in Boots in a matter of days, according to Public Health England (PHE). Sharon Peacock, of PHE‘s National Infection Service, said 3.5million antibody tests the Government has bought will be available in the ‘near future‘.

Asked whether these could be within several days, she told the House of Commons Science and Technology Committeeabsolutely’. However, Professor Peacock did not explain if the test would be free on the NHS or if suspected patients would have to pay. Health chiefs say the tests – which scour a sample of blood for antibodies made by the body to fight the virus – will initially be available for frontline healthcare staff.

The Government’s aim is to get thousands of doctors, nurses and paramedics who have had to self isolate at home as a precaution back to workPHE has not revealed who is manufacturing the tests, which detect if someone has had the infection previously and is now immune.

Personalized cancer vaccines

Therapeutic cancer vaccines were first developed 100 years ago and have remained broadly ineffective to date. Before tangible results can be achieved, two major obstacles must be overcome. Firstly, since tumor mutations are unique to each patient, cancer cell antigens must be targeted extremely precisely, which is very hard to achieve. Secondly, a safe system is needed to deliver the vaccine to the right location and achieve a strong and specific immune response.

Li Tang’s team at EPFL’s School of Engineering in Switzerland is coming up with a solution to the delivery problem. The researchers have used a polymerization technique called polycondensation to develop a prototype vaccine that can travel automatically to the desired location and activate immune cells there. The patented technique has been successfully tested in mice and is the topic of a paper appearing in ACS Central Science. Li Tang has also co-founded a startup called PepGene, with partners that are working on an algorithm for quickly and accurately predicting mutated tumor antigens. Together, the two techniques should result in a new and better cancer vaccine in the next several years.

Helping the body to defend itself

Most vaccines – against measles and tetanus for example – are preventive. Healthy individuals are inoculated with weakened or inactivated parts of a virus, which prompt their immune systems to produce antibodies. This prepares the body to defend itself against future infection.

However, the aim of a therapeutic cancer vaccine is not to prevent the disease, but to help the body defend itself against a disease that is already present. “There are various sorts of immunotherapies other than vaccines, but some patients don’t respond well to them. The vaccine could be combined with those immunotherapies to obtain the best possible immune response,” explains Li Tang. Another advantage is that vaccines should reduce the risk of relapse.

Delivering a cancer vaccine to the immune system involves various stages. First, the patient is inoculated with the vaccine subcutaneously. The vaccine will thus travel to the lymph nodes, where there are lots of immune cells. Once there, the vaccine is expected to penetrate dendritic cells, which act as a kind of alert mechanism. If the vaccine stimulates them correctly, the dendritic cells present specific antigens to cancer-fighting T-cells, a process that activates and trains the T-cells to attack them.

The procedure appears simple, but is extremely hard to put into practice. Because they are very small, the components of a vaccine tend to disperse or be absorbed in the blood stream before reaching the lymph nodes.

To overcome that obstacle, Li Tang has developed a system that chemically binds the vaccine’s parts together to form a larger entity. The new vaccine, named Polycondensate Neoepitope (PNE), consists of neoantigens (mutated antigens specific to the tumor to be attacked) and an adjuvant. When combined within a solvent, the components naturally bind together, forming an entity that is too large to be absorbed by blood vessels and that travels naturally to the lymph nodes.

Source: https://actu.epfl.ch/news/