Publisher Health

Biomarkers are components that may be present in biological samples and are related to specific diseases. Therefore, doctors can analyze biological samples from a patient to check their health condition or to monitor the progress of a specific therapy. Typically, these samples need to be purified and diluted before the analysis, and current medical diagnostic techniques rely on healthcare facilities and laboratories for these routine analyses. This is a lengthy process that requires trained personnel and expensive instrumentation to extract, transport, store, process, and analyze the samples in centralized locations. Moreover, during a period of global crisis like the ongoing pandemic, the pressure of thousands of analysis requests can saturate and collapse the healthcare system.
On the other hand, point-of-care devices, which are small automated instruments, are capable of performing diagnostics in decentralized locations and can provide quick answers. One example of such a device is the glucose meter that people with diabetes use to monitor their sugar levels in the blood. These devices can overcome the inherent limitations of having to process a sample through a centralized system, empowering anyone to be able to monitor their health from home, simply using a tiny blood sample extracted with a fingerprick.
However, the development of these devices has been burdened by the technical challenges related to measuring biological samples. Biomarkers for some diseases and infections are only present in the samples in very small amounts, which in turn imposes the challenge to develop extremely sensitive detection techniques. While increasing the surface area of the biosensor can increase the sensitivity of the instrument, these surfaces tend to be quickly clogged and contaminated, rendering them unusable.
To this end, the team led by Professor CHO, Yoon-Kyoung at the Center for Soft and Living Matter within the Institute for Basic Science (IBS) in Ulsan, South Korea recently developed a biosensor using a method to generate nanostructured and nanoporous surfaces. This combined strategy not only provides the sensor with an unprecedented sensitivity but also makes it resistant to fouling by proteins.
While previously there has been no known method to reliably create electrodes using such nanostructured and nanoporous substrates, the team reported a simple method to generate such materials. The mechanism is based on the application of electric pulses to a flat gold surface in the presence of sodium chloride and a surfactant that can form micelles in solution. These electric pulses drive a preferent reaction to etch and redeposit gold from the surface and, in turn, grow nanostructures and form the nanopores. The use of surfactant in the form of micelles is essential to the success of this strategy since it prevents the material that is being etched from diffusing away during the process, so it can be redeposited.
The formation of these nanostructures yielded a large surface area which was beneficial for increasing the sensitivity of the assays, whereas the formation of nanopore substrates was ideal to prevent contamination from the biological samples. Both the nanostructures and the nanopores’ combined benefits were key to the success of this strategy, which could be applied for the direct analysis of clinical plasma samples.
The researchers further demonstrated this new technology by building a biosensor for the detection of prostate cancer. The electrode was sensitive enough to discriminate between a group of prostate cancer and healthy donors using only a tiny amount of blood plasma or urine samples. No dilution or preprocessing steps were used, which means that the technology could easily be used for the point-of-care diagnosis of cancer.
Professor Cho stated, “We believe that this technology is essential for the future development of point-of-care devices and diagnostic tests that work with biological samples. The capability to detect low concentrations of relevant biomarkers with robust performance opens a door to possibilities in the field of diagnostics for cancer, pathogens, and other diseases.”
The findings of this research have been published in Advanced Materials (IF: 30.849) on May 17th, 2022.
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For the first time, researchers have shown what happens to the brain when a person receives a depression treatment known as repetitive transcranial magnetic stimulation (rTMS). The results were published today in the American Journal of Psychiatry.
rTMS is a depression treatment typically used when other approaches — such as medications — haven’t been effective for a patient. It is estimated that approximately 40 per cent of people with major depression do not respond to antidepressants.
During an rTMS session, a device containing an electromagnetic coil is placed against a patient’s scalp. The device then painlessly delivers a magnetic pulse that stimulates nerve cells in a region of the brain involved in mood control — called the dorsolateral pre-frontal cortex.
Although proven to be effective, the mechanisms behind how rTMS affects the brain have not been well understood.
“When we first started this research, the question we were asking was very simple: we wanted to know what happens to the brain when rTMS treatment is being delivered,” says Dr. Fidel Vila-Rodriguez, an assistant professor in UBC’s department of psychiatry and researcher at the Djavad Mowafaghian Centre for Brain Health (DMCBH).
To answer this question, Dr. Vila-Rodriguez and his team delivered one round of rTMS to patients while they were inside a magnetic resonance imaging (MRI) scanner. Since the MRI can measure brain activity, the researchers were able to see in real time what changes were happening in the brain.

A study led by researchers at the National Institute for Health and Care Research (NIHR) Leicester Biomedical Research Centre has shown that a less invasive heart procedure for a common condition is just as effective as conventional open-heart surgery. The findings are published in the Journal of the American Medical Association (JAMA) today (Tuesday 17 May).
The study compared Transcatheter Aortic Valve Implantation (TAVI) to conventional surgery in treating severe symptomatic aortic stenosis. In this condition there is a narrowing of the valve that blood flows through as it leaves the heart and treatment often requires surgery. It is estimated that 1.5% of UK adults over 55 and 3.5% of those over 75 have this condition.
The study is the first publicly funded study of its kind, receiving over £3 million from the NIHR Health Technology Assessment (HTA) programme, and involved every centre in the UK that performs TAVI.
The first TAVI in the UK was performed in Leicester in 2007 by a multidisciplinary team at Glenfield Hospital in Leicester, led by Professor Jan Kovac. In a TAVI procedure, a new valve is threaded through a small tube inserted into an artery in the groin, upper arm or chest. It provides an alternative to open-heart surgery and is widely used across the UK.
Previous studies have shown TAVI is a safe and effective treatment for people who are not eligible for conventional surgery or at high operative risk. However, this study included patients who were at lower risk and suitable for either procedure. The study found that, one year after treatment, the rates of death from any cause and other important clinical outcomes such as stroke were similar between the TAVI group and the surgery group.
The study included 913 participants who were randomised to either undergo the TAVI procedure or conventional surgery. The average age of participants was 81. Those who underwent TAVI were more likely to experience vascular complications and require pacemakers, while those who underwent surgery were more likely to experience severe bleeding. There was a greater improvement in symptoms, functional capacity and quality of life at 6 weeks in the patients who received TAVI and the quality of life advantage was still present at one year.
Professor William Toff, Professor of Cardiology in the University of Leicester’s Department of Cardiovascular Sciences, led the UK TAVI study. He said: “It’s great news for patients that TAVI is just as safe and effective as surgery even in patients at lower operative risk. This procedure is much less invasive than conventional approaches. People who would otherwise require open-heart surgery can have this procedure, and as it has a faster recovery time it means a shorter stay in hospital for patients.
“These are extremely encouraging results after one year. However, we shall continue to monitor the participants for at least 5 years to ensure no late differences in the groups emerge and to assess the durability of the TAVI valves. We hope to publish the 5-year results by the end of next year. In the meantime, patient-specific treatment recommendations should continue to be made by a multi-disciplinary heart team.”
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Materials provided by University of Leicester. Note: Content may be edited for style and length.

As part of a government effort to reduce animal testing, researchers at the National Institute of Standards and Technology (NIST) have worked with the Consumer Product Safety Commission (CPSC) and Inotiv Inc. to produce a new protocol for screening skin allergens. The method is potentially cheaper and faster than animal testing, while maintaining a similar performance.
The researchers built upon on an existing method, improving its efficiency, accessibility and quality controls. Using the new animal-free protocol, they evaluated 92 chemicals and found that their results agreed with those of a common animal test method for 77% of the compounds. The results, published today in Toxics, increase confidence in the new method’s measurements, potentially paving a route to standardization, which could both increase international trade and reduce animal testing.
Many governing bodies, including the European Union and certain U.S. states, have recently banned the sale of animal-tested cosmetics. However, animal testing is still required in some parts of the world to assess the safety of cosmetics. With regulations varying by region, it has become challenging for certain products to gain approval across the board.
Some animal-free methods of screening for skin allergens do exist, but their widespread adoption has been stymied by several limitations. For example, the direct peptide reactivity assay (DPRA) requires costly equipment that can only test a handful of samples at a time. The DPRA can be slow as well. To attain statistically meaningful conclusions about a test compound, testers would need to repeat the assay’s multiday process multiple times.
The low sample size per test also reduces opportunity for control samples that would allow researchers to identify and minimize factors that may vary between samples and skew measurements.
To increase confidence in animal-free tests and promote their adoption, several federal agencies, coordinated by a standing committee of the National Institute of Environmental Health Sciences, are assessing the reliability of new, promising methods. The CPSC, a member agency of the committee, has partnered with NIST to evaluate a method much faster than the DPRA, known as the electrophilic allergen screening assay (EASA).

Valve replacement heart surgery should be performed earlier than conventionally thought for people with aortic stenosis — according to new research from the University of East Anglia.
The condition is one of the most common and serious valve disease problems, caused by a narrowing of the aortic valve opening.
Once patients develop symptoms such as breathlessness, chest pains or blackouts then guidelines recommend replacing the narrowed valve. But many patients with aortic stenosis do not have symptoms even when they have severe narrowing of the valve and are thus not eligible for valve replacement.
New research published today shows that these patients would benefit by undergoing a valve replacement — before they suffer irreversible heart muscle damage.
Lead researcher Prof Vassilios Vassiliou, from UEA’s Norwich Medical School, said: “The heart has four valves, which allow the blood to flow in one direction efficiently. With increasing age, one of the valves, the aortic valve, becomes increasingly narrowed or ‘stenosed’.
“A lot of patients with severe aortic stenosis do not have symptoms and therefore are not eligible for valve replacement according to the current guidelines.

The path to cancer prevention is long and arduous for legions of researchers, but new work by Rice University scientists shows that there may be shortcuts.
Rice chemist Anatoly Kolomeisky, lead author and postdoctoral researcher Hamid Teimouri and research assistant Cade Spaulding are developing a theoretical framework to explain how cancers caused by more than one genetic mutation can be more easily identified and perhaps stopped.
Essentially, it does so by identifying and ignoring transition pathways that don’t contribute much to the fixation of mutations in a cell that goes on to establish a tumor.
A study in the Biophysical Journal describes their analysis of the effective energy landscapes of cellular transformation pathways implicated in a variety of cancers. The ability to limit the number of pathways to the few most likely to kick-start cancer could help to find ways to halt the process before it ever really starts.
“In some sense, cancer is a bad-luck story,” said Kolomeisky, a professor of chemistry and of chemical and biomolecular engineering. “We think we can decrease the probability of this bad luck by looking for low-probability collections of mutations that typically lead to cancer. Depending on the type of cancer, this can range between two mutations and 10.”
Calculating the effective energies that dictate interactions in biomolecular systems can predict how they behave. The theory is commonly used to predict how a protein will fold, based on the sequence of its constituent atoms and how they interact.

In a major advance for rational drug design, a Texas A&M AgriLife team has described several protein structures of a crucial player in cellular processes. The advance could bring new ideas for treatments of diseases such as Alzheimer’s, AIDS, cancer and others.
Artistic rendering of a protein kinase C C1 domain (copper), its ligand diacylglycerol (blue), and detergent (cyan). Image courtesy of Sachin Katti.
Specifically, the work describes the C1 domain of protein kinase C, PKC, which helps regulate the protein’s activity in organisms. In the structures, the C1 domain wraps around different molecules of intense therapeutic interest, providing the first reliable, atomic-resolution guide for designing drug candidates.
Published May 16 in Nature Communications, the research was directed by Tatyana Igumenova, Ph.D., associate professor in the Department of Biochemistry and Biophysics in the Texas A&M College of Agriculture and Life Sciences. The project’s primary author is Sachin Katti, Ph.D., a postdoctoral fellow working with Igumenova.
The study involved a collaboration with Inna Krieger, Ph.D., research assistant professor, and James Sacchettini, Ph.D., professor, both in the Department of Biochemistry and Biophysics.
Grants from the National Institutes of Health and the Welch Foundation supported the work.

Here’s a scenario so common that it applies to nearly 92 percent of older adults with cancer: An individual comes in for treatment and reports taking several medications that might include a drug for high blood pressure or heart disease, an antidepressant, or something for diabetes. The person may also take frequent doses of a headache pill, over-the-counter pills to relieve heartburn or reflux, antihistamines, and vitamins and minerals. But, patients may not report these as often to the medical team.
This soupy concoction defines “polypharmacy,” or the concurrent use of multiple medications — which can make a person more prone to harmful drug interactions, something that is especially dangerous for cancer patients about to undergo therapy.
Even for individuals who do not have cancer, multiple medication use is fraught with risks and tricky to navigate because of the emotions involved, said Erika Ramsdale, M.D., a Wilmot Cancer Institute oncologist, geriatrics specialist, and data scientist who led a recent study on polypharmacy published in The Oncologist journal.
“As doctors, we tell people to take medications but we don’t always do a great job of following up,” she said. “From the patient perspective, if it’s determined that a medication is no longer needed, it’s hard to stop taking it. There’s a sense of, ‘What will happen if I stop?’ or ‘Are you giving up on me?’ A lot of uncertainty and emotions are tied up in this issue.”
The longer the list of drugs and supplements a person takes, the higher the risk of inappropriate use and serious drug interactions, she said.
The fragmented nature of health care across specialties complicates the issue. “Sometimes, there is no quarterback,” Ramsdale said, which can result in “prescribing cascades,” where additional drugs are given to offset the adverse side effects of the original medications.

A comparison of four COVID-19 vaccinations shows that messenger RNA (mRNA) vaccines — Pfizer-BioNTech and Moderna — perform better against the World Health Organization’s variants of concern (VOCs) than viral vector vaccines — AstraZeneca and J&J/Janssen. Although they all effectively prevent severe disease by VOCs, the research, publishing May 17 in the open access journal PLOS Medicine, suggests that people receiving a viral vector vaccine are more vulnerable to infection by new variants.
By March 2022, COVID-19 had caused over 450 million confirmed infections and six million reported deaths. The first vaccines approved in the US and Europe that protect against serious infection are Pfizer-BioNTech and Moderna, which deliver genetic code, known as mRNA, to the bodies’ cells, whereas Oxford/AstraZeneca and J&J/Janssen are viral vector vaccines that use a modified version of a different virus — a vector — to deliver instructions to our cells. Three vaccines are delivered as two separate injections a few weeks apart, and J&J/Janssen as a single dose.
Marit J. van Gils at the University of Amsterdam, Netherlands, and colleagues, took blood samples from 165 healthcare workers, three and four weeks after first and second vaccination respectively, and for J&J/Janssen at four to five and eight weeks after vaccination. Samples were collected before, and four weeks after a Pfizer-BioNTech booster.
Four weeks after the initial two doses, antibody responses to the original SARS-CoV-2 viral strain were highest in recipients of Moderna, followed closely by Pfizer-BioNTech, and were substantially lower in those who received viral vector vaccines. Tested against the VOCs — Alpha, Beta, Gamma, Delta and Omicron — neutralizing antibodies were higher in the mRNA vaccine recipients compared to those who had viral vector vaccines. The ability to neutralize VOCs was reduced in all vaccine groups, with the greatest reduction against Omicron. The Pfizer-BioNTech booster increased antibody responses in all groups with substantial improvement against VOCs, including Omicron.
The researchers caution that their AstraZeneca group was significantly older, because of safety concerns for the vaccine in younger age groups. As immune responses tend to weaken with age, this could affect the results. This group was also smaller because the Dutch government halted use for a period.
van Gils concludes, “Four COVID-19 vaccines induce substantially different antibody responses.”
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Different types of brain damage caused by a concussion may lead to similar symptoms in children, according to research led by McGill University. A new way of studying concussions could help develop future treatments.
While most children fully recover after a concussion, some will have lasting symptoms. The findings published in eLife help explain the complex relationships that exist between symptoms and the damage caused by the injury.
The researchers found that certain combinations of brain damage were associated with specific symptoms such as attention difficulties. Other symptoms, such as sleep problems, occurred in children with multiple types of injuries. For example, damage to areas of the brain that are essential for controlling sleep and wakefulness could cause challenges with sleeping, as could damage to brain regions that control mood.
The brain’s white matter holds clues
To do this, they examined how damage to the brain resulting from concussion affected its structural connection network, known as white matter. They then used statistical modelling techniques to see how these changes related to 19 different symptoms reported by the children or their caregivers.
Analysing symptoms may advance treatment
“Despite decades of research, no new treatment targets and therapies for concussions have been identified in recent years,” says lead author Guido Guberman, a Vanier Scholar and MDCM Candidate at McGill University. “This is likely because damage to the brain caused by concussions, and the symptoms that result from it, can vary widely across individuals. In our study, we wanted to explore the relationships that exist between the symptoms of concussion and the nature of the injury in more detail.”
Guberman and his colleagues analysed data collected from 306 children, aged nine to 10 years old, who had previously had a concussion. The children were all participants in the Adolescent Brain Cognitive Development (ABCD) Study.
“The methods used in our study provide a novel way of conceptualising and studying concussions,” says senior author Maxime Descoteaux, a Professor of Computer Science at Université de Sherbrooke. “Once our results are validated and better understood, they could be used to explore potential new treatment targets for individual patients. More broadly, it would be interesting to see if our methods could also be used to gather new insights on neurological diseases that likewise cause varied symptoms among patients.”
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Materials provided by McGill University. Note: Content may be edited for style and length.