Culture

New research from the University of Sheffield has found being overweight is an additional burden on brain health and it may exacerbate Alzheimer's disease.

The pioneering multimodal neuroimaging study revealed obesity may contribute toward neural tissue vulnerability, whilst maintaining a healthy weight in mild Alzheimer's disease dementia could help to preserve brain structure.

The findings, published in The Journal of Alzheimer's Disease Reports, also highlight the impact being overweight in mid-life could have on brain health in older age.

Lead author of the study, Professor Annalena Venneri from the University of Sheffield's Neuroscience Institute and NIHR Sheffield Biomedical Research Centre, said: "More than 50 million people are thought to be living with Alzheimer's disease and despite decades of ground breaking studies and a huge global research effort we still don't have a cure for this cruel disease.

"Prevention plays such an important role in the fight against the disease. It is important to stress this study does not show that obesity causes Alzheimer's, but what it does show is that being overweight is an additional burden on brain health and it may exacerbate the disease."

She added:"The diseases that cause dementia such as Alzheimer's and vascular dementia lurk in the background for many years, so waiting until your 60s to lose weight is too late. We need to start thinking about brain health and preventing these diseases much earlier. Educating children and adolescents about the burden being overweight has on multimorbidities including neurodegenerative diseases is vital."

Researchers from the University of Sheffield and the University of Eastern Finland examined MRI brain scans from 47 patients clinically diagnosed with mild Alzheimer's disease dementia, 68 patients with mild cognitive impairment, and 57 cognitively healthy individuals.

The novel study used three complementary, computational techniques to look at the anatomy of the brain, blood flow and also the fibres of the brain.

The international team compared multiple brain images and measured differences in local concentrations of brain tissues to assess grey matter volume - which degenerates during the onset of Alzheimers - white matter integrity, cerebral blood flow and obesity.

In mild dementia patients, a positive association was found between obesity and grey matter volume around the right temporoparietal junction. This suggests obesity might contribute toward neural vulnerability in cognitively healthy individuals and those with mild cognitive impairment.

The study also found that maintaining a healthy weight in mild Alzheimer's disease dementia could help preserve brain structure in the presence of age and disease-related weight loss.

Joint author of the study, Dr Matteo De Marco from the University of Sheffield's Neuroscience Institute, said: "Weight-loss is commonly one of the first symptoms in the early stages of Alzheimer's disease as people forget to eat or begin to snack on easy-to-grab foods like biscuits or crisps, in place of more nutritional meals.

"We found that maintaining a healthy weight could help preserve brain structure in people who are already experiencing mild Alzheimer's disease dementia. Unlike other diseases such as cardiovascular disease or diabetes, people don't often think about the importance of nutrition in relation to neurological conditions, but these findings show it can help to preserve brain structure."

An interdisciplinary team of the Institut national de la recherche scientifique (INRS) used an innovative imaging technique for a better understanding of motor deficits in Amyotrophic Lateral Sclerosis (ALS). The researchers were able to follow the escape behaviour of normal and disease zebrafish models, in 3D. Their results have recently been published in Optica, the flagship journal of the Optical Society (OSA).

Professor Jinyang Liang, expert in ultra-fast imaging and biophotonics, joined an effort with Professor Kessen Patten, specialist in genetics and neurodegenerative diseases. The two groups were able to track the position of zebrafish in real time and capture the 3D motion, using a special imaging technique called dispersion-eliminated coded-aperture light field, or DECALF.

"It is a unique feature for the analysis of animal behaviours from a neurodevelopment perspective. Otherwise, we would only be able to see the movement in a plane. Losing one dimension can be misleading when studying the movement. You may think zebrafish move one way, but the reality is quite different," said the expert.

Their data revealed asymmetrical orientation angles of the left and right fins, indicating drastic changes in direction during the normal zebrafish' s escape from the stimulus. In contrast, the diseased zebrafish model showed slow responses and limited movement capacity due to motor deficits.

Conventional light field cameras capture the information not only in x and y, but also the angle at which the light rays are coming from. This way, you can trace them back to focus on where you want. According to Professor Liang, the problem with this technology is the tradeoff. The image can have a high spatial resolution or a high angle resolution, but not both. The solution for this is the coded aperture light field (CALF) imaging, which can be achieved using digital micromirror devices (DMD).

An Innovative Design

The DMD acts like a diffraction element and separates the white light into a rainbow. A DMD alone cannot use it with ambient light or sunlight. "You could always use a single-wavelength light, but it leads to other disadvantages, since the colour of the light may interfere with the nerve system and affect the experiments. For example, red light could make people aggressive, and blue light is also known to affect the mood," Professor Liang explains.

To bypass this limitation, the research team used a second DMD to cancel the rainbow induce by the other one. "We are the first to use this design to manage the colour dispersion within the entire visible spectrum, which allows us to use white light for this experiment," says Dr. Jingdan Liu, a postdoctoral fellow at INRS and the first author of this paper. "DECALF imaging could open up a new avenue for neuroimaging. For example, we could use this system to see neurons' activity. We could track the emitted light when a neuron 'fires' to know where the neuron is located in the brain and its connectivity," says Professor Liang.

"Thanks to the work of Professor Liang, we were able to see the macroscopic behaviour of zebrafish with ALS-like symptoms. We could go even further in the study of this disease by looking at the microscopic scale.Using this innovative imaging approach, we could learn about what is happening in the neural system in normal and disease states in a non-invasive manner," Professor Patten says.

Air pollution is a key risk factor for cardiovascular disease, and a major contributor to the global burden of disease. Long-term exposure to air pollution has also been linked to an increased risk of death from COVID-19. This dangerous "triple threat" of air pollution, COVID-19 and cardiovascular disease should be taken seriously, warn major health authorities.

Four leading cardiovascular organizations - the World Heart Federation (WHF), American College of Cardiology (ACC), American Heart Association (AHA) and European Society of Cardiology (ESC) - today released a joint statement urging the medical community and health authorities to mitigate the impact of air pollution on people's health.

In 2019, an estimated 6.7 million deaths, or 12 percent of all deaths worldwide, were attributable to outdoor or household air pollution.[1] As many as half of these were due to cardiovascular disease. Air pollution also increases the risk of heart attack, stroke, diabetes and respiratory diseases, which are known to raise a person's risk of experiencing some of the more severe consequences of COVID-19.

"Even before the COVID-19 pandemic, air pollution was an issue of growing concern due to its impact on people's health, although it was frequently overlooked as a risk factor for cardiovascular disease. COVID-19 has brought a new, deadly factor to the equation, and the time has come for the health community to speak up and take action," said Michael Brauer, Chair of the World Heart Federation Air Pollution Expert Group and co-author of the statement.

The statement calls for structural actions to reduce emissions of air pollutants and harmful exposure. It also highlights the important role that healthcare providers play in preventing illnesses related to air pollution, including:

Advocating for air pollution mitigation as a health measure, further research on air quality and its impact on CVD, and interventions to reduce air pollution and its effect on NCDs

Providing patients with personal measures to reduce exposure, such as room air filtration systems

Integrating air pollution into disease management approaches, for example through the use of air quality indices

Participating in the development of guidelines on air pollution and CVD

Supporting ministries of environment, energy, and transportation in their mitigation efforts

Working to educate and raise awareness on the cardiovascular benefits of clean air

Collaborating with senior decision-makers in national, regional, and global governmental institutions to make air pollution related heart disease a priority

When you think of fungi, what comes to mind may be a crucial ingredient in a recipe or their amazing ability to break down dead organic matter into vital nutrients. But new research by Shuhai Xiao, a professor of geosciences with the Virginia Tech College of Science, and Tian Gan, a visiting Ph.D. student in the Xiao lab, highlights yet another important role that fungi have played throughout the Earth's history: helping the planet recover from an ice age.

A team of scientists from Virginia Tech, the Chinese Academy of Sciences, Guizhou Education University, and University of Cincinnati has discovered the remains of a fungi-like microfossil that emerged at the end of an ice age some 635 million years ago. It is the oldest terrestrial fossil ever found. To put it into perspective, this microfossil predates the oldest dinosaurs about three times over.

Their findings were published in Nature Communications on Jan. 28.

The fossil was found in small cavities within well-studied sedimentary dolostone rocks of the lowermost Doushantuo Formation in South China. Although the Doushantuo Formation has provided a plethora of fossils to date, researchers did not expect to find any fossils toward the lower base of the dolostones.

But against all odds, Gan found a few long, thread-like filaments - one of the key characteristics of fungi.

"It was an accidental discovery," said Gan. "At that moment, we realized that this could be the fossil that scientists have been looking for a long time. If our interpretation is correct, it will be helpful for understanding the paleoclimate change and early life evolution."

This discovery is key for understanding multiple turning points throughout Earth's history: the Ediacaran period and the terrestrialization of fungi.

When the Ediacaran period began, the planet was recovering from a catastrophic ice age, also known as the "snowball Earth." At that time, ocean surfaces were frozen to a depth of more than a kilometer and it was an incredibly harsh environment for virtually any living organism, except for some microscopic life that managed to thrive. Scientists have long wondered how life ever returned to normalcy - and how the biosphere was able to grow larger and more complex than ever before.

With this new fossil in hand, Tian and Xiao are certain that these microscopic, low profile cave dwellers played numerous roles in the reconditioning of the terrestrial environment in the Ediacaran time. One role involved their formidable digestive system.

Fungi have a rather unique digestive system that plays an even greater role in the cycling of vital nutrients. Using enzymes secreted into the environment, terrestrial fungi can chemically break down rocks and other tough organic matter, which can then be recycled and exported into the ocean.

"Fungi have a mutualistic relationship with the roots of plants, which helps them mobilize minerals, such as phosphorus. Because of their connection to terrestrial plants and important nutritional cycles, terrestrial fungi have a driving influence on biochemical weathering, the global biogeochemical cycle, and ecological interactions," said Gan.

Although previous evidence stated that terrestrial plants and fungi formed a symbiotic relationship around 400 million years ago, this new discovery has recalibrated the timeline of when these two kingdoms colonized the land.

"The question used to be: 'Were there fungi in the terrestrial realm before the rise of terrestrial plants'," said Xiao, an affiliated faculty member of the Fralin Life Sciences Institute and the Global Change Center. "And I think our study suggests yes. Our fungus-like fossil is 240 million years older than the previous record. This is, thus far, the oldest record of terrestrial fungi."

Now, new questions have arisen. Since the fossilized filaments were accompanied by other fossils, Gan will set out to explore their past relationships.

"One of my goals is to constrain the phylogenetic affinities of these other types of fossils that are associated with the fungal fossils," said Gan.

Xiao is thrilled to tackle the environmental aspects of these microorganism. Sixty years ago, few believed that microorganisms, like bacteria and fungi, could be preserved as fossils. Now that Xiao has seen them with his very eyes, he plans to learn more about how they have been virtually frozen in time.

"It is always important to understand the organisms in the environmental context," said Xiao. "We have a general idea that they lived in small cavities in dolostone rocks. But little is known about how exactly they lived and how they were preserved. Why can something like fungi, which have no bones or shells, be preserved in the fossil record?"

However, it can't be said for sure if this fossil is a definitive fungus. Although there is a fair amount of evidence behind it, the investigation into these microfossils is ongoing.

"We would like to leave things open for other possibilities, as a part of our scientific inquiry," said Xiao. "The best way to put it is that perhaps we have not disapproved that they are fungi, but they are the best interpretation that we have at the moment."

Three distinct groups and labs at Virginia Tech were crucial for the identification and timestamping of this fossil. The Confocal Laser Scanning and Microscopy lab at the Fralin Life Sciences Institute helped Tian and Xiao perform initial analysis that prompted further investigation at the University of Cincinnati.

The Department of Biological Sciences' Massey Herbarium, which houses over 115,000 specimens of vascular plants, fungi, bryophytes, and lichens, provided modern fungal specimens for comparison with the fossils.

The team called in technicians to conduct geochemical analysis using Secondary Ion Mass Spectrometry, which ionize nanomoles of material from small areas that are a fraction the thickness of a hair strand, to analyze the isotopic abundance of sulfur-32 and sulfur-34 in order to understand the fossilization environment.

Advanced computerized tomography was crucial to getting the 3D morphology of the filaments, which are just a few micrometers thick. And a combination of Focused Ion Beam Scanning Electron Microscopy and Transmission Electron Microscopy allowed researchers to cut samples with surgical precision and take an even closer look at every nanometer of the filaments.

"This wasn't a single person or even a single lab that did this work," said Xiao.

Xiao also emphasized the importance of interdisciplinary research in this study and many others.

"It's very important to encourage the next generation of scientists to be trained in an interdisciplinary light because new discoveries always happen at the interface of different fields," said Xiao.

A tick saliva study reveals immune responses that could lead to better protection for cattle.

Scientists from Hokkaido University, Japan and Universidade Federal do Rio Grande do Sul and Universidade Federal do Rio de Janeiro, Brazil, have revealed that substances in tick saliva activates immune response-suppressing proteins in cattle that facilitates the transmission of tick-borne diseases. The finding was published in the journal Scientific Reports and could help in the development of alternative control strategies.

The Asian blue tick, Rhipicephalus microplus, feeds on cattle, causing skin lesions, chronic blood loss and transmission of disease-causing parasites. The costs of preventing and treating disease and loss of some cattle are considerable in many parts of the world.

Some ticks have developed resistance against currently used acaricides, the tick equivalent of insecticides. To develop alternative strategies that can better protect cattle, such as vaccines, scientists need to better understand tick infections at the molecular level. For example, scientists already know that tick saliva suppresses the immune response in cattle, facilitating the transmission of tick-borne parasites, but the exact process has not been fully clarified.

Infectious disease veterinarian, Satoru Konnai, and scientists at Hokkaido University in Japan and colleagues in Brazil investigated what happens to immune cells when they are exposed to tick saliva. The team found that substances in tick saliva, likely a lipid compound called a prostaglandin, increase the expression of two specific cellular membrane proteins on some immune cells. The interaction of these proteins, called programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1), leads to the suppression of an immune cell called helper T cell (Th1). This means that the cattle's immune response is less able to combat invading tick-borne parasites.

Further investigation showed Asian blue tick saliva contains a high concentration of prostaglandin E2, which is known to induce PD-L1 expression. However future studies need to confirm if prostaglandin E2 plays a direct role in suppressing the cattle immune response. Also, since this study involved cells in the laboratory, the team says further research in live cattle is needed.

"Our findings suggest that Asian blue tick saliva inhibits the immune responses of helper T cells, at least in part, via the interaction between PD-1 and PD-L1," says Konnai.

Associate Professor Satoru Konnai of the Laboratory of Infectious Diseases at Hokkaido University conducts research on the development of novel therapeutic strategy for intractable diseases control in animals; the pathogenesis of bovine leukemia; analysis of mechanism of tick-borne pathogen transmission and development of anti-tick vaccines.

A Quebec research team has discovered two early plasma markers to detect Alzheimer's disease five years before its onset. The results of this recent study led by the doctoral student Mohamed Raâfet Ben Khedher and postdoctoral student Mohamed Haddad, directed by Professor Charles Ramassamy of the Institut national de la recherche scientifique (INRS), have been published in the prestigious scientific journal Alzheimer's & Dementia: Translational Research & Clinical Interventions (TRCI).

The diagnosis of Alzheimer's disease is usually based on a series of psychometric tests assessing cognitive function, brain imaging and cerebrospinal fluid analysis. Yet, these tests have their limitations. "The lumbar puncture is invasive, while brain imaging is expensive and not 100% reliable. This complicates regular follow-up," says Professor Ramassamy.

Moreover, people with the disease are often being diagnosed at a late stage of the disease. "We need to find more and more early markers so we can act as soon as possible. When the disease is symptomatic, there is little, if any, way back," he explains.

The research team took up this challenge by discovering two markers, detectable through a blood test, enabling them to follow the progression of the disease. These markers are found in plasma extracellular vesicles, pockets that are released by all cells in the body and circulate in the bloodstream.

The variation of markers

The team focused specifically on the "sporadic" Alzheimer's disease, the most common type of the disease. It stems mainly from the presence of the APOE4 susceptibility gene, the E4 variant of the gene coding for apolipoprotein. Patients with this gene who developed the disease five years later had markers present that varied with the progression of the disease.

The research was carried out by analyzing blood samples collected as part of the Canadian Study of Health and Aging (CSHA). The population studied consisted of patients with cognitive problems, but not suffering from dementia, and only some of whom developed Alzheimer's disease. Professor Ramassamy hopes to analyze a larger population with pre- and post-disease samples. This would allow him to determine the progression of markers after the onset of symptoms. His research on the markers located in the vesicles, opens up the possibility for studying other diseases, such as vascular dementia.

Navigating, exploring and thinking about space are part of daily life, whether it's carving a path through a crowd, hiking a backcountry trail or maneuvering into a parking spot.

For most of human history, the driving force for day-to-day wayfinding and movement across the landscape was a need for food. And unlike other primates, our species has consistently divided this labor along gender lines.

In new research published in Nature Human Behaviour, scientists including James Holland Jones of Stanford and lead author Brian Wood of University of California, Los Angeles, argue that the increasingly gendered division of labor in human societies during the past 2.5 million years dramatically shaped how our species uses space, and possibly how we think about it.

Underlying these conclusions is a huge and detailed trove of travel data revealing stark differences in the ways men and women among the nomadic Hadza people of Tanzania use space. A contemporary hunter-gatherer society, the Hadza provide a window into a highly mobile lifestyle, which was the norm for our species before the widespread adoption of agriculture.

"We're taking gender differences as a given in this particular cultural setting, and then asking what consequences they have downstream," said Jones, an associate professor of Earth system science at Stanford's School of Earth, Energy & Environmental Sciences (Stanford Earth) and a senior fellow at Stanford Woods Institute for the Environment.

A better understanding of this dynamic could yield clues about why men and women seem to think about space differently. Research in many human populations suggests men and women are better at different types of spatial tasks. On average, women tend to excel on spatial memory tasks, while men tend to score higher on two basic measures of spatial cognition associated with movement: mental rotation of objects and accurately pointing to distant locations.

'Male work is more navigationally challenging'

The paper examines a popular theory that men's hunting for wild game would produce more extensive and sinuous travel, and that women's harvesting of plant foods would lead to more concentrated, straight-line travel to and from known locations.

While previous efforts to substantiate the theory have relied heavily on verbal accounts, the researchers here tested it by examining more than 13,000 miles of travel logged on lightweight GPS trackers worn by Hadza foragers between 2005 and 2018. "One or two researchers would walk through camp early in the morning as people were rousing," the authors write. "We would greet people at their homes or hearths and hand out GPS devices to be worn during the day."

Around nightfall, when most people had returned to camp, Wood and assistants hired in the Hadza community removed the devices. They ultimately used data from 179 people, representing 15 camps and ranging in age from two to 84 years old.

The authors also examined the degree of overlap in the lands visited by men and women. "One of the most surprising results of this study was the fact that Hadza men and women essentially occupy different worlds from a young age. In our data, most of the landscape was effectively gender-segregated," said Wood, an assistant professor of anthropology at UCLA who began working on this paper a decade ago as a postdoctoral scholar at Stanford.

To analyze the movement data, the researchers adopted techniques from the field of movement ecology and also developed custom software. As expected, the results show men walked further per day, covered more land in less direct paths and were more likely to travel alone. "In this hunting and gathering context, male work is more navigationally challenging," the researchers write.

Although some individual day journeys extended to 20 miles or more, Hadza men overall averaged eight miles per day and women - many of them accompanied by young children - averaged nearly five miles. Gender differences emerged by the age of six. From the mid-forties, the gender difference declined, mostly due to decreasing travel by men while women sustained more of their daily mileage.

Human mobility in a changing world

Detailed spatial data like those amassed in this study will aid future comparative research into human mobility, according to the authors. This holds particular resonance in light of a pandemic that has forced sudden revisions of normal movement patterns and heightened attention to the costs and benefits of different spatial habits.

Already, Wood has begun to apply technical, logistical and scientific lessons from this study to a new National Science Foundation project meant to help identify research and policy priorities to prepare the U.S. for inevitable future pandemics - in part by measuring mobility and modeling patterns of social interaction. "The study of human movement can be used to identify at-risk communities for disease transmission and spread," Wood explained.

Even when we're not in a pandemic, Jones said, people's mobility drives economic activity, social cohesion and environmental impacts. And the environment, in turn, shapes spatial behavior. That feedback loop is at the heart of some of the internal migration patterns already emerging as a response to global warming. As once-rare weather events become commonplace, Jones explained, migrant laborers will likely travel longer distances for work; more people will engage in seasonal migration to pursue agricultural work or escape hurricanes and droughts, and crop failures will drive more rural residents to urban areas.

"Changing mobility is going to be one of the key ways that humans adapt to a heated world," Jones said. "Knowing more about gender differences and other drivers for spatial behaviors across a wide swath of human populations and ecological contexts will help us anticipate how this adaptation will play out and inform policies to manage it."

WASHINGTON, D.C. and SAN DIEGO, CA -- In his inaugural address, President Joe Biden vowed that "help is on the way" to a nation grappling with a pandemic that has already claimed over 420,000 lives and counting. However, despite the promise of a better future, a new survey from West Health and Gallup finds Americans remain largely skeptical that issues as varied as managing the COVID-19 crisis, lowering healthcare costs, improving the economy, fixing immigration and addressing climate change, will improve anytime soon.

The findings from the monthly West Health-Gallup U.S. Healthcare Study are based on a nationally representative sample of 3,100 U.S. adults interviewed between Dec. 15, 2020, and Jan. 3, 2021, after the presidential election but before Biden took office and announced more detailed plans for his first 100 days.

The survey found only 27% of Americans think the management of the pandemic is heading in the right direction - though it tops all other areas including the economy (23%), immigration reform (18%), climate change (15%) and the cost of healthcare, which only 8% of people think is going the right way.

Notably, Americans are three times more likely to believe the COVID-19 pandemic is headed in the right direction than the cost of healthcare (27% vs. 8%), placing greater confidence in putting an end to a more than yearlong pandemic than reversing decades of high healthcare prices.

"Unfortunately, the only direction prices for healthcare and prescription drugs has gone is up," said Tim Lash, chief strategy officer of West Health, a nonprofit dedicated to issues related to aging and lowering healthcare costs. "Years of high prices from drug companies and broken promises from politicians to rein them in have understandably made people skeptical. Nonetheless, President Biden may have the best opportunity yet for meaningful reform."

The survey found when it comes to healthcare, the top three issues Americans want the U.S. government to focus on in President Biden's first 100 days are lowering insurance premiums (70%), cutting drug prices (66%) and reducing the uninsured rate (63%), followed by expanding care for older adults (58%) and childcare for working parents (55%). Across the board, Democrats were far more likely to place a higher priority on these issues than Republicans, particularly when it comes to lowering premiums (90% vs. 60%).

Optimism for success, however, does not run high. Only 28% report that they think the Biden Administration and new Congress will be able to enact policies that will bring down the cost of healthcare compared to 49% who are pessimistic, and 22% who have no opinion one way or the other. Similar margins were found for policies related to lowering the costs of prescription drugs. This may explain why 80% of respondents felt healthcare costs will only continue to rise over the next two years.

"President Biden and Congress can restore Americans' faith in the future of healthcare through quick, bold and decisive policy action that drives down costs. Years of promises to do so from previous politicians and policymakers have fallen flat and left Americans pessimistic and hurting from a high-priced health system," said Lash.

The task of lowering healthcare and prescription drug prices is as daunting as the situation is dire for many Americans. Over 500 drugs have already seen a median price hike of 4.8% this month alone. Meanwhile, according to the West Health-Gallup survey, more than one-quarter of adults report that in the last year there was at least one time when someone in their household did not pursue care due to its cost and some 15 million Americans (6%) know someone who died in the last five years because they couldn't afford treatment. Another 40% say they are but one negative health event away from filing for bankruptcy.

"Harnessing the rising costs of healthcare and prescription drugs are more important than ever to the American public," said Dan Witters, Gallup senior researcher. "And even as the federal government focuses on the pandemic response, dovetailing those efforts with alleviating the cost of care would certainly be expected to pay dividends with public opinion."

Pioneering research into how our bodies manufacture the cells that make blood has moved us closer to regrowing tissues and organs. The findings also may let doctors grow the cells for transplantation into people to battle cancer, blood disorders and autoimmune diseases.

Researcher Karen K. Hirschi, PhD, of the Department of Cell Biology and the Robert M. Berne Cardiovascular Research Center at the University of Virginia School of Medicine, has developed a simple and efficient way to generate "hemogenic endothelial cells." These cells are the first step in the production line of blood cells, and Hirschi's new findings provide a blueprint for creating them outside the body.

"By studying how hemogenic endothelial cells develop normally, we gain insights needed to generate them in the lab," Hirschi said. "Now that we have established a method to produce human hemogenic endothelial cells outside of the body, we will continue to improve their production and function as we learn more about the mechanisms that promote their normal development."

Building Blood-Making Factories

Hirschi's latest work, published in a pair of scientific papers, offers important insights into how hemogenic endothelial cells form and how they ultimately give rise to the cells that directly manufacture blood throughout our lives.

Writing in the prestigious journal Science, she and her team reveal a key trigger that causes the endothelial cells to "transdifferentiate," or turn into blood-making factories, during embryonic development. These blood-making (i.e. hemogenic) endothelial cells generate hematopoietic stem and progenitor cells (HSPCs) that have long been used for the treatment of cancer and other diseases. Typically, they are taken from sources such as an individual's bone marrow, but doctors would like to be able to manufacture them quickly and easily for patients on demand. "Generating human hemogneic endothelial cells in the lab from each patient that needs HSPC is the first step toward patient therapies for blood disorders," Hirschi said.

In a paper published nearly simultaneously in Cell Reports, Hirschi unveils a blueprint for creating the hemogenic endothelial cells, the source of HSPCs, outside the body. The secret is a substance called retinoic acid. You may have heard of retinoic acid in association with beauty products, but in this case its responsibilities include triggering genes to cause "hematopoietic transition" - to put more vascular endothelial cells in the business of making blood by producing HSPCs.

The new insights provided by the work "will improve our ability to apply developmental insights to the generation of distinct endothelial cell subtypes for tissue engineering and regenerative medicine," the researchers write in their new paper. "In addition, our system could likely be developed further to optimize the generation of transplantable HSPCs from human hemogenic endothelial cells for clinical therapies."

The approach offers several advances over existing means, including being quicker and less expensive, the researchers note.

"We hope our continued efforts will move us closer to treating both vascular and blood disorders," Hirschi said. "These studies highlight the importance of basic cell and developmental biology research as a foundation for devising strategies for patient-specific clinical therapies."

Hirschi was recruited from Yale in 2019 to join the faculty in the Department of Cell Biology, which has long been interested in addressing how embryos develop and applying this basic knowledge to the repair and regeneration of damaged tissues and organs.

Worldwide, over one billion people live with a disability. Historically, they have been discriminated against and stigmatized by society. To improve their rights, they should be included in political decision-making, yet there is a lack of political representatives who are known to have a disability. This under-representation may be due to several factors, including how voters perceive a political candidate with a disability. However, a new study published in Frontiers in Political Science, found for the first time that voters do not apply negative stereotypes when evaluating candidates with a disability. Rather, voters tend to perceive candidates with a disability as capable, honest, and caring.

Stereotypes as information short-cuts

To form an impression of others, and with a lack of motivation and resources to dig past the surface, we tend to use stereotypes of social groups as a basis of information. We do this in a political context as well. ''Stereotypes can serve as 'information shortcuts','' says Dr Stefanie Reher (University of Strathclyde, United Kingdom). ''Being aware of how stereotypes and assumptions might affect one's beliefs might help voters make more deliberate decisions''. She describes two types of stereotypes that might influence voters' perceptions of candidates with a disability: trait stereotypes, and stereotypes about competence and political beliefs of candidates. Trait stereotypes operate if voters perceive candidates with a disability as weaker or more vulnerable, but also as courageous or inspiring. Competence and beliefs stereotypes are at work if voters might perceive candidates with disabilities as more concerned with healthcare and minority rights, and less concerned with (for instance) defense.

The research

To study voters' perception of candidates with a disability, Reher surveyed 1,500 British participants. In the online survey, participants were presented with descriptions of two fictional candidates and were asked to assess them on several dimensions. The descriptions gave background information about the candidates: gender, age, ethnic background, profession, years of political activity, and previous experience of elected office. They either did not mention any disability or included one of three selected disabilities: paralysis below the waist, blindness, or deafness.

Overall, voters do not appear to apply negative trait stereotypes, such as incompetence and weakness, when assessing candidates with a disability. Particularly, voters perceive them as more caring, with a difference between 4% to 6% from non-disabled candidates, and more honest, with a difference between 3% to 5%. The findings also indicate that effects of competence and beliefs stereotypes are larger than trait stereotypes. Specifically, voters perceive candidates with a disability as more concerned with minority rights, healthcare, and social welfare, with a difference between 4% to 12%. Interestingly, candidates with a disability were perceived to be more left-wing, with a difference between 3% to 5%. ''The study suggests that voters consider disabled people as very capable of fulfilling the tasks of elected office,'' says Reher. ''In fact, it appears that the experience of being disabled is even seen as an asset in some policy domains, including social security and healthcare.''

Implications of the study

These findings have implications for governments and political parties. Reher continues, ''the finding that voters do not perceive disabled candidates as less competent than non-disabled candidates is very informative for governments and political parties, as well as aspiring disabled politicians themselves.'' The problem of under-representation in politics may not lay with voters. Instead, increasing different types of support for candidates with a disability is key. ''If voters do not support candidates less because they are disabled, this suggests that there are other factors preventing disabled people from reaching positions of political power'', Reher adds, ''including a lack of accessibility and financial support for reasonable adjustments, and potentially a hesitancy within parties to nominate disabled people as candidates.''

Prescription drug prices in the United States are significantly higher than in other nations, with prices in the U.S. averaging 2.56 times those seen in 32 other nations, according to a new RAND Corporation report.

The gap between prices in the U.S. and other countries is even larger for brand-named drugs, with U.S. prices averaging 3.44 times those in comparison nations.

The RAND study found that prices for unbranded generic drugs -- which account for 84% of drugs sold in the U.S. by volume but only 12% of U.S. spending -- are slightly lower in the U.S. than in most other nations.

"Brand-name drugs are the primary driver of the higher prescription drug prices in the U.S.," said Andrew Mulcahy, lead author of the study and a senior health policy researcher at RAND, a nonprofit, nonpartisan research organization. "We found consistently high U.S. brand name prices regardless of our methodological decisions."

The RAND analysis is based on 2018 data and provides the most up-to-date estimates of how much higher drug prices are in the U.S. as compared to other countries in the Organisation for Economic Co-operation and Development.

Researchers calculated price indexes under a wide range of methodological decisions. While some sensitivity analyses lowered the differences between U.S. prices compared to those in other nations, under all the scenarios overall prescription drug prices remained substantially higher in the U.S.

The analysis used manufacturer prices for drugs because net prices -- that is, the prices ultimately paid for drugs after negotiated rebates and other discounts are applied -- are not systematically available. Even after adjusting U.S. prices downward based on an approximation of these discounts to account for these discounts, U.S. prices remained substantially higher than those in other countries.

The one consistent area where prices were lower in the U.S. was generic drugs, where prices were 84% of the average paid in other nations.

"For the generic drugs that make up a large majority of the prescriptions written in the U.S., our costs are lower," Mulcahy said. "It's just for the brand name drugs that we pay through the nose."

The study found that among G7 nations, the United Kingdom, France and Italy generally have the lowest prescription drug prices, while Canada, Germany and Japan tend to have higher prices.

Although several prior studies compared drug prices in the United States with those in other countries, the most recent of these studies used data that are almost a decade old.

RAND researchers compiled their estimates by examining industry-standard IQVIA MIDAS data on drug sales and volume for 2018, comparing the U.S. to 32 nations that belong to the OECD. The data include most prescription drugs sold in the U.S. and comparison countries.

Researchers say that conducting such comparisons requires a variety of decisions and assumptions to calculate price indexes. The U.S. had consistently higher drug prices regardless of how the researchers calculated price indexes and treated outliers in the data.

The RAND team examined several subsets of prescription drugs, including brand-name originator drugs, unbranded generic drugs, biologics and nonbiologic drugs.

Some of the highest-priced drugs in the United States are brand-name drugs that can cost thousands of dollars per treatment and treat life-threatening illness such as hepatitis C or cancers.

"Many of the most-expensive medications are the biologic treatments that we often see advertised on television," Mulcahy said. "The hope is that competition from biosimilars will drive down prices and spending for biologics. But biosimilars are available for only a handful of biologics in the United States."

Researchers estimated that across all of the OECD nations studied, total drug spending was $795 billion. The U.S. accounted for 58% of sales, but just 24% of the volume.

Recent estimates are that prescription drug spending in the U.S. accounts for more than 10 percent of all health care spending. Drug spending in the U.S. jumped by 76% between 2000 and 2017, and the costs are expected to increase faster than other areas of health care spending over the next decade as new, expensive specialty drugs are approved.

SINGAPORE, 28 January 2021 - One in three adults, particularly women, younger adults, and those of lower socioeconomic status, are experiencing psychological distress related to COVID-19, researchers at Duke-NUS Medical School, Singapore, reported in the journal PLOS ONE.

COVID-19 continues to pose serious threats to public health across the globe, and interventions such as lockdowns, quarantine and social distancing are having an adverse impact on the mental well-being of populations. The pandemic has escalated the burden of psychological distress, including anxiety, depression, post-traumatic stress and insomnia. However, the factors associated with increased susceptibility to psychological distress among adults in the general population during COVID-19 are not yet well known.

"Understanding these factors is crucial for designing preventive programmes and mental health resource planning during the rapidly evolving COVID-19 outbreak," explained Professor Tazeen Jafar, from the Health Services and Systems Research Programme at Duke-NUS, who led the study. "These factors could be used to identify populations at high risk of psychological distress so they can be offered targeted remote and in-person interventions."

Prof Jafar and her team performed a meta-analysis of 68 studies conducted during the pandemic, encompassing 288,830 participants from 19 countries, to assess risk factors associated with anxiety and depression among the general population. They found that, among the people most affected by COVID-19-related anxiety or depression, women, younger adults, individuals of lower socioeconomic status, those living in rural areas and those at high risk of COVID-19 infection were more likely to experience psychological distress.

The finding that women were more likely to experience psychological distress than men is consistent with other global studies that have shown that anxiety and depression are more common in women. "The lower social status of women and less preferential access to healthcare compared to men could potentially be responsible for the exaggerated adverse psychosocial impact on women," the researchers suggested. "Thus, outreach programmes for mental health services must target women proactively."

Younger adults, aged 35 and under, were more likely to experience psychological distress than those over the age of 35. Although the reasons for this are unclear, previous studies have suggested that it might be due to younger people's greater access to COVID-19 information through the media. This current study also confirmed that longer media exposure was associated with higher odds of anxiety and depression.

Other factors associated with psychological distress included living in rural areas; lower education, lower income or unemployment; and being at high risk of COVID-19 infection. However, having stronger family and social support and using positive coping strategies were shown to reduce the risk of psychological distress.

"The general public and healthcare professionals need to be aware of the high burden of psychological distress during the pandemic as well as education on coping strategies," Prof Jafar said. "Patients need to be encouraged to seek help, and access mental health counselling services with appropriate referrals."

Professor Patrick Casey, Senior Vice-Dean for Research at Duke-NUS, commented, "Even with the tremendous advances on the vaccine front, the world has come to realise that the COVID-19 pandemic will be with us for the long haul. Professor Jafar's study contributes valuable insights on the pandemic's psychological toll on populations around the world and highlights specific groups who may benefit from additional support, whether that is from their family or a healthcare provider."

Running a successful business has its challenges, but the COVID-19 pandemic has required many owners to pivot and look for new ways to operate profitably while keeping employees and consumers safe. Research from the Indiana University Kelley School of Business found that emotional intelligence - the ability to understand, use and manage emotions to relieve stress - may be more vital to a business' survival than previously thought.

"We found that entrepreneurs benefit much more from emotional competences than other competencies -- such as IQ -- due to high uncertainty and ambiguity that comes with the world of entrepreneurship and even more applicable in a crisis," said Regan Stevenson, assistant professor ?of entrepreneurship and management and the John and Donna Shoemaker Faculty Fellow in Entrepreneurship.

"Being an entrepreneur is not a 'traditional workplace setting.' If you are an entrepreneur, you know that managing your business can often feel like you are screaming alone on an emotional rollercoaster," Stevenson added. "The extreme nature of this setting makes one's ability to manage emotions and social connections critically more important, especially so during times of major disruption and crisis."

According to recent U.S. Bureau of Labor Statistics, about a fifth of all new businesses fail within their first two years and nearly half are shuttered within five years. More than a million U.S. companies with employees were shuttered in 2020, in large part due to the COVID-19 pandemic. The number of bankruptcies in 2020 and those expected this year likely will approach levels last seen during the worst quarter of the 2008-09 financial crisis.

"The extreme nature of the pandemic has made one's ability to manage emotions and social connections critically more important, especially so during these times of major disruption and crisis," said Ernest O'Boyle, associate professor of management and entrepreneurship and the Dale M. Coleman Chair in Management.

The research found that those with a higher emotional intelligence are better able to be self-motivated and have higher social skills - even under more normal circumstances.

"Emotional Intelligence is linked to social skills such as accurately perceiving other's needs, making good first impressions, and influencing others in interpersonal interactions. These skills are important for developing business networks, which can aid in signaling legitimacy and in acquiring resources," researchers wrote. "These skills can enhance creativity and opportunity recognition; aid decision making in emotionally turbulent situations and enable adaptive responses to unpredictable events."

Previous research has suggested that cognitive intelligence was a greater predictor of success among entrepreneurs. The two factors are seldom studied together.

"While IQ is unquestionably the better predictor of job performance and career success across all jobs and careers, within the domain of entrepreneurship, emotional intelligence was the stronger predictor of success," O'Boyle added. "Those with high emotional intelligence tended to be more successful as business leaders and enjoy success than in more typical jobs and careers."

Their findings are based on an empirical study of nearly 40 previous studies and a meta-analysis of 65,826 entrepreneurs observed through that research. Their paper, "What matters more for entrepreneurship success? A meta-analysis comparing general mental ability and emotional intelligence in entrepreneurial settings," appears in Strategic Entrepreneurship Journal.

WEST LAFAYETTE, Ind. - An improved extraction method involving chia seeds may provide new options for nutritional foods, medicine capsules and anti-aging products.

A Purdue University team has developed and patented the method to separate mucilage from chia seeds, yielding a protein-rich chia seed flour with improved bioactivity and functionality compared with conventional methods.

This work was supported by the USDA National Institute of Food and Agriculture, Hatch Act formula funds project 1019794.

Mucilage is a thick and gluey substance that surrounds chia seeds and can make processing the seeds for food or pharmaceutical uses much more difficult or nearly impossible.

"We are excited about our extraction method because it opens up so many new possibilities for using chia seeds," said Uriel Urbizo, a Ph.D. graduate student in Purdue's College of Agriculture involved in the innovation team led by Andrea Liceaga, an associate professor of food science. "Our process uses temperature, ultrasonication, and vacuum-assisted filtration to offer improved efficiency to save both time and money for companies processing chia seeds for nutritional, pharmaceutical, anti-aging or other applications."

Chia seeds have been used for centuries as protein sources, but Urbizo said conventional separation methods such as freeze-drying processes can be expensive, time-consuming, damage useful components of the seeds and decrease the total yield.

The Purdue researchers also tested the method they developed for potential applications such as using the mucilage and peptides to develop films that can be used in medicine capsules and anti-aging products, respectively.

"Our method offers an improved option for creating products that use components, primarily peptides, from the chia seeds to inhibit enzymes that play a role in the aging of skin," Liceaga said.

What if scientists knew exactly what impact the SARS-CoV-2 virus had inside our lung cells, within the first few hours of being infected? Could they use that information to find drugs that would disrupt the virus' replication process before it ever gets fully underway? The discovery that several existing FDA-approved drugs--including some originally designed to fight cancer--can stop coronavirus in its tracks indicates the answer is a resounding yes.

A team of Boston University researchers--hailing from BU's National Emerging Infectious Diseases Laboratories (NEIDL), the Center for Regenerative Medicine (CReM) at BU's Medical Campus, and BU's Center for Network Systems Biology (CNSB)--embarked on a months-long, collaborative and interdisciplinary quest, combining multiple areas of expertise in virology, stem cell-derived lung tissue engineering, and deep molecular sequencing to begin answering those questions. They simultaneously infected tens of thousands of human lung cells with the SARS-CoV-2 virus, and then tracked precisely what happens in all of those cells during the first few moments after infection. As if that was not complicated enough, the team had to cool their entire high-containment research facility inside the NEIDL to a brisk 61 degrees Fahrenheit.

The result of that challenging and massive undertaking? The BU team has revealed the most comprehensive map to date of all the molecular activities that are triggered inside lung cells at the onset of coronavirus infection. They also discovered there are at least 18 existing, FDA-approved drugs that could potentially be repurposed to combat COVID-19 infections shortly after a person becomes infected. Experimentally, five of those drugs reduced coronavirus spread in human lung cells by more than 90 percent. Their findings were recently published in Molecular Cell.

Now, academic and industry collaborators from around the world are in contact with the team about next steps to move their findings from bench to bedside, the researchers say. (Although COVID-19 vaccines are starting to be rolled out, it's expected to take the better part of a year for enough people to be vaccinated to create herd immunity. And there are no guarantees that the current vaccine formulations will be as effective against future SARS-CoV-2 strains that could emerge over time.) More effective and well-timed therapeutic interventions could help reduce the overall number of deaths related to COVID-19 infections.

"What makes this research unusual is that we looked at very early time points [of infection], at just one hour after the virus infects lung cells. It was scary to see that the virus already starts to damage the cells so early during infection," says Elke Mühlberger, one of the study's senior investigators and a virologist at BU's NEIDL. She typically works with some of the world's most lethal viruses like Ebola and Marburg.

"The most striking aspect is how many molecular pathways are impacted by the virus," says Andrew Emili, another of the study's senior investigators, and the director of BU's CNSB, which specializes in proteomics and deep sequencing of molecular interactions. "The virus does wholesale remodeling of the lung cells--it's amazing the degree to which the virus commandeers the cells it infects."

Viruses can't replicate themselves because they lack the molecular machinery for manufacturing proteins--that's why they rely on infecting cells to hijack the cells' internal machinery and use it to spread their own genetic material. When SARS-CoV-2 takes over, it completely changes the cells' metabolic processes, Emili says, and even damages the cells' nuclear membranes within three to six hours after infection, which the team found surprising. In contrast, "cells infected with the deadly Ebola virus don't show any obvious structural changes at these early time points of infection, and even at late stages of infection, the nuclear membrane is still intact," Mühlberger says.

The nuclear membrane surrounds the nucleus, which holds the majority of a cell's genetic information and controls and regulates normal cellular functions. With the cell nucleus compromised by SARS-CoV-2, things rapidly take a bad turn for the entire cell. Under siege, the cells--which normally play a role in maintaining the essential gas exchange of oxygen and carbon dioxide that occurs when we breathe--die. As the cells die, they also emit distress signals that boost inflammation, triggering a cascade of biological activity that speeds up cell death and can eventually lead to pneumonia, acute respiratory distress, and lung failure.

"I couldn't have predicted a lot of these pathways, most of them were news to me," says Andrew Wilson, one of the study's senior authors, a CReM scientist, and a pulmonologist at Boston Medical Center (BMC), BU's teaching hospital. At BMC, Boston's safety net hospital, Wilson has been on the front lines of the COVID-19 pandemic since March 2020, trying to treat and save the sickest patients in the hospital's ICU. "That's why our [experimental] model is so valuable."

The team leveraged the CReM's organoid expertise to grow human lung air sac cells, the type of cell that lines the inside of lungs. Air sac cells are usually difficult to grow and maintain in traditional culture and difficult to extract directly from patients for research purposes. That's why much coronavirus research to date by other labs has relied on the use of more readily available cell types, like kidney cells from monkeys. The problem with that is kidney cells from monkeys don't react the same way to coronavirus infection as lung cells from humans do, making them a poor model for studying the virus--whatever is learned from them doesn't easily translate into clinically relevant findings for treating human patients.

"Our organoids, developed by our CReM faculty, are engineered from stem cells--they're not identical to the living, breathing cells inside our bodies, but they are the closest thing to it," says Darrell Kotton, one of the study's senior authors. He is a director of the CReM and a pulmonologist at BMC, where he has worked alongside Wilson in the ICU treating COVID-19 patients. The two of them often collaborated with Mühlberger, Emili, and other members of their research team via Zoom calls that they managed to join during brief moments of calm in the ICU.

In another recent study using the CReM's engineered human lung cells, the research team confirmed that existing drugs remdesivir and camostat are effective in combating the virus, though neither is a perfect fix for controlling the inflammation that COVID-19 causes. Remdesivir, a broad-use antiviral, has already been used clinically in coronavirus patients. But based on the new study's findings that the virus does serious damage to cells within hours, setting off inflammation, the researchers say there's likely not much that antiviral drugs like remdesivir can do once an infection has advanced to the point where someone would need to be put on a ventilator in the ICU. "[Giving remdesivir] can't save lives if the disease has already progressed," Emili says.

Seeing how masterfully SARS-CoV-2 commandeers human cells and subverts them to do the manufacturing work of replicating the viral genome, it reminded the researchers of another deadly invader.

"I was surprised that there are so many similarities between cancer cells and SARS-CoV-2-infected cells," Mühlberger says. The team screened a number of cancer drugs as part of their study and found that several of them are able to block SARS-CoV-2 from multiplying. Like viruses, cancer cells want to replicate their own genomes, dividing over and over again. To do that, they need to produce a lot of pyrimidine, a basic building block for genetic material. Interrupting the production of pyrimidine--using a cancer drug designed for that purpose--also blocks the SARS-CoV-2 genome from being built. But Mühlberger cautions that cancer drugs typically have a lot of side effects. "Do we really want to use that heavy stuff against a virus?" she says. More studies will be needed to weigh the pros and cons of such an approach.

The findings of their latest study took the four senior investigators and scientists, postdoctoral fellows, and graduate students from their laboratories almost four months, working nearly around the clock, to complete the research. Of critical importance to the team's leaders was making sure that the experimental setup had rock-solid foundations in mimicking what's actually happening when the SARS-CoV-2 virus infects people.

"Science is the answer--if we use science to ask the lung cells what goes wrong when they are infected with coronavirus, the cells will tell us," Kotton says. "Objective scientific data gives us hints at what to do and has lessons to teach us. It can reveal a path out of this pandemic."

He's particularly excited about the outreach the team has received from collaborators around the world. "People with expertise in supercomputers and machine learning are excited about using those tools and the datasets from our publication to identify the most promising drug targets [for treating COVID-19]," he says.

Kotton says the theme that's become obvious among COVID-19 clinicians and scientists is understanding that timing is key. "Once a patient is on a ventilator in the ICU, we feel limited in what we can do for their body," he says. "Timing is everything, it's crucial to identify early windows of opportunity for intervention. You can keep guessing and hope we get lucky--or you [do the research] to actually understand the infection from its inception, and take the guesswork out of drug development."