Publisher Health

McMaster University researchers have found not only how some viral infections cause severe tissue damage, but also how to reduce that damage.
They have discovered how Type I interferon (IFN) stops the immune system ‘going rogue’ and attacking the body’s own tissues when fighting viral infections, including COVID-19.
Their paper was published in the journal PLOS Pathogens today.
Senior author Ali Ashkar said IFN is a well-known anti-viral signalling molecule released by the body’s cells that can trigger a powerful immune response against harmful viruses.
“What we have found is that it is also critical to stop white blood cells from releasing protease enzymes, which can damage organ tissue. It has this unique dual function to kick start an immune response against a viral infection on the one hand, as well as restrain that same response to prevent significant bystander tissue damage on the other,” he said.
The research team investigated IFN’s ability to regulate a potentially dangerous immune response by testing it on both flu and the HSV-2 virus, a highly prevalent sexually transmitted pathogen, using mice. Data from COVID-19 patients in Germany, including post-mortem lung samples, was also used in the study.

Older breast cancer survivors with cardiometabolic risk factors who restricted food intake to eight hours during the weekday, followed by 16 hours of fasting, lowered their risk of cardiovascular disease (CVD) after a few weeks, according to a new research letter publishing today in JACC: CardioOncology. The study is a part of the upcoming mini-focus issue, “Physical Activity and Lifestyle Interventions in Cancer.”
The authors looked at 22 individuals with a body mass index who were classified as overweight or obese ( >25kg/m2), had completed cardiotoxic treatment (anthracyclines, a commonly used chemotherapy drug) within the past one to six years, and were an average age of 66 years. For eight weeks participants were allowed to eat freely between 12-8 p.m. on weekdays and at any time on the weekends. Outside of those hours, participants were asked to consume only water, black coffee or black tea. Using the Canadian Cardiovascular Society scoring system to calculate the 10-year Framingham Risk Score, the authors found that CVD risk decreased from 10.9% to 8.6% at the end of the trial period.
“This rigorously designed, well-executed single-arm feasibility study generates important hypotheses and questions about the role of time restricted eating relevant to cancer survivors,” said Bonnie Ky, MD, MSCE, editor-in-chief of JACC: CardioOncology. “For example, what is the basis of the inter-individual variation of the response to time restricted eating in the Framingham Risk Score, and will this help identify patients who are most likely to benefit from this strategy? How does diet quality affect these findings? We look forward to seeing research using practical lifestyle interventions continue to evolve and advance to improve the lives of our patients and survivors.”
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Materials provided by American College of Cardiology. Note: Content may be edited for style and length.

Statins have been hailed as a wonder drug; the cholesterol-lowering drugs have been prescribed to tens of millions of people since their approval in the late 1980s to prevent heart attack and stroke. But the drugs may yet have additional benefits, some research has hinted, including on mental health. Now, a new study examines the influence of statins on emotional bias, a marker for risk of depression. The study appears in Biological Psychiatry, published by Elsevier.
Researchers led by Amy Gillespie, PhD, at the University of Oxford, Oxford, UK, conducted the online observational study from April 2020 through February 2021, at the height of the SARS-CoV-2 pandemic, when global stress levels were elevated and the incidence of psychiatric disorders spiked.
Over 2000 participants in the UK recorded information about their current psychiatric symptoms, medications, and other lifestyle factors. They also performed cognitive tasks meant to measure memory, reward, and emotion processing, which are linked to depression vulnerability. One task required participants to identify the emotional expressions of faces, which displayed varying degrees of fear, happiness, sadness, disgust, anger, or fear.
The vast majority of subjects (84%) were not taking either medication, but a small group were taking only statins (4%), only a different class of anti-hypertension medication (6%), or both (5%).
Participants taking statins were less likely to recognize fearful or angry faces and more likely to report them as positive, indicating they had reduced negative emotional bias.
Dr. Gillespie said, “We found that taking a statin medication was associated with significantly lower levels of negative emotional bias when interpreting facial expressions; this was not seen with other medications, such as blood pressure medications.”
“We know that reducing negative emotional bias can be important for the treatment of depression,” said Dr. Gillespie. “Our findings are important as they provide evidence that statins may provide protection against depression. Of particular note, we saw these results during the high-stress context of the COVID-19 pandemic. Our findings also provide the first potential psychological explanation of statins’ mental health benefits,” in that they seem to affect emotion processing. It remains unclear exactly how statins could protect against mental illness, but one possibility is that they may work through anti-inflammatory mechanisms, which have also been implicated in depression.
John Krystal, MD, Editor of Biological Psychiatry, said of the work, “Statins are among the most commonly prescribed medications based on their ability to prevent heart attacks and strokes. These new data raise the possibility that some of their positive effects on health could be mediated by the effects of these drugs on the brain that promote emotional resilience.”
“Researchers should prioritize investigating the possible use of statins as a preventative intervention for depression. Before use in clinical practice, it is important that future research confirms the potential psychological benefits of statins through controlled, randomized clinical trials,” Dr. Gillespie concluded.
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Materials provided by Elsevier. Note: Content may be edited for style and length.

For many years after discovering a diverse population of sometimes dangerous microbes constantly living in our intestines, scientists described the situation as a form of living with the enemy. But when it comes to commensal populations of the fungus Candida albicans, the dreaded invader may be better seen as a helpful friend arriving with gifts.
That’s the key message of a study published May 17, 2022, in Cell Reports, by a team led by Sing Sing Way, MD, PhD, an infectious diseases expert at Cincinnati Children’s.
“This fungus could be invisible to our bodies if it wanted to be. It can mask many of the ways our immune system knows how to recognize it,” Way says. “Instead, our work shows that it purposely exposes itself to gain the benefit of our bodies recognizing it and not attacking it.”
Many people are familiar with the concept of probiotics, or “good” bacteria. Scientists also have learned that fungi can do good for people, including sometimes replacing bacteria in the commensal state and performing similar beneficial functions.
“However, fungi also are much more complicated than bacteria, and relatively understudied compared to bacteria,” Way says.
Blinking ‘Hello’
In years past, many scientists believed that the simple presence of certain fungi in the gut was enough to signal to the body that it had a proper balance of microbiota. Even inert fungi could be detected via the surface structures and chemicals of their cell walls.

Fragile X syndrome, the leading inherited cause of intellectual disability, is due to a genetic mutation that largely eliminates the fragile X protein, a critical element of normal brain development and function.
The fragile X protein modulates neuronal functions, including neurons within the so-called GABAergic system that regulates the activity of neural circuits. The protein’s absence throws that system off kilter, and so far, experimental therapies designed to reset the system by compensating for the missing protein’s functions have not been effective in clinical trials.
Now, researchers at Washington University School of Medicine in St. Louis have identified a previously unknown role for the fragile X protein in the GABAergic system. They have shown that the protein regulates the opening and closing of the GABA-A receptor in neurons from the brain’s memory center, thereby influencing how such neurons process information, a central part of learning and memory.
The findings, published May 17 in Cell Reports, indicate that the fragile X protein’s role is more complex than previously thought, and that finding effective therapies may depend on a more nuanced understanding of the myriad ways loss of this protein affects the brain.
“People think that since fragile X is related to the loss of a single protein, it is a simple disease that we can quickly understand and fix,” said senior author Vitaly A. Klyachko, PhD, a professor of cell biology & physiology. “But the reality is that the more we study, the more we understand it’s not simple at all. I think part of the reason why clinical trials fail may be because we don’t really understand what’s going on very well. It is possible that we need to fix more than one mechanism at the same time for patients to see any meaningful improvement.”
People with fragile X syndrome have intellectual or learning disabilities, social and behavioral problems, and characteristic physical features such as large ears and long faces. They also often are noted for their friendly dispositions. The condition affects about 1 in 7,000 males and 1 in 11,000 females, with males typically more severely affected. The fragile X gene is located on the X chromosome, so females inherit one good and one bad copy of the gene, but males have only the bad copy. There are no treatments that address the underlying cause.
The GABAergic system is based on the transmission of gamma aminobutyric acid (GABA) from one neuron to another. When it arrives, GABA binds to a receptor molecule and triggers a cascade of events in the receiving neuron that results in suppression of the activity of that neuron. An overactive GABAergic system puts people to sleep; an underactive one is linked to depression, anxiety and epileptic seizures.
To better understand the role of fragile X protein in the GABAergic system, Klyachko and first author Pan-Yue Deng, MD, PhD, an associate professor of cell biology & physiology, studied neurons from the brains of mice with and without the fragile X protein. Specifically, they recorded the activity of key information-processing neurons controlled by the GABAergic system in the hippocampus, the brain’s learning and memory center. Such neurons sense the presence of GABA primarily by using the so-called GABA-A receptor.
The receptor is a channel that can open to allow negatively charged chloride ions to flow into the cell to modulate its activity. The researchers found that fragile X protein influences how much time the GABA-A receptor spends open and how much chloride it allows into the cell, thereby setting the baseline electrical charge inside the neuron. This baseline charge, in turn, affects the neuron’s ability to distinguish between multiple signals that arrive at nearly the same time, a critical mechanism of pattern separation essential for learning and memory formation.
“The fragile X protein directly interacts with receptors that play a major role in the way neurons process information,” Klyachko said. “This is an additional function for the fragile X protein, and it may be an important one. These neuronal receptors are everywhere, and they control many critical brain functions.”
But Klyachko cautions against assuming that these findings can be easily translated into therapies for people living with fragile X syndrome. The GABAergic system is complex, and small tweaks can have unexpected and far-reaching effects on brain function, he said.
“I think there is a very strong desire — an understandable one — to immediately translate each discovery into a clinical trial,” Klyachko said. “But if we don’t understand all of the functions this protein has and we try to go after one specific mechanism, it may destabilize the other ones, and the end result is that people don’t get better. An entirely different approach to treating this disease may be possible, but I think we need to first understand much more about how it works. This is just the first stepping stone in a new direction.”

Most people don’t think much about zinc. But all living things need zinc for survival. This trace element helps many proteins fold into the right shapes to do their jobs. And in proteins known as enzymes, zinc helps catalyze chemical reactions — including many important for providing energy to cells. If zinc is absent, people, pets, and plants don’t thrive.
That’s one reason biologists at the U.S. Department of Energy’s Brookhaven National Laboratory are so interested in this element.
“We’re looking for ways to grow bioenergy plants — either plants that produce biofuels or whose biomass can be converted into fuel — and doing it on land that is not suitable for growing food crops,” said Brookhaven Lab biologist Crysten Blaby, who also holds an adjunct appointment at Stony Brook University. “So, we’re interested in strategies nature uses to survive when zinc and other micronutrients are lacking.”
In a paper just published in the journal Cell Reports, Blaby and her colleagues describe one such strategy: a so-called “chaperone” protein that delivers zinc to where it’s needed, which could be especially important when access to zinc is limited. Though scientists, including Blaby, have long suspected the existence of a zinc chaperone, the new research provides the first definitive evidence by identifying a “destination” for its deliveries.
Through a series of biochemical assays and genetics experiments, the team identified a zinc-dependent protein that cannot function properly without the chaperone. That protein, called MAP1, exists across species — from yeast and mice to plants and people. That means the findings have relevance not just for plants but also for health in humans, where zinc deficiency leads to growth and developmental impairments.
“Our goals are in bioenergy crop sustainability, but because the proteins we are studying are found nearly everywhere, our research has applications that are very broad,” Blaby said.

Adolescent athletes with high motivation for school also have high motivation for sports. Male students tend to be less interested in school than their female peers, a new study from Finland shows.
Successfully integrating elite sports with education requires motivation to commit oneself to both domains. In Europe, the EU has instructed its Member States to formulate and adopt national guidelines on dual careers of athletes. Sufficient policy actions are needed in support of combining elite sports with academic education. In Finland, for example, talented and elite adolescent athletes have the opportunity to complete their upper secondary education in special sports upper secondary schools, which offer equal competitive sport opportunities for both genders and often specialise in multiple sports.
A new study conducted among nearly 400 adolescent athletes in Finland examined the development of, and gender differences in, their task values for school and sports across the upper secondary school years. The students were aged 15-16 at the beginning of the study, and they were all completing their upper secondary education in a sports upper secondary school. They were followed four times during their upper secondary school years.
The researchers found that the task values for school and sports among the students were strongly related to each other. Students with high motivation for school also had high motivation for sports. On the other hand, students with lower motivation for school struggled to maintain their motivation for sports, too.
“In this study, we focused especially on potential gender differences. Female students are generally expected to have higher motivation for an academic career than male students, whereas in sports, gender role stereotypes often exert an impact on the importance attached to masculine characteristics. It has been suggested that, from the motivational perspective, such a masculine performance narrative directs males more easily towards dedication to sports,” Professor Jaana Viljaranta from the University of Eastern Finland says.
The results showed that male students’ school-related task values were lower than female students’ task values at the beginning of upper secondary school, and that the gender differences remained across the school years. However, no gender differences were found in the students’ motivation for an athletic career.
“These findings indicate that female students may be more committed to integrating elite sports and education than male students.”
To support the processes of dual career construction for male students, special attention should be paid to developing their motivation for school.
“Awareness of the gender differences shown in this study could help better understand what kind of support students need in sports upper secondary school to guarantee them the possibility of a dual career,” Professor Viljaranta points out.
The study was supported by the Finnish Ministry of Education and Culture and led by Adjunct Professor Tatiana V. Ryba at the University of Jyväskylä.
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Materials provided by University of Eastern Finland. Note: Content may be edited for style and length.

Scientists have developed and validated an algorithm that can help healthcare professionals identify who is most at risk of dying from COVID-19 when admitted to a hospital, reports a study published today in eLife.
The tool, which uses artificial intelligence (AI), could help doctors direct critical care resources to those who need them most, and will be especially valuable to resource-limited countries.
“The appearance of new SARS-CoV-2 variants, waning immune protection and relaxation of mitigation measures means we are likely to continue seeing surges of infections and hospitalisations,” explains the leader of this international project and senior author David Gómez-Varela, former Max Planck Group Leader and current Senior Scientist at the Division of Pharmacology and Toxicology, University of Vienna, Austria. “There is a need for clinically valuable and generalisable triage tools to assist the allocation of hospital resources for COVID-19, particularly in places where resources are scarce. But these tools need to be able to cope with the ever-changing scenario of a global pandemic and must be easy to implement.”
To develop such a tool, the team used biochemical data from routine blood draws performed on nearly 30,000 patients hospitalised in over 150 hospitals in Spain, the US, Honduras, Bolivia and Argentina between March 2020 and February 2022. This means they were able to capture data from people with different immune statuses — vaccinated, unvaccinated and those with natural immunity — and from people infected with every SARS-CoV-2 variant, from the virus that emerged in Wuhan, China, to the latest Omicron variant. “The intrinsic variability in such a diverse dataset is a great challenge for AI-based prediction models,” says lead author Riku Klén, Associate Professor at the University of Turku, Finland.
The resulting algorithm — called COVID-19 Disease Outcome Predictor (CODOP) — uses measurements of 12 blood molecules that are normally collected during admission. This means the predictive tool can be easily integrated into the clinical care of any hospital.
CODOP was developed in a multistep process, initially using data from patients hospitalised in more than 120 hospitals in Spain, to ‘train’ the AI system to predict hallmarks of a poor prognosis.
The next step was to ensure the tool worked regardless of patients’ immune status or COVID-19 variant, so they tested the algorithm in several subgroups of geographically dispersed patients. The tool still performed well at predicting the risk of in-hospital death during this fluctuating scenario of the pandemic, suggesting the measurements CODOP is based on are truly meaningful biomarkers of whether a patient with COVID-19 is likely to deteriorate.
To test whether the time of taking blood tests affects the tool’s performance, the team compared data from different time points of blood drawn before patients either recovered or died. They found that the algorithm can predict the survival or death of hospitalised patients with high accuracy until nine days before either outcome occurs.
Finally, they created two different versions of the tool for use in scenarios where healthcare resources are either operating normally or are under severe pressure. Under normal operational burden, doctors may opt to use an ‘overtriage’ version, which is highly sensitive at picking up people at increased risk of death, at the expense of detecting some people who did not require critical care. The alternative ‘undertriage’ model minimises the possibility of wrongly selecting people at lower risk of dying, providing doctors with greater certainty that they are directing care to those at the highest risk when resources are severely limited.
“The performance of CODOP in diverse and geographically dispersed patient groups and the ease of use suggest it could be a valuable tool in the clinic, especially in resource-limited countries,” remarks Gómez-Varela. “We are now working on a follow-up dual model tailored to the current pandemic scenario of increasing infections and cumulative immune protection, which will predict the need for hospitalisation within 24 hours for patients within primary care, and intensive care admission within 48 hours for those already hospitalised. We hope to help healthcare systems restore previous standards of routine care before the pandemic took hold.”
The CODOP predictor is freely accessible at: https://gomezvarelalab.em.mpg.de/codop/
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Materials provided by eLife. Note: Content may be edited for style and length.

Women with dense breast tissue and benign breast disease face an elevated risk of future breast cancer and could benefit from a tailored mammogram screening strategy, according to a large study published in the journal in Radiology.
Benign breast disease refers to non-cancerous breast lumps, cysts or nipple discharge. It is a common condition that can affect both women and men.
Research has shown that mammographic breast density and benign breast disease are strong risk factors for breast cancer. Less is known about the combined impact of the two risk factors.
The new study investigated the risk of breast cancer associated with the combination of mammographic density and benign breast disease in 3.9 million Korean women. Breast cancer screening with mammography is provided for all women in Korea age 40 years or older, providing the researchers with a vast database for analysis.
During an average follow-up of more than 10 years, more than 58,000 women developed breast cancer. Of the women who developed breast cancer, 10,729, or 18.4%, had benign breast disease.
“While these benign breast diseases are not cancerous or life-threatening, our results, together with evidence from previous findings, show that they might increase the risk of breast cancer,” said study senior author Boyoung Park, M.D., Ph.D., from the Department of Preventive Medicine at Hanyang University College of Medicine in Seoul, Korea.

Adenosine triphosphate (ATP) secreted from sensory neuron-interneuron crosstalk is key to the spreading of inflammation across joints, acting as a neurotransmitter and inflammation enhancer.
Rheumatoid arthritis is a chronic inflammatory autoimmune disorder that primarily affects joints. One of the key features of this disease is remote inflammation, where inflammation spreads from one joint to another. Research has shown that neural circuits or cells migrated from the joints are involved in inflammation spread, but the detailed mechanism by which this occurs has not been elucidated.
A team of researchers from Japan and the USA, led by Professor Masaaki Murakami at Hokkaido University, have revealed that remote inflammation spreads by neuron crosstalk, and that adenosine triphosphate (ATP) plays a key role in this process. Their findings, published in the Journal of Experimental Medicine, may lead to new therapies and treatments for inflammatory diseases.
Inflammation is a part of the natural immune response that occurs in response to infection or irritation. It is a process by which the immune system, involving immune cells, blood vessels, and molecular mediators, attempts to clear out the pathogens and damaged cells and thereafter repair the damage. However, excessive inflammation is a disorder in itself, and is seen in diseases such as hay fever, atherosclerosis, psoriasis, and rheumatoid arthritis, among others.
In this study, the authors used previous observations of the gateway reflex — an immune response mechanism whereby specific neural signals change the state of specific blood vessels to allow immune cells to enter tissue, leading to local inflammation — to hypothesize that neural crosstalk could be responsible for remote inflammation.
They tested this hypothesis through experiments in rheumatoid arthritis models in mice. The mice were divided into control and test groups. In the test groups, the sensory neural circuits between the left and right ankle joints were interrupted. Arthritis of the left ankle was then induced in both sets of mice and the spread of arthritis to the right ankle was observed.
Their results showed that the inflammation signal in one joint is transmitted to the other via a sensory neuron connection through the spinal cord, leading to inflammation in both joints. Specifically, inflammation in one joint led to an increase of ATP in both joints, which triggered an increase of a signal molecule that resulted in inflammation. Blocking this pathway prevented the spread of inflammation.
As this study was performed in mice models, it is necessary to determine if the findings apply to rheumatoid arthritis and other chronic inflammatory diseases in humans. If so, it could provide a therapeutic target for various diseases with spreading inflammation.
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Materials provided by Hokkaido University. Note: Content may be edited for style and length.