Researchers have succeeded in identifying the proteins in the coronavirus that can damage blood vessels

Nearly two years since becoming a global pandemic that has killed millions of people, the mystery of which proteins in the SARS-CoV-2 virus are responsible for severe vascular damage that could even lead to heart attack or stroke has not yet been solved. Now, for the first time, a team of experts led by Tel Aviv University has been able to identify 5 of the 29 proteins that make up the virus that are responsible for damaging blood vessels. The researchers hope that the identification of these proteins will help develop targeted drugs for COVID-19 that reduce vascular damage.
The study was led by Dr. Ben Maoz of the Department of Biomedical Engineering and Sagol School of Neuroscience, Prof. Uri Ashery of the Wise Faculty of Life Sciences and Sagol School of Neuroscience, and Prof. Roded Sharan of the Blavatnik School of Computer Science — all Tel Aviv University researchers. Also participating in the study were Dr. Rossana Rauti, Dr. Yael Bardoogo, and doctoral student Meishar Shahoah of Tel Aviv University and Prof. Yaakov Nahmias of the Institute of Life Sciences at the Hebrew University. The results of the new study were published in the journal eLife.
“We see a very high incidence of vascular disease and blood clotting, for example stroke and heart attack, among COVID patients,” says Dr. Ben Maoz. “We tend to think of COVID as primarily a respiratory disease, but the truth is that coronavirus patients are up to three times more likely to have a stroke or heart attack. All the evidence shows that the virus severely damages the blood vessels or the endothelial cells that line the blood vessels. However, to this day the virus has been treated as one entity. We wanted to find out which proteins in the virus are responsible for this type of damage.”
The novel coronavirus is a relatively simple virus — it comprises a total of 29 different proteins (compared to the tens of thousands of proteins produced by the human body). The Tel Aviv University researchers used the RNA of each of the COVID-19 proteins and examined the reaction that occurred when the various RNA sequences were inserted into human blood vessel cells in the lab; they were thereby able to identify five coronavirus proteins that damage the blood vessels.
“When the coronavirus enters the body, it begins to produce 29 proteins, a new virus is formed, that virus produces 29 new proteins, and so on,” explains Dr. Maoz. “In this process, our blood vessels turn from opaque tubes into kind of permeable nets or pieces of cloth, and in parallel there is an increase in blood clotting. We thoroughly examined the effect of each of the 29 proteins expressed by the virus, and were successful in identifying the five specific proteins that cause the greatest damage to endothelial cells and hence to vascular stability and function. In addition, we used a computational model developed by Prof. Sharan which allowed us to assess and identify which coronavirus proteins have the greatest effect on other tissues, without having seen them ‘in action’ in the lab.”
According to Dr. Maoz, the identification of these proteins may have significant consequences in the fight against the virus. “Our research could help find targets for a drug that will be used to stop the virus’s activity, or at least minimize damage to blood vessels.”
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Insomnia may be a risk factor for highly fatal brain aneurysm rupture

Insomnia may be a potential risk factor for a brain bleed from a ruptured aneurysm along with more well known risk factors of smoking and high blood pressure, according to new research published today in the Journal of the American Heart Association, an open access journal of the American Heart Association.
More than 3% of adults worldwide have unruptured blood vessel malformations in the brain called intracranial aneurysms, the majority of which will never rupture. About 2.5% of intracranial aneurysms will rupture, resulting in a subarachnoid hemorrhage (SAH), also called a brain bleed. SAH is a type of stroke that occurs when a blood vessel on the surface of the brain ruptures and bleeds into the space between the brain and the skull.
“Ruptured aneurysms are highly fatal. It is, therefore, extremely important to identify modifiable risk factors that can help prevent aneurysms from rupturing,” said study author Susanna C. Larsson, Ph.D., associate professor in the unit of cardiovascular and nutritional epidemiology at the Karolinska Institutet in Stockholm, Sweden, and the unit of medical epidemiology at Uppsala University in Uppsala, Sweden.
The researchers sought to determine whether various factors were associated with intracranial aneurysm and/or the aneurysm rupturing. They studied established risk factors such as smoking and high blood pressure and also assessed the link between aneurysms and coffee consumption, sleep, physical activity, body mass index (BMI), blood glucose levels, type 2 diabetes, blood pressure, cholesterol, chronic inflammation and kidney function.
Data from several genome-wide association studies were used to gauge genetic associations to lifestyle and cardiometabolic risk factors. Genetic information from a meta-analysis conducted by the International Stroke Genetics Consortium was used to identify nearly 6,300 cases of intracranial aneurysm and nearly 4,200 cases of aneurysmal subarachnoid hemorrhage. Cases of intracranial aneurysm and subarachnoid hemorrhage were compared to over 59,500 controls to determine genetic predisposition for aneurysms. According to the analysis: A genetic predisposition for insomnia was associated with a 24% increased risk for intracranial aneurysm and aneurysmal subarachnoid hemorrhage. The risk for intracranial aneurysm was about three times higher for smokers vs. non-smokers. The risk for intracranial aneurysm was almost three times higher for each 10 mm Hg increase in diastolic blood pressure (the bottom number in a blood pressure reading). High triglyceride levels and high BMI did not demonstrate an increased risk for intracranial aneurysm and aneurysmal subarachnoid hemorrhage.”The association between insomnia and intracranial aneurysm has not been reported previously, and these findings warrant confirmation in future studies,” Larsson said. “Our research supports the thinking that risk factors that people can change or manage may impact brain aneurysms and hemorrhage risk. Once confirmed, future studies should examine ways to incorporate this knowledge into prevention programs and therapies.”
According to a 2016 American Heart Association scientific statement, Sleep Duration and Quality: Impact on Lifestyle Behaviors and Cardiometabolic Health, insufficient and poor-quality sleep and sleep disorders are linked to a higher risk of high blood pressure. The statement summary notes that treating people with sleep disorders may provide clinical benefits, particularly for blood pressure.
Study limitations included that there was not enough information to adequately analyze some of the risk factors. In addition, the analysis included only people of European ancestry; therefore, the findings may not be generalizable to people from diverse racial and ethnic groups.
Co-authors are Ville Karhunen, Ph.D.; Mark K. Bakker, M.Sc.; Ynte M. Ruigrok, Ph.D.; and Dipender Gill, Ph.D.
The study was funded by the Swedish Research Council for Health, Working Life and Welfare funded the study.
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Harnessing Thor’s Hammer: How forensic science is unlocking the mysteries of fatal lightning strikes

As the world gathers for COP26 in Glasgow, scientists have found the smoking gun in forensic lightning pathology that will help develop life-saving knowledge to address the lethal effects of the increasing number and severity of thunderstorms and lightning strikes due to global climate change.
New research by scientists from South Africa and the UK could help forensic teams understand whether people or animals were the victims of fatal lightning strikes, based solely upon an analysis of their skeletons. Their study is published in the journal Forensic Science International: Synergy, and titled Harnessing Thor’s Hammer: Experimentally induced lightning trauma to human bone by high impulse current
Climate change is increasing and there is evidence to suggest the incidence and severity of thunderstorms and lightning strikes could increase. Sadly, fatal strikes are common on wild animals, livestock, and people — with African countries having some of the highest fatality rates in the world.
In South Africa, more than 250 people are killed annually by lightning, whereas 24, 000 people worldwide die each year. When a lightning death is suspected, the forensic pathologist determines cause of death by looking for signs of lightning-trauma to skin and organs of the deceased. However, when the body is skeletonised, soft tissues are absent and cause of death by lightning cannot be attributed.
This new research provides a tool to investigate cause of death when skeletonised remains are recovered as part of accident or death investigation.
According to Dr Nicholas Bacci, Lecturer in the School of Anatomical Sciences at Wits University and lead author of the paper, “identifying a fatality caused by lightning strike is usually done though marks left on the skin, or damage to the internal organs — and these tissues don’t survive when bodies decompose. Our work is the first research that identifies unique markers of lightning damage deep within the human skeleton and allows us to recognise lightning when only dry bone survives. This may allow us to recognise accidental death versus homicide in cases where cause is not apparent, whilst at the same time allowing us to build a more complete picture of the true incidence of lightning fatalities.”
The research was undertaken as collaboration between specialists in forensic anthropology, anatomy, lightning physics, and micro-computed tomography (micro-CT) from the University of the Witwatersrand (Wits University) in South Africa, Northumbria University in the UK, and the Nuclear Energy Corporation of South Africa (NECSA).

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Test determines antibiotic resistance in less than 90 minutes

A technique that measures the metabolic activity of bacteria with an electric probe can identify antibiotic resistance in less than 90 minutes, a dramatic improvement from the one to two days required by current techniques.
This discovery means that doctors could quickly know which antibiotics will or won’t work for a patient’s life-threatening infection, a quandary that doctors face on a daily basis in hospitals around the world. A Washington State University research team reports on their work in the journal, Biosensors and Bioelectronics.
“The idea here is to give the doctors results much more quickly so that they can make clinically appropriate decisions within that timeframe that they’re working, rather than having to wait,” said Douglas Call, Regents Professor in the Paul G. Allen School for Global Health and a co-author of the paper. “Instead of looking for growth of a culture, we look for metabolism, and that is basically what we’re detecting by the movement of these electrons so it can happen in much shorter time spans compared to a conventional culture-based assay.”
The prevalence of antibiotic resistance is increasing around the world and threatens the ability to treat many common infectious diseases. For example, millions of people in the U.S. are infected annually with drug-resistant pathogens, and thousands of people die from pneumonia or bloodstream infections that become impossible to treat.
To determine definitively whether a particular infection is resistant to antibiotics requires separating and then growing the bacteria in a lab and watching the population grow in a process that can take up to two days or more. Doctors who are faced with a sick patient often have to prescribe an antibiotic immediately without having complete information on how well it will work.
In their paper, the WSU team used a probe to directly measure the electrochemical signal of the bacteria, thereby measuring their metabolism and respiration and learning how they are faring long before they would be visible in culture. Looking at eight different strains of bacteria, the researchers were able to use the bacteria’s electric signal to determine in less than 90 minutes which were susceptible or resistant to the antibiotics.

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Lithium imaging method could shine new light on bipolar disorder, treatment

Since 1949, lithium has been a mainstay for treating bipolar disorder (BD), a mental health condition marked by extreme mood swings. But scientists still don’t have a clear understanding of how the drug works, or why some patients respond better than others. Now, researchers reporting in ACS Central Science developed a method for imaging lithium in living cells, allowing them to discover that neurons from BD patients accumulate higher levels of lithium than healthy controls.
According to the National Institutes of Health, 4.4% of U.S. adults experience BD at some time in their lives. Studies have shown that lithium-based drugs can help stabilize mood and reduce suicide risk in people with BD. However, only about one-third of BD patients respond completely to lithium treatment, and the rest respond only partially or not at all. One reason could be that the drug has an extremely narrow therapeutic range: Below a certain blood serum level of lithium, most patients do not respond, but at a slightly higher level, they can experience severe side effects. Being able to measure lithium concentrations directly in a patient’s neurons could help scientists understand how lithium works as a drug, and then they could use this knowledge to optimize the dosage. So Yi Lu and colleagues wanted to develop a method to detect and measure lithium in living cells at therapeutically relevant concentrations.
The researchers used in vitro selection to identify a DNA enzyme (DNAzyme) that catalyzes the release of a fluorescent molecule from an RNA probe, thus producing a signal, only when lithium is present. The DNAzyme was 100 times more selective for lithium over other metal ions, such as sodium and potassium, that are present at much higher concentrations in human cells, and it was sensitive enough to detect lithium at concentrations within the therapeutic range. As a proof of concept, the researchers collected skin cells from BD patients and healthy donors, reprogrammed them to stem cells and then differentiated them into neurons. The team treated the neurons with the DNAzyme-based sensor and a therapeutically relevant dosage of lithium. Using fluorescence microscopy, the researchers found that immature neurons from BD patients and healthy controls accumulated similar levels of lithium, but mature neurons from BD patients accumulated higher levels of lithium than mature control neurons. The new lithium sensor is a powerful tool to better understand the effects of lithium in treating BD, the researchers say.
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Three ways to reduce the carbon footprint of food purchased by US households

Most consumers want to make food purchases that are smart for their wallets, their health and the environment. And while switching to a vegetarian or vegan diet can lower one’s impact on greenhouse gas emissions, it may not be realistic or healthful for everyone. Now, researchers in ACS’ Environmental Science & Technology report three ways that Americans can reduce the carbon footprint of their food purchases, without requiring drastic dietary changes.
Getting food from farms to people’s plates contributes a sizeable portion of the global greenhouse gas emissions. And animals are inefficient at converting the plants they eat into energy, so meat and dairy products result in higher emissions than fruit, vegetables and grains. Based on that knowledge, previous researchers have provided suggestions for changes that individuals or households can make to reduce the emissions generated by food production. However, most of these recommendations have been based on an “average American diet.” In reality, not everyone eats the same types or quantities of foods, so to account for this diversity, Hua Cai and colleagues wanted to assess the actual groceries purchased by U.S. households and identify the hotspots of carbon emissions in these purchases.
The researchers analyzed detailed grocery purchase records of over 57,000 U.S. households in 2010, and for each home, summed the greenhouse gas emissions for growing and harvesting the food items. Data for packaging and transportation were not included because that information was unavailable. Then, they compared the emissions calculation to that which would be generated from buying foods for a benchmark healthy and sustainable diet.
The team’s analysis revealed that 71% of homes surveyed could decrease their food carbon footprint, identifying three main ways for consumers to do so. The suggestions are: Small households of one or two people should buy less food in bulk quantities, which is often more than will be eaten, and manufacturers should offer cost-effective package sizes. Cutting out foods with high caloric content and low nutritional values would result in a 29% reduction of the total potential emissions, while also potentially improving health outcomes. People should buy less savory bakery products and ready-made foods. Though those foods are responsible for relatively low carbon emissions, the large amounts of these items that are purchased adds up to significant emissions.In summary, the researchers say these strategies are initial ways people can reduce their at-home food-based carbon footprint.
The authors acknowledge funding from Purdue University Environmental and Ecological Engineering for providing the Bilsland Dissertation Fellowship.
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Does physical activity impact risk of knee osteoarthritis?

In an analysis published in Arthritis & Rheumatology, investigators did not find any link between the amount and duration of physical activity with individuals’ risk of developing knee osteoarthritis.
The analysis included six global community-based studies including a total of 5,065 participants with and without knee osteoarthritis who were followed for five to 12 years.
“Knowing that the amount of physical activity and time spent doing it is not associated with the development of knee osteoarthritis is important evidence for both clinicians and the public who may need to consider this when prescribing physical activity for health,” said co-lead author Thomas Perry, BSc, PhD, of the University of Oxford, in the UK.
Next, it will be important to understand the role of injury and specific types of activity within this association, noted co-lead author Lucy S. Gates, PhD, of the University of Southampton, and co-senior author Maria Sanchez-Santos, of the University of Oxford.
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Inflammatory cytokine levels may predict outcomes in orthopedic trauma patients

Inflammatory cytokines are molecules that are secreted by immune cells to promote inflammation. A study published in the Journal of Orthopaedic Research found that measuring inflammatory cytokines may help predict patient outcomes after traumatic injury, which is the leading cause of mortality in individuals under 50 years of age.
In the study of 58 patients with an average age of 40 years who experienced severe bone, joint, and muscle trauma, six patients (10%) suffered pulmonary complications and five (9%) had acute kidney injury.
Adding the cytokine interleukin-6 to predictive models of patient outcomes (such as what’s called the New Injury Severity Score, or NISS) significantly improved predictions of pulmonary complications, the need for intensive care, and the length of hospital stay. Adding the cytokine interleukin-8 significantly improved predictions of acute kidney injury.
“This is the first time we have combined parameters of external anatomic injury (NISS) with parameters of the internal physiologic response to injury (cytokines) to determine trauma patient outcomes,” said lead author Arun Aneja, MD, PhD, of the University of Kentucky.
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Van-Tam on Covid: 'There are some hard months to come in the winter”

Professor Jonathan Van-Tam has said that too many people think the pandemic is over, and that there are “hard months to come in the winter.”He added that the use of face coverings, and the caution people take while interacting with each other will decide how the UK copes with the virus during winter, along with the take up of vaccines and booster shots.Mr Van-Tam was replying to a question from Rachel Burden raising viewers concerns about low levels of mask wearing on public transport, during a live Q&A hosted by BBC Breakfast and Radio 5 Live.

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Cardio Before Weight Lifting May Help Boost Muscle

Twenty minutes of cycling may prime muscles in the arms to grow more while lifting.Riding or running before you lift weights could amplify the effects of the lifting, according to a helpful new study of the molecular impacts of combining endurance and resistance exercise in a single workout. The study, which involved eight physically active men, found that 20 minutes of intense cycling right before an upper-body weight routine alters the inner workings of muscles, priming them to change and grow more than with lifting alone. The new paper, published in Scientific Reports, offers practical guidance about how you might structure a gym workout for maximal benefit. It is also a bracing reminder of how potent and wide-ranging the effects of exercise may be.For decades, trainers and scientists have debated whether and how to mix cardio and resistance exercise. Some small studies suggest combining the two might up the likely gains from each, especially the resistance training. (Almost all of these experiments have been conducted in men.) But other research indicates sweaty aerobic workouts beforehand could reduce strength improvements from lifting. The authors of some of these studies speculate that molecular changes within muscles, caused by riding or running, wind up hindering some of the other desirable outcomes from lifting, an effect called exercise interference. Muscle fatigue might also play a role since, in most studies that pair cardio and resistance, volunteers exercise only their lower bodies, using their legs both for the endurance and strength training. Tired from the endurance work, the thinking goes, their leg muscles could have become unable to respond ideally to resistance training.But what if the two types of exercise targeted completely separate groups of muscles, such as legs during the cycling and arms during the weight routine? That was the scenario posed by Marcus Moberg, a professor at the Swedish School of Sport and Health Sciences in Stockholm, who studies muscle health, exercise and metabolism. In that case, would the lower-body endurance exercise augment the benefits of the upper-body weight training? Or would exerting your legs and lungs have zero — or even an unwelcome, counterproductive — impact on the muscles in your arms?To learn more, he and his collaborators recruited eight active adult men in Stockholm and invited them to the lab for measures of their current aerobic fitness and strength. Then, after the men had familiarized themselves with the lab’s workout equipment, the researchers asked them, on a separate visit, to complete a two-part workout.The men began with intense interval cycling. During this endurance exercise, the men pedaled hard for four minutes, rested for three and repeated that sequence five times. After a few minutes of rest, they next moved on to upper-body weight machines that strenuously worked their arm and shoulder muscles.During a different lab visit, the men completed the same weight routine, but with no cycling first.The researchers drew blood and took tiny tissue samples from the men’s triceps muscles before, immediately after, 90 minutes later and then three hours after each workout. (The primary reason women were not included in the study, Dr. Moberg said, was that women’s less-developed triceps muscles make such repeated biopsies difficult and possibly injurious.)Finally, the scientists microscopically examined the men’s blood and muscle samples, looking for substances that indicated how their muscles were responding to the workouts, with special emphasis on proteins and markers of gene activity believed to influence endurance and muscle mass.They found them. After their solo weight training session, the men’s muscles teemed with proteins and genetic markers known to help initiate muscle growth. Those same substances also abounded after the workout that included cycling but were joined by other proteins and gene activity associated with improved endurance.In effect, after the dual workout, the men’s muscles seemed primed to increase in both size and stamina, with no evidence that cycling had interfered, at a molecular level, with lifting. Instead, the aerobic exercise appeared to have broadened and intensified the expected benefits from weight training.“The most fascinating finding is that some biochemical factors evoked by the leg endurance exercise entered the bloodstream and were then able to influence processes in a completely different group of muscles, and in a way that seems to be beneficial for the training adaptations in the arms,” Dr. Moberg said. “It is almost like the endurance exercise performed by the legs was being transferred to some degree to the arms.” He pointed out, too, that the men lifted the same amount of weight during both arm workouts. Hard pedaling with their legs had not tired their arms.“The paper is great,” said Dr. Michael Joyner, a physiologist and anesthesiologist at the Mayo Clinic in Rochester, Minn, who was not involved in the study. Its finding, he added, that “legs might have primed greater activation of key molecular pathways in the arms is a real piece of brain candy.”Of course, this study, like so many similar experiments, involved only men. “But there is no good rationale for believing the effects would be any different in women,” Dr. Moberg said, adding he and his colleagues hope to include women in upcoming experiments with fewer biopsies. This study also was short term and looked at endurance exercise preceding weight training, and not the reverse. Some past experiments suggest lifting first has little impact, for better or worse, on aerobic exercise afterward. But those studies focused on legs, so it remains to be seen if working your arms before cardio can be as worthwhile as the other way around. But over all, the upshot of the findings, Dr. Moberg said, is that starting a workout by exercising your legs and lungs before moving to upper body lifting makes practical and physiological sense. “It can be a time-effective and potentially beneficial approach,” he said.

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