Culture

Investing in protective gear for health care workers pays off

image: Fig 5. Cumulative HCW mortality as a percentage of total workforce, by strategy.

Image: 
Risko et al, PLOS ONE, 2020 (CC BY)

Providing adequate personal protective equipment (PPE) for all health care workers around the world requires an initial investment of billions of dollars, but the returns on that investment could be close to 8000% in productivity gains, according to a new study published this week in the open-access journal PLOS ONE by Nicholas Risko of the Johns Hopkins University School of Medicine and colleagues.

As COVID-19 spread around the world in early 2020, even resource-rich health systems experienced supply shortages of PPE to protect frontline health care workers. Over 80% of the world's population lives in low- and middle-income countries (LMICs) where fragile health systems with few resources make health care workers particularly vulnerable to PPE shortages and COVID-19 infection.

In the new study, researchers calculated the cost of providing PPE to all LMIC health systems and used a model to compare the costs and effects of two PPE use scenarios for all LMICs. Data from the World Health Organization COVID-19 Essential Supplies Forecasting Tool was used, as well as estimates of national mortality and hospitalizations that had been previously calculated and published.

The model predicted that an initial global investment of $9.6 billion U.S. could save the lives of roughly 2.2 million health care workers by providing adequate PPE. This comes out to $59 dollars per case averted and $4,309 per life saved. The benefit to society yields $755.3 billion dollars, or about an 8,000% return. The largest net economic gains would be seen in the East Asia & Pacific region, South Asia, and Sub-Saharan Africa. In addition, the study shows that scaling up the provision of PPE is a required component of national strategy if the health care workforce is to be protected.

The authors add: "This study predicts the impact of supplying front-line health care workers in low and middle-income countries with protective equipment during the COVID-19 pandemic. Our central finding is that a small upfront investment will save many lives and provide a substantial economic return, whereas neglecting to protect health care workers risks heavy losses due to illness and death."

Credit: 
PLOS

Nerve cell activity shows how confident we are

image: The further they moved the slider to the left or right end, the more confident they were in their choice.

Image: 
© AG Mormann/Uni Bonn

Should I or shouldn't I? The activity of individual nerve cells in the brain tells us how confident we are in our decisions. This is shown by a recent study by researchers at the University of Bonn. The result is unexpected - the researchers were actually on the trail of a completely different evaluation mechanism. The results are published in the journal Current Biology.

You are sitting in a café and want to enjoy a piece of cake with your cappuccino. The Black Forest gateau is just too rich for you and is therefore quickly eliminated. Choosing between the carrot cake and the rhubarb crumble is much trickier: The warm weather favors the refreshingly fruity cake. Carrot cake, however, is one of your all-time favorites. So what to do?

Every day we have to make decisions, and we are much more confident about some of them than others. Researchers at the University Hospital Bonn have now identified nerve cells in the brain whose activity indicates the confidence in decisions. A total of twelve men and women took part in their experiment. "We showed them photos of two different snacks, for example a chocolate bar and a bag of chips," explains Prof. Dr. Dr. Florian Mormann from the Department of Epileptology. "They were then asked to use a slider to indicate which of these alternatives they would rather eat." The more they moved the slider from its center position towards the left or right photo, the more confident they were in their decision.

Fire rate and confidence are related

Participants had to judge a total of 190 different snack pairs in this way. At the same time, the scientists recorded the activity of 830 nerve cells each in the so-called temporal lobe. "We discovered that the frequency of the electrical pulses in some neurons, in other words their 'firing rate', changed with increasing decision confidence," explains Mormann's colleague Alexander Unruh-Pinheiro. "For instance, some fired more frequently, the more confident the respective test person was in their decision."

It is the first time that such a correlation between activity and decision confidence has been identified. The affected neurons are located in a brain region that plays a role in memory processes. "It is possible that we not only store what decision we made, but also how confident we were in it," speculates Mormann. "Perhaps such a learning process saves us from future wrong decisions."

Ethical reasons usually prohibit the study of the state of individual neurons in living humans. However, the participants in the study suffered from a severe form of epilepsy. In this form of the disease, the characteristic seizures always start in the same area of the brain. One possible treatment is therefore to remove this epileptic focus surgically. To pinpoint the exact location of the defective site, the doctors at the Clinic for Epileptology implant several electrodes in the patient. These are distributed over the entire potentially affected area. At the same time, they also allow an insight into the functioning of individual nerve cells in the brain.

Researchers at the University of Bonn were originally looking for a completely different phenomenon: When we make a decision, we assign a subjective value to each of the alternatives. "There is evidence that this subjective value is also reflected in the activity of individual neurons," says Mormann. "The fact that we instead came across this connection between fire behavior and decision confidence surprised even us."

Credit: 
University of Bonn

A new look at sunspots

image: One of the largest sunspots seen in early January 2014, as captured by NASA's Solar Dynamics Observatory. An image of Earth has been added for scale.

Image: 
NASA/SDO

NASA's extensive fleet of spacecraft allows scientists to study the Sun extremely close-up - one of the agency's spacecraft is even on its way to fly through the Sun's outer atmosphere. But sometimes taking a step back can provide new insight.

In a new study, scientists looked at sunspots - darkened patches on the Sun caused by its magnetic field - at low resolution as if they were trillions of miles away. What resulted was a simulated view of distant stars, which can help us understand stellar activity and the conditions for life on planets orbiting other stars.

"We wanted to know what a sunspot region would look like if we couldn't resolve it in an image," said Shin Toriumi, lead author on the new study and scientist at ?the Institute of Space and Astronautical Science at JAXA. "So, we used the solar data as if it came from a distant star to have a better connection between solar physics and stellar physics."

Sunspots are often precursors to solar flares - intense outbursts of energy from the surface of the Sun - so monitoring sunspots is important to understanding why and how flares occur. Additionally, understanding the frequency of flares on other stars is one of the keys to understanding their chance of harboring life. Having a few flares may help build up complex molecules like RNA and DNA from simpler building blocks. But too many strong flares can strip entire atmospheres, rendering a planet uninhabitable.

To see what a sunspot and its effect on the solar atmosphere would look like on a distant star, the scientists started with high-resolution data of the Sun from NASA's Solar Dynamics Observatory and JAXA/NASA's Hinode mission. By adding up all the light in each image, the scientists converted the high-resolution images into single datapoints. Stringing subsequent datapoints together, the scientists created plots of how the light changed as the sunspot passed across the Sun's rotating face. These plots, which scientists call light curves, showed what a passing sunspot on the Sun would look like if it were many light-years away.

https://www.youtube.com/watch?v=QJc1G8Zuqo8

"The Sun is our closest star. Using solar observing satellites, we can resolve signatures on the surface 100 miles wide," said Vladimir Airapetian, co-author on the new study and astrophysicist at NASA's Goddard Space Flight Center in Greenbelt, Maryland. "On other stars you might only get one pixel showing the entire surface, so we wanted to create a template to decode activity on other stars."

The new study, published in the Astrophysical Journal, looked at simple cases where there is just one group of sunspots visible across the entire face of the Sun. Even though NASA and JAXA missions have continually gathered observations of the Sun for over a decade, these cases are quite rare. Usually there are either several sunspots - such as during the solar maximum, which we are now moving toward - or none at all. In all the years of data, the scientists only found a handful of instances of just one isolated sunspot group.

Studying these events, the scientists found the light curves differed when they measured different wavelengths. In visible light, when a singular sunspot appears at the center of the Sun, the Sun is dimmer. However, when the sunspot group is near the edge of the Sun, it's actually brighter due to faculae - bright magnetic features around sunspots - because, near the edge, the hot walls of their nearly vertical magnetic fields become increasingly visible.

The scientists also looked at the light curves in x-ray and ultraviolet light, which show the atmosphere above the sunspots. As the atmospheres above sunspots are magnetically heated, the scientists found brightening there at some wavelengths. However, the scientists also unexpectedly discovered that the heating could also cause a dimming in the light coming from the lower temperature atmosphere. These findings may provide a tool to diagnose the environments of spots on the stars.

"So far we've done the best-case scenarios, where there's only one sunspot visible," Toriumi said. "Next we are planning on doing some numerical modeling to understand what happens if we have multiple sunspots."

By studying stellar activity on young stars in particular, scientists can glean a view of what our young Sun may have been like. This will help scientists understand how the young Sun - which was overall more dim but active - impacted Venus, Earth and Mars in their early days. It could also help explain why life on Earth started four billion years ago, which some scientists speculate is linked to intense solar activity.

Studying young stars can also contribute to scientists' understanding of what triggers superflares - those that are 10 to 1000 times stronger than the biggest seen on the Sun in recent decades. Young stars are typically more active, with superflares happening almost daily. Whereas, on our more mature Sun, they may only occur once in a thousand years or so.

Spotting young suns that that are conducive to supporting habitable planets, helps scientists who focus on astrobiology, the study of the origin evolution, and distribution of life in the universe. Several next generation telescopes in production, which will be able to observe other stars in x-ray and ultraviolet wavelengths, could use the new results to decode observations of distant stars. In turn, this will help identify those stars with appropriate levels of stellar activity for life - and that can then be followed up by observations from other upcoming high-resolution missions, such as NASA's James Webb Space Telescope.

Credit: 
NASA/Goddard Space Flight Center

School absences correlate to impaired air quality

image: School books in a classroom.

Image: 
University of Utah

In Salt Lake City schools, absences rise when the air quality worsens, and it's not just in times of high pollution or "red" air quality days--even days following lower levels of pollutions saw increased absences.

Research is still ongoing, and the evidence isn't yet conclusive enough to draw a cause-and-effect relationship between air quality and children's absences from school but the correlation, according to Daniel Mendoza, a research assistant professor in the Department of Atmospheric Sciences and visiting assistant professor in the Department of City & Metropolitan Planning, merits further exploration. Mendoza and his colleagues published their results in Environmental Research Letters.

Air pollution is harmful for not only the health, but also the education and well-being of children in our community," says study co-author Cheryl Pirozzi, assistant professor in the Division of Respiratory, Critical Care, and Occupational Pulmonary Medicine. "Even at relatively low levels that many people would not think to be harmful air pollution is associated with increased school absences."

"Any pollution is bad," Mendoza says. "And these lower levels of pollution, which are still harmful to our health, have been understudied."

The correlation

Mendoza, who also holds appointments as adjunct assistant professor in the Pulmonary Division at the School of Medicine and as senior scientist at the NEXUS Institute, and his interdisciplinary colleagues looked at absence data from 36 schools in the Salt Lake City School District and compared them with ozone and air particulate matter levels in those neighborhoods from 2015 to 2018.

This kind of neighborhood-level air quality modeling requires a network of research-quality air sensors, and such a network has been building in the Salt Lake Valley over the last several years, operated by the U and by the state Division of Air Quality. That network includes mobile sensors on light rail trains as well as stationary research and regulatory grade sensors.

"These are critical because now we can see small nuances, small differences across neighborhoods," Mendoza says. "Now we can see how one school, for example, had slightly higher or slightly lower values of ozone and particulate matter. And now, instead of looking at the difference between green and yellow days, we can actually see small amounts of variability because of the density of our networks."

To understand the findings, it's important to first review how air quality conditions are reported. Particulate matter is most often reported as PM2.5, or the amount of particulate matter with a diameter less than 2.5 microns. These particles can reach the deepest parts of our lungs and may actually pass into our bloodstream. The unit of measurement is micrograms per cubic meter (μg/m3). Ozone is a molecule made from three oxygen atoms and is highly reactive, damaging the respiratory and circulatory systems. It's reported in parts per billion (ppb).

Although the study looked at elementary, middle and high schools, the authors write that elementary students may be most vulnerable to health effects from air pollution.

"Children are particularly susceptible to the health effects of air pollution," Pirozzi says, "and it is possible that health effects, such as respiratory tract infections or asthma exacerbations, may lead to them missing more school, which can have long-term consequences for them."

Across the school district, they found, school absences increased by 1.04 per μg/m3 of particulate matter and by 1.01 per ppb of ozone, even at levels of air pollution that aren't considered harmful. The worst increase in absences happened the day after high pollution exposure - possibly because reactions to high pollution might reduce exposure and prevent further absences. But on days after low, yet still elevated, pollution, absences continued to rise on the third, fourth and fifth days of exposure--suggesting a cumulative exposure effect, Mendoza says.

"So what that really leads us to think is that even low levels of poor air quality can, in a cumulative manner lead to negative health outcomes--in this case increased school absences. Even on green air quality days, when the pollution was just slightly elevated, if we had several of those days, then kids would still be absent."

Additionally, the researchers write that there may be a disparity between eastside and westside schools. Schools on the west side, with a higher proportion of residents from minority groups, already have a higher rate of absences than the comparatively more affluent east side and are slightly more affected by the same level of pollution. The disparity isn't yet statistically significant, and Mendoza hopes that an interdisciplinary team can further study these socioeconomic factors.

Mendoza acknowledges that there may be more factors at play that could account for some of the absences. Poor air quality days in the winter tend to be colder days, for example, and some children might stay home to stay out of the cold.

"So we're not saying that this is all due to poor air quality," he says. "We do know that there are more social and demographic variables at play here, but we already know the best way to estimate the pollution is in your zip code is by quantifying the percent of minority residents."

The costs

Absences come at a cost to schools, families and the larger economy. As part of the study, the researchers tried to estimate those costs.

First, the cost to schools. Using average per-pupil spending, the authors found that the state spends $41.30 per student per day--funding that doesn't benefit a student who's absent.

Next, the cost to families. Often a child staying home from school means a parent staying home from work. At an average hourly wage of $23.74, an absence can cost an hourly worker close to $200 a day. For families who receive free or reduced lunch, the cost of food then reverts to the family on days home.

And there are costs to the larger economy as well. Factoring in lost wages, lost taxes and lost productivity due to absences, reducing air pollution by 50 percent could save Utah's economy around $426,000 per year just from reducing absences in the Salt Lake School District. This result, the authors say, shows how reducing school absenteeism can and should be considered a benefit of improving air quality in the Salt Lake Valley.

"This is definitely not negligible," Mendoza says. "This is a real definite number, very close to half a million dollars in terms of income that does not need to be lost."

Find the full study here.

Credit: 
University of Utah

More evidence of benefits of REGN-COV2 antibody cocktail to both protect from and treat disease

In June, two studies in Science reported an antibody cocktail against SARS-CoV-2 developed from studies in humanized mice and recovering patients. The two antibody cocktail was designed to bind the virus to reduce the risk of a drug-resistant form emerging. Now, expanding upon this work, researchers show this antibody cocktail offers benefits in animal models that mimic the diverse pathology of SARS-CoV-2 infection, both when administered prophylactically and therapeutically. "These findings highlight the therapeutic potential of [this approach] to both protect from and treat SARS-CoV-2 disease," the authors say. While multiple studies have described discovery and characterization of potent neutralizing monoclonal antibodies against SARS-CoV-2, evaluation of the efficacy of these antibodies in vivo is limited, and it's largely focused on the prophylactic setting. As well, no single animal model has emerged as being more relevant for human disease, which has led some to say multiple animal models may be required to mimic various settings of human infection. Building on studies Johanna Hansen et al. and Alina Baum et al. published in Science in June that identified and characterized a double antibody therapy, Baum and colleagues tested this cocktail, REGN-COV2, in rhesus macaques, which manifest mild COVID-19 symptoms, and in golden hamsters, which show symptoms that are much more severe, including rapid weight loss. When administered three days before viral challenge, treatment almost completely blocked establishment of viral infection in macaques, the authors say. This ability, they note, "matches or exceeds the effects recently shown in vaccine efficacy studies using the same animal models." In macaques treated with the drug one day after infection, the authors report faster viral clearance than in controls who'd not been treated. Next, the authors used the hamster model to evaluate the drug's ability to alter the disease course in more severe cases. Hamsters treated with the drug two days before infection exhibited a "dramatic protection from weight loss" and decreased viral load in the lungs, the authors report. They also report benefits for hamsters treated one day after infection, as compared to controls. "In conclusion," say the authors, "our data provide evidence that REGN-COV2 based therapy may offer clinical benefit in both prevention and treatment settings of COVID-19 disease, where it is currently being evaluated."

Credit: 
American Association for the Advancement of Science (AAAS)

Antibodies from patients infected with SARS-CoV in 2003 cross-neutralized SARS-CoV-2 in vitro

Antibodies in serum samples collected from patients infected with SARS-CoV during the 2003 outbreak effectively neutralized SARS-CoV-2 infection in cultured cells, according to a new study. The authors also report that, surprisingly, mice and rabbits immunized with a receptor binding domain (RBD) from a strain of SARS-CoV that infects the Himalayan palm civet elicited stronger antibody responses against SARS-CoV-2 than animals immunized with an RBD from a human SARS-CoV strain. The authors suggest that their findings may inform strategies to develop universal vaccines against emerging and future coronaviruses. Yuanmei Zhu and colleagues analyzed 20 convalescent serum samples from patients infected with SARS-CoV, determining cross-reactivity for protein antigens derived from four regions of the SARS-CoV-2 spike protein, including the S ectodomain (S), S1 subunit, RBD, and S2 subunit. While all serum samples reacted strongly with the S and S2 proteins, they reacted more weakly with the S1 and RBD proteins. A separate test using a single-cycle infection assay determined that the convalescent SARS-CoV sera efficiently prevented both SARS-CoV and SARS-CoV-2 pseudoviruses (which cannot produce viral surface proteins on their own) from infecting cells, although they inhibited SARS-CoV-2 activity less efficiently. The researchers verified their findings in animals and specifically characterized the RBD's ability to mediate cross-reactivity in mice, since the RBD is the least conserved of the spike protein sites between the two viruses. They found that anti-RBD serum from SARS-CoV cross-reacted well with SARS-CoV-2, suggesting a key antigen component is genetically conserved in the RBD sites of the two viruses. Zhu et al. note that although antibody-dependent enhancement (when binding a virus to certain antibodies actually eases its entry into host cells) was not observed in this study, the effect should be addressed during vaccine development.

Credit: 
American Association for the Advancement of Science (AAAS)

FDA support for oncology drug development during COVID-19

What The Study Did: This Viewpoint from the U.S. Food and Drug Administration puts into context recent guidance on clinical trials during COVID-19 for oncology and shares insight regarding regulatory challenges and lessons learned.

Authors: Anand Shah, M.D., of the FDA in Silver Spring, Maryland, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamaoncol.2020.4975)

Editor's Note: The article includes conflicts of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Credit: 
JAMA Network

US viewer preference for right-wing TV media linked to fewer preventive measures against COVID-19

Viewer preference for right-wing US TV media is linked to significantly fewer preventive measures against COVID-19 and behaviours likely to increase the risk of infection, finds research published in the online journal BMJ Global Health.

The media has a key role in disseminating health information. And to better understand the relationship between political bias in the media and health behaviours, the researchers wanted to find out if behaviours related to COVID-19 differed according to viewer trust in left-or right-wing TV media and whether these behaviours changed over time.

They drew on data from the Understanding America Study (UAS) COVID-19 Survey National Sample. This is an ongoing longitudinal national online survey of approximately 9000 US adults living independently.

UAS started tracking the impact of the pandemic on 10 March 2020. Follow-up surveys were issued every fortnight beginning 1 April 2020 (wave 2) to June 9 (wave 6).

Participants were asked about preventive behaviours over the past 7 days, such as hand-washing and use of face coverings, and about risky behaviours, including going out to a bar or club, attending gatherings of more than 10 people, and visiting other people's homes.

They were also asked how much they trusted 18 media sources for information on COVID-19, focusing primarily on the left wing CNN and the right wing Fox News, the two largest news outlets in the US.

And they were asked, which of 20 other sources of information they used, including professional bodies, social and traditional media, friends, family, colleagues, and the White House.

Some 4863 respondents who completed all five waves of the survey were included in the final analysis. Their responses were scored on a scale of 0-5 and added together.

Around 29% of the sample said they trusted CNN more than Fox; about half (52%) expressed no preference, and one in five (20%) said they trusted Fox more than CNN.

On average, respondents said they had used around 3 professional sources and around 6 other diverse sources to learn about the coronavirus in the preceding 7 days.

Analysis of the responses showed that people who trusted CNN were more likely to engage in preventive behaviours and less likely to report risky behaviours than those who trusted Fox News, at most time points.

Those who trusted Fox News more than CNN practised an average of 3.41 preventive behaviours, while people who trusted CNN more than Fox News practised 3.85. Fox News devotees also practised an average of 1.25 risky behaviours, while CNN fans engaged in 0.94 risky behaviours.

Health behaviours changed significantly over time, becoming more cautious, before relaxing as the pandemic unfolded. But once again, these changes varied by media preference, with the speed of change much faster among those who preferred Fox News.

People who trusted Fox News more than CNN consistently practised fewer preventive and more risky behaviours during waves 1 to 5, compared with those who trusted CNN more.

Those who expressed no media preferences practised significantly more preventive and fewer risky behaviours than those who trusted Fox News more during the last two survey waves. And they consistently exhibited significantly fewer preventive and more risky behaviours than those who trusted CNN more for all survey waves.

People aged 65 and above, women, those of non-Hispanic Asian ethnic backgrounds, and the most educated were all more likely to practise preventive behaviours, while those with a job but unable to work from home were least likely to do so.

Diversity of information was linked to more risky behaviours, while having more sources of professional information was linked to fewer risky behaviours.

This is an observational study, and as such, can't establish cause. But the findings echo those of other studies, say the researchers.

They propose two possible explanations, the first of which is that behaviours are influenced by politically "biased health messaging." Compared with CNN, Fox News "consistently downplayed the danger of the virus for the sake of political interest."

Alternatively, behaviours may be influenced by personal political beliefs, so media preference becomes a proxy for political preference instead of a source of information.

"Specifically, republican ideology has long been centred around the idea of individualism and an emphasis on personal freedom... Therefore, it is possible that people who trust Fox naturally prefer a more 'hands-off' approach and are more likely to refuse strict health policies such as self-quarantining and social distancing," the researchers suggest.

They conclude: "This study has many policy implications for the future progression of COVID-19 and health messaging in general. In a highly partisan environment, false information can be easily disseminated.

"Health messaging, despite being one of the few effective ways to slow down the spread of the virus in the absence of a vaccine, is doomed to fail if the media prioritise political interests over population health."

Credit: 
BMJ Group

Study shows similar antibody response to key SARS-CoV-2 'spike' protein in COVID-19

New research published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]) shows that antibody responses to SARS-CoV-2 are similar in COVID-19 patients with and without diabetes, and thus are unlikely to be responsible for the higher death rates in patients with diabetes.

Furthermore, they found that a particular antibody response related to the 'spike' protein of the SARS-CoV-2 virus is strongly associated with improved survival, boosting hopes that vaccines involving this same protein will have a high chance of being as effective in vulnerable patients with diabetes as they will be in the general population. The study also found that higher blood glucose levels were strongly associated with COVID-19 mortality in patients whether or not they had diabetes.

Patients with diabetes, especially type 2 diabetes, are over-represented in COVID-19 deaths and severe disease. In countries such as the UK, around 30% of people who have died with COVID-19 infection have also had diabetes, with similar numbers reported in other countries.

"Demonstrating the ability to mount an appropriate antibody response in the presence of abnormally high blood sugar (hyperglycaemia) is relevant to understand the mechanisms related to the observed worse clinical outcome of COVID-19 pneumonia in patients with diabetes and for the development of any future vaccination campaign to prevent SARS-CoV-2 infection," explain the authors, who include Professor Lorenzo Piemonti, Director of the San Raffaele Diabetes Research Institute, IRCCS Hospital San Raffaele, Milan, Italy, and colleagues.

The authors analysed the presence of three types of antibody to COVID-19 in their study: immunoglobulin G (IgG), which is evidence of past infection; IgM, which indicates more recent or current infection, and IgA, which is involved in the mucosal immune response, for example in the nose and respiratory tract where the virus enters the body.

They analysed the IgG, IgM and IgA response against multiple antigens of SARS-CoV-2 in a cohort of 509 patients with documented diagnosis of COVID-19, prospectively followed at the IRCCS Hospital San Raffaele. These patients were all adults (aged 18 years or over) and admitted between 25 February and 19 April 2020. These patients had all signed consent forms to have blood samples taken and stored, in order to help with COVID-19 research efforts. The researchers analysed the patients' clinical outcomes and antibody levels according to the presence of hyperglycaemia, including either diagnosed or undiagnosed diabetes, at the time of, or during, hospitalisation.

Among patients with confirmed COVID-19, 139 (27.3%) had diabetes: 90 (17.7%) had diabetes diagnosed prior to the hospital admission while 49 (9.6%) had diabetes diagnosed at the time of admission (newly diagnosed). Diabetes was associated with increased levels of inflammatory biomarkers and hypercoagulopathy (increased blood clotting), as well as leucocytosis (increased leukocytes, a type of white blood cell in the immune system) and neutrophilia (high levels of neutrophils, another type of white blood cell).

Diabetes was independently associated with 2.3 times increased risk of death, even after adjustment for age, sex and other relevant comorbidities. Furthermore, a strong association between higher glucose levels and risk of death was found, irrespective of diabetes diagnosis, with statistical modelling showing that each increase in blood sugar of 1.1 mmol/l resulted in a 14% increased risk of COVID-19 related death, regardless of whether the patient had diabetes. The range of blood sugar values in patients without diabetes was 4.1 to 6.6 mmol/l, while in those with diabetes the range was much greater, from 5.1 to 14.3 mmol/l.

The immune response in terms of the above antibodies against SARS-CoV-2 in patients with diabetes was present and almost identical, in both timing and antibody levels, to that of patients without diabetes, with only marginal differences. The response was also not influenced by blood glucose levels.

Of the measured antibody responses, positivity for IgG against the SARS-CoV-2 spike receptor-binding domain (RBD) (which the virus uses to enter human cells) was predictive of survival rate, both in the presence or absence of diabetes. Overall, the presence of these particular antibodies was associated with a 60% reduction in the death rate of patients with COVID-19, with a 63% reduction death risk in patients with diabetes, and a 57% reduction in those without. This is important, say the authors, because many SARS-CoV-2 vaccines currently in development are targeting this so-called 'spike protein' in the virus.

The authors say: "Patients with either diagnosed or undiagnosed diabetes are more likely to experience severe symptoms and death from COVID-19 pneumonia. Frailty, pre-existing comorbid conditions and a potential underlying immune system dysfunction could contribute to a poorer outcome."

They conclude: "We found that diabetes or high blood sugar does not impair the immune response against SARs-CoV-2. The evidence that presence of IgG antibodies against the so-called 'spike protein' is associated with a remarkable protective effect - about a 60% reduction - in COVID-19 mortality in patients with diabetes allows for cautious optimism on the efficacy of future vaccines against SARs-COV-2 in people with diabetes, who are particularly vulnerable in this deadly pandemic."

Credit: 
Diabetologia

Stress-free gel

image: Researchers at The University of Tokyo find a new type of formation of gels with less internal mechanical stress by controlling particle interactions, with implications for food preparation and our knowledge of intracellular gelation

Image: 
Institute of Industrial Science, the University of Tokyo

Tokyo, Japan - Researchers in the Institute of Industrial Science at The University of Tokyo studied a new method for creating semisolid colloidal systems with less internal mechanical stress by delaying network formation. This work may help scientists better understand biological processes involving cytoplasm.

Within soft-matter physics, gels are a relatively familiar sight. Certain particle suspensions can be turned into a semisolid when particles join to form a stiff network. Think of Jell-O, in which a soupy mix of gelatin proteins sets into a delicious, free-standing dessert. Gels play important roles in biology, and may be involved in how cells move and respond to changing external conditions.

Scientists at The University of Tokyo studied the mechanism by which dispersed particles, called colloids, join together during gelation. Most gel networks are thought to form before dynamical motion stops, which leads to built-in mechanical stress. If the creation of the networks could be delayed, they could be made free from such stress and more stable .

"A net under mechanical tension is stretched and sometimes broken. Conventional colloidal gels suffer from such stress, and thus, are not so stable. Stress-free gels are free from this problem," first author Hideyo Tsurusawa explains.

The team found that network formation (percolation) occurs after the formation of a mechanically stable structure and the cessation of particle motion for a lower concentration of colloidal particles compared with the one at which traditional gels form. The researchers used confocal microscopy and computer simulations to better understand both conventional and stress-free gelation. Systems with fluorescently-labeled poly(methyl methacrylate) colloids could be monitored to see how long it took for networks to form and for particle motion to be arrested.

The choice between these two types of gelation is determined by the large and small relationship between the two characteristic times, i.e., "time until the mechanically stable structure is formed" and "time to percolation". Furthermore, when the interaction between the particles is short-range, the large and small relationship is determined solely by the volume fraction of the colloid.

"We found that colloidal gelation can universally be grouped into the two types. This universal classification of the gelation of particle systems is expected to make a significant contribution to the understanding of gelation in the field of soft matter and biology.," senior author Hajime Tanaka says. "Our findings could be applied to developing new industrial processes that create semisolid products, including foodstuffs, more efficiently."

Credit: 
Institute of Industrial Science, The University of Tokyo

Light stimulation makes bones heavier

image: Laser irradiation causes photomechanical response, photobiological activation reaction, and photochemical response in the various tissues and cells. Downregulation of Sost expression in the bone tissue was observed after Er:YAG laser bone ablation. Because sclerostin (coded by Sost) suppressed bone formation by inhibiting canonical Wnt signaling pathway, there is a possibility that Er:YAG laser irradiation to the bone enhances bone formation.

Image: 
Department of Periodontology,TMDU

Researchers from Tokyo Medical and Dental University (TMDU) show that laser irradiation inhibits expression of the osteogenesis inhibitor protein sclerostin without causing inflammation, providing a potential therapeutic option for osteoporosis

Tokyo, Japan - Osteoporosis is a disease in which bone loses mass as a result of age or other influences. This weakening is the leading cause of fractures in the elderly, often after trivial injuries, and makes treating these "pathological fractures" a challenge. Bone health is a dynamic process of continual remodeling controlled by multiple factors. Sclerostin, a glycoprotein coded by the gene SOST, is produced by bone cells and suppresses bone formation. Now, researchers at Tokyo Medical and Dental University (TMDU) have shown that laser irradiation, by inhibiting sclerostin expression without inducing inflammation, shows promise as a new treatment modality for osteoporosis.

Lasers have been used in medical and dental practice for their beneficial photo-biomodulation effects on tissue healing. The benefits of low-level laser therapy are now gaining increased attention in spheres of medicine and dentistry that require enhanced bone regeneration.

The team knew that in periodontal surgery, bone that underwent controlled destruction using a specific type of laser known as an Er:YAG laser healed faster than bone subjected to conventional bur drilling. Thus, they wondered whether Er:YAG laser irradiation modified SOST expression in bone. "We set out to compare comprehensive and sequential gene expression and biological healing responses in laser-ablated, bur-drilled, and untreated bone, as well as investigating the bio-stimulation effect of an Er:YAG laser on osteogenic cells," explains Yujin Ohsugi, lead author.

Using microarray analysis, the researchers first studied gene expression patterns in rat skull bones during healing at 6, 24, and 72 hours after drilling or laser treatment. Immunohistochemical analysis at 1 day was performed to detect sclerostin expression. Additionally, oseteogenic cell cultures were irradiated in vitro and assessed for cell death and sclerostin concentration.

"We confirmed decreased sclerostin expression after laser irradiation both in vivo and in vitro," affirms Sayaka Katagiri, corresponding author. "Interestingly, sequential microarray analysis revealed a clear distinction in the gene expression pattern between bur-drilled and laser-ablated bones at 24 hours, with the former alone showing enriched inflammation-related pathways. Significantly, at 6 hours following laser ablation, the Hippo signaling pathway that limits tissue overgrowth was enriched but inflammation-related pathways remained unaffected, suggesting that laser irradiation worked thorough mechanical bio-stimulation."

The finding that mechanical stimulation of laser irradiation inhibits the pathways that suppress bone regeneration without provoking inflammation may aid development of laser-based therapeutic methods. Such methods might be used in treatments for osteoporosis and to induce or promote bone regeneration in medical and dental procedures.

Credit: 
Tokyo Medical and Dental University

Lack of support prolongs unemployment

Everyone has to call in sick at work at some point. With caseworkers at the employment office, however, a sudden absence has direct economic consequences for a third party: The people they support are unemployed on average five percent longer if a meeting is canceled, which corresponds to a period of twelve days. This may sound rather trivial, but it can entail considerable costs for both the welfare state and the individual concerned.

Amelie Schiprowski, economist of the Cluster of Excellence ECONtribute at the Universities of Cologne and Bonn (Germany), evaluated Swiss unemployment insurance data from 2010 to 2012 and investigated how much the personal interaction with caseworkers matters for unemployed individuals. She found out: The duration of unemployment depends to a large extent on how reliable and committed the support provided by the employment office is.

Regular support important for reintegration

Caseworkers at the employment office help to reintegrate unemployment benefit recipients into the labor market. A spontaneous absence of a caseworker reduces the average number of meetings that an unemployed individual can attend. As there are only about two to three meetings per half-year, one missed meeting corresponds in the analyzed data to about 40 percent of support time. The cancellation of a meeting results on average in a five percent longer unemployment spell. This means in turn that regular support is very important for successful reintegration.

Quantity and quality are important

The economist divided the observed caseworkers into two groups according to their productivity; productivity means how quickly, on average, the people they supported found a job again. The result: Absences of less productive caseworkers have no negative effect, while the absence of a more productive caseworker extends unemployment by an average of 13 percent. The negative impact of a canceled appointment therefore depends on the quality of the support.

Investment in human capital can reduce duration of unemployment

The paper highlights the economic importance of staff at the employment office. "Caseworkers are underestimated as an important resource for welfare states," says Amelie Schiprowski. Every day of additional unemployment is expensive for the state. Unemployment could be decreased by reducing the workload of individual caseworkers to facilitate more individual meetings, and by investing into the quality of the support provision.

Credit: 
University of Bonn

World's largest experiment shows shack fires move with devastating speed

image: Photo of the fire experiment

Image: 
Stellenbosch University

Twenty shacks destroyed in five minutes. That's how quickly fires can spread in informal settlements.

This is one of the major results of the world's largest informal settlement fire experiment consisting of twenty homes.

The experiment was conducted by the Fire Engineering Research Unit at Stellenbosch University (FireSUN) in collaboration with the Western Cape Disaster Management, Fire & Rescue Services and the Breede Valley Municipality (BVM) Fire Department who hosted the experiment and provided significant assistance to the overall research efforts. The work forms part of a collaborative project with the University of Edinburgh looking at how to reduce the impact of such fires, which has been funded by the UK-based Global Challenges Research Fund.

The results of the experiment have been published recently in Fire Technology, one of the leading academic journals in fire safety.

[A video of the experiment can be watched at https://youtu.be/kkXr6ueakAU with the technical details being found at https://rdcu.be/b7Z9e.]

"People often criticise the Fire Department for not acting swiftly, but our experiment showed that a fire can move really, really fast. Firefighters have always known this, but now we have better experimental data to understand the problem and analyse interventions," says Prof Richard Walls from FireSUN who managed the overall project.

"From our experiment we could see that certain interventions currently being implemented would have been ineffective for slowing down this fire. For instance, fire-resistant paint would have had little impact due to the intensity of the fire and the fact that the fire ignited homes through any small openings in these structures, negating the influence of coatings. Also, doors and windows in a densely-packed settlement will always provide an easy entrance for fire."

The experiment was designed by Walls' colleague Dr Nico de Koker who also analysed the results.

He says the experiment was designed to simulate a 'fire line' which would be found in a dense settlement as a large fire moves through it. "We included extensive instrumentation, thermal-imaging cameras, a drone and other equipment in the experiment to provide data on flame lengths, temperatures experienced, spread rates and details regarding when homes ignited."

Walls points out that from the time the first homes were ignited until the time the last homes caught alight was around five minutes.

"This is a frightening figure when it is considered that often it can take many minutes for a resident to notice a fire, to contact the local fire brigade (often the wrong number is called), a fire truck to be dispatched and then possibly has to drive a long distance, for fighters to find the burning dwellings (in the midst of a settlement with no street names), to setup and finally extinguish the fire."

"After around 16 minutes there were almost no homes left standing in the experiment, there was simply a pile of scrap metal lying on the floor. Temperatures of up to around 1200°C were measured, and flames many meters long emerged from dwellings."

Highlighting the value of the experiment, Deputy Fire Chief Josephus Pretorius of the BVM notes that their firefighters regularly risk their lives to fight these very dangerous fires. "It is exciting that our municipality has been able to make this research possible, so that we can better understand how these fires spread and behave."

Echoing his sentiments, Marlu Rust of the Western Cape Disaster Management, Fire & Rescue Services explains that "We have been actively working on ways to improve fire safety in informal settlements, and have worked closely with Stellenbosch University over the past years. Our fire departments have major challenges in trying to fight such fires so it is important that government, academia and communities are working together to find solutions."

Walls says that from this research experiment, and many others, the team has been developing a good understanding of fire spread in settlements.

"Although there are no easy solutions to the problem, at least the data is immediately showing what sort of interventions are likely to be less effective. Computer models have been developed to simulate fire spread through settlements, and may soon be useful decision-making tools for analysing risk in settlements, and potentially for developing fire safety strategies."

Walls adds that this experiment, amongst others, also helped to shed light on the performance of products (e.g. detectors, fire-resistant paints, extinguishers and warning systems to municipalities) used to prevent an informal settlement fire; how fast these fires spread; and how to suppress them as efficiently as possible and how communities can assist.

He says a final set of experiments conducted after this large-scale test are currently being analysed to provide further insight on a number of aspects. Also, a series of tests have been undertaken to understand the effectiveness of community-based suppression systems.

Credit: 
Stellenbosch University

Inhibiting epileptic activity in the brain

image: The DUSP4 protein is located on the border between epileptic and non-epileptic brain tissue

Image: 
UIC/Jeffrey Loeb

Epileptic seizures often originate in small, localized areas of the brain where neurons abnormally fire in unison. These electrical impulses disrupt proper brain functioning and cause seizures. But what makes regions where seizures start different from parts of the brain where electrical impulses remain normal? More importantly, what prevents these epileptic centers from growing?

The answer to these questions may lie in a new discovery by researchers at the University of Illinois Chicago. Dr. Jeffrey Loeb and his colleagues found that a protein -- called DUSP4 -- was increased in healthy brain tissue directly adjacent to epileptic tissue. Their research suggests that boosting levels of DUSP4 could be a novel way of preventing or treating epilepsy.

Their findings are reported in the journal Neurobiology of Disease.

"If epileptic brain regions spread throughout the brain with nothing to stop them, the seizures would overwhelm the brain, it would not be survivable," said Loeb, UIC professor and head of neurology and rehabilitation at the College of Medicine and corresponding author on the study. "We wondered if there were natural ways that epileptic brain areas are quarantined. We searched for genes at the border between epileptic and normal brain tissue that may help prevent the spread of epilepsy."

Loeb and colleagues analyzed thousands of genes in tissues from 20 patients who underwent surgery to treat their epilepsy. During these surgical procedures, brain tissue from epileptic areas and directly adjacent, non-epileptic tissue was removed. Tissue not required for pathological evaluation was stored in the University of Illinois NeuroRepository -- a human brain tissue bank and research database that links clinical, radiological, physiological, histological and molecular/genomic data to thousands of human tissue samples.

The researchers used a mathematical modeling technique called cluster analysis to sort through huge numbers of genes from the epileptic versus the nonepileptic tissue. They identified a number of genes that were increased -- or "upregulated" -- in or near epileptic tissues and the observed that DUSP4 fell into a different cluster than most of the pro-epileptic genes.

In previous research, Loeb and colleagues identified a signaling pathway that was highly upregulated in areas of the brain where epileptic seizures started. In an animal model, suppression of the pathway --known as the mitogen-activated protein kinase, or MAPK, pathway -- reduced epileptic electrical activity in the brain.

"We were excited about DUSP4 because it is known to be a potent MAPK pathway inhibitor in cancer cells," Loeb said. "Seeing this gene activated at the borders and shutting off MAPK signaling genes in the human brain led us to believe that the protein cordons off epileptic regions so that they don't enlarge or spread, similar to how in a ship you might get a leak in one area, but you can close and seal off doors to keep the leak isolated. That's how we think DUSP4 is working to keep epileptic focal points from enlarging."

In addition to the gene, when the researchers went back to look at the protein's levels in their tissue samples, they found that tissue from brain regions with lower epileptic activity had lower MAPK activity and higher levels of the DUSP4 protein.

Loeb and colleagues currently are investigating potential drugs that can upregulate or augment the activity of DUSP4 to help treat or even prevent epilepsy.

"These DUSP4-targeting drugs would represent a new kind of 'disease-modifying' treatment for epilepsy, which currently does not exist," Loeb said.

Credit: 
University of Illinois Chicago

Coronavirus antibodies last at least three months after infection, study suggests

image: Coronavirus antibodies can last at least three months after a person becomes infected with the virus that causes COVID-19, according to a new study published Thursday in Science Immunology.

Image: 
Temerty Faculty of Medicine

Coronavirus antibodies can last at least three months after a person becomes infected with the virus that causes COVID-19, according to a new study published today in Science Immunology.

Researchers from the Lunenfeld-Tanenbaum Research Institute (LTRI) at Sinai Health and the Temerty Faculty of Medicine at the University of Toronto used both saliva and blood samples from COVID-19 patients to measure and compare antibody levels for over three months post-symptom onset.

They found that antibodies of the IgG class that bind to the SARS-CoV-2 spike protein are detectable for at least 115 days, representing the longest time interval measured. The study is also the first to show these antibodies can also be detected in the saliva.

"Our study shows that IgG antibodies against the spike protein of the virus are relatively durable in both blood and saliva," said Jennifer Gommerman, professor of immunology at the University of Toronto and leader of the saliva testing effort. "Our study suggests saliva may serve as an alternative for antibody testing. While saliva is not as sensitive as serum, it is easy to collect."

The saliva assay was developed at the University of Toronto, while a team at LTRI, led by senior investigator Anne-Claude Gingras, a professor of molecular genetics at the University of Toronto, executed the serum assay.

"The LTRI platform for detection of antibodies in serum, or blood, is incredibly robust and well suited for assessing the prevalence of infection within the community," said Gingras. "This is another tool that can help us better understand and even overcome this virus."

Most people who recover from COVID-19 develop immune agents in their blood called antibodies that are specific to the virus. These antibodies are useful in indicating who has been infected, regardless of whether they had symptoms or not.

A large team of scientists collaborated on the study. Dr. Allison McGeer, a senior clinician scientist at LTRI and principal investigator of the Toronto Invasive Bacterial Diseases Network, along with Dr. Mario Ostrowski at St. Michael's Hospital of Unity Health Toronto provided access to the paired saliva and serum samples from dozens of patients for the study.

The study was co-led by graduate students Baweleta Isho, Kento Abe, Michelle Zuo and Alainna Jamal. Dr. James Rini, a professor of biochemistry and molecular genetics at the University of Toronto, and Yves Durocher from the National Research Council of Canada provided key protein reagents for the saliva studies.

The durability of the antibody response to SARS-CoV-2 has been debated in recent months. An earlier study published in Nature Medicine suggested the antibodies can disappear after two months for some individuals who had the virus but did not experience symptoms.

This study led by the Toronto team is in agreement with findings from leading immunologists in the U.S. in describing the antibody response as longer lasting.

While the team admits there is a lot they still don't know about antibody responses to SARS-CoV-2 infection, including how long the antibodies last beyond this period or what protection they afford against re-infection, this research could have broader implications in the development of an effective vaccine.

"This study suggests that if a vaccine is properly designed, it has the potential to induce a durable antibody response that can help protect the vaccinated person against the virus that causes COVID-19," Gommerman said.

Credit: 
University of Toronto