Culture

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.

Time may be our worst enemy, and aging its most powerful weapon. Our hair turns grey, our strength wanes, and a slew of age-related diseases represent what is happening at the cellular and molecular levels. Aging affects all the cells in our body's different tissues, and understanding its impact would be of great value in fighting this eternal enemy of all ephemeral life forms.

The key is to first observe and measure. In a paper published in Cell Reports, scientists led by Johan Auwerx at EPFL started by asking a simple question: how do the tissues of aging mice differ from those of mice that are mere adults?

To answer the question, the researchers used the multiple techniques to measure the expression of everyone one of the thousands of mouse's genes, and to identify any underlying epigenetic differences. The researchers not only measured different layers of information, but they did it across three different tissues: liver, heart, and muscle.

The data collectively allowed them to define an aging "footprint" that can serve as a field for investigation. But while many of the known aging manifestations were recovered, different tissues behaved differently.

"We will never have a thorough understanding of aging by studying a single tissue, and this applies to many other processes and diseases," says lead author Maroun Bou Sleiman. "Data, whether freshly produced or reused, is the key to understanding complex systems, and we are just scratching the surface."

Through multiple bioinformatics analyses, the scientists identified certain genes and proteins that may be controlling the complex aging process. By including human population data, they also showed that many of the "players" they identified in the mouse genome may be also relevant in human aging.

Finally, the researchers used human genetic data to show that some of the "players" may also explain why some humans live longer than others. "Our final goal is not to stop ageing, but to age better and disease-free, and to do that, we will need to characterize this system," says Johan Auwerx. "This is a perfect example of cross-species integration starting from the laboratory mouse and ending in human population data that takes us one step closer to understanding one of the most complex processes in biology."

Steroid hybrid molecules have recently attracted great attention from researchers in recent years owing to their bioactive properties. Earlier a team of researchers led by Dr. Bumal Banik and colleagues, reported the synthesis of several steroid-peptide conjugates of a potential biologically important class of steroid hybrid molecules. During the course of this study, the researchers have come to realize the diverse and interesting biological activities of hetero-steroids. The team recently performed microwave-induced synthesis of steroid-peptide conjugates based on some hetero-steroids containing N, O and S coupling with N-(tert-butoxycarbonyl)-L-phenylalanine as the amino acid residue following Ugi-4-component reaction (Ugi-4-CR). Hetero-steroids are first synthesized from available steroids. These are subjected to Ugi-4-CR to obtain a number of hetero-steroid-peptide conjugates - a new class of steroid-peptide conjugate. Their research findings have been published in a in Current Organic Synthesis.

The synthesis of hetero-steroid-amino acid conjugate starting from epiendrosterone to incorporate a heterocyclic ring fused to its D-ring is described in the article. To synthesize the Hetero-steroid-amino acid conjugate starting from easily available progesterone, a different approach is adopted. The Heterosteroid-amino acid conjugate is also prepared starting from 3β-acetoxy-19-formyloxy-7-iodo-6-nor-5,7-seco-pregnan-5,20-dione.

The team believes that this method will undoubtedly find a significant place in organic synthesis processes. "Microwave-promoted Ugi-4CR towards the synthesis of a new class of hybrid molecules, viz., Hetero-steroid-amino acid conjugates based on hetero-steroidal amines is a useful addition to synthetic organic chemistry." Says Dr Banik. "Additionally, hetero-steroid-amino acid conjugates may have diverse biological properties, which adds to their value.", he concludes. Under classical conditions, synthesis of many of these compounds as described here proves to be problematic due to the occurrence of undesirable side reactions. In contrast, the microwave method is proved to be excellent in terms of the yields of the products and rapidity of the reactions.

To circumvent current tobacco advertising, promotion and sponsorship (TAPS) laws in Australia, tobacco companies are incentivising retailers with cash payments, all-expenses paid holidays, exclusive parties and tickets to sporting events to drive tobacco sales.

Published today in Global Public Health, this is the first study to use interviews with former tobacco industry employees as key informants to understand the tactics that tobacco companies use to exploit gaps in the Australian legislation.

"Direct advertising of tobacco to consumers has long been banned, however this study exposes that tobacco companies continue to market their products through thousands of tobacco retailers," said lead author Christina Watts from University of Sydney and Tobacco Control Policy at Cancer Council NSW.

"Tobacco companies have focused their marketing budget on retailers as they are one of the only remaining avenues to communicate directly with consumers.

Under Australian legislation, incentives and benefits connected to the sale of tobacco cannot be provided to consumers, however, such laws do not explicitly apply to tobacco retailers. A recent sample survey of Australian tobacco retailers found that one-third had received a benefit or incentive from a tobacco company in return for doing something for the company.

In the study, former tobacco industry employees described covert tobacco marketing and promotion strategies to retailers including:

- Providing financial incentives such as price promotions, cash payments and rebates

- Providing experiential incentives such as all-expenses paid holidays, exclusive parties and events, tickets to international sporting events (with events used to indirectly promote products)

- Incentivising retail staff to reach sales targets and upskilling them to be effective tobacco brand ambassadors.

These strategies had the ultimate objective of increasing market share and driving sales through increased retailer loyalty and rapport.

"Despite the tobacco industry's repeated argument that such promotional activities are only to increase their individual market share, rather than drive new sales, our research shows that incentives were provided to encourage retailers to reach or exceed sales targets and to push products directly to consumers," said Ms Watts.

Study supervisor Dr Becky Freeman from the University of Sydney's Faculty of Medicine and Health said that changes to the current tobacco advertising, promotion and sponsorship laws are urgently needed in Australia.

"The tobacco industry continues to market its deadly products, while pretending to be a "reformed" company that supports public health.

"Tobacco companies appear to be exploiting current laws by using the retail environment as an indirect channel to reach consumers.

"By only restricting tobacco marketing practices aimed directly at consumers, Australian legislation has failed to respond to the importance of retail marketing in the promotion of tobacco. This has enabled tobacco companies to funnel resources into this 'last line of marketing' of their products.

"We're calling for Australian laws to be strengthened to prohibit all marketing of tobacco products - with no contributions allowed of any kind to any event, activity, or individual.

"Restrictions must address direct product advertising to tobacco retailers, in order to prevent any ongoing and future covert promotion of tobacco," she said.

Australia is considered to be a global leader in tobacco control with a suite of measures to restrict tobacco marketing activities such as:

- bans on tobacco advertising, promotion and sponsorship

- plain packaging with graphic health warnings

- removal of visible displays of tobacco products at point-of-sale.

These measures have contributed to daily smoking rates declining in Australia from 24 percent of adults in 1991 to 11 percent in 2019.

The Nuffield Council on Bioethics has today published a 'bioethics briefing note' which highlights a pressing need for data on egg freezing success rates to be presented more clearly, accessibly, and transparently. At present, research suggests that women find these data difficult to navigate.

Frances Flinter, Nuffield Council member and Emeritus Professor of Clinical Genetics at Guy's and St Thomas' NHS Foundation Trust, said:

"It's vital for women thinking about freezing their eggs to be able to make informed choices. To do this, they need easy access to data on their chances of success across various stages of the process - from freezing and thawing eggs, to having a live birth. But they also need clinics to be frank about the process, and about what is known and unknown about egg freezing. This is especially important given egg freezing's increasing popularity."

Egg freezing as an employment benefit

One area where clear information and research are likely to be important in the future is where egg freezing is offered as part of an employment benefits package. Although this isn't common in the UK at present, it is beginning to be offered by some companies.

For some women, being offered egg freezing as an employment benefit could feel empowering and give a sense of being in more control over their reproductive future. For others, the offer might make them feel pressured to delay motherhood. If more employers consider providing this benefit, research needs to focus on women's needs and their experiences of using such schemes.

The Nuffield Council also highlights that offering egg freezing as part of a benefits package is not the only option for employers to support employees' reproductive choices. Improvements to family-friendly work environments, childcare subsidies, and family leave also have a key role to play.

Other conclusions

The briefing note also reports that:

The way social egg freezing is presented and marketed is potentially of concern and should be the focus of closer attention. Concerns raised on this issue include the trivialisation of egg freezing in media coverage, the role of social media influencers' promotion of the technology, the use of algorithms that target women with egg freezing adverts, and irresponsible marketing strategies, including events where egg freezing is discussed over prosecco. Research also suggests that women can feel pressure to freeze to avoid blaming themselves later. It is important that marketing strategies consider such research so that women's anxieties are not exploited.

There appear to be few arguments against increasing the storage limit for social egg freezing from its current limit of ten years. Changes to this limit are currently being considered by the Government.

Proven fact: we remember our altruistic behaviour more easily than selfish actions or misdeeds that go against our own moral sense. Described as 'unethical amnesia' by scientists, it is generally explained by self-image maintenance. But could these selective oversights, not necessarily conscious, have a more strategic aim? To find out, a team of behavioural economists from the CNRS (1) recruited 1322 volunteers in an online experiment which took place over two sessions. The first session involved 20 repetitions of a lottery task, the results of which determined the participants' monetary payoff; however, as the participants had to self-report the outcomes they had the opportunity to cheat (2). During the second session, three weeks later, the same participants were monetarily incentivised to recall as accurately as possible the outcomes they had reported in the previous session. Half of the volunteers were informed that they would then have the opportunity to voluntarily return some of the money if they had overreported their outcomes in the first session. It was within this configuration that the participants were most prone to amnesia, as reported by scientists in PNAS on 28th September 2020. In other words, they remembered their cheating behaviour less accurately when they knew they would have to make a moral decision again, even though they could earn more money by remembering the reported outcomes. It was as if forgetting this incident would allow them to restore their reputation, making it more acceptable for a future breach of morality.

To manage and conserve natural ecosystems, it is essential to know how biodiversity changes. As one of those questions, it is important to know whether we are we gaining or loosing species. However, getting reliable measurements to study this is a complex task. Data can be collected by researchers during field trips, but a vast amount of data is also provided by different initiatives such as citizen science programs. However, to ensure measurements are reliable, samples need to be representative of the real world. If samples are not representative, they are biased.

In their study, scientists from iDiv, UL and MLU showed that a bias can dramatically change the measurements of biodiversity change. They focused on the so-called site-selection bias, where sampling sites are not selected representatively. For example, if a person wanted to find out how the number of butterfly species is changing in the area over the next ten years, this person will likely not choose a typical and average spot, such as a little meadow behind a supermarket. Instead, a place such as a clearing in the park may seem well suited. Thus, the sampling site is biased towards where many butterfly species can be found. This is the site-selection bias.

Site-selection bias may amplify or even revers trends

Using a computer simulation, the scientists showed that this bias can lead to false conclusions about how biodiversity changes. "If we measure biodiversity at places that have unusually many species, statistical principles suggest that we will more likely observe a drop in species numbers over time," said first author Dr Andrea Mentges from iDiv and UL. The biased choice of where to take samples may manipulate the collected data and even lead to wrong conclusions. "We found that site-selection bias can even make our measurements point into the wrong direction: while for example in reality we are gaining species, our measurements would falsely suggest that the number of species goes down. This makes clear how important it is to choose representative sampling sites."

The scientists analysed how wide-spread such site-selection biases are, and found that they can potentially occur in many data sources, such as data collected by museums, national parks, citizen scientists and academic researchers. Whether the site-selection bias affects the measurements depends on the purpose of the collection. The data on the butterflies counted in the local park may still be informative, said Andrea Mentges: "Such data can be used to find out if a certain butterfly species can still be found in the area or if new species are immigrating. But if we use it to find out whether butterfly numbers are increasing or decreasing in the surrounding landscape, we might be wrong."

Citizen scientists more likely to choose 'cool' spots

For their study, the scientists also looked at 44 citizen science initiatives. In many programmes, participants were allowed to choose sites themselves. This free site selection can potentially lead to a bias - depending strongly on the training participants received. Andrea Mentges said: "We assume that if people are not explicitly told that it is important to choose a 'normal' site they will always tend to choose a 'cool' spot. That's why we think such programmes can potentially be problematic when there is no in-person training or instructions available online that also focus on site selection."

In Germany, such training is not very common in citizen science initiatives. Although information material is available to interested participants this may not always prevent a site-selection bias - for example, when participants are encouraged to look for meadows and flower-rich wayside for their observations. "These are great initiatives that collect a lot of useful data," said Andrea Mentges. "But it may not be suitable for some research questions - for example, whether the number of a certain butterfly species such as the small tortoiseshell is going up or down in general." However, such site-selection biases can easily be prevented. Prof Dr Jonathan Chase, head of the Biodiversity Synthesis group at iDiv and professor at MLU, said: "The most objective way would be to use systematic, computer-based site-selection schemes, these are also applied more and more often. But it's always a fine line between scientific accuracy and practical feasibility. And, of course, citizen science programmes owe their existence to the motivation of the many volunteers contributing with their data."

Despite the great advances in cancer research in recent years, treatments that can cause very severe adverse effects are still used. This is the case of neuropathy caused by chemotherapy with platinum derivatives, such as Cisplatin and Oxaliplatin. These are widely used drugs that can damage the peripheral nervous system causing a progressive and increasing loss of sensitivity, which may even affect the mobility. The appearance of these adverse effects may force to reduce the dose or change the treatment for a less effective second-line treatment.

To design drugs that alleviate or avoid the adverse effects of Cisplatin, it is important to know the mechanism by which it causes neuropathy. And this is precisely the focus of the study carried out by a team from the Bellvitge Biomedical Research Institute (IDIBELL), the Catalan Institute of Oncology (ICO), the Bellvitge University Hospital (HUB) and the Autonomous University of Barcelona (UAB), which has shown that Cisplatin induces senescence of peripheral neurons through overexpression of the p21 protein, which would explain the neuropathy.

"This discovery represents a paradigm shift in the field, because until now it was believed that oxidative stress and apoptosis cell death caused Cisplatin neuropathy", says Dr. Jordi Bruna, project leader. The study, published in the Neuro-Oncology journal, shows that neurons respond to Cisplatin damage by generating a series of metabolic changes. These changes induce them to enter in a kind of permanent hibernation, called senescence, which would be causing neuropathic symptoms, and not the direct death of neurons as previously believed.

The study shows the overexpression of the p21 protein induced by the administration of Cisplatin. This is a protein that in response to injury can regulate both, senescence and cellular apoptosis processes. However, the study shows that the pathways involved in apoptosis are not activated. Furthermore, both electron microscopy studies and molecular markers of cellular senescence have confirmed that neurons show morphological characteristics of senescence after treatment with Cisplatin.

"Neurons are the paradigm of a highly differentiated cell that cannot replicate, and senescense processes, classically described in replicative cells, are more controversial in non-replicative cells. Therefore, our work contributes to other recent studies that point that senescence processes can be relevant in different neurological pathologies" says Dr. Esther Udina, researcher at the Institut de Neurociències of the UAB (INc-UAB) and co-author of this research.

Until now, clinical trials of neuroprotective treatments aimed to alleviate platinum neuropathy have failed. Dr. Bruna concludes that "this could be because the treatments were focused on preventing neuronal apoptosis," and adds, "this study provides new targets to alleviate platinum neuropathy. These neuroprotective treatments, administrated with chemotherapy, could prevent the onset of neuropathy, and are less likely to interfere with antitumor efficacy than those aimed to prevent apoptosis". " In this way, chemotherapy with Cisplatin would not be limited depending on the appearance of this common adverse effect."

These studies used a mouse model that perfectly mimics the clinical characteristics of the patients. By a cell separation method, each neuron of the dorsal spinal ganglion was individualized and, the genes that were expressed at each moment were studied, with the subsequent validation with protein expression. It is an innovative method that has never been used in this field of research.