Cohort study indicates that selenium may be protective against advanced prostate cancer
by American Association for Cancer Research

A greater level of toenail selenium was associated with a significant decrease in the risk for advanced prostate cancer, according to data presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

"This could mean, based on our data and based on data from other studies, that selenium is a modifiable risk factor of advanced, clinically relevant prostate cancer," said Milan S. Geybels, M.Sc., a doctoral candidate in cancer epidemiology at Maastricht University, in Maastricht, the Netherlands.

The Netherlands Cohort Study on diet and cancer is a prospective cohort study that includes 58,279 men who were aged 55 to 69 years at entry in September 1986. Geybels and colleagues analyzed data from 898 men who were diagnosed with advanced prostate cancer during 17.3 years of follow-up of the cohort.

According to Geybels, previous studies investigating the association between selenium levels and prostate cancer have yielded varying results. One large clinical trial showed that selenium supplementation had no protective effect, while several prospective, observational studies indicated that higher levels of selenium were associated with a reduced prostate cancer risk, especially for advanced prostate cancer.

"Our study is interesting because we specifically investigated men with advanced prostate cancer, a type of prostate cancer associated with a poorer prognosis," Geybels said. "Also, while most of the prior research, including the large clinical trial, involved men with moderate-to-high selenium levels, men in The Netherlands Cohort Study have selenium levels that range from low to moderate. This is important because low selenium is expected to be related to a higher disease risk."

He and his colleagues chose toenail selenium as the study biomarker because it reflects long-term exposure, as opposed to blood, which is best for monitoring recent selenium exposures.

The data revealed that greater levels of toenail selenium were associated with a substantially reduced risk for advanced prostate cancer. Men with the highest toenail selenium levels had a more than 60 percent lower risk for advanced prostate cancer compared with men with the lowest toenail selenium levels.

"Our findings need to be replicated in further prospective studies, with an extended follow-up for the assessment of incident advanced prostate cancer, and with a wide range of toenail selenium that includes low selenium levels," Geybels said. "If our results can be confirmed, a prevention trial of selenium and prostate cancer in a low-selenium population may be justified."

Taking additional selenium will not reduce cancer risk
by Wiley

Although some people believe that taking selenium can reduce a person's risk of cancer, a Cochrane Systematic Review of randomised controlled clinical trials found no protective effect against non-melanoma skin cancer or prostate cancer. In addition, there is some indication that taking selenium over a long period of time could have toxic effects.

These conclusions were reached after researchers scanned the medical literature, looking for trials that studied the effects of taking selenium supplements and observational studies on selenium intake. The researchers located 49 prospective observational studies and six randomised controlled trials.

Looking at the data from observational studies gave some indication that people may be marginally protected from cancer if they had a higher selenium intake than those with a lower intake, and that the effect was slightly greater for men than women. "These conclusions have limitations because the data came from a wide variety of trials, and so it is difficult to summarise their findings," says lead researcher Dr Gabriele Dennert of the Institute for Transdisciplinary Health Research, Berlin, Germany, who coordinated the work of the international team of experts.

When the team of researchers looked at the more carefully conducted randomised controlled trials, any sign of benefit disappeared. "In fact, the results of the Nutritional Prevention of Cancer Trial and the Selenium and Vitamin E Cancer Prevention Trial raised concerns about possible harmful effects from long-term use of selenium supplements," says Dennert.

The researchers believe that there is a need for more research looking at selenium's effect on liver cancer and think that it would be worth investigating the possible gender differences that appear to be present in the uncontrolled studies.

"However, we could find no evidence to recommend regular intake of selenium supplements for cancer prevention in people whether or not they already have enough selenium," says Dennert.

Does selenium prevent cancer? It may depend on which form people take
by American Chemical Society

Scientists are reporting that the controversy surrounding whether selenium can fight cancer in humans might come down to which form of the essential micronutrient people take. It turns out that not all "seleniums" are the same — the researchers found that one type of selenium supplement may produce a possible cancer-preventing substance more efficiently than another form of selenium in human cancer cells. Their study appears in the ACS' journal Biochemistry.

Hugh Harris and colleagues note that although the Nutritional Prevention of Cancer clinical trial showed that selenium reduced the risk of cancer, a later study called the Selenium and Vitamin E Cancer Prevention Trial did not show a benefit. A major difference between the trials was the form of selenium that was used. To find out whether different types of selenium have different chemopreventive properties, the researchers studied how two forms—SeMet and MeSeCys—are processed in human lung cancer cells.

The researchers found that MeSeCys killed more lung cancer cells than SeMet did. Also, lung cancer cells treated with MeSeCys processed the selenium differently than than cells treated with SeMet. They say that these findings could explain why studies on the health benefits of selenium sometimes have conflicting results.

Selenium may prevent high risk-bladder cancer

A study published in the December issue of Cancer Prevention Research, a journal of the American Association for Cancer Research, suggests that selenium, a trace mineral found in grains, nuts and meats, may aid in the prevention of high-risk bladder cancer.

Researchers from Dartmouth Medical School compared selenium levels in 767 individuals newly diagnosed with bladder cancer to the levels of 1,108 individuals from the general population. Findings showed an inverse association between selenium and bladder cancer among women, some smokers and those with p53 positive bladder cancer.

In the entire study population, there was no inverse association between selenium and bladder cancer, but women (34 percent), moderate smokers (39 percent) and those with p53 positive cancer (43 percent) had significant reductions in bladder cancer with higher rates of selenium.

"There are different pathways by which bladder cancer evolves and it is thought that one of the major pathways involves alterations in the p53 gene," said corresponding author Margaret Karagas, Ph.D., professor of community and family medicine of the Norris Cotton Cancer Center at Dartmouth. "Bladder cancers stemming from these alternations are associated with more advanced disease."

While other studies have shown a similar association between selenium and bladder cancer among women, this study is one of the first to show an association between selenium and p53 positive bladder cancer.

"Ultimately, if it is true that selenium can prevent a certain subset of individuals, like women, from developing bladder cancer, or prevent certain types of tumors, such as those evolving through the p53 pathway, from developing, it gives us clues about how the tumors could be prevented in the future and potentially lead to chemopreventive efforts," Karagas said.

Karagas hopes to replicate these findings on a larger scale in order to examine the connection between selenium and bladder cancer in women and those with p53 tumors, as well as with patient prognosis.

Selenium supplements could be harmful to people who already have enough selenium in their diet: study
by Lancet

Although additional selenium might benefit people who are lacking in this essential micronutrient, for those who already have enough selenium in their diet (including a large proportion of the USA population), taking selenium supplements could be harmful, and might increase the risk of developing type-2 diabetes, concludes a new review of the evidence published Online First in The Lancet.

"The intake of selenium varies hugely worldwide. Intakes are high in Venezuela, Canada, the USA, and Japan, but lower in Europe. Selenium-containing supplements add to these intakes, especially in the USA where 50% of the population takes dietary supplements", explains Margaret Rayman from the University of Surrey, Guilford, UK, author of the study.

Selenium is a natural occurring trace mineral found in soil and foods and is essential in small amounts for good health. Low selenium intake or status (levels in the blood) has been linked with an increased risk of death, poor immune function, and cognitive decline. Higher selenium intake or status has been shown to enhance male fertility, have antiviral effects, and provide some protection against cancers of the prostate, lung, colorectal system, and bladder.

But the evidence also suggests that selenium has a narrow therapeutic range and at high levels might have harmful effects such as increasing the risk of type-2 diabetes.

Over the last 10 years, the use of selenium supplements has become widespread, largely due to the belief that selenium can reduce the risk of cancer and other diseases. Selenium supplements have been marketed for a multitude of conditions largely based on the results of observational studies. However, findings from clinical trials to confirm their efficacy have been mixed.

The Review reveals that studies in different populations with different selenium status and genetic background have produced divergent results.

According to Rayman, these conflicting results can be explained by the fact that supplementation with selenium, as for many nutrients, is only beneficial when intake is inadequate.

She notes that the greatest benefit from selenium supplementation is likely to be in people with low blood selenium levels. However, to date, the largest trials have been done in countries where selenium status is good (like the USA), and more trials are needed in populations with low selenium status.

The Review also suggests that the interaction between selenium intake or status and genetic background could be important—people could be more or less genetically receptive to the benefits of selenium-containing proteins (selenoproteins) in the body or to selenium supplements: "Since polymorphisms in selenoproteins affect both selenium status and disease risk or prognosis, future studies must genotype participants."

Rayman concludes: "The crucial factor that needs to be emphasised is that people whose blood plasma selenium is already 122 µg/L or higher—a large proportion of the US population (the average level in American men is 134 µg/L)—should not take selenium supplements. However, there are various health benefits, and no extra risk, for people of lower selenium status (plasma level less than 122 µg/L), who could benefit from raising their status to 130-150 µg/L—a level associated with low mortality."*

Supplements are not nutritious
Selenium supplementation, for example in mineral tablets, might not be that beneficial for the majority of people according to researchers writing in the open access journal Genome Biology. Although this trace element is essential in the diet of humans, it seems that we have lost some of the need for selenium, which occurs in proteins and is transported in blood plasma, when our evolutionary ancestors left the oceans and evolved into mammals.

The research team including Alexey Lobanov and Vadim Gladyshev of the University of Nebraska-Lincoln and Dolph Hatfield of the National Institutes of Health conducted the genetic analysis. “Several trace elements are essential micronutrients for humans and animals but why some organisms use certain ones to a greater extent than others is not understood” comments Gladyshev. “We’ve found that the evolutionary change from fish to mammals was accompanied by a reduced use of proteins containing selenium.”

Selenium-containing proteins evolved in prehistoric times. Several human disorders have been associated with a deficiency in the trace element, among them are Keshan disease, a heart disorder affecting primarily children in certain provinces of China where the soil is deficient in selenium, and Myxedermatous Endemic Cretinism, a rare form of mongolism attributed to deficiencies in selenium and iodine found in certain areas of Africa. Selenium supplementation was thought to be necessary to prevent these and other diseases even in the areas with adequate selenium supply.

The evolved reduced reliance on selenium invites questions regarding the widely accepted use of supplements incorporating this trace element to maximize amounts of proteins that rely on it. Supplements are taken without knowing which groups of the population can benefit.

Interestingly, only 20% of lower organisms use selenium-based proteins, and, for example, fungi and vascular plants do not. Some insects have also lost the need for selenium during the course of evolution. Aquatic environments seem to favor an increased reliance on selenium because of environmental factors. Selenoprotein-rich Sea urchins, for instance, feed on algae, which themselves contain a lot of selenium.

Gladyshev concludes: “The evolved reduced utilization of selenium-containing proteins in mammals raises important questions in human and animal nutrition. Selenoprotein expression is regulated such that people don’t need to rely so heavily on dietary selenium which is often present in excess amounts in the diet. Individuals should consider their age, sex and medical needs before taking such supplements on a regular basis.”

Source: BioMed Central

What makes cobalt essential to life?
by John Hewitt , Phys.org

Credit: Wikipedia
Cobalt sits in the center of the corrin ring of vitamin B12 and the important cobalamins we derive from it. Perhaps surprisingly, only two of our enzymes bother to use these painfully constructed and meticulously channeled cofactors. Why do our cells go to such great lengths to get a little bit of the cobalt magic, and what catalytic properties might make it so special?

Other uncommon essential metals, like molybdenum, selenium and iodine, are similarly used only sparingly in cells, and yet we retain the ability to completely synthesize all the useful derivatives for these elements. To tame molybdenum, we construct an elaborate molybdopterin cofactor, while to harness iodine, we assemble thyroxine. To incorporate selenium into the few selenoproteins that require it, the elaborate SECIS machinery shuffles the mRNA code to attract a unique tRNA, upon which its cysteine cargo is transformed into selenocysteine. In each of these cases, researchers understand the special properties of the metals involved that make them indispensable.

For example, compared to sulfur, selenium is a better nucleophile that will react with reactive oxygen species faster, but its lack of π-bond character means that it can also be more readily reduced. Selenoproteins like GPX4 (glutathione peroxidase) are correspondingly more resistant to both overoxidation and irreversible inactivation. Similarly, the ineluctable requirement for molybdenum, a two-electron redox compound that can shuttle between the +4/+5 and the +5/+6 redox couples, reflects several not-so-common skills. It can perform diverse and energetically challenging redox reactions; it can act as an electron sink or source at low redox potential; and (along with the much rarer tungsten) can effectively transfer oxygen and sulfur atoms during reactions taking place at low potential.

A noteworthy attempt to divine the essential cobalt character was advanced in a recent commentary in PNAS by geochemist extraordinaire Michael Russell. Poised between Fe and Ni in the periodic table, Russell notes that "the element is particularly 'energy-dense' with paired electrons in the outer orbit. Its occurrence as a metal alloy in serpentinites with a variable valence extending from Co+ through to Co4+, its various spin states, and its contrasting conformations render it unique, with untold contributions to be made to electronics, catalysis and the emergence of life. Indeed, Co–Fe cooperation has just been investigated at the opposite end of the redox spectrum—the electrocatalysis of the O2 evolution reaction. Substitutions of Co are either unfeasible, as in metabolism and in some double-atom catalysis, or they lie in the somewhat remote future."

Russell's comments are in response to an earlier article by He et. al. who demonstrated that hydrothermal reduction of bicarbonate into long-chain hydrocarbons (≤24 carbons) is possible through the use of iron and cobalt metals. These findings potentially explain both the abiogenic origin of petroleum, and key events in life's emergence. Since remnants of the porphyrins and corrins that are critical to life can be found amidst petroleum deposits, a critical question becomes: Did life invent these molecules, or did they first use abiotic facsimiles of these molecules and only later evolve the concomitant ability to synthesize them for themselves?

The response to my question from Russell was that, in his opinion, life likely invented corrin-like coordination by way of a four-amino-acid-peptide glycine-glycine-histidine motif capable of entrapping the cobalt atom. Curiously, porphyrins, which house iron or copper in their centers, and chlorins, which do the same with magnesium, must be contracted into corrins to bind cobalt. This specificity seemingly comes despite the near identical atomic radii (around 125 pm) for the contiguous Fe, Co, Ni, Cu elemental lineup. In Russell's view, cobalt (and other transition metals) required at life's emergence were active in deposits of the mineral green rust, also known as fougerite, at alkaline hydrothermal vents. Cobalt corrinoid joined with iron-sulfur clusters form the heart of primitive acetyl coenzyme-A pathways of the acetogens and the methanogens lying at the bottom of our evolutionary tree. This Co(FeS) protein mediates the attachment or detachment of a methyl group to or from carbon monoxide or another entity involved in the biosynthesis of acetyl-CoA.

The form of vitamin B12 used by our methylmalonyl-CoA mutase enzyme located in mitochondria for fatty acid and amino acid breakdown is known as adenosylcobalamin (AdoCbl). The other cobalamin-utilizing enzyme, methionine synthase, acts in the cytosol and uses a methylcobalamin cofactor wherein the adenosyl group is replaced by a methyl group. Land plants and fungi neither synthesize or require cobalamin as they lack methylmalonyl-CoA mutase, and have different kind of methionine synthase that doesn't require B12. When these enzymes are not working properly, their precursor molecules can presumably build up to high levels, causing problems like demyelinating disease and pernicious anemia.

While cobalt's thermal stability and high energy density make it an ideal component for the cathodes of lithium batteries, its usefulness to life comes from its many other unique properties, some discovered, and some still yet to be found.

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JANUARY 19, 2022

Magnetism at the root of enhanced 'green' catalysis
by MagnetoCat SL

Graphical abstract. Credit: DOI: 10.1021/acscatal.1c03135
The research group at MagnetoCat SL (Alicante, Spain) published a fundamental theoretical work on magnetism in heterogeneous catalysis in ACS Catalysis. The group, composed by Ph.D. student Miss Chiara Biz, Dr. Mauro Fianchini and Dr. Jose Gracia, laid out a complex and comprehensive theoretical treatment linking electronic spin, magnetism and heterogeneous catalysis. This treatment concerns the behavior of correlated electrons in solids and the quantum mechanical "tricks" they implement to avoid each other while balancing repulsions and attractions.

It is known that relativity and quantum mechanics enforce a quantized magnetic moment upon an electron known as spin. When many of these spins cooperate together in complex materials, several combinations and domains are possibly formed. The macroscopic resultant of these domains is trivially called magnetism.

Magnetism affects the catalytic properties of materials, according to the group at MagnetoCat.

However, the footprint of magnetism in heterogeneous catalysis has been somewhat disregarded by chemists for the longest time, so why look into it now?

The answer is simple: Because magnetism may lead to achieve "greener" and more sustainable chemistry in the years to come. The great enhancement brought by magnetism on catalysis paved the way to improved processes for hydrogen production and water splitting. Moreover, abundant magnetic metals, like iron, cobalt and nickel, may serve as an excellent replacement for heavier, rarer and more expensive metals (like platinum or gold) in catalytic structures. Environment and economy, hand in hand.

The group at MagnetoCat already made computational predictions during 2020 on the superior activity of platinum-metal alloys (where metal is iron, cobalt and nickel) compared to pure platinum in hydrogen fuel cells and they are positively sure that the experiments will soon confirm the predictions and pave the way to industrial implementation. The group is now working on the computationally-driven catalytic design of magnetic catalysts within the framework of the SPINCAT project.

Catalyst surface analysed at atomic resolution
by Ruhr-Universitaet-Bochum

Fig. 1: OER activity of Co2FeO4 and CoFe2O4 nanoparticles. a, b Linear sweep voltammetry (LSV) curves recorded at a scan rate of 10 mV/s in 1.0 M KOH on glassy carbon electrodes deposited with Co2FeO4 and CoFe2O4 nanoparticles in the pristine state and after 100, 500 and 1000 cycles of cyclic voltammetry (CV) measurements, c, d CVs of Co2FeO4 and CoFe2O4 after one, 100, 500 and 1000 cycles recorded at a scan rate of 50 mV/s in 1.0 M KOH under OER conditions, e, f Tafel slopes of Co2FeO4 and CoFe2O4 in the pristine and after 100, 500 and 1000 cycles, derived from the LSV curves in a, b. Source data are provided as a Source Data file. The error bars of Tafel slopes in e, f were measured by linear curve fitting. Credit: DOI: 10.1038/s41467-021-27788-2
Researchers from the Ruhr-Universität Bochum, the University of Duisburg-Essen and the Max Planck Institute for Chemical Energy Conversion in Mülheim an der Ruhr cooperated on the project as part of the Collaborative Research Centre "Heterogeneous oxidation catalysis in the liquid phase."

At RUB, a team headed by Weikai Xiang and Professor Tong Li from Atomic-scale Characterisation worked together with the Chair of Electrochemistry and Nanoscale Materials and the Chair of Industrial Chemistry. Institutes in Shanghai, China, and Didcot, UK, were also involved. The team presents their findings in the journal Nature Communications, published online on 10 January 2022.

Particles observed during the catalysis process

The researchers studied two different types of nanoparticles made of cobalt iron oxide that were around ten nanometres. They analyzed the particles during the catalysis of the so-called oxygen evolution reaction. This is a half reaction that occurs during water splitting for hydrogen production: hydrogen can be obtained by splitting water using electrical energy; hydrogen and oxygen are produced in the process. The bottleneck in the development of more efficient production processes is the partial reaction in which oxygen is formed, i.e. the oxygen evolution reaction. This reaction changes the catalyst surface that becomes inactive over time. The structural and compositional changes on the surface play a decisive role in the activity and stability of the electrocatalysts.

For small nanoparticles with a size around ten nanometres, achieving detailed information about what happens on the catalyst surface during the reaction remains a challenge. Using atom probe tomography, the group successfully visualized the distribution of the different types of atoms in the cobalt iron oxide catalysts in three dimensions. By combining it with other methods, they showed how the structure and composition of the surface changed during the catalysis process—and how this change affected the catalytic performance.

"Atom probe tomography has enormous potential to provide atomic insights into the compositional changes on the surface of catalyst nanoparticles during important catalytic reactions such as oxygen evolution reaction for hydrogen production or CO2 reduction," concludes Tong Li.

Smartphone app can vibrate a single drop of blood to determine how well it clots
by University of Washington

Researchers at the University of Washington have developed a new blood-clotting test that uses only a single drop of blood and a smartphone vibration motor and camera. The system includes a plastic attachment that holds a tiny cup of blood beneath the phone's camera (shown here). Note: This photo simulates how this system works, and the "blood" shown here is not real. Credit: Mark Stone/University of Washington
Blood clots form naturally as a way to stop bleeding when someone is injured. But blood clots in patients with medical issues, such as mechanical heart valves or other heart conditions, can lead to a stroke or heart attack. That's why millions of Americans take blood-thinning medications, such as warfarin, that make it harder for their blood to clot.

Warfarin isn't perfect, however, and requires patients to be tested frequently to make sure their blood is in the correct range—blood that clots too easily could still lead to a stroke or a heart attack while blood that doesn't clot can lead to extended bleeding after an injury. To be tested, patients either have to go to a clinic laboratory or use a costly at-home testing system.

Researchers at the University of Washington have developed a new blood-clotting test that uses only a single drop of blood and a smartphone vibration motor and camera. The system includes a plastic attachment that holds a tiny cup beneath the phone's camera.

A person adds a drop of blood to the cup, which contains a small copper particle and a chemical that starts the blood-clotting process. Then the phone's vibration motor shakes the cup while the camera monitors the movement of the particle, which slows down and then stops moving as the clot forms. The researchers showed that this method falls within the accuracy range of the standard instruments of the field.

The team published these findings Feb. 11 in Nature Communications.

"Back in the day, doctors used to manually rock tubes of blood back and forth to monitor how long it took a clot to form. This, however, requires a lot of blood, making it infeasible to use in home settings," said senior author Shyam Gollakota, UW professor in the Paul G. Allen School of Computer Science & Engineering. "The creative leap we make here is that we're showing that by using the vibration motor on a smartphone, our algorithms can do the same thing, except with a single drop of blood. And we get accuracy similar to the best commercially available techniques."

Researchers at the University of Washington have developed a new blood-clotting test that uses only a single drop of blood and a smartphone vibration motor and camera. The system includes a plastic attachment that holds a tiny cup of blood beneath the phone's camera. A person adds blood to the cup, which contains a chemical that starts the blood clotting process and a small copper particle (shown here as the oblong blue shape in the top right of the red circle). Note: This photo simulates how this system works, and the "blood" shown here is not real. Credit: Mark Stone/University of Washington
Doctors can rank blood-clotting ability using two numbers:

the time it takes for the clot to form, what's known as the "prothrombin time" or PT
a ratio calculated from the PT that allows doctors to more easily compare results between different tests or laboratories, called the "international normalized ratio" or INR
"Most people taking this medication are taking it for life. But this is not a set-and-forget type of thing—in the U.S., most people are only in what we call the 'desirable range' of PT/INR levels about 64% of the time," said co-author Dr. Kelly Michaelsen, assistant professor of anesthesiology and pain medicine in the UW School of Medicine. "This number is even lower—only about 40% of the time—in countries such as India or Uganda where there is less frequent testing. How can we make this better? We need to make it easier for people to test more frequently and take ownership of their health care."

Patients who can monitor their PT/INR levels from home would only need to go to see a clinician if the test suggested they were outside of that desirable range, Michaelsen said.

The researchers wanted an inexpensive device that could work similarly to how at-home blood sugar monitors work for people with diabetes: A person can prick their finger and test a drop of blood.

"We started by vibrating a single drop of blood and trying to monitor waves on the surface," said lead author Justin Chan, a UW doctoral student in the Allen School. "But that was really challenging with such a small amount of blood."

The team added a small copper particle because its motion was so much more reliable to track.

"As the blood clots, it forms a network that tightens. And in that process, the particle goes from happily bouncing around to no longer moving," Michaelsen said.

Researchers at the University of Washington have developed a new blood-clotting test that uses only a single drop of blood and a smartphone vibration motor and camera. Shown here are lead author Justin Chan (left, holding the device), a UW doctoral student in the Paul G. Allen School of Computer Science & Engineering, and co-author Dr. Kelly Michaelsen (right), assistant professor of anesthesiology and pain medicine in the UW School of Medicine. Credit: Mark Stone/University of Washington
To calculate PT and INR, the phone collects two time stamps: first when the user inserts the blood and second when the particle stops moving.

"For the first time stamp, we're looking for when the user inserts a capillary tube containing the sample in the frame," Chan said. "For the end of the measurement, we look directly at the interior of the cup so that the only movement within those frames is the copper particle. The particle stops moving abruptly because blood clots very quickly, and you can observe that difference between frames. From there we can calculate the PT, and this can be mapped to INR."

The researchers tested this method on three different types of blood samples. As a proof of concept, the team started with plasma, a component of blood that is transparent and therefore easier to test. The researchers tested plasma from 140 anonymized patients at the University of Washington Medical Center. The team also examined plasma from 79 patients with known blood-clotting issues. For both these conditions, the test had results that were similar to commercially available tests.

To mimic what a patient at home would experience, the team then tested whole blood from 80 anonymized patients at both Harborview and the University of Washington medical centers. This test also yielded results that were in the accuracy range of commercial tests.

This device is still in a proof-of-concept stage. The researchers have publicly released the code and are exploring commercialization opportunities as well as further testing. For example, currently all these tests have been done in the lab. The next step is to work with patients to test this system at home. The researchers also want to see how the system fares in more resource-limited areas and countries.

"Almost every smartphone from the past decade has a vibration motor and a camera. This means that almost everyone who has a phone can use this. All you need is a simple plastic attachment, no additional electronics of any kind," Gollakota said. "This is the best of all worlds—it's basically the holy grail of PT/INR testing. It makes it frugal and accessible to millions of people, even where resources are very limited."

Additional co-authors on this paper are Joanne Estergreen, clinical laboratory supervisor in the UW School of Medicine's laboratory medicine and pathology department, and Dr. Daniel Sabath, professor of laboratory medicine and pathology in the UW School of Medicine.

Study: Nearly 1 in 7 COVID patients in ICU experienced severe bleeding when given full-dose blood thinners
by Marcene Robinson, University at Buffalo

Credit: Wikimedia Commons
Patients with COVID-19 in the intensive care unit (ICU) prescribed full-dose blood thinners are significantly more likely to experience heavy bleeding than patients prescribed a smaller yet equally effective dose, according to a recent University at Buffalo-led study.

The research, which compared the safety and effectiveness of blood clot treatment strategies for more than 150 critically ill COVID-19 patients at two hospitals, found that almost all patients who experienced significant bleeding were mechanically ventilated and receiving full-dose anticoagulants (blood thinners).

The results, published last month in Hospital Pharmacy, may inform treatment guidelines for blood clots in hospitalized COVID-19 patients, who are at an increased risk for both blood clots and severe bleeding. Previous reports have found that 17% of hospitalized COVID-19 patients experience blood clots, says first author Maya Chilbert, PharmD, clinical assistant professor in the UB School of Pharmacy and Pharmaceutical Sciences.

"A wide variety of practice exists when it comes to approaching blood clots in hospitalized patients with COVID-19, and there is little data to suggest improved outcomes using one strategy versus another," says Chilbert. "Caution should be used in mechanically ventilated patients with COVID-19 when selecting a regimen to treat blood clots, and the decision to use full-dose blood thinners should be based on a compelling indication rather than lab markers alone."

Additional investigators in the UB School of Pharmacy and Pharmaceutical Sciences include Collin Clark, PharmD, clinical assistant professor, and Ashley Woodruff, PharmD, clinical associate professor. The research was also conducted by investigators at the Buffalo General Medical Center, Millard Fillmore Suburban Hospital and Erie County Medical Center.

The study analyzed the outcome of blood clot treatments and the rate of bleeding events for more than 150 patients with COVID-19 who received either of two blood thinner regimens: a full-dose based on patient levels of D-dimer (a protein present in the blood after a blood clot dissolves), and the other a smaller but higher-than-standard dosage.

The average patient age was 58, and all experienced elevated levels of D-dimer, fibrinogen (a protein that helps the body form blood clots), and prothrombin time (a test that measures the time it takes for blood plasma to clot).

Nearly 14% of patients who received full-dose blood thinners experienced a significant bleeding event, compared to only 3% of patients who received a higher-than-standard dosage. All patients who experienced bleeding events were mechanically ventilated. No difference was reported in the regimens' effectiveness at treating blood clots.

Further investigation is needed to determine the optimal strategy for treating blood clots and bleeding in hospitalized COVID-19 patients, says Chilbert.

Benefits of high-dose blood thinners in COVID-19 patients remain unclear
by George Washington University

Credit: Unsplash/CC0 Public Domain
While COVID-19 infected patients should be treated with standard anticoagulation therapies, such as blood thinning medication, a new study by researchers at the George Washington University (GW) shows that anticoagulating patients at higher doses, without traditional medical indications to do so, may be ineffective and even harmful. The study was published in the journal Thrombosis Research.

"COVID-19 patients appear to have an increased incidence of blood clots. Many hospitals and health care providers began to use high doses of blood thinners to prevent these clots or treat them preemptively," said Juan Reyes, MD, MPH, co-author of the study and director of hospital medicine at the GW School of Medicine and Health Sciences (SMHS). "We wanted to review the data of our subset of COVID-19 patients treated with blood thinners to determine if the higher-dose medication was helpful."

The research team evaluated 402 patients diagnosed with COVID-19 admitted to GW Hospital between March 15 and May 31, 2020. Clinical outcomes were compared between 152 patients treated with high-dose blood thinners, and 250 patients treated with the standard low-dose blood thinners, typically prescribed to hospitalized medical patients. "Our findings did not demonstrate any additional benefit for those treated with higher doses of blood thinners above and beyond the standard of care," said Shant Ayanian, MD, MS, co-author and assistant professor of medicine at GW SMHS.

"While it's true that COVID-19 patients could be dying of blood clots, the data we've evaluated does not support giving every patient a high dose of blood thinners. That's a challenge, as the benefits still remain unclear," said Lei Lynn, MD, first author of the study and assistant professor of medicine at GW SMHS. "We caution against an aggressive blood thinner regimen for everyone, unless there is clear evidence to do so."

At the beginning of the pandemic, all patients admitted with COVID-19 to the GW Hospital were treated with standard dose anticoagulation, unless contraindicated. As awareness of the elevated risk of blood clots developed, many providers began treating patients with high-dose blood thinners. At GW Hospital, for non-critically ill patients, medical teams were advised to especially consider initiating a high dose of anticoagulation if a patient's D-dimer level exceeded 3 micrograms per milliliter. The research team previously published a study finding higher levels of the biomarker D-dimer, a medical indicator found in the blood, is associated with higher odds of clinical deterioration and death from COVID-19. This study is the first of its kind to utilize D-dimer levels to analyze clinical outcomes of anticoagulation in patients who are not critically ill.

"Though we would have loved to have seen a clinical benefit to our patients from anticoagulation, our research found that higher doses of blood thinners were potentially harmful, with no clear benefits," said Karolyn Teufel, MD, co-author of the study and assistant professor of medicine at GW SMHS. "Our research highlights the challenges with treating COVID-19. So much remains unknown."

"The effect of anticoagulation on clinical outcomes in novel Coronavirus (COVID-19) pneumonia in a U.S. cohort" was published in Thrombosis Research.

Blood thinners as a treatment for COVID-19? What the science says and what it means for you
by Karlheinz Peter, Hannah Stevens and James McFadyen, The Conversation

Credit: Shutterstock
A spate of recent media headlines have described blood thinning medications—which include aspirin and warfarin—as a "breakthrough treatment" for COVID-19 that could "save lives".

It's early days yet but a growing body of research evidence suggests COVID-19 causes abnormalities in blood clotting, which means blood thinning drugs may have a role to play in treatment.

Here's what the research says on this question—and how it applies to you.

Mounting evidence

When COVID-19 first emerged, it was thought the illness was a typical respiratory disease causing symptoms such as fever, sore throat, dry cough, and potentially lung infection (pneumonia) and a build-up of fluid in the lungs making it difficult to breathe.

However, as we outlined in a previous article in The Conversation, 30-70% of COVID-19 patients admitted to intensive care units, developed blood clots.

These rates of blood clotting appear to be much higher than what is expected when compared with people who are hospitalised for reasons other than COVID-19.

Blood clots in the veins often present in the legs (deep vein thrombosis) and are dislodged into the lungs (called pulmonary embolism); approximately one in four COVID-19 patients admitted to intensive care will develop a pulmonary embolism (where an artery in the lungs gets blocked).

Arterial blood clots associated with COVID-19 can lead to strokes, including in younger patients, with potentially devastating outcomes.

In addition, COVID-19 appears to cause tiny blood clots that can block small vessels in the lungs. These "micro" blood clots may be a key reason why patients with COVID-19 often have very low oxygen levels.

Blood clots appear to be associated with a higher risk of dying from COVID-19. Likewise, elevated markers of blood clotting are associated with an increased risk of admission to the intensive care unit and a worse prognosis overall.

Should blood thinners be standard treatment for COVID-19 patients in hospital?

Because the rate of blood clotting is so high, all people admitted to hospital with COVID-19 should receive a low dose of blood thinner medication to prevent blood clots. This prophylactic dose of blood thinner is standard across most hospitals in Australia.

However, many blood clots in COVID-19 are occurring despite the use of low-dose blood thinners. As such, it is a question of intense discussion whether people admitted to hospital with severe COVID-19 should receive a higher-than-usual dose of blood thinners to prevent blood clots and improve clinical outcomes.

A recent study from the US suggests patients admitted to hospital and prescribed full dose blood thinners had a better chance of survival and lower chance of needing a ventilator.

However, this finding has to be confirmed before the higher dose can be generally recommended. Fortunately, several research studies are underway in Europe, the UK and elsewhere to test and answer this question definitively.

Several other blood thinner treatments are also being evaluated in people with COVID-19. Aspirin is commonly prescribed to people who are at high risk of strokes or heart attacks. There are now studies underway examining if aspirin can reduce risk of blood clotting in people with COVID-19. In the US, some stronger clot-busting medications are also being trialled in people with severe COVID-19.

It is important to note blood thinners are not without risk, as this treatment can increase the risk of bleeding. So without definite evidence to support the benefit of high dose blood thinners in all hospitalized patients with COVID-19, the decision to use higher doses of blood thinning medication outside of a clinical trial must be made on an individual basis.

Should I take an aspirin to prevent blood clots?

There is no evidence aspirin or other blood thinners should be taken to prevent blood clots in the general population. Also, there is no evidence blood thinners are required to prevent blood clots for people with mild COVID-19 who are isolating at home. Because blood thinners can cause bleeding, they should not be taken unless prescribed by a doctor.

It is important for people who are taking blood thinners for another reason to continue taking these medications as normal, particularly if they are diagnosed with COVID-19.

In summary, our understanding of COVID-19 and how the coronavirus attacks the body continues to rapidly evolve. Researchers from around the world are publishing data almost daily. However, not all of this research has been peer reviewed.

If you develop symptoms, the most important thing you can do is to get tested for COVID-19 and talk to your doctor about potential treatments, including hospital admission and then about blood thinning medication.

Similar to our colleagues in the UK and the US, we as doctors specialized in the field of blood clotting are indeed optimistic and hope clinical studies currently underway will show rigorous strategies for prevention and treatment of blood clotting will help to reduce severity and improve survival of patients with COVID-19.

Genomic surveillance helps prepare for rabies outbreaks in bats
by Anna Zarra Aldrich, University of Connecticut

A big brown bat at BatFest in Hannibal, Missouri. Credit: Courtney Celley/USFWS
The COVID-19 pandemic and the significant impact of emerging variants have shown the importance of understanding viruses in as much detail as possible.

Luckily there are many ways scientists can learn more about zoonotic diseases, like genetic sequencing. Data gathered from detailed genetic sequencing can tell us a lot about a virus, like how it spreads and its evolutionary history.

This same lesson can be applied to another public health concern—rabies in bats.

Dong-Hun Lee, assistant professor of infectious disease epidemiology in the College of Agriculture, Health and Natural Resources recently identified the currently circulating rabies viruses in bats submitted to the Connecticut Veterinary Medical Diagnostic Laboratory (CVMDL) and shared his findings in Viruses.

This study is the first to collect genetic sequencing data from bat rabies viruses in the Northeast.

Bats are the most frequently reported rabid wildlife species in the United States. According to the CDC, bats are responsible for 70% of rabies deaths among people who are infected with the rabies virus in the United States during 1960–2018.

Rabies vaccine can prevent rabies. If an unvaccinated person does not receive appropriate medical care after an exposure, human rabies is almost 100% fatal. In 2021, there were five rabies cases in the United States, three of which were deaths.

"Rabies in bats should be a major public health consideration in the United States," says Lee, who is a member of the CVMDL and the Department of Pathobiology and Veterinary Science.

Between 2018 and 2019, Lee and Risatti tested 88 bats brought for rabies testing at the CVMDL by community members and local animal control units. These bats did not bite a human; those cases are handled by the Connecticut Department of Public Health.

Of those 88 bats, six tested positive for rabies. Lee and Risatti then sequenced the complete genomes of the rabies viruses.

Guillermo Risatti, professor of pathobiology and director of the CVMDL, is co-author on the paper.

"We are seeing these bats testing positive for rabies," Risatti says. "The next step is saying 'okay, what type of viruses are they carrying?'"

They identified four unique viruses: three in non-migratory big brown bats and one in a migratory hoary bat. Two samples did not have enough material to sequence.

The viruses in the big brown bats were closest to viruses found in Pennsylvania, New York, and New Jersey. The virus in the hoary bat, however, bore a close genetic relatedness to viruses in Arizona, Washington, Idaho, and Tennessee.

This information emphasizes how migration patterns can move viruses around and potentially allow them to establish in local populations.

The CVMDL is the only laboratory in the state studying rabies in bats in hopes of supporting disease tracking and disease preparedness.

"It's really important to be ready for future outbreaks," Lee says. "For epidemiological investigations, we need baseline data. It would be nice to have a baseline before we have an issue."

Prior to this research, the most recent whole-genome rabies study in bats was from Tennessee in 2004.

These findings will serve as baseline data for a potential future rabies outbreak. Having this level of detailed genetic information will allow scientists to understand how the virus spread and if existing vaccines will be effective.

"In case you have some kind of expansion of a virus, it's good to know what the viruses look like and what gives them some kind of competitive advantage—that's why they can expand in a population," Risatti says. "And at the end of the day, it's to know if the vaccines are still useful."

Risatti and Lee say they intend to continue this genomic surveillance on the CVMDL's bat samples to contribute to the body of genetic information available on rabies viruses. They may also look at other viruses bats could be carrying, such as coronaviruses.

Mayo Clinic Minute: Bats can be a rabies threat
by Jason Howland

Credit: CC0 Public Domain
October is Bat Month and a good time to make sure they are not roosting in your home. The Humane Society of the United States has tips to evict them so they don't hibernate in your home for the winter.

Bats play an important role in many ecosystems around the world. They are a major predator of night-flying insects, including pests that cost farmers billions of dollars annually. However, bats pose the biggest rabies threat in the U.S., according to the Centers for Disease Control and Prevention. Most bats are not rabid. However, because rabies can only be determined by laboratory testing, there is concern about possible exposure.

The most dangerous threat of rabies in the U.S. is flying overhead.

"It used to be thought, well, it's a rabid dog. But the more common way of getting rabies is from the silver-haired bat," says Dr. Gregory Poland, director of the Mayo Clinic Vaccine Research Group.

The deadly virus is transmitted from the saliva of infected animals to humans, usually through a bite. However, bats don't always bite.

"Sometimes the saliva will drool onto you, and you could have a minor open cut," says Dr. Poland. "Or sometimes a bat will lick on the skin and, again, transmit the virus that way."

Dr. Poland says that's why if you wake up and find a bat in the room, you should get the rabies vaccine.

"People think: 'Well, the bat's in the house. We woke up with it, doesn't look like it bit anybody.' Doesn't matter. Rabies is such a severe disease with no cure, no treatment for it, that the safer thing to do is give the rabies vaccine," says Dr. Poland.

That includes an immune globulin and multidose rabies series, which is not cheap. A typical series of rabies vaccines cost anywhere from $3,000 to $7,000.

Infected bats pose highest rabies risk in US: CDC
Infected bats are the leading cause of rabies deaths in the United States, according to a report released Wednesday by health authorities which found the risk posed by dogs had significantly fallen.

Bats were responsible for 70 percent of rabies deaths in the US between 1960 and 2018, a striking figure because they account for just a third of the 5,000 rabid animals reported each year.

But the overall risk remains very low: of the approximately 59,000 rabies deaths worldwide every year, only two occur in the United States.

"Bats play a critical role in our ecosystem and it is important people know that most of the bats in the US are not rabid," said Emily Pieracci, the lead author of the report for the Centers for Disease Control and Prevention (CDC).

"The problem comes when people try to handle bats they think are healthy because you really can't tell if an animal has rabies just by looking at it.

"The best advice is to avoid contact with bats—and other wildlife—to protect yourself from rabies."

The CDC said people may be underestimating the risk posed by the winged mammals and failing to recognize a bat scratch or bite, which can be smaller than the top of a pencil eraser, but this contact could still spread rabies.

On the other hand, people often worry about squirrels and opossum, but these animals generally don't carry the virus.

The report found that domestic dogs present much less of a risk than in the past thanks to the routine use of pet vaccines and the availability of post-exposure prophylaxis (PEP), which combines the rabies vaccine and rabies immune globulin to prevent infection after exposure to the virus.

Each year about 55,000 Americans get PEP treatment after being bitten or scratched by an infected or suspected infected animal.

However, exposure to rabid dogs while overseas was found to be the second-leading cause of rabies in Americans, and the CDC encouraged travelers to research the risks of their destination before traveling and even consider pre-exposure vaccines.

The rabies virus is transmitted through saliva, most commonly from the bite or scratch of an infected animal.

But the virus won't go on to cause the disease if people seek prompt treatment with PEP before the onset of symptoms, which can include increased aggression, fever, excess salivation and partial paralysis.

There is no treatment once signs of the disease begin, and it is fatal in humans and animals within one to two weeks.

FEBRUARY 12, 2022

Norway lifts final COVID curbs on social distancing
Norway on Saturday lifted its final COVID restrictions, scrapping social distancing and masks in crowded spaces despite a surge in Omicron infections.

"The metre is disappearing. We are taking away the recommendation on social distancing," Prime Minister Jonas Gahr Store told reporters at a press conference.

"Now we can now socialise like we did before, in nightlife, at cultural events and other social occasions. And on the way to and from work on buses, trains and ferries," he said.

Norway lifted most of its other COVID curbs earlier this month, including remote working, crowd size limits and restricted alcohol sales in bars and restaurants.

The requirement to isolate for four days after a positive COVID test was meanwhile on Saturday downgraded to a recommendation, and children with respiratory symptoms are no longer required to get tested for COVID.

Gahr Store stressed however that "the pandemic is not over", and advised unvaccinated people and those in risk groups to continue practising social distancing and wear masks where social distancing is not possible.

The Norwegian Institute of Public Health (FHI) said the country had yet to see the peak of the Omicron surge, but it was expected soon.

The agency's director Camilla Stoltenberg told reporters the number of COVID hospitalisations had risen by 40 percent in the past week.

As of Friday, 986,851 cases and 1,440 virus-related deaths had been recorded in Norway, where more than 91 percent of the population has received at least two doses of the vaccine.

FHI estimates that three to four million people from a population of 5.4 million may be infected by this summer.

Norway scraps most COVID curbs despite Omicron surge
Credit: Pixabay/CC0 Public Domain
Norway on Tuesday announced it would scrap most of its COVID restrictions despite an Omicron-fuelled surge in infections, saying society must "live with" the virus.

The Omicron variant has caused case numbers to soar in Norway, but hospital admissions for severely ill COVID patients have not increased in a population with wide vaccine coverage.

"We have finally reached the point where we can lift lots of the health measures we have had to live with this winter," Prime Minister Jonas Gahr Store told a press conference.

"We are going to have to live with a high level of infections—we can live with a high level of infections," he added.

Norwegians will not have to quarantine if they are a contact of an infected person, although daily testing is recommended for five days, and the isolation period for COVID cases will fall from six to four days.

Remote working will no longer be obligatory and an unlimited number of people can visit other households and attend sporting events.

Travellers entering the Scandinavian nation will no longer have to undergo testing.

Restrictions on alcohol sales in bars and restaurants will also end.

The measures come into effect at 11 pm (2200 GMT) Tuesday.

Masks will remain mandatory in settings like public transport and shops where it is impossible to follow the recommended social distancing guidelines of one metre.

Norway will therefore not go as far as neighbouring Denmark, which on Tuesday became the first European Union country to remove all of its domestic COVID curbs.

More than 781,000 cases and 1,440 virus-related deaths have been recorded in Norway, where almost 91 percent of the population is fully vaccinated.

Norway's public health institute estimates that three to four million people from a population of 5.4 million could have been infected by this summer.

Study shows GABAergic neurons in the hypothalamus trigger automatic defensive attacks in mice
by Ingrid Fadelli, Science X Network, Medical Xpress

When confronted by extreme threats, human and animals sometimes defend themselves by fighting against the threats. Xie and colleagues report that this important survival behavior is controlled by GABAergic neurons in the anterior hypothalamic nucleus of mice. The image illustrates a drunken hero who was bravely fighting against a ferocious tiger. Credit: Xie et al.
In his most renowned work, "On the Origin of Species," Charles Darwin introduced the idea that species need to continuously fight for their existence, and that only the most fit for a given environment survive. This notion, commonly known as the "survival of the fittest," has now been discussed and explored by countless scientists worldwide.

Although Darwin suggested that only the fittest species survive, he did not explain how this struggle for survival is reflected in the brains of humans and other animals. In recent years, many studies rooted in evolution, ethology and neuroscience have tried to answer this rather elusive question.

Researchers at the National Institute of Biological Sciences in Beijing, Beijing Normal University and other institutes in China have recently carried out a study investigating the neural underpinnings of innate defensive behaviors in mice. These are aggressive behaviors that animals can automatically adopt when responding to threatening stimuli in their environment.

The team's recent paper, published in Nature Neuroscience, suggests that mechanically evoked defensive behaviors are at least in part controlled by GABAergic neurons in the anterior hypothalamic nucleus (AHN), a central region within the frontal part of the hypothalamus. The anterior hypothalamus is a vital brain region known to be associated with self-regulatory bodily functions, including the regulation of the body's internal temperature and sleep.

"One goal of our laboratory is to elucidate how the brain initiates diverse behaviors for prey-predator competition, an important form of 'struggle for existence,'" Peng Cao, one of the researchers who carried out the study, told Medical Xpress. "In our previous studies, we systematically explored the brain circuits that underlie predator avoidance and prey capture in mice. In our new work we focused on anti-predator defensive attacks."

As part of their recent study, Cao and his colleagues carried out a series of experiments on mice. In these experiments, they triggered defensive behaviors in the mice using experimental stimuli and then tried to determine the neural underpinnings of these behaviors. They found that GABAergic neurons in the AHN mediated the mice's experimentally evoked defensive attacks.

"The brain area that may control mechanically evoked defensive attack should fit three fundamental criteria," Cao explained. "Firstly, the inhibition of neurons in this brain area should suppress mechanically evoked defensive attacks. Second, the neurons in this brain area should encode mechanical force and optimally respond to noxious mechanical stimuli. Third, the activation of these neurons should evoke attack behavior and suppress other types of ongoing behaviors."

In their experiments, Cao and his colleagues were able to show that GABAergic neurons in the AHN fit all these three criteria. Their study thus identifies the AHN as a central brain center behind defensive attack behaviors in mice.

"We found that photoinhibition of vGAT+ AHN neurons abrogated mechanically evoked defensive attack," Cao said. "Then, using fiber photometry, we found that vGAT+ AHN neurons specifically respond to noxious mechanical stimuli. Finally, using single-unit recording, we showed that vGAT+ AHN neurons encode the strength of mechanical force. We found that photostimulation of vGAT+ AHN neurons evoked attack behavior toward a live predator and suppressed other ongoing behaviors."

The findings gathered by this team of researchers shed some new light on the neural underpinnings of survival-related defensive behaviors in mice. Future studies could try to determine whether GABAergic neurons in the AHN are responsible for these same behaviors in other animal species, including humans.

As many violent crimes in human societies arise in response to aggression or danger, this recent study could ultimately have broad and far-reaching implications. For instance, it could pave the way towards a better understanding of how the human brain initiates violent crimes in response to real or perceived environmental threats.

"We now plan to expand our research on defensive attack," Cao added. "For instance, we will explore how the amygdala, the center of fear, may be involved in mechanically evoked defensive attack, which will then allow us to compare the involvement of the AHN and amygdala in defensive attack

Children with autism have difficulty sensing and comprehending internal bodily signals
by Zhang Nannan, Chinese Academy of Sciences

Credit: Unsplash/CC0 Public Domain
Dr. Raymond Chan's team from the Institute of Psychology of the Chinese Academy of Sciences has recently developed an innovative Eye-tracking Interoceptive Accuracy Task (EIAT) that is easily and specifically to examine interoceptive accuracy in children with autistic spectrum disorders (ASD). Results were published on Autism Research on January 27.

Interoception refers to the awareness and integration of internal signals including heartbeats and breathing patterns. Empirical findings suggest that interoception correlates with understanding of self and other's emotional status and learning. Interoception is therefore important for us to maintain a physiological equilibrium to achieve an optimal functional of daily lives.

Children with autistic spectrum disorders (ASD), including those with high level of autistic traits are considered to exhibit impairment in interoceptive accuracy. However, the extant literature provides mixed findings and should be interpreted cautiously with different methodologies.

In this study, the researchers administered EIAT to 30 children with ASD, 20 children with comorbid ASD and attention-deficit/hyperactive deficits (ADHD), and 63 typically-developing children with high and low levels of autistic traits. They also collected subjective measures from parents of these children.

According to the researchers, ASD children with and without comorbid ADHD exhibited lower interoceptive accuracy than typically-developing children.

They also found that typically-developing children with high level autistic traits also exhibited reduced interoceptive accuracy comparing to typically-developing children with low level of autistic traits. Interoceptive accuracy was found to correlate with ASD and ADHD symptoms negatively. More importantly, they also found atypical cardiac interoception in children with ASD.

Taken together, these findings highlight that difficulties in sensing and comprehending internal bodily signals in childhood may be related to both ASD and ADHD symptoms. These findings have important implications to understand the altered sensory processing observed in children with ASD and ADHD.

Interoceptive accuracy differs across life stages, weaker in those with autism
by Zhang Nannan, Chinese Academy of Sciences

Credit: Pixabay/CC0 Public Domain
Interoception is the ability to process and integrate signals originating from oneself internally, including heartbeats and breathing patterns. This ability is important for maintaining homeostasis (i.e., physiological equilibrium at all times) in order to achieve an optimal functional of daily lives. On the other hand, recent findings also suggest that autism spectrum disorders are associated with a wide range of sensory integration impairments including interoceptive accuracy.

However, it is still not clear whether individuals with subclinical features of autism (autistic traits sharing similar but less severe impairments in social and communicative skills comparing to clinically diagnosed cases of autism) also exhibit similar impairments in interoceptive accuracy. It is also not clear how interoceptive ability and its association with autistic traits vary in different age groups.

In order to address this issue, Dr. Raymond Chan's team from the Institute of Psychology of the Chinese Academy of Sciences (CAS) has developed an innovative paradigm involving eye-tracking measures to examine the multidimensional interoception and autistic traits in different age groups.

In so doing, they recruited 114 healthy college students aged 19–22 and explored the correlations among autistic traits and interoceptive accuracy using an "Eye-tracking Interoceptive Accuracy Task" (EIAT), which presents two bouncing shapes and requires participants to look at the one bouncing in synchronous with their real-time heartbeat.

This task requires no verbal report or key-pressing, so it has the advantage over other tasks for exploring interoceptive accuracy in preschool children and individuals with psychiatric disorders or speech impairments.

Their findings showed that autistic traits correlated significantly with the ability to describe and express emotion (alexithymia) but not with the different dimensions of interoception such as interoceptive accuracy (performance of interoceptive ability on behavioural tests), interoceptive sensibility (subjective sensitivity to internal sensations on self-report questionnaires) and interoceptive awareness (personal insight into interoceptive aptitude).

They then recruited 52 preschool children aged four to six, 50 adolescents aged 12–16 and 50 adults aged 23–54 to specifically examine relationship of autistic traits and interoceptive accuracy across the three age groups.

Results showed that interoceptive accuracy evolves from childhood to early adulthood, and then declines with age. Adolescents aged from 12 to 16 years exhibited the highest average accuracy. Finally, curvilinear regression of the whole dataset portrayed the developmental trajectory of interoceptive accuracy as having a reverted U-shape trend that peaks in early adulthood.

Taken together, based on the newly developed innovative task that does not require participants to make verbal reports or key-pressing, Dr. Chan's findings suggest that interoceptive accuracy significantly differs between typically-developing preschool children, adolescents and adults. The study also highlights the need for future study into preschool children with suspected autism spectrum disorders.

This study was supported by a grant from the National Science Foundation of China and the CAS Key Laboratory of Mental Health of the Institute of Psychology. It was published in the Journal of Autism and Developmental Disorders titled "Multidimensiona l interoception and autistic traits across life stages: Evidence from a novel eye-tracking task."

Study shows brain differences in interpreting physical signals in mental health disorders
by University of Cambridge

Credit: Unsplash/CC0 Public Domain
Researchers have shown why people with mental health disorders, including anorexia and panic disorders, experience physical signals differently.

The researchers, from the University of Cambridge, found that the part of the brain which interprets physical signals from the body behaves differently in people with a range of mental health disorders, suggesting that it could be a target for future treatments.

The researchers studied 'interoception' - the ability to sense internal conditions in the body—and whether there were any common brain differences during this process in people with mental health disorders. They found that a region of the brain called the dorsal mid-insula showed different activity during interoception across a range of disorders, including depression, schizophrenia, eating disorders and anxiety disorders.

Many people with mental health disorders experience physical symptoms differently, whether that's feeling uncomfortably full in anorexia, or feeling like you don't have enough air in panic disorder.

The results, reported in The American Journal of Psychiatry, show that activity in the dorsal mid-insula could drive these different interpretations of bodily sensations in mental health. Increased awareness of the differences in how people experience physical symptoms could also be useful to those treating mental health disorders.

We all use exteroception—sight, smell, hearing, taste and touch—to navigate daily life. But interoception—the ability to interpret signals from our body—is equally important for survival, even though it often happens subconsciously.

"Interoception is something we are all doing constantly, although we might not be aware of it," said lead author Dr. Camilla Nord from the MRC Cognition and Brain Sciences Unit. "For example, most of us are able to interpret the signals of low blood sugar, such as tiredness or irritability, and know to eat something. However, there are differences in how our brains interpret these signals."

Differences in interoceptive processes have previously been identified in people with eating disorders, anxiety and depression, panic disorder, addiction and other mental health disorders. Theoretical models have suggested that disrupted cortical processing drives these changes in interoceptive processing, conferring vulnerability to a range of mental health symptoms.

Nord and her colleagues combined brain imaging data from previous studies and compared differences in brain activity during interoception between 626 patients with mental health disorders and 610 healthy controls. "We wanted to find out whether there is something similar happening in the brain in people with different mental disorders, irrespective of their diagnosis," she said.

Their analysis showed that for patients with bipolar, anxiety, major depression, anorexia and schizophrenia, part of the cerebral cortex called the dorsal mid-insula showed different brain activation when processing pain, hunger and other interoceptive signals when compared to the control group.

The researchers then ran a follow-up analysis and found that the dorsal mid-insula does not overlap with regions of the brain altered by antidepressant drugs or regions altered by psychological therapy, suggesting that it could be studied as a new target for future therapeutics to treat differences in interoception.

"It's surprising that in spite of the diversity of psychological symptoms, there appears to be a common factor in how physical signals are processed differently by the brain in mental health disorders," said Nord. "It shows how intertwined physical and mental health are, but also the limitations of our diagnostic system—some important factors in mental health might be 'transdiagnostic', that is, found across many diagnoses."

In future, Dr. Nord is planning studies to test whether this disrupted activation could be altered by new treatments for mental health disorders, such as brain stimulation.

Increased risk of dying from COVID for people with severe mental disorders
by Umea University

Credit: Unsplash/CC0 Public Domain
People with severe mental disorders have a significantly increased risk of dying from COVID-19. This has been shown in a new study from Umeå University and Karolinska Institutet in Sweden. Among the elderly, the proportion of deaths due to COVID-19 was almost fourfold for those with severe mental disorders compared to non-mentally ill people in the same age.

"We see a high excess mortality due to COVID-19 among the elderly with severe mental disorders, which gives us reason to consider whether this group should be given priority for vaccines," says Martin Maripuu, associate professor at Umeå University.

In the current study, the researchers studied data covering the entire Swedish population over the age of 20 during the period from 11 March to 15 June 2020. Among citizens with severe mental disorder, 130 people died from COVID-19 during this period, which corresponded to 0.1 percent of the group. Among people who had not been diagnosed with a severe mental disorder, the mortality rate was almost halved, 0.06 percent.

Above all, after the age of 60, people with severe mental disorders had a higher excess mortality compared with the general population of the same age. In the age group 60-79 years, death from COVID-19 was almost four times as common among people with a severe mental disorders.

In the study, severe mental disorder was referred to as psychotic disorders, such as schizophrenia and bipolar disorder. The study did not include depression or anxiety in the term, although these conditions can also be severe.

As to what exactly causes the excess mortality in COVID-19 among people with severe mental disorders, the study itself provides no answer.

"It might be that severe mental disorders can lead to premature biological aging, that the disease impairs health and the immune system in general or that this group has other risk factors such as obesity. It is always important to address both, mental and physical health problems of people with these disorders," says Martin Maripuu.

In total, almost eight million individuals formed basis for the study. The study has been published in the scientific journal Frontiers in Psychiatry.

FEBRUARY 11, 2022

Engineered antibody helps block SARS-CoV-2 transmission
by UC Davis

Engineered FuG1 antibody competitively interferes with the furin function needed for the SARS-CoV-2 virus to become highly transmissible. Credit: UC Davis
Researchers at UC Davis Health have engineered a novel antibody, FuG1, that can directly interfere with the cell-to-cell transmission ability of SARS-CoV-2, the virus that causes COVID-19.

FuG1 targets the enzyme furin, which the virus uses for its efficient chain of infections in human cells. The approach could be added to existing SARS-CoV-2 antibody cocktails for greater function against emerging variants.

A study evaluating the efficacy of the engineered antibody was published today in Microbiology Spectrum.

"We developed an approach that interferes with the transmission chain of SARS-CoV-2. The COVID-19 vaccines are a great lifesaver in reducing hospitalizations and severe illness. Yet, we are now learning that they may not be as effective in controlling the transmissibility of the virus," said Jogender Tushir-Singh, senior author of the study.

Tushir-Singh is an associate professor in the Department of Medical Microbiology and Immunology and a member of the UC Davis Comprehensive Cancer Center therapeutics program. His research uses rational protein engineering to generate multi-targeting antibodies as cancer therapeutics. When the pandemic hit, he began thinking of similar strategies that might work to limit the spread of the coronavirus.

Enzyme activates SARS-CoV-2 spike protein

Furin, found throughout the human body, is involved in various functions of cells. It is a type of enzyme, a protease, that can break down proteins into smaller components. It does this by cutting, or cleaving, the polybasic peptide bonds within the proteins.

In cleaving these bonds, furin often acts as a switch, changing an inactive protein into an active one. For example, furin cleaves the inactive proparathyroid hormone into parathyroid hormone, which regulates calcium levels in the blood.

It can also cleave and activate viruses that enter human cells. Pathogens that utilize furin in their human host include HIV, influenza, dengue fever and SARS-CoV-2.

COVID-19 virus exploits host furin system

When SARS-CoV-2 infects a human cell, it is in its active state, having already "cleaved" its spike protein, a key protein that binds to ACE2 receptors to gain entry.

But when the virus is being synthesized within the host cell—when it is replicating—the spike is in an inactive state. The virus needs to use the host cell's furin to cut the spike protein into two parts, S1 and S2, which makes the spike active on the viral particles for efficient transmissibility upon release.

"The virus exploits the host's furin to transmit from one cell to another and another. This added activation step is what makes the virus highly transmissible," said Tanmoy Mondal, the first author for the study and a post-doctoral researcher at UC Davis Health.

But inhibiting furin to limit the SARS-CoV-2 chain of infection cycle is not a straightforward mechanism.

"Furin is found throughout the human body and is needed for the normal functioning of many biological processes. Stopping furin from doing its job causes high body toxicity. That is why the standard furin inhibitor drugs are not a clinically feasible option," Tushir-Singh said.

Instead, he and his team engineered a conjugated antibody targeting the SARS-CoV-2 spike protein. The design is similar to therapeutic monoclonal (IgG) antibodies but includes an added feature—Fc-extended peptide—that specifically interferes with the host furin. The researchers named this approach FuG1.

FuG1 allows the interruptions of the furin function to limit spike activation, thus specifically limiting the viral transmissibility during its chain of infection in host cells. The high affinity, variable-domain-targeting spike in FuG1 is key for furin-targeting specificity to avoid potential toxicity.

Antibody interferes with spike cleavage and stability

The team evaluated the engineered furin disrupter, FuG1, in human lung tissue cells. Tests were run with the original SARS-CoV-2 variant and pseudoviruses. They found that:

Adding the furin disruptor peptide did not interfere with the function of the antibody or its ability to bind to the SARS-CoV-2 spike.
FuG1 significantly impacted the spike cleavage at furin sites.
FuG1 additionally interfered with the overall stability of the SARS-CoV-2 spike protein, which in general is necessary for infecting cells and transmissibility of the virus.
The next steps for the team will be a series of experiments in mice. They will also test the engineered antibody against current variants like omicron.

Tushir-Singh is cautiously optimistic that variants such as omicron will not yield many differences. "The FuG1 antibody is logical in targeting the newly acquired biological component of SARS-CoV-2 transmissibility—the furin spike cleavage. Since our approach targets the viral assembly process itself, rather than ACE2 neutralization, as long as newly emerging SARS-CoV-2 variants do not interfere with FuG1 antibody binding, it is highly likely this sort of strategy would interfere with viral transmissibility," Tushir-Singh said.

In addition to targeting SARS-CoV-2, Tushir-Singh thinks this approach could be applied to future coronaviruses or any other virus that utilizes proteases like furin to infect cells for their pathology.

NIH scientists identify mechanism that may influence infectivity of SARS-CoV-2 variants
by National Institutes of Health

Creative rendition of SARS-COV-2 virus particles with spike proteins dotting their surfaces. Image not to scale. Credit: National Institute of Allergy and Infectious Diseases, NIH
Scientists at the National Institutes of Health have found that a process in cells may limit infectivity of SARS-CoV-2, and that mutations in the alpha and delta variants overcome this effect, potentially boosting the virus's ability to spread. The findings were published online in the Proceedings of the National Academy of Sciences. The study was led by Kelly Ten Hagen, Ph.D., a senior investigator at NIH's National Institute of Dental and Craniofacial Research (NIDCR).

Since the coronavirus pandemic began in early 2020, several more-infectious variants of SARS-CoV-2, the virus that causes COVID-19, have emerged. The original, or wild-type, virus was followed by the alpha variant, which became widespread in the United States in early 2021, and subsequently the delta variant, which is the most prevalent strain circulating today. The variants have acquired mutations that help them infect people and spread more easily. Many of the mutations affect the spike protein, which the virus uses to get into cells. Scientists have been trying to understand how these changes alter the virus's function.

"Throughout the pandemic, NIDCR researchers have applied their expertise in the oral health sciences to answer key questions about COVID-19," said NIDCR Director Rena D'Souza, D.D.S., Ph.D. "This study offers fresh insights into the greater infectivity of the alpha and delta variants and provides a framework for the development of future therapies."

The outer surface of SARS-CoV-2 is decorated with spike proteins, which the virus uses to attach to and enter cells. Before this can happen, though, the spike protein must be activated by a series of cuts, or cleavages, by host proteins, starting with the furin enzyme. In the alpha and delta variants, mutations to the spike protein appear to enhance furin cleavage, which is thought to make the virus more effective at entering cells.

Studies have shown that in some cases protein cleavage can be decreased by the addition of bulky sugar molecules—a process carried out by enzymes called GALNTs—next to the cleavage site. Ten Hagen's team wondered if this happens to the SARS-CoV-2 spike protein, and, if so, whether it changes the protein's function.

To find out, the scientists studied the effects of GALNT activity on spike protein in fruit fly and mammalian cells. The experiments showed that one enzyme, GALNT1, adds sugars to wild-type spike protein, and this activity reduces furin cleavage. By contrast, mutations to the spike protein, like those in the alpha and delta variants, decrease GALNT1 activity and increase furin cleavage. This suggested that GALNT1 activity may partially suppress furin cleavage in wild-type virus, and that the alpha and delta mutations overcome this effect, allowing furin cleavage to go unchecked.

Further experiments supported this idea. The researchers expressed either wild-type or mutated spike in cells grown in a dish. They observed the cells' tendency to fuse with their neighbors, a behavior that may facilitate spread of the virus during infection. The scientists found that cells expressing mutated spike protein fused with neighbors more often than cells with the wild-type spike. Cells with wild-type spike also fused less often in the presence of GALNT1, suggesting that its activity may limit spike protein function.

"Our findings indicate that the alpha and delta mutations overcome the dampening effect of GALNT1 activity, which may enhance the virus's ability to get into cells," said Ten Hagen.

To see if this process might also occur in people, the team analyzed RNA expression in cells from healthy volunteers. The researchers found wide expression of GALNT1 in lower and upper respiratory tract cells that are susceptible to SARS-CoV-2 infection, indicating that the enzyme could influence infection in humans. The scientists theorized that individual differences in GALNT1 expression could affect virus spread.

"This study suggests that GALNT1 activity may modulate viral infectivity and provides insight into how mutations in the alpha and delta variants may influence this," Ten Hagen said. The knowledge could inform future efforts to develop new interventions.

COVID-19 antibodies remain in the body 10 months after infection
by King's College London

Credit: Pixabay/CC0 Public Domain
A study published in Nature Microbiology looked at the antibodies of 38 patients and healthcare workers in St Thomas' Hospital who were infected within the first wave of COVID-19, before they were vaccinated.

Despite an initial decline in antibody levels just after infection, results showed that most people (18/19 patients) maintained detectable antibody levels 10 months after they were infected.

Antibodies help to fight COVID-19 by binding to the SARS-CoV-2 virus, preventing the virus from infecting cells. These results show how long antibodies remain in the body to fight future infections.

The researchers, led by Dr Katie Doores from the School of Immunology & Microbial Sciences, also tested how antibodies that were created to fight against a specific SARS-CoV-2 variant would respond to other variants. They looked at the original SARS-CoV-2 variant, as well as the alpha, beta, and delta variants.

While antibodies from a specific SARS-CoV-2 variant were able to generate a strong response to an infection from their own variant, results showed that antibodies were less effective when fighting against different variants.

Antibodies bind to the spike protein on the SARS-CoV-2 virus, and vaccines mimic this protein to create the immune response against SARS-CoV-2.

Mutations in the new SARS-CoV-2 variants (alpha, beta, delta) have created concerns about whether the vaccines that were developed to target the original SARS-CoV-2 variant would be effective against the new variants, and whether new vaccines should be designed against these variants.

Dr Liane Dupont said that "this study provides unique insight into the cross-neutralizing antibody responses induced by different SARS-CoV-2 variants."

However, these results suggest that there were differences in the spike protein of alpha, beta, and delta variants. This means that vaccines designed around one of these new variants may be less effective against other variants.

These results also show that our current vaccines designed around the original SARS-CoV-2 variant provides the best protection against all variants and should be used for vaccination programs.

This research follows on from a previous study, also led by Dr Katie Doores, that looked at COVID-19 antibody responses within three months.

Dr Katie Doores added that "this research was possible due to the close collaboration with clinical colleagues at St Thomas' Hospital who were able to sequence the viruses infecting hospitalized patients.

Structural changes in the SARS-CoV-2 Alpha and Beta variants identified
by Children's Hospital Boston

Mutations in the SARS-CoV-2 variants cause changes in the electrostatic potential (electric charge at rest) on the spike surface. Here, positively charged areas are shown in blue and negatively charged areas in red. In the Beta variant, the receptor-binding domain (RBD) and N-terminal domain (NTD) have changed substantially, affecting the ability of antibodies to bind to and neutralize the virus. Credit: Bing Chen, PhD, Boston Children's Hospital
New SARS-CoV-2 variants are spreading rapidly, and there are fears that current COVID-19 vaccines won't protect against them. The latest in a series of structural studies of the SARS-CoV-2 variants' "spike" protein, led by Bing Chen, Ph.D., at Boston Children's Hospital, reveals new properties of the Alpha (formerly U.K.) and Beta (formerly South Africa) variants. Of note, it suggests that current vaccines may be less effective against the Beta variant.

Spike proteins, on the surface of SARS CoV-2, are what enable the virus to attach to and enter our cells, and all current vaccines are directed against them. The new study, published in Science on June 24, used cryo-electron microscopy (cryo-EM) to compare the spike protein from the original virus with that the Alpha and Beta variants.

The structural findings indicate that mutations in the Beta variant (also known as B.1.351) change the shape of the spike surface at certain locations. As a result, neutralizing antibodies induced by current vaccines are less able to bind to the Beta virus, which may allow it to evade the immune system even when people are vaccinated.

"The mutations make antibodies stimulated by the current vaccine less effective," says Chen, from the division of Molecular Medicine at Boston Children's. "The Beta variant is somewhat resistant to the current vaccines, and we think a booster with the new genetic sequence can be beneficial for protecting against this variant."

However, the study also found that mutations in the Beta variant make the spike less effective in binding to ACE2—suggesting that this variant is less transmissible than the Alpha variant.

Reassurance on the Alpha variant; more variant studies underway

As for the Alpha variant (B.1.1.7), the study confirms that a genetic change in the spike (a single amino acid substitution) helps the virus bind better to ACE2 receptors, making it more infectious. However, testing indicates that antibodies elicited by existing vaccines can still neutralize this variant.

To be a heightened threat, the researchers say, a SARS-CoV-2 variant would need to do three things: spread more easily, evade the immune system in vaccinated people or those previously exposed to COVID-19, and cause more severe disease. Fortunately, the Alpha and Beta variants do not meet all these criteria.

"Our data suggest that the most problematic combination of such mutations is not yet present in the existing variants examined here," the researchers write.

Chen's team also plans to report the structures of other variants of concern, including the Delta variant (B.1.617.2), in the near future. Those investigations are still under way.

What should I know about the delta variant?
by Aniruddha Ghosal

What should I know about the delta variant? Credit: AP Illustration/Peter Hamlin
What should I know about the delta variant?

It's a version of the coronavirus that has been found in more than 80 countries since it was first detected in India. It got its name from the World Health Organization, which names notable variants after letters of the Greek alphabet.

Viruses constantly mutate, and most changes aren't concerning. But there is a worry that some variants might evolve enough to be more contagious, cause more severe illness or evade the protection that vaccines provide.

Experts say the delta variant spreads more easily because of mutations that make it better at latching onto cells in our bodies. In the United Kingdom, the variant is now responsible for 90% of all new infections. In the U.S., it represents 20% of infections, and health officials say it could become the country's dominant type as well.

It's not clear yet whether the variant makes people sicker since more data needs to be collected, said Dr. Jacob John, who studies viruses at the Christian Medical College at Vellore in southern India.

Studies have shown that the available vaccines work against variants, including the delta variant.

Researchers in England studied how effective the two-dose AstraZeneca and Pfizer-BioNTech vaccines were against it, compared with the alpha variant that was first detected in the U.K.

The vaccines were protective for those who got both doses but were less so among those who got one dose.

It's why experts say it's important to be fully vaccinated. And it's why they say making vaccines accessible globally is so critical.

COVID-19: How vaccines work against the Delta variant
Credit: Pixabay/CC0 Public Domain
The Delta variant of the coronavirus, first identified in India, is a cause for global concern with studies showing it is more contagious and resistant to vaccines than other forms of COVID.

But there is also evidence vaccines retain important effectiveness against Delta after two doses.

Here is what we know about how variants respond to jabs.

Fewer antibodies...

Several lab tests show that the Delta variant seems to have stronger resistance to vaccines than other variants do.

A British study published in The Lancet medical journal in early June looked at levels of neutralising antibodies produced in vaccinated people exposed to the Delta, Alpha (first identified in Britain) and Beta (first identified in South Africa) variants.

It found that antibody levels in people with two doses of the Pfizer/BioNTech shot were six times lower in the presence of the Delta variant than in the presence of the original COVID-19 strain on which the vaccine was based.

The Alpha and Beta variants also provoked lower responses, with 2.6 times fewer antibodies for Alpha and 4.9 times fewer for Beta.

A French study from the Pasteur Institute concluded that neutralising antibodies produced by vaccination with the Pfizer/BioNTech jab are three to six times less effective against the Delta variant than against the Alpha variant.

... but vaccines still work

Although they represent an essential marker, the levels of antibodies measured in a lab are not enough to determine the efficacy of a vaccine.

In particular they do not take into account a second immune response in the form of killer T cells—which attack already-infected cells and not the virus itself.

As a result, real-world observations are crucial to measuring vaccine effectiveness—and the first results are reassuring.

According to data published on Monday by Public Health England, vaccination with Pfizer/BioNTech and AstraZeneca is as effective at preventing hospitalisation in the case of the Delta variant as it is in the case of the Alpha variant.

Two doses of the Pfizer/BioNTech jab prevent 96 percent of hospitalisations due to the Delta variant, while AstraZeneca prevents 92 percent, according to a study involving 14,000 people.

Previous data released by British health authorities at the end of May come to similar conclusions for less serious forms of the illness.

The Pfizer/BioNTech vaccine is 88 percent effective against symptomatic COVID caused by the Delta variant two weeks after the second dose, while the jab is 93 percent effective for cases caused by the Alpha variant.

AstraZeneca shows efficacy of 60 percent against cases caused by the Delta variant and 66 percent in the case of Alpha.

Scottish authorities published similar data on Monday in The Lancet.

The team behind the Sputnik V jab meanwhile tweeted on Tuesday that theirs was "more efficient against the Delta variant... than any other vaccine that published results on this strain so far".

They did not publish results but said the study by the Gamaleya Center, a Russian research institute, had been submitted for publication in an international peer-reviewed journal.

One dose not enough

Among authorised vaccines only one—developed by Janssen—is given in one dose instead of two, and not enough data exists to determine its effectiveness against the Delta variant.

For the others, lab and real-world tests both conclude that one dose of any vaccine only gives limited protection against the Delta variant.

"After a single dose of Pfizer-BioNTech, 79% of people had a quantifiable neutralising antibody response against the original strain, but this fell to... 32% for B.1.617.2 (Delta)," says the lab study from June.

The Pasteur Institute found that a single dose of AstraZeneca would have "little to no efficacy" against the Delta variant.

Data from the British government confirms the tendency in real-world scenarios: both vaccines were 33 percent effective against symptomatic cases caused by Delta 3 weeks after the first dose compared to around 50 percent effectiveness against the Alpha variant.

In the UK—where the Delta variant is now responsible for 96 percent of new cases—these findings pushed the government on Monday to reduce the waiting period between doses from 12 weeks to eight for people over 40.

In France the wait has been reduced to three weeks from five for a second dose of the Pfizer/BioNTech and Moderna vaccines.

The Pfizer/BioNTech jab does however offer very high (94 percent) protection against hospitalisation due to the Delta variant after one dose.

Shots and social distancing

Scientists agree that the best defence against the Delta variant is to get a full two-dose vaccination against coronavirus.

Top French scientist Jean-François Delfraissy says creating a "block of vaccinated people" will help keep the Delta variant from spreading throughout the population.

A US study from June 10 points to the importance of vaccination to keeping the list of variants from growing.

"Increasing the proportion of the population immunised with current safe and effective authorised vaccines remains a key strategy to minimise the emergence of new variants and end the COVID-19 pandemic", it says.

Antoine Flahault, who heads up the University of Geneva's Institute of Global Health, insists it is still crucial to observe social distancing, share infection information, and observe restrictions when necessary to "keep virus circulation low".

The more the virus circulates, he says, the more opportunity it has to mutate and generate new variations.

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JUNE 14, 2021

Two jabs mostly prevent hospitalisation with Delta variant: UK body
Credit: Pixabay/CC0 Public Domain
Two doses of COVID-19 vaccines are "highly effective" in preventing hospital admission with the Delta variant, Public Health England said on Monday.

Scientists said two jabs of the Pfizer/BioNTech vaccine stopped the need for in-patient treatment in 96 percent of cases.

With a double dose of the Oxford/AstraZeneca shot, the rate was 92 percent, PHE added.

The findings were published as Britain grapples with a surge in coronavirus cases, most of which were of the Delta strain, which first emerged in India.

The increase is again raising concerns about the potential strain on hospitals, prompting calls to postpone a planned lifting of all social distancing curbs on June 21.

The restrictions have been in place since January, when the Alpha strain of the coronavirus, which was first identified in Kent, southeast England, spread rapidly.

The government, which began a mass-vaccination programme with the Pfizer/BioNTech jab in December last year, is pushing for more people to get two jabs.

PHE said the vaccine effectiveness for the Delta variant is comparable to that for the Alpha strain.

Head of immunisation Mary Ramsay said: "These hugely important findings confirm that the vaccines offer significant protection against hospitalisation from the Delta variant."

Further investigations were under way to determine the level of protection against death from the Delta variant, PHE said, but added that it was expected to be "high".

The public health body looked at 14,019 cases of the new variant in England between April 12 and June 4.

Previous analysis indicated that one dose of vaccine is 17 percent less effective in preventing a person developing symptoms from the Delta variant than the Alpha one.

But the latest research showed there was only a small difference after two doses.

Simon Kolstoe, senior lecturer in evidence-based healthcare at the University of Portsmouth, said the inoculation programme was clearly working.

Nearly 57 percent of the UK's adult population has had two doses, according to government statistics.

But he added: "We can only be confident in lifting all restrictions once we know that the link between large-scale infections and hospital admissions has been broken.

"The vaccine certainly seems to be doing its job in breaking this link but a few more weeks to get more people vaccinated certainly seems like a sensible option."

Delta variant '40 percent more transmissible': UK health minister
Colorized scanning electron micrograph of an apoptotic cell (green) heavily infected with SARS-COV-2 virus particles (yellow), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIH/NIAID
The Delta variant of the coronavirus is estimated to be 40 percent more transmissible than the Alpha variant that caused the last wave of infections in the UK, Britain's health minister said Sunday.
But people who have received two doses of vaccine, should be equally protected against either variant, he added.

"That figure, around 40 percent more transmissible, is indeed the latest advice I have," Health Secretary Matt Hancock told Sky News.

The Delta variant, also known as the Indian variant, is now the dominant strain in the UK, according to Public Health England figures.

It was the Alpha variant, previously known as the Kent variant, that forced the UK into lockdown in January.

Hancock said the 40 percent figure came from the government body of scientific advisors, SAGE.

Concerns are mounting over whether the emergence of the Delta variant threatens the government's provisional June 21 deadline for lifting virus restrictions.

Hancock acknowledged that the Delta variant "does make the calculation more difficult for June 21".

"We'll look at the data for another week and then make a judgement," he told the BBC on Sunday, stressing that the government was "absolutely open" to delaying the lifting of restrictions.

Double vaccinations effective

The minister nevertheless stressed that those who have had two doses of vaccine should be protected against illness from the Delta variant.

Public Health England said last month that research showed double vaccination was similarly effective against both the Kent and Delta variants.

"The best scientific advice I have at this stage is that, after one jab, it's not quite as effective against the new Delta variant, but after both jabs, it is," Hancock told the BBC.

So far hospitalisations are "broadly flat", with very few hospitalised after receiving both vaccine doses, he added.

The UK has so far given more than 27 million people two doses—more than 50 percent of adults—while more than 40 million have had one dose.

Hancock said the government was "taking clinical advice" on whether to extend the vaccination programme to children over 12, who are believed to be playing a major role in spreading the virus. But this would not be mandatory, he added.

UK officials: Vaccines effective against Indian variant
by Sylvia Hui

Credit: Pixabay/CC0 Public Domain
British health officials expressed optimism Sunday that the coronavirus restrictions remaining in England can be lifted in June after an official study found that the Pfizer and AstraZeneca vaccines offer effective protection against the variant first identified in India.

Authorities in Britain have expressed concern in recent weeks that increasing cases of the Indian variant could jeopardize the U.K.'s so-far successful plan to reopen its economy. More than 2,880 cases of the Indian variant have been recorded in England, figures show.

The government has said the variant appears to be more transmissible, but there was still uncertainty about how concerning this was.

Jenny Harries, chief executive of the U.K. Health Security Agency, said officials in England are on track to proceed with the final stage of unlocking the country from June 21 if the public remains cautious.

"It's looking good if people are continuing to observe all of the safety signals," she told the BBC. However, she warned that the Indian variant is starting to become the dominant strain in parts of northwestern England, and people in hotspot areas need to be vigilant.

Health Secretary Matt Hancock also said he was "increasingly confident" the country can follow its unlocking plans.

Their comments came after a study by Public Health England found that two doses of the Pfizer or AstraZeneca vaccines offer "high levels of protection" against symptomatic disease from the Indian variant.

The study, which took place between April 5 and May 16, found that the Pfizer vaccine is 88% effective against the variant after two doses. That compared with 93% effectiveness against the variant first identified in Kent, England, researchers said.

The AstraZeneca jab was 60% effective after both doses against the Indian variant, compared with 66% against the Kent variant.

Both vaccines were only 33% effective against symptomatic disease from the Indian variant three weeks after the first dose.

Tough lockdown rules eased in most parts of the U.K. earlier this month, largely thanks to an efficient vaccine rollout program. Socializing indoors in limited numbers are again allowed in homes, restaurants and pubs, and a blanket ban on traveling abroad was also partly lifted.

Officials have said they plan to reopen nightclubs and allow large events like festivals from June 21 if infection rates continue to stay low.

More than 37.7 million people, or 72% of the adult population, have had their first vaccine dose in the U.K. About 42% have had their second dose.

Newly developed inhaled vaccine delivers broad protection against SARS-CoV-2, variants
by McMaster University

Michael D’Agostino demonstrates how a nebulizer would deliver an inhaled vaccine. A new study has found the McMaster-developed vaccine to be effective against variants of concern. Credit: McMaster University
Scientists at McMaster University who have developed an inhaled form of COVID vaccine have confirmed it can provide broad, long-lasting protection against the original strain of SARS-CoV-2 and variants of concern.

The research, recently published in the journal Cell, reveals the immune mechanisms and significant benefits of vaccines being delivered directly into the respiratory tract, rather than by traditional injection.

Because inhaled vaccines target the lungs and upper airways where respiratory viruses first enter the body, they are far more effective at inducing a protective immune response, the researchers report.

The reported preclinical study, which was conducted on animal models, has provided the critical proof of concept to enable a Phase 1 clinical trial that is currently under way to evaluate inhaled aerosol vaccines in healthy adults who had already received two doses of a COVID mRNA vaccine.

The tested COVID vaccine strategy was built upon a robust tuberculosis vaccine research program established by Zhou Xing, a co-lead author of the new study and a professor at the McMaster Immunology Research Centre and Department of Medicine.

"What we've discovered from many years' research is that the vaccine delivered into the lung induces all-around protective respiratory mucosal immunity, a property that the injected vaccine is lacking," Xing says.

Currently authorized COVID vaccines are all injected.

"We wanted, first and foremost, to design a vaccine that would work well against any variant," explains the study's co-lead author Matthew Miller, an associate professor at McMaster's Michael G. DeGroote Institute for Infectious Disease Research.

The McMaster COVID vaccine represents one of only a handful developed in Canada. The urgent work is a critical mission of Canada's Global Nexus for Pandemics and Biological Threats, which is based at McMaster.

Researchers compared two types of adenovirus platforms for the vaccine. The viruses serve as vectors that can deliver vaccine directly to the lungs without causing illness themselves.

"We can remain ahead of the virus with our vaccine strategy," says Miller. "Current vaccines are limited because they will need to be updated and will always be chasing the virus."

Both types of the new McMaster vaccine are effective against highly transmissible variants because they are designed to target three parts of the virus, including two that are highly conserved among coronaviruses and do not mutate as quickly as spike. All COVID vaccines currently approved in Canada target only the spike protein, which has shown a remarkable ability to mutate.

"This vaccine might also provide pre-emptive protection against a future pandemic, and that's really important because as we've seen during this pandemic—and as we saw in 2009 with the swine flu—even when we are able to rapidly make a vaccine for a pandemic virus, it's already way too late. Millions of people died, even though we were able to make a vaccine in record time," says Miller.

"We have revealed in our report that besides neutralizing antibodies and T cell immunity, the vaccine delivered into the lungs stimulates a unique form of immunity known as trained innate immunity, which is able to provide very broad protection against many lung pathogens besides SARS-CoV-2," Xing adds.

In additional to being needle and pain-free, an inhaled vaccine is so efficient at targeting the lungs and upper airways that it can achieve maximum protection with a small fraction of the dose of current vaccines—possibly as little as 1 percent—meaning a single batch of vaccine could go 100 times further, the researchers say.

"This pandemic has shown us that vaccine supply can be a huge challenge. Demonstrating that this alternative delivery method can significantly extend vaccine supply could be a game changer, particularly in a pandemic setting," says Brian Lichty, an associate professor in the Department of Medicine who co-led the preclinical study along with Miller, Xing and the senior trainees Sam Afkhami and Michael D'Agostino, who are the joint first authors of the study.

Repeated seasonal influenza vaccines also provide kids better protection against future flu pandemics, study finds
by McMaster University

Lead researcher Matthew Miller says children and adults are fundamentally different in their immune responses to influenza virus. Credit: JD Howell/McMaster University
Researchers at McMaster University have found that children who receive years of season-specific flu vaccines develop antibodies that also provide broader protection against new strains, including those capable of causing pandemics.

The same ability does not exist in adults.

The findings, reported today in the journal Cell Reports Medicine, could inform the design of a universal influenza virus vaccine for children, who are especially vulnerable to serious complications from flu, such as pneumonia, dehydration and, in rare cases, death.

"Little is known about how seasonal flu vaccination impacts the immune responses in children, who are a major source of flu transmission and a very high-risk group," explains Matthew Miller, lead author of the study and Associate Professor at the Michael G. DeGroote Institute for Infectious Diseases Research. "Understanding how seasonal vaccination and different vaccine formulations shape childhood immunity is critical for effective prevention."

Children and adults are fundamentally different in their immune responses to influenza virus, explains Miller, whose lab is part of McMaster's Global Nexus for Pandemics and Biological Threats. Unlike small children, most adults have been infected with and vaccinated against flu many times throughout their lives.

"When we give adults vaccines, they make a very specific immune response against seasonal strains," says Miller. "Adults simply don't generate immune responses to seasonal flu vaccines capable of protecting them from pandemic viruses like children can."

The researchers spent three years studying immune responses in children between the ages of 6 months and 17 years. They found that as the children grew older, they became less capable of producing broadly protective antibodies, because of their repeated exposure to influenza, through infection or vaccination.

While COVID-19 related measures such as distancing and masking have also resulted in lower rates of influenza, Miller warns the flu will return, possibly in dangerous forms.

Influenza has caused five pandemics in the last 100 years. The Spanish Flu of 1918-19 killed roughly 50 million people worldwide at a time when the global population was about 1.8 billion—less than a quarter what it is today.

For the study, researchers also compared two forms of vaccine: the conventional flu shot and a nasal spray vaccine that works in the upper respiratory tract, where infection first takes hold.

Both worked equally well at generating broadly protective antibodies, which is welcome news for parents seeking a painless alternative to needles.

"This is an important finding because it means we have flexibility in terms of the type of vaccines we can use to make a universal vaccine for children. We now know that children's immune systems are much more flexible than adults' when it comes to being able to teach them how to make these broadly protective responses," says Miller.

Intranasal flu vaccine with nanoparticles offers robust protection, researchers find
by Georgia State University

Credit: Pixabay/CC0 Public Domain
An influenza vaccine administered through the nose and constructed with nanoparticles that enhance immune response offers strong protection against different influenza virus strains, according to researchers in the Institute for Biomedical Sciences at Georgia State University.

The intranasal vaccine contributed to multifaceted immune responses, leading to robust cross protection against influenza in mice. The vaccine consists of PEI-HA/CpG nanoparticles. PEI (polyethyleneimine), a robust and versatile delivery system, can simultaneously carry antigens (hemagglutinin, HA) that induce an immune response in the body, and adjuvants (CpG) that enhance the body's immune response to an antigen for optimal immunoenhancement.

These comprehensive immune responses and cross protection were long lasting, exhibiting defense from influenza virus over six months after immunization. The findings are published in the journal ACS Applied Materials & Interfaces.

Intranasal vaccination is an ideal approach for infectious respiratory diseases such as influenza. Seasonal influenza vaccines generally induce narrow immune responses that rapidly decline, which leaves populations vulnerable to novel influenza strains. Advancements in influenza vaccine technology are needed to protect against a wide range of influenza viruses. Intranasal vaccination can improve local mucosal immune responses by preventing influenza infection at the portal of virus entry.

In the influenza virus, HA is a protein that plays a crucial role in the early stages of virus infection. Influenza HA has a head region and stalk region. Current influenza vaccines elicit immune responses against the HA head, but this head region is highly changeable and accounts for lowered efficiency against different strains. The HA stalk region is more conservative across different strains of influenza viruses.

Protein antigens that are administered intranasally are usually less able to provoke an immune response, so adjuvants are needed to have highly efficient intranasal vaccines. Adjuvants, such as CpG, can enhance and manipulate immune responses, thus improving the potency and breadth of protection.

"The PEI-HA/CpG nanoparticles show good potential as a cross-protective influenza vaccine candidate," said Dr. Baozhong Wang, corresponding author of the study and a professor in the Institute for Biomedical Sciences at Georgia State. "The combination of PEI and CpG in the PEI-HA/CpG nanoparticle group contributed to the multifaceted immune responses, leading to vigorous cross protection. The incorporation of CpG and antigens into the same nanoparticle enhanced cellular immune responses.

"Our results revealed that the nanoparticles significantly enhanced HA immunogenicity, or the ability to provoke an immune response, providing cross protection against different influenza virus strains. The conserved HA stalk region induced substantial antibodies in the nanoparticle immunization groups."

"Nanoparticle platforms have shown intriguing characteristics and great potentials in the development of next-generation cross-protective influenza vaccines," said Dr. Chunhong Dong, the first author of the study and a postdoctoral fellow in the Institute for Biomedical Sciences. "However, challenges exist to the successful research and development of nanoparticle vaccines. Though no apparent adverse effects were observed in the study, a more comprehensive safety evaluation of the nanoparticle adjuvant system is needed before clinical trials."

Intranasal influenza vaccine enhances immune response and offers broad protection, researchers find
by Georgia State University

Credit: CC0 Public Domain
An influenza vaccine that is made of nanoparticles and administered through the nose enhances the body's immune response to influenza virus infection and offers broad protection against different viral strains, according to researchers in the Institute for Biomedical Sciences at Georgia State University.

Recurring seasonal flu epidemics and potential pandemics are among the most severe threats to public health. Current seasonal influenza vaccines induce strain-specific immunity and are less effective against mismatched strains. Broadly protective influenza vaccines are urgently needed.

Intranasal vaccines are a promising strategy for combatting infectious respiratory diseases, such as influenza. They are more effective than vaccines injected into a muscle because they can induce mucosal immune responses in respiratory tracts, preventing infection at the portal of virus entry. They can also stimulate systemic immune responses throughout the body.

Scientists can overcome vaccine safety concerns and the long production phase of virus-based influenza vaccines by constructing intranasal vaccines with recombinant proteins or peptides. However, these vaccines are poor at producing immune responses, so it's necessary to have potent mucosal adjuvants, substances that enhance the body's immune response to antigens (the molecular structures on pathogens). The absence of appropriate mucosal adjuvants currently hinders the development of such a vaccine.

In this study, the researchers developed an intranasal influenza vaccine using recombinant hemagglutinin (HA), a protein found on the surface of influenza viruses, as the antigen component of the vaccine. HA is integral to the ability of influenza virus to cause infection.

They also created a two-dimensional nanomaterial (polyethyleneimine-functionalized graphene oxide nanoparticles) and found that it displayed potent adjuvant (immunoenhancing) effects on influenza vaccines delivered intranasally. The findings are published in the journal Proceedings of the National Academy of Sciences.

"Conventional flu vaccines predominantly induce antibody responses," said Dr. Baozhong Wang, senior author of the study, principal investigator of the National Institutes of Health grant supporting the study and a professor in the Institute for Biomedical Sciences. "However, recent research demonstrates that lung resident memory T cell responses are indispensable for optimal cross-protection against pulmonary influenza infection. The development of lung resident T cell responses requires vaccination by a respiratory route or influenza virus infection. Our research opens a new path for the development of needle-free and logistically simplified intranasal flu vaccines for cross-protection."

"In our study, we reported for the first time that two-dimensional graphene oxide nanomaterials had a potent adjuvant effect in boosting the immune responses of intranasal hemagglutinin (HA) vaccines," said Dr. Chunhong Dong, lead author of the study and a postdoctoral research Fellow in Dr. Baozhong Wang's lab in the Institute for Biomedical Sciences.

"This study gives new insights into developing high performance intranasal vaccine systems with two-dimensional sheet-like nanoparticles," Dong said. "The graphene oxide nanoparticles have extraordinary attributes for drug delivery or vaccine development, such as the ultra-large surface area for high-density antigen loading, and the vaccine showed superior immunoenhancing properties in vitro and in vivo. The nanoplatform could be easily adapted for constructing mucosal vaccines for different respiratory pathogens."

The study, conducted in mice and cell culture, found the nanoparticles significantly enhanced immune responses at mucosal surfaces and throughout the body in mice. The robust immune responses conferred immune protection against influenza virus challenges by homologous (same) virus strains and heterologous (different) virus strains.

The results are also promising because needle-free, intranasal influenza vaccines possess superior logistical advantages over traditional injectable vaccines, such as easy administration with high acceptance for recipients and the avoidance of biohazardous waste.

Intranasal influenza vaccine spurs strong immune response in Phase 1 study
by NIH/National Institute of Allergy and Infectious Diseases

3-D print of influenza virus. The virus surface (yellow) is covered with proteins called hemagglutinin (blue) and neuraminidase (red) that enable the virus to enter and infect human cells. Credit: NIH
An experimental single-dose, intranasal influenza vaccine was safe and produced a durable immune response when tested in a Phase 1 study published in the Journal of Clinical Investigation. The investigational vaccine, called Ad4-H5-VTN, is a recombinant, replicating adenovirus vaccine designed to spur antibodies to hemagglutinin, a protein found on the surface of influenza viruses that attaches to human cells.

The investigational vaccine was developed by Emergent Biosolutions Inc., (Gaithersburg, Maryland). It was administered intranasally (28 study participants), as an oral capsule (10 participants) and via a tonsillar swab (25 participants) to healthy men and non-pregnant women ages 18 to 49 years.

The participants who received the vaccine intranasally or via tonsillar swab showed significantly higher H5-specific neutralizing antibody levels compared to the group receiving the vaccine capsule orally. The participants who received the intranasal vaccine shed viral DNA for two-to-four weeks, but virus could be cultured for a median of only one day. Participants had evidence of H5-specific CD4+ and CD8+ T-cell responses. Additionally, volunteers who received the intranasal vaccine had high levels of serum neutralizing antibodies at 26 weeks after vaccination, and this level was unchanged at three to five years after a single intranasal dose of the vaccine. The duration of viral shedding correlated with a high magnitude of neutralizing antibody response at week 26. In addition, the intranasal vaccine induced a mucosal antibody response in the nose, mouth, and rectum.

The study authors speculate that replication-competent vector vaccines may have advantages over other types of vaccines because they can express viral proteins at higher levels and for longer durations. Additionally, this type of vaccine induces a mucosal immune response that is critical for limiting transmission of viruses that infect mucosal tissues.

The vaccine platform could be highly adaptable for use against other viruses including HIV and SARS-CoV-2, according to the authors.

Eating prunes may help protect against bone loss in older women
by Katie Bohn, Pennsylvania State University

Credit: Pixabay/CC0 Public Domain
It's already well known that prunes are good for your gut, but new Penn State research suggests they may be good for bone health, too.

In a research review, the researchers found that prunes can help prevent or delay bone loss in postmenopausal women, possibly due to their ability to reduce inflammation and oxidative stress, both of which contribute to bone loss.

"In postmenopausal women, lower levels of estrogen can trigger a rise of oxidative stress and inflammation, increasing the risk of weakening bones that may lead to fractures," said Connie Rogers, associate professor of nutritional sciences and physiology. "Incorporating prunes into the diet may help protect bones by slowing or reversing this process."

The review was recently published in the journal Advances in Nutrition.

Osteoporosis is a condition in which bones become weak or brittle that can happen to anyone at any age, but according to the researchers is most common among women over the age of 50. The condition affects more than 200 million women worldwide, causing almost nine million fractures each year.

While medications exist to treat osteoporosis, the researchers said there is a growing interest for ways to treat the condition with nutrition.

"Fruits and vegetables that are rich in bioactive compounds such as phenolic acid, flavonoids and carotenoids can potentially help protect against osteoporosis," said Mary Jane De Souza, professor of kinesiology and physiology, "with prunes in particular gaining attention in previous research."

According to the researchers, bones are maintained throughout adult life by processes that continually build new bone cells while removing old ones. But after the age of 40, this breaking down of old cells begins to outpace the formation of new ones. This can be caused by multiple factors including inflammation and oxidative stress, which is when free radicals and antioxidants are unbalanced in the body.

Prunes, however, have many nutritional benefits such as minerals, vitamin K, phenolic compounds and dietary fiber—all which may be able to help counter some of these effects.

For their review, the researchers analyzed data from 16 preclinical studies in rodent models, ten preclinical studies and two clinical trials. Across the studies, the researchers found evidence that eating prunes helped reduce inflammation and oxidative stress and promoted bone health.

For example, the clinical trials found that eating 100 grams of prunes—about 10 prunes—each day for one year improved bone mineral density of bones in the forearm and lower spine and decreased signs of bone turnover.

Additionally, eating 50 or 100 grams of prunes a day for six months prevented loss of total bone mineral density and decreased TRAP-5b—a marker of bone resorption—compared to women who didn't eat prunes.

"Taken together, evidence from in vitro, preclinical studies, and limited clinical studies suggest prunes may help to reduce bone loss," Rogers said. "This may be due to altered bone turnover and by inhibiting inflammation and suppressing markers of oxidative stress."

The researchers said one potential mechanism for the effects is prunes triggering a change in the gut microbiome that then lowers inflammation in the colon. This may then lower levels of pro-inflammatory cytokines and markers of oxidative damage.

In the future, the researchers plan to further report on the effects of prune consumption for 12 months on bone outcomes, inflammatory pathways and the gut microbiota in a randomized controlled trial that was led by De Souza.

Men with high levels of body fat may be at risk for osteoporosis
by The Endocrine Society

Men with high levels of body fat have lower bone density and may be more likely to break a bone than those with normal levels of body fat, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

Most studies have shown positive or neutral effects of body fat mass—the weight of fat in your body—on bone health. Lean mass is the entire weight of your body, including organs, skin and bones, minus fat. Health care providers often assume people with higher body weight have high bone density and are at low risk of fracture, and these patients are less likely to be screened for osteoporosis.

"We found that higher fat mass was related to lower bone density, and these trends were stronger in men than women," said Rajesh K. Jain, M.D., of University of Chicago Medicine. "Our research suggests that the effect of body weight depends on a person's makeup of lean and fat mass, and that high body weight alone is not a guarantee against osteoporosis."

The researchers analyzed the bone mineral density and body composition data of 10,814 people under 60 years old from the National Health and Nutrition Examination Survey (NHANES) 2011-2018. They found a strong positive association between lean mass and bone mineral density in both men and women. Conversely, fat mass had a moderately negative association with bone mineral density, especially in men.

"Health care providers should consider osteoporosis screening for patients with high body weight, especially if they have other risk factors like older age, previous fracture, family history, or steroid use," Jain said.

Diabetes, metabolic syndrome in mice treated with novel class of compounds
by Julia Evangelou Strait, Washington University School of Medicine

Researchers at Washington University School of Medicine in St. Louis have shown, in mice, that a new class of compounds they developed can improve several aspects of metabolic syndrome. Such conditions often lead to cardiovascular disease, the leading cause of death worldwide. Pictured are two of the compounds (yellow) in the new class—SN-401 (left) and SN-406 (right). Credit: Susheel K. Gunasekar (Sah Lab), Pratik R. Chheda (Kerns Lab)
A study in mice—led by researchers at Washington University School of Medicine in St. Louis—shows that a new class of compounds the scientists developed can improve multiple aspects of metabolic syndrome. An increasingly common group of conditions that often occur together, metabolic syndrome includes type 2 diabetes, high cholesterol, fat buildup in the liver, and excess body fat, especially around the waist. This syndrome often leads to cardiovascular disease, the leading cause of death worldwide.

The study is published in the journal Nature Communications.

Testing one of the compounds referred to as SN-401, the researchers found it treats diabetes by improving the ability of the pancreas to secrete insulin and boosting the ability of other tissues to utilize that insulin to more effectively remove sugar from the bloodstream. In an effort to optimize the treatment, the researchers fine-tuned the compound—creating a class of related compounds—based on their studies of a key protein called SWELL1 (also LRRC8a). The gradual decline of this protein may have a central role in the development of diabetes and other aspects of metabolic syndrome.

"Our goal is to develop better therapies for cardiovascular disease, including diabetes and metabolic syndrome, which are major risk factors for worsening heart and vascular problems," said senior author Rajan Sah, MD, Ph.D., an associate professor of medicine. "We have many treatments for diabetes, but even with those therapies, cardiovascular disease remains a leading cause of death among patients with type 2 diabetes. There is a need for new treatments that work differently from the current standard-of-care therapies."

The protein Sah and his colleagues studied is called SWELL1 because of its role in sensing the size or volume of cells. Their new research reveals that the protein also helps to control insulin secretion from the pancreas and improve insulin sensitivity, including in skeletal muscle and adipose tissue, the body's fat stores.

Surprisingly, the researchers showed that SWELL1 does both of these seemingly independent tasks because the protein has a previously unknown double life. It acts as a signaling molecule, turning on cellular tasks that govern how well cells use insulin and also facilitates the pancreas' secretion of insulin into the bloodstream.

"This protein, SWELL1, has a sort of dual personality," Sah said. "The compound binds to SWELL1 in a manner that stabilizes the protein complex so as to enhance expression and signaling across multiple tissues, including adipose, skeletal muscle, liver, the inner lining of blood vessels, and pancreatic islet cells. This restores both insulin sensitivity across tissue types and insulin secretion in the pancreas."

Sah and his colleagues showed that the SN-401 compound improved multiple aspects of metabolic syndrome in two groups of mice that each developed diabetes from different causes, one because of a genetic predisposition and the other due to a high-fat diet. In addition to improving insulin sensitivity and secretion, treatment with the compound also improved blood sugar levels and reduced fat buildup in the liver. Most of these studies were conducted with an injected form of the compound, but the researchers showed evidence that it also could be effective if taken by mouth.

The researchers further showed that the compound does not have a big impact on blood sugar in healthy mice, which is important for its potential as a future possible therapy. Current medications for diabetes can result in blood sugar levels that are too low. The evidence suggests that this compound does not lower blood sugar in situations when it doesn't need to.