Culture

Based on a manual recently discovered in a 3,500-year-old medical papyrus, University of Copenhagen Egyptologist Sofie Schiødt has been able to help reconstruct the embalming process used to prepare ancient Egyptians for the afterlife. It is the oldest surviving manual on mummification yet discovered.

In ancient Egypt, embalming was considered a sacred art, and knowledge of the process was the preserve of very few individuals. Most secrets of the art were probably passed on orally from one embalmer to the other, Egyptologists believe, so written evidence is scarce; until recently, only two texts on mummification had been identified.

Egyptologists were therefore surprised to find a short manual on embalming in a medical text that is primarily concerned with herbal medicine and swellings of the skin. The manual has recently been edited by University of Copenhagen Egyptologist Sofie Schiødt:

- Many descriptions of embalming techniques that we find in this papyrus have been left out of the two later manuals, and the descriptions are extremely detailed. The text reads like a memory aid, so the intended readers must have been specialists who needed to be reminded of these details, such as unguent recipes and uses of various types of bandages. Some of the simpler processes, e.g. the drying of the body with natron, have been omitted from the text, Sofie Schiødt explains. She adds:

- One of the exciting new pieces of information the text provides us with concerns the procedure for embalming the dead person's face. We get a list of ingredients for a remedy consisting largely of plant-based aromatic substances and binders that are cooked into a liquid, with which the embalmers coat a piece of red linen. The red linen is then applied to the dead person's face in order to encase it in a protective cocoon of fragrant and anti-bacterial matter. This process was repeated at four-day intervals.

Although this procedure has not been identified before, Egyptologists have previously examined several mummies from the same period as this manual whose faces were covered in cloth and resin. According to Sofie Schiødt, this would fit well with the red linen procedure described in this manuscript.

Four was the key number

The importance of the Papyrus Louvre-Carlsberg manual in reconstructing the embalming process lies in its specification of the process being divided into intervals of four, with the embalmers actively working on the mummy every four days.

- A ritual procession of the mummy marked these days, celebrating the progress of restoring the deceased's corporeal integrity, amounting to 17 processions over the course of the embalming period. In between the four-day intervals, the body was covered with cloth and overlaid with straw infused with aromatics to keep away insects and scavengers, Sofie Schiødt says.

The Papyrus Louvre-Carlsberg

The manuscript, which Sofie Schiødt has been working on for her PhD thesis, is the Papyrus Louvre-Carlsberg - so called because one half of the papyrus belongs to the Louvre Museum in Paris and the other half is part of the University of Copenhagen's Papyrus Carlsberg Collection. The two parts of the papyrus originally belonged to two private collectors, and several sections of it are still missing. Based on the palaeography, that is, the sign forms, the six metre long papyrus is dated to approximately 1450 BC, which means that it predates the only two other examples of embalming texts by more than a thousand years.

The bulk of the papyrus, which is the second-longest medical papyrus surviving from ancient Egypt, deals with herbal medicine and skin illnesses. Specifically, it contains the earliest-known herbal treatise, which provides descriptions of the appearance, habitat, uses, and religious significance of a divine plant and its seed as well as a lengthy treatise on swellings of the skin, which are seen as illnesses sent forth by the lunar god Khonsu.

The papyrus is planned for publication in 2022 as a collaboration between the Louvre Museum and the Papyrus Carlsberg Collection. If you are interested in a copy of Sofie Schiødt's PhD thesis "Medical Science in Ancient Egypt: A translation and interpretation of Papyrus Louvre-Carlsberg (PLouvre E 32847 + PCarlsberg 917)", which she defended 8 February 2021, please contact her at zcq348@hum.ku.dk.

The embalming process

The embalming, which was performed in a purpose-built workshop erected near the grave, took place over 70 days that were divided into two main periods - a 35-day drying period and a 35-day wrapping period.

During the drying period, the body was treated with dry natron both inside and outside. The natron treatment began on the fourth day of embalming after the purification of the body, the removal of the organs and the brain, and the collapsing of the eyes.

The second 35-day period was dedicated to the encasing of the deceased in bandages and aromatic substances. The embalming of the face described in the Papyrus Louvre-Carlsberg belonged to this period.

The entire 70-day embalming process was divided into intervals of 4 days, with the mummy being finished on day 68 and then placed in the coffin, after which the final days were spent on ritual activities allowing the deceased to live on in the afterlife.

"Everyone's unique" is a popular maxim. All people are equal, but there are of course individual differences. This was no different with dinosaurs. A study by researchers at the University of Bonn and the Dinosaur Museum Frick in Switzerland has now revealed that the variability of Plateosaurus trossingensis was much greater than previously assumed. The paleontologists examined a total of 14 complete skulls of this species, eight of which they described for the first time. The results have now been published in the scientific journal "Acta Palaeontologica Polonica".

Plateosaurus lived during the Late Triassic, about 217 to 201 million years ago. "With well over 100 skeletons, some of them completely preserved, it is one of the best known dinosaurs," says Dr. Jens Lallensack, who researched dinosaur biology at the University of Bonn and has been working at Liverpool John Moores University (UK) for several months. The herbivore had a small skull, a long neck and tail, powerful hind legs and strong grasping hands. The spectrum is considerable: Adult specimens ranged from a few to ten meters in length, weighing between about half a ton and four tons.

The first bones of Plateosaurus were found as early as 1834 near Nuremberg, making it the first dinosaur found in Germany, and one of the first ever. Between 1911 and 1938, excavations unearthed dozens of skeletons from dinosaur "graveyards" in Halberstadt (Saxony-Anhalt) and Trossingen (Baden-Württemberg). A third such cemetery was discovered in the 1960s in Frick, Switzerland. "It's the only one where there are still digs every year," Lallensack says. The material from Frick, which is described in detail for the first time, includes eight complete and seven fragmentary skulls excavated by Swiss paleontologist and dinosaur researcher Dr. Ben Pabst and his team.

Natural variation between individuals

Dinosaurs have been preserved for posterity mainly through bones. Paleontologists rely on anatomical details to distinguish different species. "A perpetual difficulty with this is that such anatomical differences can also occur within a species, as natural variation between individuals," Lallensack reports. Researchers at the University of Bonn and the Dinosaur Museum Frick (Switzerland) have now been able to show that Plateosaurus anatomy was significantly more variable than previously thought - and the validity of some species needs to be re-examined. These findings were made possible by analyses of 14 complete and additional incomplete skulls of Plateosaurus. "Such a large number of early dinosaurs is unique," says paleontologist Prof. Dr. Martin Sander of the University of Bonn.

Can all these fossils from Germany and Switzerland really be assigned to a single species? Answering this question has become all the more urgent since Martin Sander and Nicole Klein of the University of Bonn published in "Science" in 2005. According to this, Plateosaurus was probably already warm-blooded like today's birds, but was able to adapt its growth to the environmental conditions - something that today can only be observed in cold-blooded animals. "This hypothesis is of great importance for our understanding of the evolution of warm-bloodedness," reports Lallensack. However, until now the observed individually distinct growth patterns could alternatively be explained by the assumption that there was not only one, but several species present. The current study debunks this.

Bone deformations during fossilization

The researchers have now carefully documented the variations in skulls of different sizes. A significant portion of the differences can be attributed to bone deformation during fossilization deep below the Earth's surface. Individual variations must be distinguished from this: The posterior branch of the zygomatic bone, which is sometimes bifurcated and sometimes not, appeared most striking to the researchers. A strongly sculptured bone bridge over the eye was also present only in some skulls. The relative size of the nasal opening also varies.

"It becomes apparent that each skull has a unique combination of features," Lallensack notes, emphasizing the distinct individuality of these dinosaurs. The uniquely large number of skulls studied made it possible to show that the differences in characteristics were variations within a species and not different species. "Only if as many finds as possible are excavated and secured will we obtain the high quantities needed to prove species affiliation and answer fundamental questions of biology" says Sander.

Researchers at the Lady Davis Institute (LDI) at the Jewish General Hospital have discovered that increased levels of the protein OAS1 are associated with reduced mortality and less severe disease requiring ventilation among patients with COVID-19. Using drugs that boost OAS1 levels could be explored to try to improve these outcomes. The findings are published today in Nature Medicine.

"Our analysis shows evidence that OAS1 has a protective effect against COVID-19 susceptibility and severity," explains Dr. Brent Richards, a senior investigator at the LDI's Centre for Clinical Epidemiology and Professor of Medicine, Human Genetics, Epidemiology and Biostatistics at McGill University. "This is a very exciting development in the race to identify potential therapies to treat patients because there are already therapies in pre-clinical development that boost OAS1 and could be explored for their effect against SARS-CoV-2 infection."

Understandably, a great deal of effort is being invested in vaccine development. However, with hundreds of millions of people already infected around the world, it is important not to neglect the search for disease-specific therapies since few such therapies have been identified. Moreover, given the prevalence of vaccine hesitancy in the community and uncertainty as to how long any vaccine will prove to be protective, COVID-19 is most probably going to be a global issue for years to come. Thus, the need for therapeutic treatments will continue.

Researchers in Dr. Richards' lab explored proteins detectable in peripheral blood as a potential target. The challenge lay in determining which proteins play a causal role in disease progression, since their levels may also be influenced by COVID-19 itself or other confounding factors. Recent advances in proteomic technology - that is, the capacity to isolate and measure hundreds of circulating proteins at once - combined with genetic analyses through Mendelian randomization (MR) makes possible the delicate work of untangling which proteins affected COVID-19 adverse outcomes, rather than vice versa.

From genetic determinants of 931 circulating proteins, Dr. Sirui Zhou, a post-doctoral fellow at the LDI and first author on the paper, found that increase in OAS1 levels was associated with reduced COVID-19 death or ventilation, hospitalization, and susceptibility in up to 14,134 COVID-19 cases and 1.2 million controls. The results were consistent in multiple sensitivity analyses. They proceeded to measure OAS1 levels in 504 patients with different COVID-19 outcomes from the Biobanque Québec COVID-19, and found that increased OAS1 levels in post-infection patients were associated with protection against very severe COVID-19, hospitalization, and susceptibility.

"The protective effect was particularly large," points out Dr. Zhou, "such that we observed a 50% decrease in the odds of very severe COVID-19 per standard deviation increase in OAS1 circulating levels. Interestingly, for non-African peoples, this protective effect is likely inherited from a Neanderthal derived form of OAS1 called p46."

This form of OAS1 likely emerged in people of European ancestry through interbreeding with Neanderthals tens of thousands of years ago. Evolutionary pressure slowly increased the prevalence of this form of OAS1, such that it is now detectable in more than thirty-percent of people of European descent. It is likely that the form of the protein has served as protection against earlier pandemics.

Because drug development, even in the accelerated environment of pandemic research, takes time it is particularly exciting that molecules which can increase OAS1 activity are currently in pre-clinical development for eventual deployment in clinical trials.

"Our recommendation is that those medications that trigger increased OAS1 levels be further studied for their effect on COVID-19 outcomes so that we may better treat infected patients," said Dr. Richards.

A new study using leading edge technology has shed surprising light on the ancient habitat where some of the first dinosaurs roamed in the UK around 200 million years ago.

The research, led by the University of Bristol, examined hundreds of pieces of old and new data including historic literature vividly describing the landscape as a "landscape of limestone islands like the Florida Everglades" swept by storms powerful enough to "scatter pebbles, roll fragments of marl, break bones and teeth."

The evidence was carefully compiled and digitised so it could be used to generate for the first time a 3D map showing the evolution of a Caribbean-style environment, which played host to small dinosaurs, lizard-like animals, and some of the first mammals.

"No one has ever gathered all this data before. It was often thought that these small dinosaurs and lizard-like animals lived in a desert landscape, but this provides the first standardised evidence supporting the theory that they lived alongside each other on flooded tropical islands," said Jack Lovegrove, lead author of the study published today in Journal of the Geological Society.

The study amassed all the data about the geological succession as measured all round Bristol through the last 200 years, from quarries, road sections, cliffs, and boreholes, and generated a 3D topographic model of the area to show the landscape before the Rhaetian flood, and through the next 5 million years as sea levels rose.

At the end of the Triassic period the UK was close to the Equator and enjoyed a warm Mediterranean climate. Sea levels were high, as a great sea, the Rhaetian Ocean, flooded most of the land. The Atlantic Ocean began to open up between Europe and North America causing the land level to fall. In the Bristol Channel area, sea levels were 100 metres higher than today.

High areas, such as the Mendip Hills, a ridge across the Clifton Downs in Bristol, and the hills of South Wales poked through the water, forming an archipelago of 20 to 30 islands. The islands were made from limestone which became fissured and cracked with rainfall, forming cave systems.

"The process was more complicated than simply drawing the ancient coastlines around the present-day 100-metre contour line because as sea levels rose, there was all kinds of small-scale faulting. The coastlines dropped in many places as sea levels rose," said Jack, who is studying Palaeontology and Evolution.

The findings have provided greater insight into the type of surroundings inhabited by the Thecodontosaurus, a small dinosaur the size of a medium-sized dog with a long tail also known as the Bristol dinosaur.

Co-author Professor Michael Benton, Professor of Vertebrate Palaeontology at the University of Bristol, said: "I was keen we did this work to try to resolve just what the ancient landscape looked like in the Late Triassic. The Thecodontosaurus lived on several of these islands including the one that cut across the Clifton Downs, and we wanted to understand the world it occupied and why the dinosaurs on different islands show some differences. Perhaps they couldn't swim too well."

"We also wanted to see whether these early island-dwellers showed any of the effects of island life," said co-author Dr David Whiteside, Research Associate at the University of Bristol.

"On islands today, middle-sized animals are often dwarfed because there are fewer resources, and we found that in the case of the Bristol archipelago. Also, we found evidence that the small islands were occupied by small numbers of species, whereas larger islands, such as the Mendip Island, could support many more."

The study, carried out with the British Geological Survey, demonstrates the level of detail that can be drawn from geological information using modern analytical tools. The new map even shows how the Mendip Island was flooded step-by-step, with sea level rising a few metres every million years, until it became nearly completely flooded 100 million years later, in the Cretaceous.

Co-author Dr Andy Newell, of the British Geological Survey, said: "It was great working on this project because 3D models of the Earth's crust can help us understand so much about the history of the landscape, and also where to find water resources. In the UK we have this rich resource of historical data from mining and other development, and we now have the computational tools to make complex, but accurate, models."

Biologists from RUDN University confirmed that a well-known spasmolytic drug called hymecromone can suppress the inflammatory response in astrocytes, important glial cells of the central nervous system. Potentially, it could be used to develop medications against Alzheimer's disease and other neurodegenerative conditions. The results of the study were published in the International Journal of Molecular Sciences.

All pathological processes in the nervous system, such as neurodegenerative diseases, injuries, or intoxications, are associated with inflammations. It is due to the reaction of many auxiliary cells, including astrocytes that support the neural activity in the brain. When inflamed, astrocytes produce many antiinflammatory molecules (cytokines, interleukins, and oxylipins) that aggravate and speed up the inflammatory process. Neuroinflammation almost always results in the death of nerve cells. A team of biologists from RUDN University together with their colleagues from Lomonosov Moscow State University confirmed that the intensity of inflammation can be brought down by limiting the number of anti-inflammatory molecules produced by astrocytes. To do so, they suggested using hymecromone, a drug that is currently used to treat spasms.

"Astrocytes can synthesize hyaluronic acid, one of the main components of the brain's extracellular matrix. Our studies demonstrated that when hyaluronic acid is added to the astrocytes, it affects the production of the main anti-inflammatory molecules. In this work, we tested hymecromone that suppresses the synthesis of hyaluronic acid and measured its effect on the inflammatory response of astrocytes," said Dmitry Chistyakov, PhD, a senior researcher at the Center for Collective Use (Research and Education Center) at RUDN University, and a researcher at Lomonosov Moscow State University.

The team studied the effect of hymecromone on astrocytes in a rat brain cell culture. Cell culture samples were treated with a liposaccharide that activated the receptors in charge of the inflammation, and then with hymecromone. In order to assess the efficiency of the drug, the team extracted RNA from astrocytes and measured the activity of the genes that regulate the production of the anti-inflammatory molecules. The levels of hyaluronic acid and cytokines were measured in cell supernatants. The changes in the synthesis of signal lipids (oxylipins) were evaluated using the methods of high-efficiency liquid chromatography and tandem mass spectrometry.

Hymecromone turned out to suppress the production of anti-inflammatory molecules: tumor necrosis factor α and interleukins IL-6 and IL-1β, as well as oxylipins. At the same time, it increased the development of IL-10 that helps stop the inflammation. Having measured the levels of hyaluronic acid, the team confirmed that astrocytes actively produced this substance in response to liposaccharides. However, when a cell culture at the initial stages of the immune response was treated with hymecromone, the levels of hyaluronic acid dropped down. At the same time, hymecromone failed to have the same effect on the cells that did not inflame after contact with the liposaccharide. In these cultures, astrocytes continued to produce hyaluronic acid in regular quantities.

According to the biologists, it is still early to say for sure that the anti-inflammatory properties of hymecromone are rooted in its ability to reduce the production of hyaluronic acid. Still, the team is positive that these processes are connected.

"We managed to confirm that hymecromone is a promising compound that can be used to treat neuroinflammation. The mechanisms of its anti-inflammatory activity require further studies but given that this drug is widely used in clinical practice, the possibilities of such research are vast. Its efficiency can be safely tested when treating many pathologies that require inflammatory response suppression," added Dmitry Chistyakov from RUDN University.

An insecticide used to control pest infestations on squash and pumpkins significantly hinders the reproduction of ground-nesting bees -- valuable pollinators for many food crops, a new University of Guelph study has revealed.

This first-ever study of pesticide impacts on a ground-nesting bee in a real-world context found female hoary squash bees exposed to imidacloprid dug 85 per cent fewer nests, collected less pollen from crop flowers and produced 89 per cent fewer offspring than unexposed bees.

"Because they're not making nests and not collecting pollen, they cannot raise offspring," said Dr. Susan Willis Chan, a post-doc in the School of Environmental Sciences (SES), who conducted the study with Dr. Nigel Raine, holder of the Rebanks Family Chair in Pollinator Conservation in SES. "That means imidacloprid-exposed populations are going to decline."

Neonicotinoids (or neonics) are neurotoxic insecticides that kill insects by attacking their nervous systems, affecting learning, foraging and navigation in many kinds of bees. Farmers use the neonic imidacloprid to control cucumber beetles, the most damaging crop pest for squash and pumpkins.

Many species of ground-nesting bees, including the hoary squash bee, are responsible for pollination of numerous fruits, vegetables and oilseed crops in North America, said Chan.

"Solitary ground-nesting bees make up about 70 per cent of bee species. It's a really important ecological group and is also really important in crop pollination," she said.

However, these ground-dwellers are often overlooked when it comes to evaluating the impacts of pesticides on pollinators, she added.

Published recently in Scientific Reports , the study involved three years of monitoring the foraging and nesting behaviour of squash bees.

To mimic field conditions, Chan held the bees in mesh-covered enclosures that still allowed exposure to sun and rain and other environmental factors. She applied pesticides in ways that mirror actual use in farmers' fields.

Chan tested three insecticide treatments: the neonic imidacloprid applied to soil at planting time; the neonic thiamethoxam applied as a seed treatment; and an anthranilic diamide (an emerging non-neonic insecticide) sprayed onto growing plants. A fourth group without insecticides served as a control.

Studying the bees for three years allowed the team to show longer-term impacts of imidacloprid exposure on reduced nest-building, foraging and offspring reduction.

Bees visiting squash plants treated with anthranilic diamide collected significantly less pollen than those in the control group but had no fewer nests or offspring. Chan saw no measurable effects from the thiamethoxam seed treatment on pollen harvesting, nest construction or offspring production.

"Farmers and regulators need to look at alternatives to applying imidacloprid to soil for controlling pests on squash and pumpkins," she said.

"My recommendation to pumpkin and squash farmers is to stay away from imidacloprid applied to soil to keep their squash bees healthy."

Raine said it's likely other solitary, ground-nesting species are also being affected.

Noting that other ground-nesters live in farm fields, he said, "The sort of impacts from soil-applied pesticide exposure we've seen in this study could affect many other species of wild bees."

He said current regulatory assessments for insect pollinators fail to consider risks associated with soil pesticide residues. "Our results highlight why this should be changed to better characterize risk for the many bee species that spend a large proportion of their life in soil."

Given the importance of pollinating insects to crop production, Chan said, "Farmers need to protect their crops from pests, but they also absolutely need to protect pollinators from the unintended effects of pesticides."

Referring to imidacloprid, she said, "The data on this particular product are so clear that there's really no question about what has to happen. We have to find something else."

URBANA, Ill. - Economists and urban planners generally agree that local pollution sources disproportionally impact racial minorities in the U.S. The reasons for this are largely unclear, but a University of Illinois study provides new insights into the issue.

"Our work finds experimental evidence that racial discrimination in the home-renting process actively sorts minority renters into neighborhoods with higher levels of pollution," says Peter Christensen, assistant professor in the Department of Agricultural and Consumer Economics (ACE) and an affiliate in Center for the Economics of Sustainability at University of Illinois.

Christensen and co-authors Ignacio Sarmiento-Barbieri, U of I, and Christopher Timmins of Duke University conducted an empirical study to investigate racial bias in residential sorting.

A range of social and economic factors influence the rental search process, Christensen explains. A combination of differences in information about pollution exposure, neighborhood preference, and the relationship between race and income disparity can make it difficult to isolate a specific reason why a renter ends up with a certain property.

Therefore, the researchers used a correspondence experiment to isolate the effect of racial bias from property managers on the search process in housing markets with major polluting facilities.

Even in a particular ZIP code, neighborhoods can differ drastically in environmental quality, so the researchers categorized the 2,900 properties included in the study as lying within a low, medium, or high exposure area using an Environmental Protection Agency measure of pollution concentration.

Christensen's team at the National Center for Supercomputing Applications (NCSA) designed a "discrimination bot" that could identify properties in those markets and make large numbers of inquiries from fictitious renters on a major online housing platform. The bot would randomly vary the racial/ethnic identities of the prospective renters using a set of first/last names shown to elicit perceptions of Black, White, or Latin-X identities in the U.S.

The researchers tested for group differences in responses from the same property manager to the different identities.

"The results confirmed a troublingly high degree of racial bias in the online housing market," Christensen says. "In neighborhoods with a low pollution concentration, we measured a 59% relative response rate to inquiries from renters with Black and Latin-X sounding names. In other words, these renters were 41% less likely than those with white-sounding names to receive a response."

The results were even more striking for male renters with Black-sounding names in low-pollution neighborhoods - this group received just a 28% relative response rate to their inquiries.

Overall, the disparities were smaller in medium-exposure neighborhoods, with the relative response rate for minority-sounding names rising to 71%.

In high-exposure neighborhoods, the study found no evidence of racial discrimination, except those with Latin-X sounding names were actually slightly more likely to receive a response.

These results imply serious effects of racial disparities in pollution exposures and the broader welfare of minority communities, Christensen notes.

Overall, minority renters are more likely to be sorted into neighborhoods with high pollution concentrations. Those who actively seek out low-pollution housing are constrained to a smaller offering of properties, thus spending more time, money, and energy to search for a safe place to live.

Christensen and his co-authors emphasize their experimental data have limitations. The study only encompassed interactions taking place on a single online rental platform, raising questions about whether or not the results hold in other housing markets. Renter names in correspondence experiments are designed to elicit racial identification and may not be representative of the U.S. population. More work is needed to examine effects on the U.S. population as a whole or to identify differences across regions.

While the study does provide strong evidence discrimination continues to limit housing opportunities in minority communities, it does not examine whether pollution concentration specifically influences a landlord's decision to reply. Other factors affect these decisions and it isn't clear if landlords are generally aware of pollution in the area.

Regardless of the motives of rental property managers, the findings demonstrate that discriminatory practices limit housing options for minorities in neighborhoods with clean air, while providing no such search barriers in neighborhoods with higher levels of pollution. This likely exacerbates disparities in residential pollution exposures and contributes to respiratory illnesses, heart disease, hypertension and stress, as well as other health conditions.

"Our work makes a strong case for spending more resources on enforcing and investigating fair housing policy, for which funding has declined in recent years, and the need to consider implicit racial bias in the creation of future policies," Christensen concludes.

When patients with COVID-19 arrive in emergency rooms, there are relatively few ways for doctors to predict which ones are more likely to become critically ill and require intensive care and which ones are more likely to enjoy a quick recovery.

New Yale research could help them identify important early clues. In a recent study, researchers report that a series of biomarkers, or biological signals, associated with white blood cell activation and obesity can predict severe outcomes in COVID-19 patients.

The findings appear in the Feb. 26 edition of Blood Advances.

"Patients with high levels of these markers were much more like to require care in the intensive care unit, require ventilation, or die due to their COVID-19," said Dr. Hyung Chun, the lead author, an associate professor of medicine in cardiovascular medicine and pathology and director of translational research at the Yale Pulmonary Vascular Disease Program.

Previously, a few laboratory studies had identified possible indicators of severe COVID-19, including D-dimer levels, a measure of blood coagulation, and levels of proteins known as cytokines, which are released as part of inflammatory responses in the body. However, until now, no laboratory marker could predict which patients with COVID-19 would eventually become critically ill prior to showing clinical signs and symptoms of severe disease.

For the new study, Yale researchers used proteomic profiling -- a screen for multiple proteins within the blood -- to analyze samples taken from 100 patients who would go on to experience different levels of COVID-19 severity. In all cases, the blood samples were collected on the patients' first day of admission. The researchers also analyzed clinical data for over 3,000 additional patients with COVID-19 within the Yale New Haven Hospital system.

They found that five proteins (resistin, lipocalin-2, HGF, IL-8, and G-CSF) that are associated with neutrophils, a type of white blood cell, were elevated in the COVID-19 patients who later became critically ill. Many of these proteins had previously been associated with obesity but not with COVID-19 or other viral illnesses.

Notably, the elevated neutrophil biomarkers for patients who would go on to experience more serious symptoms were evident before those symptoms appeared. All COVID-19 patients who were admitted or transferred to the ICU had elevated neutrophil activation markers, while these biomarkers remained low for patients who never developed severe illness. None of the patients with lower neutrophil biomarker levels died.

"This is one of the first demonstrations that a set of biomarkers in the blood of COVID patients can predict eventual ICU admission, even before such patients become critically ill," said study author Dr. Alfred Lee, associate professor of medicine in hematology, director of the Yale Medical Oncology-Hematology Fellowship Program, and a member of the Yale Cancer Center.

Having early knowledge of these indicators could significantly improve patient treatment, the researchers said.

"If a diagnostic test [for these biomarkers] could be ordered early, it could give us a better sense of who is more likely to become critically ill and will benefit from a higher level of care and consideration for therapies that affect the immune system early on in their hospitalization," said Chun. "Many of these drugs do carry potential side effects, and these tests may help identify those patients who would benefit the most."

The study also underscores the connection between COVID-19 and obesity, researchers said. The Centers for Disease Control and Prevention notes that obesity and severe obesity increase risk of severe illness from COVID-19. Obesity triples the risk of hospitalization from COVID-19, and levels of body mass index has been found to correlate with the risk of death from COVID-19.

Neutrophils are inflammatory cells, said Lee, so it makes sense that they would be elevated in the context of both obesity -- which involves chronic, low-grade inflammation -- and COVID-19, which causes hyperinflammation in the most severe cases, leading to tissue damage and organ failure.

"There are also signs that neutrophils might participate in thrombosis or blood clotting," said Lee, another troubling hallmark of COVID-19.

The researchers will expand their study into the relationship between biomarkers and COVID-19 by looking at patients who have recovered from acute illness.

"We are hoping these findings motivate other groups to look at their own patient populations," said Chun, adding that they'll need additional validation studies that would support developing diagnostic tests for these biomarkers.

The research involved collaborators from across many different Yale departments, including Matthew L. Meizlish, an M.D.-Ph.D. student; Dr. Alex Pine, an assistant professor of medicine in hematology and staff physician at the VA Medical Center in West Haven; Jason Bishai, a graduate student; Hanming Zhang and C-Hong Chang, postdoctoral fellows; and Dr. David van Djik, an assistant professor of medicine in cardiology.

"The evolution of our findings really shows the power of collaboration, which has emerged as one hopeful aspect of this devastating pandemic that we will continue to harness for the benefit of the patients," said Lee.

PHOENIX, Arizona, February 26, 2021- Promising new research shows aerobic exercise may help slow memory loss for older adults living with Alzheimer's dementia.

ASU Edson College of Nursing and Health Innovation Professor Fang Yu led a pilot randomized control trial that included 96 older adults living with mild to moderate Alzheimer's dementia.

Participants were randomized to either a cycling (stationary bike) or stretching intervention for six months. Using the Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) to assess cognition, the results of the trial were substantial.

The six-month change in ADAS-Cog was 1.0±4.6 (cycling) and 0.1±4.1 (stretching), which were both significantly less than the expected 3.2±6.3-point increase observed naturally with disease progression.

"Our primary finding indicates that a six-month aerobic exercise intervention significantly reduced cognitive decline in comparison to the natural course of changes for Alzheimer's dementia. However, we didn't find a superior effect of aerobic exercise to stretching, which is likely due to the pilot nature of our trial. We don't have the statistical power to detect between-group differences, there was substantial social interaction effect in the stretching group, and many stretching participants did aerobic exercise on their own." Yu said.

The findings are described in a recently published article, Cognitive Effects of Aerobic Exercise in Alzheimer's Disease: A Pilot Randomized Controlled Trial, in the Journal of Alzheimer's Disease.

Yu says their results are encouraging and support the clinical relevance of promoting aerobic exercise in individuals with Alzheimer's dementia to maintain cognition.

"Aerobic exercise has a low profile of adverse events in older adults with Alzheimer's dementia as demonstrated by our trial," said Yu. "Regardless of its effect on cognition, the current collective evidence on its benefits supports the use of aerobic exercise as an additional therapy for Alzheimer's disease."

Transfer RNAs (tRNAs) deliver specific amino acids to ribosomes during translation of messenger RNA into proteins. The abundance of tRNAs can therefore have a profound impact on cell physiology, but measuring the amount of each tRNA in cells has been limited by technical challenges. Researchers at the Max Planck Institute of Biochemistry have now overcome these limitations with mim-tRNAseq, a method that can be used to quantify tRNAs in any organism and will help improve our understanding of tRNA regulation in health and disease.

A cell contains several hundred thousand tRNA molecules, each of which consists of only 70 to 90 nucleotides folded into a cloverleaf-like pattern. At one end, tRNAs carry one of the twenty amino acids that serve as protein building blocks, while the opposite end pairs with the codon specifying this amino acid in messenger RNA during translation. Although there are only 61 codons for the twenty amino acids, cells from different organisms can contain hundreds of unique tRNA molecules, some of which differ from each other by only a single nucleotide. Many nucleotides in tRNAs are also decorated with chemical modifications, which help tRNAs fold or bind the correct codon.

The levels of individual tRNAs are dynamically regulated in different tissues and during development, and tRNA defects are linked to neurogical diseases and cancer. The molecular origins of these links remain unclear, because quantifying the abundance and modifications of tRNAs in cells has long remained a challenge. The team of Danny Nedialkova at the MPI of Biochemistry has now developed mim-tRNAseq, a method that accurately measures the abundance and modification status of different tRNAs in cells.

Modification roadblocks and resolutions

To measure the levels of multiple RNAs simultaneously, scientists use an enzyme called reverse transcriptase to first rewrite RNA into DNA. Millions of these DNA copies can then be quantified in parallel by high-throughput sequencing. Rewriting tRNAs into DNA has been tremendously hard since many tRNA modifications block the reverse transcriptase, causing it to stop synthesizing DNA.

"Many researches have proposed elegant solutions to this problem, but all of them relieve only a fraction of the modification roadblocks in tRNAs", explains Danny Nedialkova, Max Planck Research Group Leader at the Max Planck Institute of Biochemistry. "We noticed that one specific reverse transcriptase seemed to be much better at reading through modified tRNA sites. By optimizing the reaction conditions, we could significantly improve the enzyme's efficiency, enabling it to read through nearly all tRNA modification roadblocks", adds Nedialkova. This made it possible to construct DNA libraries from full-length tRNA copies and use them for high-throughput sequencing.

The mim-tRNAseq computational toolkit

The analysis of the resulting sequencing data also presented significant challenges. "We identified two major issues: the first one is the extensive sequence similarity between different tRNA transcripts", explains Andrew Behrens, PhD student in Nedialkova's group and first author of the paper. "The second one comes from the fact that an incorrect nucleotide (a misincorporation) is introduced at many modified sites during reverse transcription. Both make it extremely challenging to assign each DNA read to the tRNA molecule it originated from", adds Behrens.

The team tackled these issues with novel computational approaches, including the use of modification annotation to guide accurate read alignment. The resulting comprehensive toolkit is packaged into a freely available pipeline for alignment, analysis and visualization of tRNA-derived sequencing data . Researchers can use mim-tRNAseq to not only measure tRNA abundance, but also to map and quantify tRNA modifications that induce nucleotide misincorporations by the reverse transcriptase. "mim-tRNAseq opens up myriad possibilities moving forward," says Nedialkova. "We expect it will help us and others to tackle many outstanding questions about tRNA biology in health and disease."

BOSTON - Two novel calculators for predicting which patients admitted to the hospital with COVID-19 are at greatest risk of requiring mechanical ventilation or of in-hospital death have been developed and validated by Massachusetts General Hospital (MGH). In a study published in The Lancet's EClinicalMedicine, researchers describe how these models could enable clinicians to better stratify risk in COVID-infected patients to optimize care and resource utilization in hospitals faced with ICU capacity constraints.

"Information that can accurately predict severity of the clinical course at the time of hospital admission has been limited," says senior author Rajeev Malhotra, MD, a cardiologist at MGH and investigator in the MGH Cardiovascular Research Center. "Using a combination of past medical history, vital signs, and laboratory results at the time of patient admission, we developed models that can differentiate between risk for mechanical ventilation and risk for in-hospital mortality. While other studies have focused on 30-day hospital outcomes, we followed all COVID-19 patients to the end of their hospital course since a significant number are hospitalized well beyond 30 days."

The research team compiled this clinical information from 1,042 patients confirmed with COVID-19 who were admitted to five hospitals in the Mass General Brigham health care system during the first three months of the pandemic. Significant associations between clinical, hemodynamic, and laboratory data and the endpoints of in-hospital mortality and mechanical ventilation provided the building blocks for two separate risk stratification models known as the VICE (Ventilation in COVID Estimate) and DICE (Death in COVID Estimate) scores.

Predictive VICE factors uncovered by researchers were diabetes mellitus, oxygen saturation of the blood, and two inflammatory markers: C-reactive protein and lactate dehydrogenase. DICE factors predictive of mortality were age, male sex, coronary artery disease, diabetes mellitus, body mass index, platelet count, and a variety of inflammatory and infectious markers.

"By inputting clinical values into these online calculators, physicians can risk-stratify COVID-19 patients upon admission and determine which ones may need the most intensive care and management," says lead author Christopher Nicholson, PhD, a senior research fellow with the MGH Cardiovascular Research Center. "These risk scores allow them to predict with greater than 80% accuracy--higher than established models--patient outcomes, as well as demand for mechanical ventilators and ICU beds, which could impact end-of-life decisions involving COVID-19 patients."

Researchers were surprised to learn that age was not a significant predictor of whether a patient would require mechanical ventilation. Indeed, other than the youngest patients, the percentage of hospitalized COVID-19 patients requiring mechanical ventilation was similar in each decade of life, though there was a clear correlation between age and risk of in-hospital death, with only 15% survival in patients over 84 requiring mechanical ventilation. Nor was age a predictor of how long a patient would need ventilation. The study found that 59% of patients in the 25-to-34 age group required more than 14 days of ventilation, similar to older age groups.

"We were astonished to see the impact of this disease on young people admitted to the hospital," emphasizes Nicholson. "Our data showed they are just as likely to be put on a mechanical ventilator as older people, and to require a long duration of ventilation."

Another significant finding from the study was that regular use of statins was associated with reduced in-hospital mortality, underscoring the strong links among COVID-19, cardiovascular disease, and inflammation. In another encouraging finding, researchers did not observe any relationship between minority ethnic background of COVID-19 patients and worse clinical outcomes after adjusting for clinical risk.

"What we've generally learned from this disease is how different it is from any other we've seen in the ICU," says Malhotra, who has managed COVID patients in the cardiac intensive care unit at MGH over the past year. "For that reason, we were focused on developing a novel approach to evaluate and predict outcomes with our risk stratification calculator."

In recent years, engineers have found ways to modify the properties of some "two- dimensional" materials, which are just one or a few atoms thick, by stacking two layers together and rotating one slightly in relation to the other. This creates what are known as moiré patterns, where tiny shifts in the alignment of atoms between the two sheets create larger-scale patterns. It also changes the way electrons move through the material, in potentially useful ways.

But for practical applications, such two-dimensional materials must at some point connect with the ordinary world of 3D materials. An international team led by MIT researchers has now come up with a way of imaging what goes on at these interfaces, down to the level of individual atoms, and of correlating the moiré patterns at the 2D-3D boundary with the resulting changes in the material's properties.

The new findings are described today in the journal Nature Communications, in a paper by MIT graduate students Kate Reidy and Georgios Varnavides, professors of materials science and engineering Frances Ross, Jim LeBeau, and Polina Anikeeva, and five others at MIT, Harvard University, and the University of Victoria in Canada.

Pairs of two-dimensional materials such as graphene or hexagonal boron nitride can exhibit amazing variations in their behavior when the two sheets are just slightly twisted relative to each other. That causes the chicken-wire-like atomic lattices to form moiré patterns, the kinds of odd bands and blobs that sometimes appear when taking a picture of a printed image, or through a window screen. In the case of 2D materials, "it seems like anything, every interesting materials property you can think of, you can somehow modulate or change by twisting the 2D materials with respect to each other," says Ross, who is the Ellen Swallow Richards Professor at MIT.

While these 2D pairings have attracted scientific attention worldwide, she says, little has been known about what happens where 2D materials meet regular 3D solids. "What got us interested in this topic," Ross says, was "what happens when a 2D material and a 3D material are put together. Firstly, how do you measure the atomic positions at, and near, the interface? Secondly, what are the differences between a 3D-2D and a 2D-2D interface? And thirdly, how you might control it -- is there a way to deliberately design the interfacial structure" to produce desired properties?

Figuring out exactly what happens at such 2D-3D interfaces was a daunting challenge because electron microscopes produce an image of the sample in projection, and they're limited in their ability to extract depth information needed to analyze details of the interface structure. But the team figured out a set of algorithms that allowed them to extrapolate back from images of the sample, which look somewhat like a set of overlapping shadows, to figure out which configuration of stacked layers would yield that complex "shadow."

The team made use of two unique transmission electron microscopes at MIT that enable a combination of capabilities that is unrivalled in the world. In one of these instruments, a microscope is connected directly to a fabrication system so that samples can be produced onsite by deposition processes and immediately fed straight into the imaging system. This is one of only a few such facilities worldwide, which use an ultrahigh vacuum system that prevents even the tiniest of impurities from contaminating the sample as the 2D-3D interface is being prepared. The second instrument is a scanning transmission electron microscope located in MIT's new research facility, MIT.nano. This microscope has outstanding stability for high-resolution imaging, as well as multiple imaging modes for collecting information about the sample.

Unlike stacked 2D materials, whose orientations can be relatively easily changed by simply picking up one layer, twisting it slightly, and placing it down again, the bonds holding 3D materials together are much stronger, so the team had to develop new ways of obtaining aligned layers. To do this, they added the 3D material onto the 2D material in ultrahigh vacuum, choosing growth conditions where the layers self-assembled in a reproducible orientation with specific degrees of twist. "We had to grow a structure that was going to be aligned in a certain way," Reidy says.

Having grown the materials, they then had to figure out how to reveal the atomic configurations and orientations of the different layers. A scanning transmission electron microscope actually produces more information than is apparent in a flat image; in fact, every point in the image contains details of the paths along which the electrons arrived and departed (the process of diffraction), as well as any energy that the electrons lost in the process. All these data can be separated out so that the information at all points in an image can be used to decode the actual solid structure. This process is only possible for state-of-the-art microscopes, such as that in MIT.nano, which generates a probe of electrons that is unusually narrow and precise.

The researchers used a combination of techniques called 4D STEM and integrated differential phase contrast to achieve that process of extracting the full structure at the interface from the image. Then, Varnavides says, they asked, "Now that we can image the full structure at the interface, what does this mean for our understanding of the properties of this interface?" The researchers showed through modeling that electronic properties are expected to be modified in a way that can only be understood if the full structure of the interface is included in the physical theory. "What we found is that indeed this stacking, the way the atoms are stacked out-of-plane, does modulate the electronic and charge density properties," he says.

Ross says the findings could help lead to improved kinds of junctions in some microchips, for example. "Every 2D material that's used in a device has to exist in the 3D world, and so it has to have a junction somehow with three-dimensional materials," she says. So, with this better understanding of those interfaces, and new ways to study them in action, "we're in good shape for making structures with desirable properties in a kind of planned rather than ad hoc way."

"The methodology used has the potential to calculate from the acquired local diffraction patterns the modulation of the local electron momentum," he says, adding
that "the methodology and research shown here has an outstanding future and high interest for the materials science community."

Dropping out of high school, having schizophrenia, or being diagnosed with a co-occurring personality disorder increases the likelihood of someone becoming a "high utilizer" of inpatient psychiatric hospital services, according to a new study by researchers at The University of Texas Health Science Center at Houston (UTHealth). A high utilizer is someone who has been admitted three or more times within one year.

The research was published today in The Journal of Health Care for the Poor and Underserved.

For their findings, researchers used machine learning to analyze deidentified electronic health record data from 9,840 patients admitted to UTHealth Harris County Psychiatric Center from January 2014 to December 2016. It is the first study of its kind to examine high utilizer trends in an academic safety net psychiatric hospital in a large, diverse region, where many patients are from underserved and disadvantaged populations.

"Many people don't realize that half of all health care expenses in the U.S. are incurred by 5% of the population," said Jane Hamilton, PhD, MPH, assistant professor in the Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences at McGovern Medical School at UTHealth and first author of the study. "These high utilizers are a very small number of individuals who are consuming a high number of resources. We need to figure out why they keep coming back so we can put supports around them to stop the trend."

Instead of a traditional statistical approach, where researchers would first examine each factor's independent relationship with utilization, the team leveraged machine learning, a form of artificial intelligence, to examine all factors at once.

"A machine learning algorithm called the 'elastic net' was able to predict utilization by including all of the predictors in the model at the same time," said Robert Suchting, PhD, assistant professor in the Faillace Department of Psychiatry and Behavioral Sciences and study co-author. "Traditionally, including all of the predictors at the same time can lead to unstable estimates of the strength of each predictor's relationship. The elastic net quantifies each predictor's relationship to the outcome, making it much easier to determine which predictors are strongest."

By identifying years of education, a schizophrenia diagnosis, and a co-occurring personality disorder diagnosis (being diagnosed with a personality disorder and another psychiatric condition concurrently), as the main predictors of high utilization, researchers were able to highlight suggestions for each predictor:

Less than 12 years of education: When working with psychiatric patients with limited education, mental health providers should routinely assess for mental health literacy and connect patients with educational support programs to improve health outcomes.

Schizophrenia and co-occurring personality disorders: Patients experiencing a first episode of psychosis, or the first signs of schizophrenia, comprise a subpopulation requiring enhanced efforts and prioritization for better identification and treatment at this critical phase of illness. Additionally, the routine assessment and treatment for co-occurring personality disorders should be integrated into community-based psychiatric treatment.
Hamilton, who studies social determinants of health, writes in the paper that many high utilizers have complex health needs, are more likely to be from socially disadvantaged groups, and have limited access to community-based health care and social services.

"Both schizophrenia and personality disorders can be difficult to treat, and many patients with these diagnoses are disadvantaged and vulnerable to health disparities. We really need evidence-based treatments in place to help these patients avoid repeat hospitalizations, and this study is a great first step in helping to identify the appropriate outpatient resources to help these patients remain stable in the community and avoid repeat hospitalizations," Hamilton said.

Hamilton is working with Lokesh Shahani, MD, MPH, chief medical officer of UTHealth Harris County Psychiatric Center, to strategize how to leverage the study to improve care transitions for these patients as they move from inpatient to outpatient care.

"Rehospitalization in a psychiatric hospital affects patient care and adds financial burden to our current health care system," said Shahani, an assistant professor in the Faillace Department of Psychiatry and Behavioral Sciences. "Using results from this current study, we will be able to better identify patients at high risk for rehospitalization. This would help us design and provide new treatment modalities to reduce their likelihood of future hospitalization."

MISSOULA - University of Montana researchers and their partners have discovered a slimy strategy used by bacteria to defeat antibiotics and other drugs used to combat infections afflicting people with cystic fibrosis. The research was published Feb. 23 in the journal Cell Reports.

Cystic fibrosis is a life-threatening disease that causes persistent lung infections and limits a person's ability to breathe over time. A common strain of bacteria, Pseudomonas aeruginosa, often thrives in the lungs of people with cystic fibrosis, as well as in wounds from burns or diabetic ulcers. Once a P. aeruginosa infection is established, it can be incredibly difficult to cure, despite repeated courses of antibiotics.

Dr. Laura Jennings, a research assistant professor in UM's Division of Biological Sciences and an affiliate with the University's Center for Translational Medicine, said their research showed that the stubborn germs living in the lungs of cystic fibrosis patients create a self-produced carbohydrate slime. And this slime makes the bacteria more resistant to the antibiotics prescribed by doctors, as well as drugs that reduce the thickness of mucus.

"We found the first direct evidence that these carbohydrates are produced at the sites of infection," Jennings said. "We showed that one of the carbohydrates, called Pel, sticks to extracellular DNA, which is abundant in the thick mucus secretions prominent in cystic fibrosis lungs.

"This interaction makes a slimy protective layer around the bacteria, making them harder to kill," she said. "As such, it reduces the pathogen's susceptibility to antibiotics and drugs aimed at reducing the thickness of airway mucus by digesting DNA."

She said the work supports a hypothesis that it's the carbohydrates that group, or aggregate, the bacteria in cystic fibrosis lungs.

"This is important because we know that physically breaking up bacterial aggregates can restore bacterial susceptibility to killing with antibiotics and cells of the immune system," Jennings said. "Therefore, understanding the mechanisms that promote bacterial aggregation may facilitate new therapeutic approaches aimed at digesting the carbohydrates holding bacterial cells together."

The research also suggests that the carbohydrate Pel likely diminishes the efficacy of the most commonly used therapeutics for cystic fibrosis, which are inhaled antibiotics and a drug that breaks down the thickness of the airway mucus, making it easier to cough up.

Robots that could take on basic healthcare tasks to support the work of doctors and nurses may be the way of the future. Who knows, maybe a medical robot can prescribe your medicine someday? That's the idea behind 3D structural-sensing robots being developed and tested at Simon Fraser University by Woo Soo Kim, associate professor in the School of Mechatronic Systems Engineering.

"The recent pandemic demonstrates the need to minimize human-to-human interaction between healthcare workers and patients," says Kim, who authored two recent papers on the subject - a perspective on the technology and a demonstration of a robots' usefulness in healthcare. "There's an opportunity for sensing robots to measure essential healthcare information on behalf of care providers in the future."

Kim's research team programmed two robots, a humanoid figure and a robotic arm, to measure human physiological signals, working from Kim's Additive Manufacturing Lab located in SFU Surrey's new engineering building. The robotic arm, created using Kim's 3D printed origami structures, contains biomedical electrodes on the tip of each finger. When the hand touches a person, it detects physiological signals, including those from an electrocardiogram (which monitors heartbeat), respiration rate, electromyogram (monitoring electrical signals from muscle movements) and temperature.

The humanoid robot can also monitor oxygen levels, which could be used to monitor the condition of those who develop severe COVID-19. The data can be viewed in real-time on the robot's monitor or sent directly to the healthcare provider.

Kim plans further development and testing of the robot together with healthcare collaborators. At this stage, the robots are capable of passively gathering patient information. But within the next decade, he says it's conceivable that healthcare robots fitted with artificial intelligence could take a more active role, interacting with the patient, processing the data they have collected and even prescribing medication.

Further study will also need to involve determining acceptance levels for this type of technology among various age groups, from youth to seniors, in a hospital setting.