Culture

Background: Persistent poverty means that a county has had poverty rates of 20 percent or more in U.S. Census data from 1980, 1990, and 2000. These areas, representing about 10 percent of all U.S. counties, are primarily located in the rural South.

Persistent-poverty counties typically have larger populations of racial and ethnic minorities; more children under age 18; less formal education; and greater unemployment. They are also more likely to have high rates of cancer risk factors such as obesity or cigarette smoking, Moss added. She drew a distinction between counties with persistent poverty and those with current poverty, which is defined as 20 percent or more of the population living in poverty according to the 2007-2011 American Community Survey.

"Counties that have experienced persistent poverty face health risks that have accumulated for decades, and they have fewer current or past resources to protect public health," she said.

How the Study was Conducted: In this study, Moss and colleagues examined cancer mortality rates in persistently poor counties compared with other counties. The median income in the persistently poor counties was $32,156, compared with $47,154 in the counties not experiencing persistent poverty.

The researchers calculated 2007-2011 county-level, age-adjusted, overall, and type-specific cancer mortality rates.

Results: They found that the overall cancer mortality rate in persistent-poverty counties was 201.3 deaths per 100,000 people, compared with 179.3 per 100,000 people in counties not experiencing persistent poverty.

For each cancer type studied, mortality was between 11 and 50 percent higher in the counties with persistent poverty. For example, the mortality rate from lung/bronchus cancer was 16.5 percent higher; from colorectal cancer, 17.7 percent higher; from stomach cancer, 43.2 percent higher; and from liver and intrahepatic bile duct cancer, 27.6 percent higher in the persistent-poverty counties than in the counties not experiencing persistent poverty.

Author's Comments: Moss said the disparities in various cancer types reflected a number of persistent risk factors that are more common in poorer communities, such as smoking, excess weight, and higher rates of infections. These factors, in turn, are likely related to fewer systemic opportunities for accessing good health, for example, fewer job prospects, inadequate health care facilities, and less safe housing and occupational environments. However, Moss said further research should examine other potential causes of the disparities. For example, it is possible that chronic stress associated with less access to health care, more chronic unemployment, and other financial factors may lead to inflammation that gives rise to some cancers, she said.

In general, the counties experiencing current but not persistent poverty had higher cancer mortality rates than the overall U.S. population, but lower rates than the persistently poor counties. Moss said the results of this study indicate that researchers should distinguish between persistent poverty and current poverty, since persistent poverty is associated with the strongest risk of cancer mortality. She said the long-entrenched societal problems surrounding persistent poverty merit local and national interventions to improve health outcomes.

"To prevent health disparities, we need tools, people, and systems to ensure that everyone in this country has access to the tools they need to thrive, including socioeconomic opportunities, equity, and respect, as well as prevention resources and health care services," Moss said.

"We need interventions in these communities to change cancer-causing behaviors, to make cancer screening more accessible, to improve treatment, and to promote quality of life and survivorship," she continued. "Efforts to reduce the risk of cancer in these counties will require strategic coordination, collaboration, and funding, with input from community members every step of the way."

Study Limitations: The study's chief limitation is that it did not account for residential history, so the researchers could not determine whether the amount of time spent in a persistently poor county affected cancer mortality risk.

Cannabinoids, a class of prescription pills that contain synthetically-made chemicals found in marijuana, are associated with a 64 per cent increase in death among older adults with chronic obstructive pulmonary disease (COPD), according to the first published data on the impact of cannabinoids on the respiratory health of individuals with the lung disease.

The findings, published Wednesday in Thorax, have significant clinical implications as more physicians prescribe cannabinoids to patients with COPD to treat chronic muscle pain, difficulty sleeping and breathlessness.

The study, led by St. Michael's Hospital of Unity Health Toronto, found that cannabinoids can contribute to negative respiratory health events in people with COPD, including hospitalization and death. COPD is a progressive lung disease that causes difficulty breathing and chronic productive coughing, and can be associated with a variety of non-respiratory issues, like chronic muscle pain and insomnia.

"Cannabinoid drugs are being increasingly used by older adults with COPD, so it is important for patients and physicians to have a clear understanding of the side-effect profile of these drugs," says Dr. Nicholas Vozoris, lead author, a respirologist at St. Michael's and an associate scientist at the hospital's Li Ka Shing Knowledge Institute.

"Our study results do not mean that cannabinoid drugs should be never used among older adults with COPD. Rather, our findings should be incorporated by patients and physicians into prescribing decision-making. Our results also highlight the importance of favouring lower over higher cannabinoid doses, when these drugs actually do need to be used."

The study analyzed the health data of over 4,000 individuals in Ontario ages 66 years and older with COPD from 2006 to 2016. The data was equally split into two groups: older adults with COPD who were new cannabinoid users and older adults with COPD not using cannabinoids. Older adults in Ontario with COPD who were new cannabinoid users represented 1.1 per cent of the data, which was made available by ICES.

Researchers observed particularly worse health outcomes among patients with COPD who were using higher doses of cannabinoids. Compared to non-users, new higher-dose cannabinoid users had a 178 per cent relative increase in hospitalizations for COPD or pneumonia, and a 231 per cent relative increase in all-cause death.

"Older adults with COPD represent a group that would likely be more susceptible to cannabinoid-related respiratory side-effects, since older adults less efficiently break down drugs and hence, drug effects can linger in the body for longer - and since individuals with COPD have pre-existing respiratory troubles and respiratory compromise," says Dr. Vozoris, who is also a scientist at ICES.

Researchers conducted a sub-analysis to explore what impact cannabinoid drugs versus opioid drugs had on respiratory outcomes among older adults with COPD, since cannabinoid drugs are often prescribed as an alternative to opioids to treat chronic pain. The research team did not find evidence to support that cannabinoids were a safer choice over opioids for older adults with COPD in so far as respiratory health outcomes.

JUPITER, FL - Sept. 30, 2020 - Scripps Research chemist Matthew Disney, PhD, and colleagues have created drug-like compounds that, in human cell studies, bind and destroy the pandemic coronavirus' so-called "frameshifting element" to stop the virus from replicating. The frameshifter is a clutch-like device the virus needs to generate new copies of itself after infecting cells.

"Our concept was to develop lead medicines capable of breaking COVID-19's clutch," Disney says. "It doesn't allow the shifting of gears."

Viruses spread by entering cells and then using the cells' protein-building machinery to churn out new infectious copies. Their genetic material must be compact and efficient to make it into the cells.

The pandemic coronavirus stays small by having one string of genetic material encode multiple proteins needed to assemble new virus. A clutch-like frameshifting element forces the cells' protein-building engines, called ribosomes, to pause, slip to a different gear, or reading frame, and then restart protein assembly anew, thus producing different protein from the same sequence.

But making a medicine able to stop the process is far from simple. The virus that causes COVID-19 encodes its genetic sequence in RNA, chemical cousin of DNA. It has historically been very difficult to bind RNA with orally administered medicines, but Disney's group has been developing and refining tools to do so over more than a decade.

The scientists' report, titled "Targeting the SARS-CoV-2 RNA Genome with Small Molecule Binders and Ribonuclease Targeting Chimera (RIBOTAC) Degraders," appears Sept. 30 in the journal ACS Central Science.

Disney emphasizes this is a first step in a long process of refinement and research that lies ahead. Even so, the results demonstrate the feasibility of directly targeting viral RNA with small-molecule drugs, Disney says. Their study suggests other RNA viral diseases may eventually be treated through this strategy, he adds.

"This is a proof-of-concept study," Disney says. "We put the frameshifting element into cells and showed that our compound binds the element and degrades it. The next step will be to do this with the whole COVID virus, and then optimize the compound."

Disney's team collaborated with Iowa State University Assistant Professor Walter Moss, PhD, to analyze and predict the structure of molecules encoded by the viral genome, in search of its vulnerabilities.

"By coupling our predictive modeling approaches to the tools and technologies developed in the Disney lab, we can rapidly discover druggable elements in RNA," Moss says. "We're using these tools not only to accelerate progress toward treatments for COVID-19, but a host of other diseases, as well."

The scientists zeroed in on the virus' frameshifting element, in part, because it features a stable hairpin-shaped segment, one that acts like a joystick to control protein-building. Binding the joystick with a drug-like compound should disable its ability to control frameshifting, they predicted. The virus needs all of its proteins to make complete copies, so disturbing the shifter and distorting even one of the proteins should, in theory, stop the virus altogether.

Using a database of RNA-binding chemical entities developed by Disney, they found 26 candidate compounds. Further testing with different variants of the frameshifting structure revealed three candidates that bound them all well, Disney says.

Disney's team in Jupiter, Florida quickly set about testing the compounds in human cells carrying COVID-19's frameshifting element. Those tests revealed that one, C5, had the most pronounced effect, in a dose-dependent manner, and did not bind unintended RNA.

They then went further, engineering the C5 compound to carry an RNA editing signal that causes the cell to specifically destroy the viral RNA. With the addition of the RNA editor, "these compounds are designed to basically remove the virus," Disney says.

Cells need RNA to read DNA and build proteins. Cells have natural process to rid cells of RNA after they are done using them. Disney has chemically harnessed this waste-disposal system to chew up COVID-19 RNA. His system is called RIBOTAC, short for "Ribonuclease Targeting Chimera."

Adding a RIBOTAC to the C5 anti-COVID compound increases its potency by tenfold, Disney says. Much more work lies ahead for this to become a medicine that makes it to clinical trials. Because it's a totally new way of attacking a virus, there remains much to learn, he says.

"We wanted to publish it as soon as possible to show the scientific community that the COVID RNA genome is a druggable target. We have encountered many skeptics who thought one cannot target any RNA with a small molecule," Disney says. "This is another example that we hope puts RNA at the forefront of modern medicinal science as a drug target."

Venus might not be a sweltering, waterless hellscape today, if Jupiter hadn't altered its orbit around the sun, according to new UC Riverside research.

Jupiter has a mass that is two-and-a-half times that of all other planets in our solar system -- combined. Because it is comparatively gigantic, it has the ability to disturb other planets' orbits.

Early in Jupiter's formation as a planet, it moved closer to and then away from the sun due to interactions with the disc from which planets form as well as the other giant planets. This movement in turn affected Venus.

Observations of other planetary systems have shown that similar giant planet migrations soon after formation may be a relatively common occurrence. These are among the findings of a new study published in the Planetary Science Journal.

Scientists consider planets lacking liquid water to be incapable of hosting life as we know it. Though Venus may have lost some water early on for other reasons, and may have continued to do so anyway, UCR astrobiologist Stephen Kane said that Jupiter's movement likely triggered Venus onto a path toward its current, inhospitable state.

"One of the interesting things about the Venus of today is that its orbit is almost perfectly circular," said Kane, who led the study. "With this project, I wanted to explore whether the orbit has always been circular and if not, what are the implications of that?"

To answer these questions, Kane created a model that simulated the solar system, calculating the location of all the planets at any one time and how they pull one another in different directions.

Scientists measure how noncircular a planet's orbit is between 0, which is completely circular, and 1, which is not circular at all. The number between 0 and 1 is called the eccentricity of the orbit. An orbit with an eccentricity of 1 would not even complete an orbit around a star; it would simply launch into space, Kane said.

Currently, the orbit of Venus is measured at 0.006, which is the most circular of any planet in our solar system. However, Kane's model shows that when Jupiter was likely closer to the sun about a billion years ago, Venus likely had an eccentricity of 0.3, and there is a much higher probability that it was habitable then.

"As Jupiter migrated, Venus would have gone through dramatic changes in climate, heating up then cooling off and increasingly losing its water into the atmosphere," Kane said.

Recently, scientists generated much excitement by discovering a gas in the clouds above Venus that may indicate the presence of life. The gas, phosphine, is typically produced by microbes, and Kane says it is possible that the gas represents "the last surviving species on a planet that went through a dramatic change in its environment."

For that to be the case, however, Kane notes the microbes would have had to sustain their presence in the sulfuric acid clouds above Venus for roughly a billion years since Venus last had surface liquid water -- a difficult to imagine though not impossible scenario.

"There are probably a lot of other processes that could produce the gas that haven't yet been explored," Kane said.

Ultimately, Kane says it is important to understand what happened to Venus, a planet that was once likely habitable and now has surface temperatures of up to 800 degrees Fahrenheit.

"I focus on the differences between Venus and Earth, and what went wrong for Venus, so we can gain insight into how the Earth is habitable, and what we can do to shepherd this planet as best we can," Kane said.

COLUMBUS, Ohio - When people have the option to click "like" on a media article they encounter online, they spend less time actually reading the text, a new study suggests.

In a lab experiment, researchers found that people spent about 7 percent less time reading articles on controversial topics when they had the opportunity to upvote or downvote them than if there was no interactive element.

The finding was strongest when an article agreed with the reader's point of view.

The results suggest that the ability to interact with online content may change how we consume it, said Daniel Sude, who led the work while earning a doctoral degree in communication at The Ohio State University.

"When people are voting whether they like or dislike an article, they're expressing themselves. They are focused on their own thoughts and less on the content in the article," Sude said.

"It is like the old phrase, 'If you're talking, you're not listening.' People were talking back to the articles without listening to what they had to say."

In another finding, people's existing views on controversial topics like gun control or abortion became stronger after voting on articles that agreed with their views, even when they spent less time reading them.

"Just having the ability to like an article you agreed with was enough to amplify your attitude," said study co-author Silvia Knobloch-Westerwick, professor of communication at Ohio State.

"You didn't need to read the article carefully, you didn't have to learn anything new, but you are more committed to what you already believed."

The study, also co-authored by former Ohio State doctoral student George Pearson, was published online recently in the journal Computers in Human Behavior and will appear in the January 2021 print edition.

The study involved 235 college students. Before the study, the researchers measured their views on four controversial topics used in the experiment: abortion, welfare benefits, gun control and affirmative action.

Participants were then showed four versions of an online news website created for the study, each on one of the controversial topics. Each webpage showed headlines and first paragraphs for four articles, two with a conservative slant and two with a liberal slant. Participants could click on the headlines to read the full stories.

Two versions of the websites had a banner that said, "Voting currently enabled for this topic," and each article had an up arrow or down arrow that participants could click on to express their opinion.

The other two websites had a banner that said, "Voting currently disabled for this topic."

Participants were given three minutes to browse each website as they wished, although they were not told about the time limit. The researchers measured the time participants spent on each story and whether they voted if they had the opportunity.

As expected, for each website, participants spent more time reading articles that agreed with their views (about 1.5 minutes) than opposing views (less than a minute).

But they spent about 12 seconds less time reading the articles they agreed with if they could vote.

In addition, people voted on about 12 percent of articles that they didn't select to read, the study showed.

"Rather than increasing engagement with website content, having the ability to interact may actually distract from it," Sude said.

The researchers measured the participants' views on the four topics again after they read the websites to see if their attitudes had changed at all.

Results showed that when participants were not able to vote, time spent reading articles that agreed with their original views strengthened these views. The more time they spent reading, the stronger their views became.

When participants were able to vote, their voting behavior was as influential as their reading time. Even if they stopped reading and upvoted an article, their attitudes still became stronger.

"It is important that people's views still became stronger by just having the opportunity to vote, Knobloch-Westerwick said.

"When they had the opportunity to vote on the articles, their attitudes were getting more extreme with limited or no input from the articles themselves. They were in an echo chamber of one."

Sude said there is a better way to interact with online news.

"Don't just click the like button. Read the article and leave thoughtful comments that are more than just a positive or negative rating," he said.

"Say why you liked or disliked the article. The way we express ourselves is important and can influence the way we think about an issue."

Small watery droplets on the edges of blueberry bush leaves are loaded with nutrients for many insects, including bees, wasps and flies, according to a Rutgers-led study, the first of its kind.

The study, published in the journal Proceedings of the Royal Society B: Biological Sciences, suggests that these droplets are an important but underexplored feature in plants, with profound implications for insects in agricultural and natural ecosystems.

"Our study shows for the first time that plant 'guttation' - fluid from sap secreted at the edges and tips of leaves - is a nutrient-rich source of food for insects," said senior author Cesar Rodriguez-Saona, a professor and extension specialist in the Department of Entomology in the School of Environmental and Biological Sciences at Rutgers University-New Brunswick.

Many insects such as bees, wasps and flies drink the small droplets, which arise on nights with high levels of moisture in soil, and biologists considered them only as a source of water for insects. But the droplets are rich in carbohydrates and contain proteins that are essential for many insect species, according to Rodriguez-Saona.

In an experiment in Rutgers blueberry fields, insects with three different feeding lifestyles (an herbivore, a parasitic wasp and a predator) increased their ability to survive and reproduce when they fed on plant guttation droplets during their entire adult lives.

The droplets were also present in blueberry fields through the entire season and their presence doubled the abundance of beneficial insects - parasitic wasps and predators - that protect plants from pests. As a result, droplets might reduce the many problems caused by pests in crops, including invasive pests. And the researchers suggest that might occur in numerous crops where the droplet phenomenon is common, such as rice, wheat, barley, rye, oats, sorghum, corn, tobacco, tomatoes, strawberries and cucumbers, among others.

"These findings are important for the conservation of beneficial insects because they can find and feed on droplets when pollen, nectar, hosts or prey are scarce," Rodriguez-Saona said.

Overall, the results demonstrate that the droplet phenomenon is highly reliable, compared with other plant-derived food sources such as nectar, and it increases the communities and fitness of insects, the study says.

Next steps include investigating the nutritional quality of droplets from other plant species and their fitness benefits for insects, as well as testing whether insecticides remain in droplets after being applied and affect beneficial insects.

It's called senescence, when stressed cells can no longer divide to make new cells, and it's considered a factor in aging and in some diseases. Now scientists have some of the first evidence that at a younger age at least, senescent cells show up quickly after a major injury and are protective.

Their model is hemorrhagic shock, a significant loss of blood and the essential oxygen and nutrients it delivers that accounts for about 30-40% of trauma-related deaths from things like car accidents and shootings; and their focus the liver, one of the many major organs that can fail in response.

Medical College of Georgia scientists report in the journal Aging Cell that shortly after hemorrhagic shock occurs, a population of liver cells quickly become senescent.

“If the cells switch immediately to a senescent state, they may help prevent organ failure,” says Dr. Raghavan Pillai Raju, biomedical researcher in the MCG Department of Pharmacology and Toxicology and the study’s corresponding author.

To find out if the rapid movement to senescence they saw for some liver cells was good or bad, they gave some of the rats in their studies senolytics, a relatively new class of drugs that target senescent cells for elimination. Laboratory studies of these drugs have shown they can prevent or improve age-related problems like frailty, cataracts and vascular and heart dysfunction. Early trials in humans have also reported success in reducing the progression of problems like diabetes and kidney related damage.

But when younger rats in hemorrhagic shock were given the drugs as part of the fluids used for resuscitation shortly after blood loss, they all quickly died.

“We wondered if it was the drugs themselves that were lethal to the rats,” said Dr. Xiaogang Chu, MCG research associate and the study’s first author. Animals and humans may not respond the same to a drug. However when they gave senolytics to healthy rats, they were fine.

“The results suggest that the induction of acute senescence may be a necessary process in hemorrhagic shock,” they write. Death of the senescent cells appears to exacerbate the tissue injury resulting from blood loss, and the drugs that target those cells also have off-target effects that are problematic with an injury as opposed to age-related senescence, they write.

They also wanted to know if giving a drug cocktail to improve organ function by strengthening cell powerhouses called mitochondria, which are weakened by the blood and oxygen deficit, would alter emergence of the senescent cells in the liver. They found the cell population that quickly emerged was essentially the same as those without the organ-specific support.

Raju and his colleagues suspect the rapid transition to senescence that occurred in a population of liver cells was an attempt to stabilize after the trauma, and likely transient.

This is the first evidence that cellular senescence can develop within a few hours after tissue injury, that hemorrhagic injury can make that happen and that the senescent cells that emerge are not detrimental in this scenario.

Cell senescence is known to be triggered by cell stress, like DNA damage, activation of oncogenes, dysfunction of the mitochondria and oxidative stress, an unhealthy buildup of reactive oxygen species that contributes to a number of maladies like heart disease, and a factor in normal aging. In fact, there are parallels between significant injury and aging, particularly the fact that mitochondrial function -- energy production by the cell -- decreases in both, Raju says.

"As we age, our cells slowly stop dividing, they express certain markers, they secrete certain proteins like cytokines and this state of cellular arrest of proliferation under stress, this is senescence," says Raju. Senescence is an important function throughout life that starts as soon as development, when endless decisions are being made about which cells to keep and eliminate, or at least quieten, and continues throughout life as part of your daily cell activity.

While not a given, senescence can be a death sentence for cells, which start to secrete factors called SASPs, which get the attention of the immune system so the cell may be tagged for elimination by immune cells called macrophages, which find and consume them.

But it may also make cells far less vulnerable to programmed cell death, or apoptosis, which cells can initiate when they have irreparable damage, like what may result from dramatic loss of blood and oxygen, Raju says. "Apoptosis is suicide versus homicide," he says. And senescence appears to enable cells to opt for a lower-functioning state instead of death.

This "hunkered down" state, which rapidly followed hemorrhagic shock, may enable the liver cells to survive until the blood, oxygen and nutrient deficit passes, he says, but what fraction of cells switch to this hunkered mode and whether, as speculated, they can reverse the state remain unknowns he wants to pursue. Raju's team has documented apoptosis by some liver cells in response to hemorrhagic shock.

"I want to see if these senescent cells are persisting or dying," Raju says. He also wants to know the impact of using the senescent cell suppressing drugs before injury, to further assess the drugs' impact and see if the rapid emergence of senescent cells is impacted.

They also found increased levels of the SASPs, or senescence-associated secretory phenotype markers, things like growth factors and enzymes that break down proteins and peptides, secreted at high levels by senescent cells, again much like in the livers of aged rats. SASPs can be good and bad, causing problems like insulin resistance and inflammation, but also aiding wound healing and tissue regeneration. The SASP complement can vary depending on what sent a cell into senescence and the cell type. There were also upticks in proteins, for example, that can arrest the cell cycle and mediators of DNA damage known to be critical to cell senescence, along with others.

While many of our cells routinely are not actively dividing, they have that potential, Raju says. Cell division is important to replace high turnover cells in areas like the gut and skin, and also to enable wound healing, but even that rate slows with age.

Other than the fact that senescence can prevent cells from becoming rapidly dividing cancer cells, it is widely considered a detriment to health in aging. The MCG scientists suspected the liver cells showing signs of senescence would be bad too, and that killing them might help patients, as it appears to do in aging, Raju says. But instead they found senescence is not bad and may actually be good in the aftermath of injury. In fact, the cells can even heal in this hunkered-down state.

Raju got interested in senescence because of his interest in injury, which can happen across a lifetime. But there are definite trends that recovery rates decrease with age, says Raju, who would like to help change that.

"Survival rates decrease significantly as we pass middle age," he says. Middle age starts about age 40 and just under 50% of Americans fall into that category, according to a 2019 Brookings Institution study of U.S. Census Bureau data.

The liver, which has unique abilities to regenerate in the face of injury or disease, peaked his interest because there was some thought that you could both induce and reverse senescence in this resilient organ.

While he says you can't generalize that what happens in one tissue, like the liver, will happen in another organ, Raju expects something similar happens in other organs in the face of serious injury. Whether the apparent positive effect of senescence in response to injury holds at an older age, when injury recovery declines, is another question they want to answer.

With implications for the transmission of diseases like COVID-19, researchers have found that ordinary conversation creates a conical 'jet-like' airflow that quickly carries a spray of tiny droplets from a speaker's mouth across meters of an interior space.

"People should recognize that they have an effect around them," said Howard Stone, the Donald R. Dixon '69 and Elizabeth W. Dixon Professor of Mechanical and Aerospace Engineering at Princeton University. "It's not just around your head, it is at the scale of meters."

Although scientists have not yet fully identified the transmission mechanisms of COVID-19, current research indicates that people without symptoms could infect others through tiny droplets created when they speak, sing or laugh. Stone and co-lead researcher Manouk Abkarian, of the University of Montpellier in France, wanted to learn how widely and quickly exhaled material from an average speaker could spread in an interior space.

"Lots of people have written about coughs and sneezes and the kinds of things you worry about with the flu," Stone said. "But those features are associated with visible symptoms, and with this disease we are seeing a lot of spread by people without symptoms."

In an article published Sept. 25 in the Proceedings of the National Academy of Sciences, the researchers concluded that for interior activities, normal conversations can spread exhaled material at least far as, if not beyond, social distancing guidelines recommended by the World Health Authority (1 meter) and U.S. officials (2 meters.) The work examined particle flow in an interior space without good ventilation.

Stone and Abkarian stressed that they are not public health experts and are not making medical recommendations. However, they said public health officials should consider the aerodynamic movement of aerosolized particles generated by speech alone already as an important factor for directed spreading.

"It certainly highlights the importance of ventilation," Stone said. "Especially if you have an extended conversation."

The researchers also said that while masks do not completely block the flow of aerosols, they play a critical role in disruption of the 'jet-like' air flow from a speaker's mouth, preventing the quick transport of droplets on large length scales bigger than 30 cm.

"Masks really cut this flow of tremendously," Stone said. "This identifies why (most) masks play a big role. They cut everything off."

The researchers specialize in fluid dynamics, which describes the movement of liquids and gasses. Using a high-speed camera, they film the movement of a mist of tiny droplets illuminated by a laser sheet in front of a person speaking several different phrases adjacent to the sheet. The phrases ranged from short statements like "we will beat the corona virus" to nursery rhymes including "Peter Piper picked a peck" and "Sing a song of six pence." The researchers selected the phrases to include different sounds that affect turbulent flows in a speaker's exhalation.

The researchers found that plosive sounds like 'P' create puffs of air in front of the speaker while a conversation created what the researchers called a "train of puffs." Each puff creates a small vortex of air in front of the speaker, and the interaction of these vortices creates a cone-shaped 'jet-like' airflow from the speaker's mouth. The researchers found that this airflow could easily and very quickly carry tiny particles away from the speaker.

Abkarian said that even a short phrase can move the particles past the 1-meter distancing recommended by the World Health Organization in a matter of seconds.

The researchers said the distance depends in part on the duration of the conversation. Someone speaking for more time will send particles farther. They said that the 6-foot distancing rule may not be a sufficient barrier in an interior space without good ventilation.

"If you speak for 30 seconds in a loud voice, you are going to project aerosol more than six feet in the direction of your interlocutor," Stone said.

In the paper, the researchers found that aerosols ejected during speech typically reached the 2-meter distance in about 30 seconds, and over that distance the aerosols' concentration diluted to about 3 percent of the original volume. It was beyond the paper's scope to say whether the dilution was sufficient to protect against infection, although the researchers noted that many will find this concentration to be higher than expected. The researchers said they hoped the information could help public health officials to make that determination. They also noted that longer conversations had the potential to spread more material and spread the virus over a larger distance.

"However, more extended discussions, and meetings in confined spaces, mean that the local environment will potentially contain exhaled air over a significantly longer distance," the researchers wrote.

The researchers said the experiment showed that a social distance of 6 feet (2 meters) did not work like a wall to protect people. Over time, conversations can cause material to move past the distance, particularly inside buildings.

The train of puffs created by a conversation causes a more complex turbulent flow than single jets of air and researchers had to account for it in their calculations. The researchers used the data from the experiments to create a mathematical framework to quantify the transport of droplets from the speaker's mouth to the surrounding area. They noted that the work does not account for movement of the speaker's head or body and background air movement caused by ventilation and other speakers. Analyzing those factors would require further work.

PITTSBURGH, Sept. 29, 2020 - A study from the University of Pittsburgh School of Medicine and Cedars-Sinai addresses a mystery first raised in March: Why do some people with COVID-19 develop severe inflammation? The research shows how the molecular structure and sequence of the SARS-CoV-2 spike protein--part of the virus that causes COVID-19--could be behind the inflammatory syndrome cropping up in infected patients.

The study, published this week in the Proceedings of the National Academy of Sciences, uses computational modeling to zero in on a part of the SARS-CoV-2 spike protein that may act as a "superantigen," kicking the immune system into overdrive as in toxic shock syndrome--a rare, life-threatening complication of bacterial infections.

Symptoms of a newly identified condition in pediatric COVID-19 patients, known as Multisystem Inflammatory Syndrome in Children (MIS-C), include persistent fever and severe inflammation that can affect a host of bodily systems. While rare, the syndrome can be serious or even fatal.

The first reports of this condition coming out of Europe caught the attention of study co-senior author Moshe Arditi, M.D., director of the Pediatric Infectious Diseases and Immunology Division at Cedars-Sinai and an expert on another pediatric inflammatory disease--Kawasaki disease.

Arditi contacted his long-time collaborator, Ivet Bahar, Ph.D., distinguished professor and John K. Vries Chair of computational and systems biology at Pitt School of Medicine, and the two started searching for features of the SARS-CoV-2 virus that might be responsible for MIS-C.

Bahar and her team created a computer model of the interaction between the SARS-CoV-2 viral spike protein and the receptors on human T cells, the foot soldiers of the immune system. Under normal circumstances, T cells help the body fight off infection, but when these cells are activated in abnormally large quantities, as is the case with superantigens, they produce massive amounts of inflammatory cytokines--small proteins involved in immune system signaling--in what's known as a "cytokine storm."

Using this computer model, the team was able to see that a specific region on the spike protein with superantigenic features interacts with T cells. Then, they compared this region to a bacterial protein that causes toxic shock syndrome and found striking similarities in both sequence and structure. Importantly, the proposed SARS-CoV-2 superantigen showed a high affinity for binding T cell receptors--the first step toward touching off a runaway immune response.

"Everything came one after another, each time a huge surprise. The pieces of the puzzle ended up fitting extremely well," said Bahar, co-senior author on the study.

By finding protein-level similarities between SARS-CoV-2 and the bacterial structure that causes toxic shock syndrome, the researchers said they may have opened up new avenues for treating not only MIS-C patients, but also adults with COVID-19 infection experiencing cytokine storm.

The researchers also collaborated with scientists studying adult COVID-19 patients in Germany and found that those who experienced severe symptoms had a T cell response similar to what is seen in people exposed to superantigens and very different from the T cell response in patients who had only mild symptoms.

"Our research finally begins to unravel the potential mechanisms involved and raises the possibility that therapeutic options for toxic shock syndrome, such as intravenous immunoglobulin and steroids, may be effective for managing and treating MIS-C in children and hyperinflammation in adult coronavirus patients," said Arditi, professor of pediatrics and biomedical sciences at Cedars-Sinai.

Arditi's and Bahar's labs are now using the ideas generated by this study to search for and test antibodies specific to the SARS-CoV-2 superantigen, with the goal of developing therapies that specifically address MIS-C and cytokine storm in COVID-19 patients.

The research team of INRS (Institut national de la recherche scientifique) Professor Mohamed Mohamedi has designed a green membraneless fuel cell that uses oxygen from the air. The results of this innovative microfluidic application--a first in Canada--were published in Renewable and Sustainable Energy Reviews.

Conventional fuel cells are ubiquitous. They power electric cars on today's roads and were part of the computers used in the 1969 Apollo moon landing. These fuel cells lose voltage as they are used and eventually stop working. This happens because alcohol molecules (methanol or ethanol) in the fuel cell's anode compartment crossover the membrane separating them from the cathode compartment. Oxygen molecules in the cathode compartment react with the alcohol, causing a drop in voltage.

Numerous scientists have unsuccessfully tried to develop a membrane that stops alcohol molecules from passing through it. Professor Mohamed Mohamedi, a lead author of the study published on September 8, took another tack: developing a fuel cell without a membrane.

His novel solution costs less and requires fewer steps to manufacture, but it fails to address a key challenge. "When the membrane is removed, the methanol or ethanol reacts with the oxygen, just like in conventional fuel cells. To prevent voltage drops, we had to develop selective electrodes in the cathode compartment. These electrodes, designed by doctoral student Juan Carlos Abrego-Martinez, remain inactive in the presence of alcohol molecules but are sensitive to the oxygen that generates electricity," Professor Mohamedi explains. He notes another unique property of this membraneless fuel cell: it uses oxygen from the air around it.

From Model to Prototype

The first step the researchers took in building a working prototype was to run numerical simulations created by Alonso Moreno Zuria, INRS postdoctoral fellow and a lead author of the study. Through computer modelling, the team tested different configurations of selective electrodes in the fuel cell. "Conventional fuel cells are like sandwiches, with the membrane in the middle. We chose instead to work on a single-layer design. We had to determine how to arrange and space the electrodes to maximize fuel use while keeping ambient air oxygen concentration in mind," says Professor Mohamedi.

Once the researchers settled on a configuration, they tested a prototype that became a proof of concept. The membraneless fuel cell powered an LED for four hours using only 234 microlitres of methanol. The researchers want to optimize the fuel cell so it can use ethanol, a greener fuel that can be produced from biomass and agricultural waste. Ethanol also provides more power per equivalent unit of volume.

The team expects the fuel cell to power portable electronics such as mobile phones and microsystems such as air pollution sensors. Unlike conventional batteries that store electricity and must be recharged, fuel cells continue to produce energy as long as fuel is available. "This energy supply method is particularly effective when recharging is not possible. Imagine being in the middle of the desert, without electricity. You could recharge your mobile phone using a small capsule of ethanol that you connect to the device," says Professor Mohamedi.

This pioneering technology has already attracted industry attention even though the research team is only at the prototype stage.

Post-traumatic stress disorder (PTSD) affects eight million adults in the US, including hundreds of thousands of veterans of the conflicts in Iraq and Afghanistan. And as the COVID crisis continues to take its toll on everyone's mental health, PTSD symptoms are on the rise in the general population. But diagnosing PTSD is a time-consuming process, taking upwards of 30 minutes--too long for most clinical visits.

Now, researchers from the VA Boston Healthcare System and the Boston University School of Public Health (BUSPH) have used machine learning to explore streamlining the "gold standard" diagnostic tool for PTSD.

Published in the journal Assessment, the study finds that six of the 20 questions could be cut from the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (SCID-5), while maintaining accuracy in a veteran population. The study also finds that different questions in the SCID-5 are more or less important for male or for female veterans.

"We found that several of the PTSD items could be removed because they did not make substantial contributions to accurate prediction of PTSD relative to the other PTSD items. It's likely that some of these items are removable because they are redundant with other items. Other items may be removable because they aren't specific enough to PTSD," says study lead author Tammy Jiang, a doctoral candidate in epidemiology at BUSPH.

However, a machine learning system is still no match for a human mental health provider, who can interpret test results and evaluate the complexities and nuances of what a patient is going through.

"Our study is only a first step--but an important one, because it shows that machine learning methods can be used to help inform efforts to make care more efficient, without sacrificing or degrading the quality of care provided," says study co-author Dr. Jaimie Gradus, associate professor of epidemiology at BUSPH.

The researchers used data from the SCID-5 assessments of 1,265 veterans of the Afghanistan and Iraq conflicts, and a kind of machine learning system called "random forests" (made up of "forests" of decision trees). The random forests system learned how strongly different items in the diagnostic predicted a PTSD diagnosis. This allowed the researchers to identify which items had weak enough associations that they could be cut while still maintaining at least 90% accuracy.

For the 1,265 veterans in the sample--half of them male and half female--the researchers identified six items that could be cut: dissociative reactions; reckless or self-destructive behavior; irritable behavior and anger; hypervigilance; persistent inability to experience positive emotions; and exaggerated startle response.

The most important item for a diagnosis was detachment or estrangement from others. This was true both for the whole sample and for male and female veterans separately. However, the researchers found that different items could be cut for male and for female veterans:

For the male veterans, they identified four items that could be cut: inability to recall important aspects of a traumatic event; dissociative reactions; reckless or self-destructive behavior; and hypervigilance.

For the female veterans, they identified six: reckless or self-destructive behavior; dissociative reactions; persistent inability to experience positive emotions; irritable behavior and angry outbursts; exaggerated startle response; and hypervigilance.

"This study demonstrates very clearly that the most efficient manner of diagnosing PTSD may differ for men and women. This finding is especially critical in a setting like VA, which serves a small but growing number of women veterans," says study senior author Dr. Brian Marx, staff psychologist at the National Center for PTSD at the VA Boston Healthcare System and a professor of psychiatry at the BU School of Medicine.

Marx says the study has exciting implications for the future, at the VA and beyond. "Although we already have reliable and valid screening measures for PTSD that are used in VA healthcare and other settings, they are only capable of providing provisional diagnostic determinations, which require verification using gold standard clinical diagnostic interviews," he says. "Our findings potentially pave a path from which we could eventually skip right to an abbreviated--but still gold standard--diagnostic interview that would accurately identify those with PTSD and get them into treatment as soon as possible."

And with the COVID-19 pandemic leading to more PTSD, depression, anxiety, substance use, and other disorders in the general population, "the application of machine learning methods to streamline mental health assessments may help reduce the burden," Jiang says, "and help people receive care more efficiently."

As many as 70% of very premature infants (born earlier than 32 weeks gestation) show signs of white matter abnormalities at birth. But only some of those infants go on to develop cognitive, language, motor, or behavioral disorders as they grow.

Now, scientists say a new software tool can employ MRI scan data to predict which infants are most at risk of these brain developmental issues. The tool's latest milestone--predicting the risk of motor development disorders (e.g. cerebral palsy) --were detailed online Sept. 28, 2020, in Scientific Reports.

The study was led by Nehal Parikh, DO, MS, a neonatologist and researcher with the Perinatal Institute at Cincinnati Children's who has been working on this line of research for 12 years. He and his collaborators have published several papers exploring the value of measuring diffuse white matter abnormality (DWMA) as a biomarker for brain disorders.

A quantitative look at white matter diffusion

"While most researchers and doctors have concluded that DWMA is not pathologic, our novel studies are concluding otherwise," Parikh says. "Most studies have diagnosed DWMA qualitatively based on visual readings from radiologists (yes/no, mild/moderate/severe). These subjective diagnoses have been unreliable and therefore have not been significantly associated with neurodevelopmental disorders."

However, quantifying the volume of DWMA, does allow for risk stratification, Parikh says. The method also allows for earlier diagnosis. Currently, affected children are not diagnosed with these disorders until 2 to 5 years of age.

The first publications related to the software date back to 2013, with findings reported in Neuroimage, PLOS ONE and Pediatric Neurology that showed an association between DWMA volume and cognitive and language development at 2 years of age.

Earlier this year, they externally validated their findings and reported in the Journal of Pediatrics that DWMA volume significantly predicts cognitive and language development at 2 years of age. Additionally, in Pediatric Neurology, the team reported DWMA volume associations with the two most common neonatal diseases, bronchopulmonary dysplasia and retinopathy of prematurity.

Now, the tool shows that DWMA volume significantly and independently predicts motor development deficits, including cerebral palsy, at 3 years of age.

What's next

Parikh says the team is close to completing a large cohort study called the Cincinnati Infant Neurodevelopment Early Prediction Study (CINEPS) to further validate the findings.

"We plan to work with MRI manufacturers to incorporate our software onto their systems in order to provide objective diagnosis of DWMA at the point of care," Parikh says. "This advance will permit accurate parental counseling and early risk stratification to enable targeted early intervention therapies."

CAMBRIDGE, MA - September 29, 2020--Rapid Reviews: COVID-19 (RR:C19), is an open-access overlay journal published by the MIT Press that accelerates peer review of COVID-19-related research preprints to advance new and important findings and prevent the dissemination of false or misleading scientific news.

For the month of September, the preprints selected for review covered a wide range of subjects with peer reviewers finding an argument for re-envisioning US public health, employment, and anti-discrimination law around social solidarity particularly noteworthy. Also of immediate interest will be papers on whether rescue inhalers protect against COVID-19 related deaths and whether a new diagnostic tool that detects loss of smell can help identify asymptomatic patients.

Peer reviewers also flag as potentially informative but do not fully support the claims that high viral load indicates higher mortality or that Sofosbuvir protects human brain organoids against SARS-CoV-2. They voice caution for these results.

New peer reviews from RR:C19, in order of the evidence scale rating (strong, reliable, potentially informative, not informative, or misleading) as provided by each of the reviewers:

"The Personal Responsibility Pandemic: Centering Solidarity in Public Health and Employment Law" by Lindsay F. Wiley, et al. Preprint | Reviews

Evidence Scale Rating: Strong/Strong

Summary: The authors make a convincing argument for re-envisioning US public health, employment and anti-discrimination law around social solidarity, and a compelling case for further scholarship that considers the public health implications of employment law. Reviewers: Pamela Egan, Ken Jacobs, and Michael C. Duff

"Inhaled corticosteroid use and risk COVID-19 related death among 966,461 patients with COPD or asthma: an OpenSAFELY analysis" by Anna Schultze, et al. Preprint | Reviews

Evidence Scale Rating: Strong/Reliable

Summary: This well-conducted, high powered study provides strong evidence of that inhaled corticosteroids do not protect against COVID-19 related deaths. Reviewers: Philip W. Ind and Bulent Karadag

"Quantitative Assessment of Olfactory Dysfunction Accurately Detects Asymptomatic COVID-19 Carriers" by Anindya Bhattacharjee, et al. Preprint | Reviews

Evidence Scale Rating: Strong/Reliable

Summary: This study offers a quantitative approach for identifying asymptomatic COVID-19 patients paired with a diagnostic device optimized for use in the current pandemic. The claims are reliable, but minor follow up studies will better define implementation constraints. Reviewers: Christopher von Bartheld, Rafal Butowt, and Danielle Reed

"HIV infection and COVID-19 death: population-based cohort analysis of UK primary care data and linked national death registrations within the OpenSAFELY platform" by Krishnan Bhaskaran, et al. Preprint | Reviews

Evidence Scale Rating: Reliable/Reliable

Summary: This study is an important effort to add to the literature on COVID-19 mortality rates among HIV-positive individuals; however, the extremely small relevant sample size, and a number of confounders, make its specific policy implications suspect. Reviewers: Norman Hearst and Caroline Sabin

"Immunoreactive peptide maps of SARS-CoV-2 and other human coronaviruses" by Nischay Mishra, et al. Preprint | Reviews

Evidence Scale Rating: Reliable/Reliable

Summary: This study presents a microarray-based screen that identifies immunoreactive peptide fragments recognized by antibodies present in COVID19+ patients. The primary findings are reliable; however, extrapolating these findings to other analytical approaches require validation. Reviewers: Seema Mishra, Nicolas Winssinger, Lluc Farrera-Soler, Jean-Pierre Daguer, and Sofia Barluenga

"Electoral Repercussions of a Pandemic: Evidence from the 2009 H1N1 Outbreak" by Emilio Gutierrez, et al. Preprint | Reviews

Evidence Scale Rating: Reliable/Reliable

Summary: This paper shows reliable evidence that the timing of 2009 swine flu in Mexico affected voting behavior in the next election. However, there may be different interpretations regarding the influence of other causal factors. Reviewers: Elisa Maffioli and Albert Falcó-Gimeno

"Association of D-dimer and fibrinogen magnitude with hypercoagulability by thromboelastography in severe COVID-19" by Abhimanyu Chandel, et al. Preprint | Reviews

Evidence Scale Rating: Strong/Potentially Informative

Summary: Fibrinogen & G-reactive protein levels correlate with macrothrombosis in critically ill COVID-19 patients, providing a more practical way of identifying at-risk patients. Reviewer consensus is that the paper is potentially informative but has serious methodological limitations. Reviewers: Fady Gerges, Abdallah Almaghraby, Jing Jin, James Horowitz, and Eugene Yuriditsky

"Human organ chip-enabled pipeline to rapidly repurpose therapeutics during viral pandemics" by Longlong Si, et al. Preprint | Reviews

Evidence Scale Rating: Strong/Potentially Informative

Summary: This study employs microfluidic devices to test candidate therapeutics blocking SARS-CoV-2 entry and demonstrates amodiaquine efficacy in preclinical models. The claims presented in this work are reliable but could be strengthened through more rigorous model characterization. Reviewers: Cathryn Sundback, Jeffrey T Borenstein, Ashley L Gard, and Jennifer P Wang

"Reopening universities during the COVID-19 pandemic: A testing strategy to minimize active cases and delay outbreaks" by Lior Rennert, et al. Preprint | Reviews

Evidence Scale Rating: Strong/Potentially Informative

Summary: Pre-entry screening of students entering universities for COVID-19 may help limit the spread of COVID-19, but further analysis is warranted to know the true impact. The modeling is too simple for a complex situation, and should take into account other critical factors. Reviewers: Dominique Gibert, Mohak Gupta, Rishika Mohanta, and Arthur Reingold

"Health Disparities and COVID-19: A Retrospective Study Examining Individual and Community Factors Causing Disproportionate COVID-19 Outcomes in Cook County, Illinois, March 16-May 31, 2020" by Larissa Unruh, et al. Preprint | Reviews

Evidence Scale Rating: Reliable/Potentially Informative

Summary: This study provides further empirical evidence about the racial differences in COVID-19 morbidity and mortality. The preprint is potentially informative and somewhat reliable, but there are unmeasured confounders and it lacks some clarity around some data points. Reviewers: Philip Schluter and Zahid Butt

"Is Higher Viral Load in SARS-CoV-2 Associated With Death?" by Klinger Soares Faico-Filho, et al. Preprint | Reviews

Evidence Scale Rating: Potentially Informative

Summary: This study is potentially informative but the results should be approached with caution. The claim that high viral load indicates higher mortality is not fully supported. Multiple confounding variables have not been taken into account. Reviewers: Maria Drogari-Apiranthitou, Chen Yeng, and Michael Meisner

"Sofosbuvir protects human brain organoids against SARS-CoV-2" by Pinar Mesci, et al. Preprint | Review

Evidence Scale Rating: Potentially Informative

Summary: This study claims brain organoids are permissive to SARS-CoV-2 infection and use this model to demonstrate neuroprotective effects of Sofosbuvir. While the findings are compelling, the experiments performed and the data offered are insufficient to deem the stated claims reliable. Reviewers: Ben Maoz and Jay Gopalakrishnan

Misfolding and aggregation of normally soluble proteins are common pathological features of many neurodegenerative diseases, including Alzheimer's, Parkinson's, Creutzfeldt-Jacob and Huntington's diseases. For example, Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) are characterized by accumulation of misfolded α -synuclein in neuronal and/or glial cells, and therefore these diseases are termed α synucleinopathies. In PD and DLB, α-synuclein pathologies are mainly observed in neurons in the form of Lewy bodies and Lewy neurites, while glial cytoplasmic inclusions are seen in oligodendrocytes in MSA. Previous studies have suggested that α synuclein has the properties of prion, seed dependent aggregation, cell to cell propagation and the existence of distinct aggregate conformations (strains). There is a relationship between protein aggregate conformation and clinical phenotype in prion diseases, however, whether differences in the strains of α synuclein aggregates account for the different pathologies remained unclear. In this study, Suzuki and colleagues at TMIMS clarified a possible molecular mechanism to account for the different pathologies induced by different α synuclein strains.

First, Suzuki and colleagues prepared recombinant α-synuclein monomer, agitated it in the presence or absence of salt at a physiological concentration and generated two types of α-synuclein fibrils, α-synuclein fibrils (+) and α-synuclein fibrils (-), from identical monomer. Next, they injected α-synuclein fibrils (+) and α-synuclein fibrils (-) into striatum of wild-type mice, and after one month, they examined the accumulation of phosphorylated α synuclein deposits resembling those observed in patients' brains. They found that α-synuclein fibrils (-) induced Lewy body/Lewy neurite-like abnormal phosphorylated α-synuclein deposits through the mouse brain, whereas few phosphorylated α-synuclein deposits were induced by α-synuclein fibrils (+) (Figure). To further study the difference in the formation of pathological α-synuclein aggregates in neurons, Suzuki and colleagues compared the ability of the two α-synuclein strains to induce seed-dependent aggregation of α-synuclein in primary mouse cortical neurons. They observed a dramatic increase of phosphorylated α-synuclein accumulation, which is also positive for ubiquitin, only in the case of α-synuclein fibrils (-), while little accumulation was seen with α synuclein fibrils (+). They also found that not only ubiquitinated α-synuclein, but also other ubiquitinated proteins were accumulated in cells treated with α-synuclein fibrils (-), whereas there was no significant increase of ubiquitinated protein accumulation in cells treated with α-synuclein fibrils (+).

Next, Suzuki and colleagues examined proteasome activity in the presence of these two types of α-synuclein fibrils and found that only α-synuclein fibrils (-) apparently inhibited proteasome activity in vitro. They also investigated the interaction of 26S proteasome with the fibrils and found α-synuclein fibrils (-) co-precipitated with purified 26S proteasome complex. These results indicate that only α synuclein fibrils (-) interact with 26S proteasome and impair the proteasome activity.

Next, Suzuki and colleagues wanted to elucidate the structural difference of the two types of α-synuclein fibrils. They investigated the core regions and exposed regions of these α-synuclein fibrils and found that α-synuclein fibrils (-) have a smaller core region while α-synuclein fibrils (+) had a larger core region, extending to the C-terminal regions. This indicates that α-synuclein fibrils (-) have amyloid structure with a more exposed C-terminal region than α-synuclein fibrils (+). Thus, they considered that the C-terminal region of α-synuclein fibrils (-) might interact with 26S proteasome and impair its activities. To confirm this hypothesis, Suzuki and colleagues next examined the seeding activity and the effects on proteasome activity of C-terminally truncated α-synuclein fibrils formed in the absence of salt. They prepared C terminally 20-residue-truncated α-synuclein monomer (residues 1-120) and agitated it in the absence of salt. The resulting assemblies (αSΔC20 fibrils (-)) showed fibrillar morphology and then they treated primary mouse cortical neurons with αSΔC20 fibrils (-) and found only little accumulation of phosphorylated α-synuclein and ubiquitinated proteins. In addition, the catalytic activity of 26S proteasome was not impaired in the presence of αSΔC20 fibrils (-) and αSΔC20 fibrils (-) did not co-precipitated with 26S proteasome. Considering all these results, the C-terminal region of α-synuclein is exposed only in α synuclein fibrils (-) and this region interacts with 26S proteasome and impairs its activity.

The C-terminal region (residues 96-140) of α-synuclein is acidic and contains negatively charged residues, including aspartate and glutamate, as well as proline residues. When intermolecular repulsion at the C-terminal region is weakened by changes in ionic strength, exposure of the C-terminal region decreases, and more tightly packed α-synuclein fibrils are formed in the presence of salt. On the other hand, in the absence of salt, intermolecular repulsion at the C-terminal region causes the formation of α-synuclein fibrils in which the C-terminal region is exposed (Figure). Only this latter type of α-synuclein fibrils can interact with 26S proteasome complex in vitro, causing inhibition of 26S proteasome activity. If this also occurs in cells or brains, abnormal α synuclein aggregates, which might be partially degraded by proteasome, would be accumulated.

According to the prion hypothesis, differences in disease symptoms and lesions are caused by differences in the conformation of strains. Therefore, if α-synuclein is prion-like, differences in the structure of α-synuclein aggregates should cause the differences in the lesions observed in various α-synucleinopathies. In this study, Suzuki and colleagues confirmed that different pathologies were caused by two α-synuclein strains with different structures, and they also found that these α-synuclein strains differ in their ability to inhibit 26S proteasome activity. It is a noteworthy finding in this work that one of the two differently structured fibrils formed from identical monomer under different conditions inhibited proteasome, while the other did not. This clearly raises the possibility that inhibition of proteasome by abnormal α-synuclein plays a role in the pathology. These results provide a possible molecular mechanism to account for the different lesions induced by distinct α-synuclein strains. Considering that PD and MSA have different structures of accumulated α-synuclein, it seems highly likely that the structures of α-synuclein fibrils determine the lesions observed in these diseases.

A recent study published by researchers from the University of Seville shows that university students make excessive use of their mobile phones. The study relates the number of hours that young people spend sitting down, their level of physical activity and state of mind when using a mobile phone. Students with lower levels of physical activity used their mobile phones almost three times more than others. Those reporting poorer sleep quality also used these devices more.

Another recent publication by the same research group went into these issues in greater detail and shows that young people (university students aged 20-36) used their mobile phone 6h/day on average before lockdown, increasing to over 8h/day on average during lockdown. "These data are very worrying if we consider that scientific evidence shows that a high number of hours sitting (more than 8 h/day) or an excessive use of screen devices (3-4 h/day) is linked with a higher risk of mortality," reiterates US professor Borja Sañudo.

The conclusions of the research show that the containment measures adopted during COVID-19 had a major impact on the habits of this demographic group, especially on their levels of physical activity which decreased significantly, but also on their sedentary lifestyle, increasing the time they remained seated (approximately 6h/day on average before the lockdown and about 10h/day during). These bad habits had a negative impact on the health of these young people and significantly worsened their sleep quality.

Studies such as these highlight the need to take measures that encourage people to avoid a sedentary lifestyle, contributing to increasing physical activity levels and reducing the use of mobile phones, and thus improving the population's health through behavioural changes.