Culture

Zombies or enemies flashing right before your eyes and the dizzying feeling of standing on the edge of a cliff using virtual reality and augmented reality (AR and VR) are no longer exclusive to the games or media industries. Those technologies allow us to conduct virtual conferences, share presentations and videos, and communicate in real time in the virtual space. But because of the high cost and bulkiness of VR and AR devices, the virtual world is not within easy reach.

Recently, a South Korean research team developed moldable nanomaterials and a printing technology using metamaterials, allowing the commercialization of inexpensive and thin VR and AR devices.

Professor Junsuk Rho of the departments of mechanical engineering and chemical engineering and doctoral student in mechanical engineering Gwanho Yoon at POSTECH with Professor Heon Lee and researcher Kwan Kim of department of material science at Korea University have jointly developed a new nanomaterial and large-scale nanoprinting technology for commercialization of metamaterials. The research findings, which solve the issue of device size and high production costs that were problematic in previous researches, were recently published in Nature Communications, a prestigious scientific journal.

Metamaterials are substances made from artificial atoms that do not exist in nature but they freely control the properties of light. An invisible cloak that makes an illusion of disappearance by adjusting the refraction or diffraction of light, or metaholograms that can produce different hologram images depending on the direction of light's entrance, uses this metamaterial.

Using this principle, the ultrathin metalens technology, which can replace the conventional optical system with extremely thinness, was recently selected as one of the top 10 emerging technologies to change the world in 2019 at the World Economic Forum.

In order to make metamaterials, artificial atoms smaller than the wavelengths of light must be meticulously constructed and arranged. Until now, metamaterials have been produced through a method called electron beam lithography (EBL)*.

However, EBL has hindered the commercialization or production of sizable metamaterials due to its slow process speed and high cost of production.

To overcome these limitations, the joint research team developed a new nanomaterial based on nanoparticle composite that can be molded freely while having optical characteristics suitable for fabricating metamaterials. The team also succeeded in developing a one-step printing technique that can shape the materials in a single-step process.

The team succeeded in producing an ultrathin metalens that is 100 times thinner than the strand of a human hair by using this newly developed technology. Metamaterials can be made into one-thousandth of thickness of heavy glass or plastic lenses. This is the first time in the world such ultrathin metalens was produced in a single-step printing process.

If the cost of making a metalens at the performance of conventional glass lenses were one million won (USD 8,200) per unit, this technology enables the production at about 10,000 won (USD 8), which is 1/100 the cost and 1/10,000 the thickness in a simplified process.

Professor Rho, who led the research, stated, "This one-step printing technology of nanomaterials allows the fabrication of metamaterials over 100 times faster than the conventional electron beam lithography." He added, "These lenses can not only make the existing thick, large VR and AR lenses or glasses dramatically lighter and smaller, but can also be applied to curved or flexible panels, which facilitates the use of metamaterials in large omnidirectional invisible cloaks or in curved or bendable wearable devices at a fraction of the cost."

An alternating cycle of 50 days of strict lockdown followed by 30 days of easing could be an effective strategy for reducing the number of COVID-19-related deaths and admissions to intensive care units, say an international team of researchers.

The coronavirus pandemic has imposed an unprecedented challenge on global healthcare systems, societies and governments. The virus SARS-CoV-2, which causes COVID-19 disease, has been detected in every country, with more than 4.6 million confirmed cases and a death toll of 312,000 worldwide to date.

There are currently no effective treatments for the disease and a widely-available vaccine is likely to be at least a year away. The principal strategy to control the disease globally has focused on measures that minimise person-to-person transmission of SARS-CoV-2 through social distancing; including isolating suspected infected individuals, shielding vulnerable groups, school closures, and lockdowns.

While such measures are effective at slowing disease spread and preventing health systems becoming overwhelmed, these measures can also lead to significant job losses, financial insecurity and social disruption. As such, there is a growing concern that these interventions may be unsustainable over the long term. An alternative approach may be to alternate stricter measures with intervals of relaxed social distancing (with measures of effective "test-contact trace-isolate" and shielding of the vulnerable kept in place).

However, it is unclear what the frequency and duration of such dynamic interventions should be and which strategy could be adapted globally across countries with diverse health and economic infrastructures.

To address these uncertainties, an international team of researchers from the Global Dynamic Interventions Strategies for COVID-19 Collaborative Group modelled three scenarios across sixteen countries, from Belgium to India, that vary in setting and income. Their results are published today in the European Journal of Epidemiology.

In particular, the researchers were interested in the difference in impact between strategies aimed at mitigation and those aimed at suppression. Mitigation measures reduce the number of new infections, but at a relatively slow rate. These might include a combination of measures, such as general social distancing, hygiene rules, case-based isolation, shielding of vulnerable groups, school closures or restricting of large public events. On the other hand, suppression measures lead to a faster reduction in the number of new infections by applying additional interventions such as strict physical distancing, including lockdown.

The first scenario modelled the impact of imposing no measures. As might be expected, the number of patients requiring treatment in intensive care units (ICUs) would quickly exceed the available capacity significantly for every single country, resulting in a total of 7.8 million deaths across the 16 countries. Under this scenario, the duration of the epidemic would last nearly 200 days in the majority of the countries included.

The second scenario modelled a rolling cycle of 50-day mitigation measures followed by a 30-day relaxing. Such a strategy would be likely to reduce the R number (the number of people each infected individual goes on to infect) to 0.8 in all countries. However, it would still be insufficient to keep the number of patients requiring ICU care below the available critical care capacity. While proving effective for the first three months for all the countries, after the first relaxation, the number of patients requiring ICU care would exceed the hospital capacity and would result in 3.5 million deaths across the 16 countries. In this scenario, the pandemic would last approximately 12 months in high-income countries, and about 18 months or longer in the other settings.

The final scenario involved a rolling cycle of stricter, 50-day suppression measures followed by a 30-day relaxing. Such intermittent cycles would reduce the R number to 0.5 and keep ICU demand within national capacity in all countries. Since more individuals remain susceptible at the end of each cycle of suppression and relaxation, such an approach would result in a longer pandemic, lasting beyond 18 months in all countries. However, a significantly smaller number of people - just over 130,000 across the 16 countries modelled - would die during that period.

In comparison, the team found that after a continuous, three-month strategy of strict suppression measures, most countries would reduce new cases to near zero. Looser, mitigation strategies would require approximately 6.5 months to reach the same point. However, such prolonged lockdowns would be unsustainable in most countries due to potential knock-on impacts on economy and livelihood.

Dr Rajiv Chowdhury, a global health epidemiologist the University of Cambridge, UK, and lead author on the paper, said: "Our models predict that dynamic cycles of 50-day suppression followed by a 30-day relaxation are effective at lowering the number of deaths significantly for all countries throughout the 18-month period.

"This intermittent combination of strict social distancing, and a relatively relaxed period, with efficient testing, case isolation, contact tracing and shielding the vulnerable, may allow populations and their national economies to 'breathe' at intervals - a potential that might make this solution more sustainable, especially in resource-poor regions."

The researchers say that the specific durations of these interventions would need to be defined by specific countries according to their needs and local facilities. The key is to identify a pattern that allows countries to protect the health of the population not only from COVID-19 but also from economic hardship and mental health issues.

Professor Oscar Franco from the University of Bern, Switzerland, said: "Our study provides a strategic option that countries can use to help control COVID-19 and delay the peak rate of infections. This should allow them to buy valuable time to shore up their health systems and increase efforts to develop new treatments or vaccines.

"There's no simple answer to the question of which strategy to choose. Countries - particularly low-income countries - will have to weigh up the dilemma of preventing COVID-19 related deaths and public health system failure with the long-term economic collapse and hardship."

The largest prospective study of adult COVID-19 patients in USA to date confirms that critical illness is common among hospitalized patients (22%, 257/1150). Critically ill COVID-19 patients frequently require mechanical ventilation (79%, 203/257) and death rates among such patients are high (39%, 101/257). Risk factors associated with in-hospital death, including older age and chronic heart and lung disease, are consistent with reports from Italy, China and the UK.

A detailed report from 257 COVID-19 patients admitted to two hospitals in New York City, USA from 2 March to 1 April 2020, and followed for at least 28 days, is published today in The Lancet, offering a snapshot of how the virus affects adults requiring hospital care.

The study reports a high incidence of critical illness (22%, 257/1150) and a high dependency on mechanical ventilation to support breathing in critically ill patients (79%, 203/257). The researchers say this has important implications for US hospital systems and specifically the need to prepare for large numbers of patients requiring intensive care.

The findings mirror reports from China, Italy and the UK, with older age and pre-existing conditions being the strongest risk factors associated with poor outcomes.

Dr Natalie Yip, one of the authors of the study, from Columbia University Irving Medical Centre, USA, says: "In the USA, there have been almost 1.5 million confirmed cases of COVID-19 and nearly 90,000 deaths [1]. Although the clinical spectrum of disease has been characterised in reports from China and Italy, until now, detailed understanding of how the virus is affecting critically ill patients in the US has been limited to reports from a small number of cases. Our study aimed to identify risk factors associated with death in critically ill COVID-19 patients in a US hospital setting." [2]

The study focused on two hospitals in New York City, USA, affiliated with Columbia University Irving Medical Center in northern Manhattan. Between 2 March and 1 April 2020, 1,150 adults (aged 18 or over) were admitted to both hospitals with laboratory confirmed COVID-19. Of those admitted to hospital, 257 (22%) were critically ill and required treatment in a high dependency or intensive care unit. The most common symptoms reported were shortness of breath, fever, cough, muscle pain and diarrhoea. As of 28 April 2020, almost 40% of the critically ill patients had died (39%, 101/257) and more than one third remained in hospital (37%, 94/257). Less than one quarter had been discharged alive (23%, 58/257).

More than three quarters of the critically ill patients required mechanical ventilation to help them breathe (79%, 203/257). Patients spent an average of 18 days on a ventilator (range 9-28 days). This rate is higher than reported in smaller studies of cases from Washington state, USA [3, 4], but is in line with a recent report from Italy [5], the researchers say. In addition, almost one third of patients developed severe kidney damage and required therapy to support kidney function, such as dialysis (31%, 79/257).

The majority of critically ill patients were men (67%, 171/257). Critical illness was more common in older patients (median age 62 years) but around one in five patients were aged under 50 (22%, 55/257). More than 80% of critically ill patients had at least one chronic illness, the most common of which were high blood pressure (63%, 162/257) and diabetes (36%, 92/257). Nearly half of the patients were obese (46%, 119/257), consistent with trends seen in the UK. Almost two-thirds of critically ill patients were Hispanic or Latino (62%, 159/257) and around one in five were black or African American (19%, 49/257).

People with pre-existing lung or heart conditions had the highest risk of poorer outcomes. High blood pressure was also associated with poorer survival for critically ill patients, consistent with reports from China and Italy.

5% of critically ill patients were employed as healthcare workers (13/257). It is not possible to determine with certainty whether they became infected while working in a clinical setting because the virus was already circulating widely in the community at the time. However, the finding highlights the risks facing frontline healthcare workers and underlines the importance of consistent access to personal protective equipment for hospital staff.

Dr Max O'Donnell, senior author of the study, from Columbia University Irving Medical Centre, USA, says: "Our study provides in-depth understanding of how COVID-19 may be affecting critically ill patients in US hospitals. Of particular interest is the finding that over three quarters of critically ill patients required a ventilator and almost one third required renal dialysis support. This has important implications for resource allocation in hospitals, where access to equipment and specialised staff needed to deliver this level of care is limited." [2]

The researchers caution that their findings may not be generalizable to other hospital settings as they only looked at patients from two hospitals in New York City. This is particularly important when considering the demographic characteristics of the patient population. Studies involving patient groups that are more racially, ethnically and geographically diverse will be needed in order to confirm these findings.

Writing in a linked Comment article, Dr Giacomo Grasselli, who was not involved in the study, from the University of Milan, said: "The study by Cummings and colleagues shows that clinicians can produce high-quality research even when facing an overwhelming clinical workload. However, despite providing important insights, this work leaves us with some unanswered questions. While waiting for the availability of a COVID-19 vaccine, further studies are required to improve and personalise patient treatment, with particular attention to the role of initial non-invasive respiratory support strategies, timing of intubation, optimal setting of mechanical ventilation, and efficacy and safety of immunomodulating agents and anticoagulation strategies."

When early tetrapods transitioned from water to land the way they breathed air underwent an evolutionary revolution. Fish use muscles in their head to pump water over their gills. The first land animals utilized a similar technique--modern frogs still use their head and throat to force air into their lungs. Then another major transformation in vertebrate evolution took place that shifted breathing from the head to the torso. In reptiles and mammals, the ribs expand to create a space in the chest that draws in breath. But what caused the shift?

A new study published on May 12 in Scientific Reports posits a new hypothesis--the intermediate step was driven by locomotion.

When lizards walk, they bend side-to-side in a sprawling gait. The ribs and vertebrae are crucial to this movement, but it was unclear how until now. Researchers captured the 3-D motion of lizard ribs and vertebrae using XROMM, a combination of CT scans and X-ray videos. They recorded three savannah monitor lizards and three Argentine black and white tegus walking slowly on a treadmill. The resulting images revealed that while the spine is bending, every rib in both species rotated substantially around its vertebral joint, twisting forward on one side of the body and backward on the other side alternatively with each stride. The mechanics follow nearly the same pattern as when the reptiles inhale and exhale.

"It's really exciting because we didn't previously have plausible hypotheses for how rib-breathing evolved," said first author Robert Cieri, a postdoc at the University of the Sunshine Coast and who conducted the research while at the University of Utah, where he is still affiliated. "We're proposing that these rib movements first started to facilitate locomotion, then were co-opted for breathing."

The work also included John Capano and Elizabeth Brainerd at Brown University, and undergraduate Samuel Hatch at the U.

Why did the lizard cross the road? To catch its breath.

Reptiles, birds and mammals, all considered amniotes, use costal aspiration where the ribs and vertebrae control breathing by expanding and contracting. The motion is facilitated by the ribs rotating around the vertebrocostal joints--where the ribs and vertebrae meet. It's possible that an early amniote ancestor first used these rib movements to enhance its lateral undulation, the side-to-side trunk motion that helps propel lizards forward. During locomotion, each limb has two phases: First is propulsion, which is when the foot is pushing against the ground. Second is swing, which is when the foot is in the air. The new research found that during the arm's propulsion phase, the ribs on the same side of the body rotate towards the head, and while it's in the swing phase, they rotate towards the tail. This mimics what the scientists previously found the ribs doing inhalation and exhalation--but this time simultaneously on both sides.

Early tetrapods used sprawling, undulatory locomotion, but likely still had a head-driven breathing system. The authors propose that rib movements and increased costal joint mobility evolved during locomotion to increase stride length, hold the thorax steady, or as the passive result of the ribs moving to prevent being bunched together as the animals bended. At some point, early amniotes evolved the ability to express these rib movements on both sides simultaneously, which allowed for the expansion and contraction of the trunk that support inhalation and exhalation.

"Aspiration breathing was one of the key innovations that allowed amniotes to diversify on land. We were surprised and thrilled to find clues to how it evolved from a study on locomotion," co-author Brainerd said.

A collaboration between scientists at the Medical University of South Carolina and clinicians at the Greenwood Genetic Center has yielded new findings about how a particular gene might regulate brain development.

A paper published in Biological Psychiatry showcases how the researchers connected problems in mice with a defective copy of the MEF2C gene to issues suffered in real life by patients seen at the Greenwood Genetic Center who also have a defective copy of that gene.

Those patients have a rare form of autism called MEF2C haploinsufficiency syndrome. Basically, one of their two MEF2C genes in each cell is nonfunctioning, and the one non-mutated copy of the gene isn't powerful enough to regulate brain development the way it should, said Christopher Cowan, Ph.D., chairman of the Department of Neuroscience, whose lab conducted the study. The result in humans includes an inability to use language to communicate, epilepsy, repetitive movements, low muscle tone and breathing problems.

Cowan said the results of the study raise new prospects for treatment.

"We know the problem. The individuals have half as much MEF2C as they need. So, from a therapy standpoint, I think it opens a lot of interesting doors. We can think about ways to introduce more MEF2C into the brain during critical periods of development," he said.

It's not yet clear when interventions could be effective or if there is a developmental point of no return, he said. However, he noted that most children with this syndrome experience seizures by 20 months old, which could be a trigger for genetic testing and then potential treatment.

Cowan has been studying MEF2C for more than a decade. He'd previously found the MEF2 family is involved in synaptic pruning, the process by which the brain becomes more efficient as it prunes away redundant or irrelevant synaptic connections; this process occurs through young adulthood but is most active in the preschool and elementary school years. He'd also observed a connection to fragile X syndrome, the most common inherited form of autism.

When Cowan moved to South Carolina in 2016, he gave a talk at the Greenwood Genetic Center about his latest research findings, including information about MEF2C. More recently, the paper's joint lead authors, Adam Harrington, a postdoctoral scholar, and Catherine Bridges, an MUSC medical scientist training program student, both made presentations at a South Carolina Autism and Neurodevelopmental Disorders Consortium conference about their work on MEF2C in mice.

There to hear the talks was Steve Skinner, M.D., director of the Greenwood Genetic Center. As he listened, Skinner realized he'd just seen a patient with this gene dysfunction. Cowan and his team were excited about the opportunity to connect and interested in meeting human patients, Skinner said.

From there, the collaboration blossomed.

Cowan said that when they first created a mouse model of MEF2C haploinsufficiency syndrome, they looked to the scientific literature to see what gene mutations had already been found. They realized that nearly all the mutations were in the DNA binding region, affecting the most highly conserved portion of the protein MEF2C. Highly conserved protein regions have barely changed through millions of years of evolution - they remain nearly identical whether in yeast, flies or humans, strongly suggesting they serve a very important function.

And this particular protein is a transcription factor, which sits in the nucleus of the cell, binds to DNA and turns on hundreds of other genes, Cowan said. Those other genes must be activated at just the right time for neurons to mature, form appropriate connections and change in response to experiences, he said. That the mutations were occurring in this "hub" gene hinted that the mutations were causing problems for the protein to bind to DNA.

Indeed, the mouse model that was given one good copy and one inactive copy of MEF2C showed social deficits, hyperactivity, repetitive behavior and a significant reduction in ultrasonic vocalizations, Cowan said.

"We don't know for sure what mouse ultrasonic vocalization means to another mouse, but they generate them in social contexts," Cowan said. Researchers consider vocalizations a "species-appropriate communication mode," and this communication problem in mice mirrors the communication problems of the children in the study, he said.

When the team analyzed the genes in the mouse brains that were abnormally expressed and compared them to the human genome, two areas pinged. The first was excitatory neurons, and the second was the microglia, what Cowan calls "the brain's resident immune cell." Microglia eat up dead cells after an injury or a stroke and also physically remove synaptic material to help with pruning during normal brain development.

The scientists then removed MEF2C from just the neuronal cells or just the microglia, which produced different subsets of autism-like behaviors.

"For the field, I think it's important because it's starting to help us appreciate that neurodevelopmental disorders are probably a convergence of dysfunction or altered development of multiple different cell types. This has treatment implications as well because you can't just target the neuronal population. You can't just target microglia. You're probably going to have to think about the cluster of different cooperating cell types in the brain that lead to a typically functioning brain,"' Cowan said.

Research is continuing with cooperation from families across the world with children with this disorder. They're a small group, relatively speaking, but the internet and social media have given patients with rare disorders the opportunity to combine forces in looking for answers and even charting a path for research, Skinner said. For example, parents of children with Rett syndrome, another rare neurodevelopmental disorder, noted that their children often suffered from gallbladder diseases at a young age. Nowhere was this described in the scientific literature, but the parents saw the common thread among their children. As they began pressing for confirmation, Skinner said, researchers began looking at the question and found the connection the parents had intuited.

"Parents want to drive research to eventually find a treatment for their children," Skinner said.

The parents of children with MEF2C haploinsufficiency syndrome deeply appreciate the opportunity to talk to a researcher like Cowan, he said. The online support and information group, which consists of a few hundred families from across the world, is participating in further research, too. The research team recruited a Clemson University graduate student who developed a questionnaire that she sent to these families. It covers topics like when symptoms appeared, which symptoms appeared and treatments they have tried.

Skinner said the cooperative effort with MUSC has been rewarding.

"It's been a very collegial and collaborative relationship," he said. "Dr. Cowan has been very receptive to fielding questions from us, from the patients and families."

Cowan, for his part, said the relationship has been helpful in providing real-world context for his lab's work.

"Right in our own backyard, here in South Carolina, there are the tools and the research capabilities to be able to attack these really complex problems in biology. It's been a really great collaboration," he said.

BLOOMINGTON, Ind. -- As millions continue working from home during the pandemic or are required to report to jobs as essential employees, many have raised questions about how these work conditions impact our health -- and not just as they relate to COVID-19.

A new study from the Indiana University Kelley School of Business finds that our mental health and mortality have a strong correlation with the amount of autonomy we have at our job, our workload and job demands, and our cognitive ability to deal with those demands.

"When job demands are greater than the control afforded by the job or an individual's ability to deal with those demands, there is a deterioration of their mental health and, accordingly, an increased likelihood of death," said Erik Gonzalez-Mulé, assistant professor of organizational behavior and human resources at the Kelley School and the paper's lead author.

"We examined how job control -- or the amount of autonomy employees have at work -- and cognitive ability -- or people's ability to learn and solve problems -- influence how work stressors such as time pressure or workload affect mental and physical health and, ultimately, death," he said. "We found that work stressors are more likely to cause depression and death as a result of jobs in which workers have little control or for people with lower cognitive ability."

On the other hand, Gonzalez-Mulé and his co-author, Bethany Cockburn, assistant professor of management at Northern Illinois University, found that job demands resulted in better physical health and lower likelihood of death when paired with more control of work responsibilities.

"We believe that this is because job control and cognitive ability act as resources that help people cope with work stressors," Gonzalez-Mulé said. "Job control allows people to set their own schedules and prioritize work in a way that helps them achieve their work goals, while people that are smarter are better able to adapt to the demands of a stressful job and figure out ways to deal with stress."

The study, "This Job Is (Literally) Killing Me: A Moderated-Mediated Model Linking Work Characteristics to Mortality," appears in the current issue of the Journal of Applied Psychology. It is a follow-up to previous research the pair published in 2017, which was the first study in the management and applied psychology fields to examine the relationship between job characteristics and mortality.

The researchers used data from 3,148 Wisconsin residents who participated in the nationally representative, longitudinal Midlife in the United States survey. Of those in their sample, 211 participants died during the 20-year study.

"Managers should provide employees working in demanding jobs more control, and in jobs where it is unfeasible to do so, a commensurate reduction in demands. For example, allowing employees to set their own goals or decide how to do their work, or reducing employees' work hours, could improve health," Gonzalez-Mulé said. "Organizations should select people high on cognitive ability for demanding jobs. By doing this, they will benefit from the increased job performance associated with more intelligent employees, while having a healthier workforce.

"COVID-19 might be causing more mental health issues, so it's particularly important that work not exacerbate those problems," Gonzalez-Mulé said. "This includes managing and perhaps reducing employee demands, being aware of employees' cognitive capability to handle demands and providing employees with autonomy are even more important than before the pandemic began."

Researchers in the Ludwig Center at the Johns Hopkins Kimmel Cancer Center report they have identified a drug treatment that could--if given early enough--potentially reduce the risk of death from the most serious complication of Coronavirus disease 2019 (COVID-19), also known as SARS-CoV-2 infection.

Prazosin, a U.S. Food and Drug Administration-approved alpha blocker that relaxes blood vessels, may specifically target an extreme inflammatory process often referred to as cytokine storm syndrome (CSS) that disproportionately affects older adults with underlying health conditions, and is associated with disease severity and increased risk of death in COVID-19 infection. Using it pre-emptively to address COVID-19-associated hyperinflammation of the lungs and other organs has the potential to reduce deaths in the most vulnerable populations, they say.

In a report of their findings published April 30 in the Journal of Clinical Investigation, the researchers caution that although they believe if given early enough after viral exposure, the drug could prevent some deaths, it would not work in patients with advanced stages of the disease. They also emphasize that controlled clinical trials for this novel use of prazosin are needed before it can be safely recommended.

The investigators published the letter, they said, in hopes of stimulating rapid efforts to conduct such trials.

In the letter, the researchers described how they have been working in collaboration with researchers in the Johns Hopkins Divisions of Rheumatology and Infectious Diseases, and Departments of Neurology and Neurosurgery, to identify chemical ways of safely blocking the actions of catecholamines and cytokine responses. Together, catecholamines and cytokines enhance the inflammatory process that leads to severe COVID-19 symptoms, explains Chetan Bettegowda, M.D., Ph.D., Jennison and Novak Families Professor of Neurosurgery, who is senior author of the paper.

"The purpose of our article is to make the biomedical community aware of the potential of this approach and to stimulate additional basic and clinical research. Although, we are excited about this idea, we stress that a clinical trial is necessary to know if this intervention will help COVID patients, and that is where we are focusing all of our attention," says Bettegowda.

In mouse models of CSS, they found that prazosin--commonly used to treat blood pressure, prostate gland enlargement and other conditions--blocked catecholamines (hormones released by the adrenal glands when the body is under stress), reduced cytokine levels, and increased survival after exposure to agents that trigger cytokine storm responses similar to those observed in COVID-19.

Drugs that target CSS have been found to reduce the risk of death from other viral illnesses by up to 55%, according to preliminary results from a retrospective clinical study.

Prazosin is taken by mouth, costs less than $25 per month in the United States, and has been safely taken by millions of people over the last two decades. This should enable highly expedited clinical trials in people early after exposure to the SARS-CoV-2 virus, say the researchers.

"All drugs can have unanticipated side effects when used in new situations, so it is critical to evaluate the effectiveness and side effects of this drug in controlled clinical trials before it can be safely recommended for public use. This is particularly important for drugs like prazosin, which are already sold in pharmacies," says Bettegowda.

Maximilian Konig, M.D., research fellow and lead author of the report, says a vaccine remains the best long-term hope to prevent deaths from COVID-19 but notes, at present, there are hundreds of individuals throughout the world who are dying every day. "Prazosin is already widely available, known to be safe and inexpensive, and the regulatory path for use in individuals exposed to the virus is straightforward," he says.

The CSS treatment was granted Food and Drug Administration approval to be studied in a clinical trial for individuals with COVID-19.

Sometimes proteins misfold. When that happens in the human brain, the pileup of misfolded proteins can lead to neurodegenerative diseases like Alzheimer's, Parkinson's and ALS.

Proteins do not misbehave and misfold out of the blue. There is a delicate ecosystem of biochemical interactions and environments that usually let them twist, unfold, refold and do their jobs as they're meant to.

However, as researchers from Michigan Technological University explore in an article published in ACS Chemical Neuroscience, even a small change may cause long-term consequences.

For amyloid beta peptides -- considered a major hallmark of Alzheimer's disease -- a common chemical modification at a particular location on the molecule has a butterfly effect that leads to protein misfolding, aggregation and cellular toxicity.

Ashutosh Tiwari, associate professor of chemistry at Michigan Tech, explains that misfolded amyloid beta proteins tend to pile up and form aggregates, which can form stringy fibrils or balled-up amorphous shapes.

To understand what causes the different shapes and to assess their toxicity, Tiwari's team looked at acetylation.

Acetylation is one of the most common chemical modifications proteins undergo, but one of the least researched in terms of how it affects amyloid beta toxicity. On amyloid beta proteins, acetylation can occur at two sites: lysine 16 and lysine 28.

The team found that acetylation at lysine 16 led to the disordered aggregates that formed sticky but flexible amorphous structures and showed high levels of toxicity. They also found the aggregates showed higher free radical formation.

"No one has done a systematic study to show if you acetylate amyloid beta it changes how the aggregate looks, then it changes its biophysical properties and hence toxicity," Tiwari said. "What we're saying is that the shape, stickiness and flexibility of the aggregated protein structure can play a vital role in the cellular toxicity and may also affect the mechanism of toxicity."

In Alzheimer's, these aggregates accumulate in the part of the brain that affects memory. It's a disease that the Alzheimer's Organization reports is the sixth leading cause of death in the US and will cost the nation about $305 billion in 2020. Tiwari says what we truly need to understand about the disease is that there is no single cause, no single trigger, and probably no silver bullet because of the chemistry involved.

"This is how a subtle change on a single position can affect a whole protein's aggregation," Tiwari said, adding that the effect of acetylation on tau, another protein aggregation, has been far more studied than amyloid beta. Also, many researchers still think a misfolded protein has to look a certain way to become problematic, and that other misfolded forms are less of an issue.

Tiwari agrees some of the proteins' changes are subtle, and compares discerning the differences and their effects to snow tires. Snow tires have deeper treads and a more flexible material to handle winter roads, but it's hard to point out those features at highway speeds. Like different kinds of tires, protein shapes can appear indistinguishable at a distance.

"This is not something that can be viewed from afar -- it's a touch-and-feel property," Tiwari said. "We have to interrogate these properties. We have to look at these structures more deeply from both morphology and biophysical perspectives."

When we do, we may better understand the complexity of the misfolded proteins and amyloid beta toxicity that can cause neurodegenerative diseases like Alzheimer's.

COLD SPRING HARBOR, NEW YORK -- In an important, comprehensive, and timely review, an expert team from the University of California Berkeley details the methodologies used in nucleic acid-based tests for detecting the presence of SARS-CoV-2, the virus that causes COVID-19. They show that these tests vary widely in applicability to mass screening and urge further improvements in testing technologies to increase speed and availability.

Testing for the presence of the SARS-CoV-2 virus has been extensively discussed during the COVID-19 pandemic. The most sensitive tests measure the presence of the virus' genetic material, RNA, in a patient's sample, suggesting an ongoing infection. A huge effort is needed to scale up COVID-19 testing to a level required to ensure public safety. Many tests take several hours to complete and require extensive human labor as well as materials and equipment that are not universally available. There is a pressing need for alternatives, and the research community worldwide has provided a large number of them in journal articles and preprints (papers that have not yet been peer reviewed). The Berkeley scientists have assessed these approaches and show that some tests take minutes, some take hours, many are done in different ways, and they vary in cost and potential for mass use. The authors are "hopeful that the explosion of creative and multifaceted approaches to COVID-19 nucleic-acid testing will continue to seed solutions as society addresses the COVID-19 pandemic."

According to a UC Davis study, adolescents and young adults with autism spectrum disorder (ASD) and those with typical development show similar proactive cognitive control. However, symptoms of depression in individuals with autism were linked to less proactive control.

Cognitive control refers to a set of mental processes that coordinate thoughts and behaviors to fit one's goals and intentions. One type of cognitive control is proactive control, characterized by being actively ready and prepared by focusing on goal-relevant information ahead of time.

"Proactive control is a very important cognitive function that allows you to plan and prepare how to direct your attention. It allows you to follow directions or achieve certain goals without getting distracted," said Marie Krug, assistant project scientist in the Solomon Lab at the UC Davis MIND Institute and lead author of the study.

Autism, depression symptoms and cognitive control

In this study, published May 14 in the Journal of Abnormal Psychology, the researchers examined whether proactive control is different in adolescents and young adults with ASD than in individuals with typical development. They also studied how repetitive behaviors (a symptom of ASD) and psychological disorders (such as depression, anxiety and attention-deficit/hyperactivity disorder) are related to proactive control.

The study consisted of 88 participants (44 with ASD and 44 with typical development) between the ages of 12 and 22. The participants were enrolled in the Cognitive Control in Autism (CoCoA) Study at the UC Davis MIND Institute.

The researchers assessed proactive control using a picture-word Stroop test. They asked participants to name animals depicted in drawings with a superimposed word. They calculated "interference effects" by measuring the difference in the participants' reaction time between difficult incongruent trials (with nonmatching animal pictures and words) and simpler congruent trials (with matching animal pictures and words). They used two versions of the Stroop task: a mostly congruent block and a mostly incongruent block.

The researchers calculated proactive control as the reduction in the participant's interference effect for the mostly incongruent block compared to the mostly congruent block.

The study did not find any association between proactive control and repetitive behaviors, anxiety or attention-deficit/hyperactivity problems in the ASD group. Participants with autism who had more symptoms of depression showed less ability to implement proactive control.

People with autism experience depression four times more often than their neurotypical peers. One key symptom of depression is rumination, the act of dwelling on negative thoughts. Rumination may drain or limit cognitive resources needed to exercise proactive control. This was especially true in mostly incongruent blocks where cognitive resources are needed the most.

"This study helps us better understand the cognitive strengths and challenges in persons with autism," said Marjorie Solomon, professor of psychiatry and behavioral sciences at UC Davis and senior author of the study. "It also provides clues on the impact of co-existing conditions such as depression on these persons with autism, and thereby aids researchers with treatment development."

Researchers at the Beckman Institute at the University of Illinois at Urbana-Champaign have developed a new technique that can determine the specific molecular form, location, and the amount of lipids in samples of rat brain tissue. The technique provides more information than previous methods.

The paper "Quantitative Imprint Mass Spectrometry Imaging of Endogenous Ceramides in Rat Brain Tissue with Kinetic Calibration" was published in Analytical Chemistry.

"The brain is like a bar of butter. The most common molecules are water and lipids," said Jonathan Sweedler, James R. Eiszner Family Endowed Chair in Chemistry and the director of the School of Chemical Sciences. "Unfortunately, we don't fully understand the chemical complexity of lipids in the brain, which makes it hard to know their functions and how they are affected by different diseases."

Previous research in the field determined the lipid composition in a brain region, but not the localization or amount. The Sweedler Research Group refined a new technique called mass spectroscopy imaging that measures all three. "The technique allows us to look at a slice of a rat brain and figure out the locations of specific and unusual lipids," Sweedler said.

Members of the Sweedler Research Group imprinted the tissues onto slides containing chemicals that could diffuse into the tissues and vice versa. "It's like taking a piece of paper with ink and putting silly putty on it and seeing the image on the silly putty," Sweedler said. Using this technique, the researchers were able to determine the distribution and amount of ceramides, which are important in learning and memory, in the tissue samples.

However, there are disadvantages to the technique. "Although it works well for certain categories of lipids, we haven't shown that it works for the molecules found in the brain," Sweedler said. "Additionally, it requires more steps because you have to prepare the brain sample and the surfaces that have the chemical coating."

The researchers hope that this technique will help them look at how the lipid composition changes in response to pain medicines and drugs of abuse. This may help in the search for alternatives to existing treatments for chronic pain.

Medical personnel treating coronavirus cases in China have higher rates of anxiety and other mental health symptoms than the general population, according to a new study in the open-access journal PLOS ONE by Ning Sun of Ningbo College of Health Science in Ningbo China, and colleagues.

During the height of China's COVID-19 outbreak this year, more than 30,000 medical personnel from around China provided direct support to critically ill COVID-19 patients in Hubei province, the epicenter of the pandemic. These healthcare providers were confronted by stressors not typical to their usual jobs. Anecdotal evidence has suggested that the psychological toll of being on the front line of this pandemic may lead to an uptick in mental health disorders among healthcare providers.

In the new study, 560 medical personnel from 12 hospitals in eight provinces and cities across China completed an online questionnaire regarding their mental health status. The survey, carried out in January and February 2020, collected demographic information, information about COVID-19 exposure and work, and used the well-established Symptom-Checklist-90 (SCL-90) to quantify mental health symptoms. The subjects were 75 percent nurses and 25 percent doctors, with 72 percent being female.

The healthcare providers surveyed scored higher on scales of somatization (experiencing physical symptoms of psychiatric conditions), obsessive-compulsive symptoms, anxiety, phobic anxiety and psychoticism compared to a national average (p

The authors add: "The overall mental health status of medical personnel responding to new coronavirus pneumonia is generally higher than that of the norm group in China. The results of this study should contribute to measures to alleviate the psychological pressures on medical personnel dealing with the new coronavirus epidemic in China."

To better understand and mitigate the health risks faced by astronauts from exposure to space radiation, we ideally need to be able to test the effects of Galactic Cosmic Rays (GCRs) here on Earth under laboratory conditions. An article publishing on May 19, 2020 in the open access journal PLOS Biology from Lisa Simonsen and colleagues at the NASA Langley Research Center, USA, describes how NASA has developed a ground-based GCR Simulator at the NASA Space Radiation Laboratory (NSRL), located at Brookhaven National Laboratory.

Galactic cosmic rays comprise a mixture of highly energetic protons, helium ions, and higher charge and energy ions ranging from lithium to iron, and they are extremely difficult to shield against. These ions interact with spacecraft materials and human tissues to create a complex mixed field of primary and secondary particles.

The biological effects from these heavy ions and mixtures of ions are poorly understood. Using recently developed fast beam switching and controls systems technology, NSRL demonstrated the ability to rapidly and repeatedly switch between multiple ion-energy beam combinations within a short period of time, while accurately controlling the extremely small daily doses delivered by the heavier ions.

The authors describe how the simulator was developed, with a view to balancing the definition of mission-relevant radiation environments, facility limitations and beam selection, required hardware and software upgrades, as well as animal care and handling constraints.

In June of 2018, thirty-three unique ion-energy beam combinations were delivered in rapid sequential order (under 75 minutes), cumulatively mimicking the GCR environment experienced by shielded astronauts on a deep space mission. The following October, acute and highly fractionated GCR simulation doses were delivered to three animal model systems over four weeks to investigate mixed-field quality and dose-rate effects on the risks of radiogenic cancers, cardiovascular disease, and adverse effects on the central nervous system.

Over the past 30 years, most research on understanding space radiation-induced health risks has been performed using acute exposures of mono-energetic single-ion beams. Now a mixed field of ions can be studied collectively in the same animal cohort, thereby drastically reducing the number of animals, husbandry, and research costs. This achievement marks a significant step forward and enables a new era of radiobiology research to accelerate our understanding and mitigation of health risks faced by astronauts during long duration exploration missions or interplanetary travel to Mars.

Dr. Akhilesh K. Gaharwar, associate professor, has developed a highly printable bioink as a platform to generate anatomical-scale functional tissues. This study was recently published in the American Chemical Society's Applied Materials and Interfaces.

Bioprinting is an emerging additive manufacturing approach that takes biomaterials such as hydrogels and combines them with cells and growth factors, which are then printed to create tissue-like structures that imitate natural tissues.

One application of this technology could be designing patient-specific bone grafts, an area that is gaining interest from researchers and clinicians. Managing bone defects and injuries through traditional treatments tends to be slow and expensive. Gaharwar said that developing replacement bone tissues could create exciting new treatments for patients suffering from arthritis, bone fractures, dental infections and craniofacial defects.

Bioprinting requires cell-laden biomaterials that can flow through a nozzle like a liquid, but solidify almost as soon as they're deposited. These bioinks need to act as both cell carriers and structural components, requiring them to be highly printable while providing a robust and cell?friendly microenvironment. However, current bioinks lack sufficient biocompatibility, printability, structural stability and tissue?specific functions needed to translate this technology to preclinical and clinal applications.

To address this issue, Gaharwar's research group is leading efforts in developing advanced bioinks known as Nanoengineered Ionic-Covalent Entanglement (NICE) bioinks. NICE bioinks are a combination of two reinforcement techniques (nonreinforcement and ionic-covalent network), which together provide more effective reinforcement that results in much stronger structures.

Once bioprinting is complete, the cell-laden NICE networks are crosslinked to form stronger scaffolds. This technique has allowed the lab to produce full-scale, cell-friendly reconstructions of human body parts, including ears, blood vessels, cartilage and even bone segments.

Soon after the bioprinting, the enclosed cells start depositing new proteins rich in a cartilage-like extracellular matrix that subsequently calcifies to form a mineralized bone over a three-month period. Almost 5 percent of these printed scaffolds consisted of calcium, which is similar to cancellous bone, the network of spongy tissue typically found in vertebral bones.

To understand how these bioprinted structures induce stem cell differentiation, a next-generation genomics technique called whole transcriptome sequencing (RNA-seq) was utilized. RNA-seq takes a snapshot of all genetic communication inside the cell at given moment. The team worked with Dr. Irtisha Singh from Texas A&M Health Science Center, who served as a co-investigator.

"The next milestone in 3D bioprinting is the maturation of bioprinted constructs toward the generation of functional tissues," Gaharwar said. "Our study demonstrates that NICE bioink developed in our lab can be used to engineer 3D-functional bone tissues."

In the future, Gaharwar's team plans to demonstrate in vivo functionality of the 3D-bioprinted bone tissue.

Palm oil is often associated with tropical deforestation above all else. However, this is only one side of the story, as agricultural scientists from the University of Göttingen and the IPB University Bogor (Indonesia) show in a new study. The rapid expansion of oil palm has also contributed considerably to economic growth and poverty reduction in local communities, particularly in Asia. The study was published in the Annual Review of Resource Economics.

For the study, the researchers evaluated results from over 30 years of research on the environmental, economic and social consequences of oil palm cultivation in Africa, Asia and Latin America. They combined the results from the international literature with their own data from Indonesia, which they have been collecting since 2012 as part of an interdisciplinary German-Indonesian Collaborative Research Centre (CRC 990). Indonesia is the largest palm oil producer and exporter in the world. A large proportion of the palm oil produced in Indonesia is exported to Europe and the USA, where it is used by the food, fuel and cosmetics industries.

The research data show that the expansion of oil palm in some regions of the world - especially Indonesia and Malaysia - contributes significantly to tropical deforestation and the loss of biodiversity. Clearing forestland also leads to substantial carbon emissions and other environmental problems. "However, banning palm oil production and trade would not be a sustainable solution," says Professor Matin Qaim, agricultural economist at the University of Göttingen and first author of the study. "The reason is that oil palm produces three times more oil per hectare than soybean, rapeseed, or sunflower. This means that if palm oil was replaced with alternative vegetable oils, much more land would be needed for cultivation, with additional loss of forests and other natural habitats."

Banning palm oil would also have negative economic and social consequences in the producing countries. "It is often assumed that oil palm is only grown on large industrial plantations," says Qaim. "In reality, however, around half of the world's palm oil is produced by smallholder farmers. Our data show that oil palm cultivation increases profits and incomes in the small farm sector, in addition to raising wages and creating additional employment for rural labourers. Although there are incidences of conflicts over land, overall the oil palm boom has significantly reduced rural poverty in Indonesia and other producing countries."

"The goal should be to make palm oil production more environmentally and climate-friendly," says Professor Ingo Grass, agricultural ecologist at the University of Hohenheim and co-author of the study. "High yields on the already-cultivated land are important, in order to reduce additional deforestation. Mosaic landscapes, where oil palm is combined with patches of forest and other crops in agroforestry systems, could also help to protect biodiversity and ecosystem functions," he adds.

The authors conclude that developing and implementing more sustainable production systems are challenges which require both innovative research and policymaking. Clearly and fairly defined land rights and improved access for smallholder farmers to training, credit and modern technologies would be important steps forward. Consumers can contribute by shopping for food, fuel, and cosmetics more consciously and avoiding waste wherever possible.