Culture

Our dreams' weirdness might be why we have them, argues new AI-inspired theory of dreaming

image: This illustration represents the overfitted brain hypothesis of dreaming, which claims that the sparse and hallucinatory quality of dreams is not a bug, but a feature, since it helps prevent the brain from overfitting to its biased daily sources of learning

Image: 
Georgia Turner

The question of why we dream is a divisive topic within the scientific community: it's hard to prove concretely why dreams occur and the neuroscience field is saturated with hypotheses. Inspired by techniques used to train deep neural networks, Erik Hoel (@erikphoel), a research assistant professor of neuroscience at Tufts University, argues for a new theory of dreams: the overfitted brain hypothesis. The hypothesis, described May 14 in a review in the journal Patterns, suggests that the strangeness of our dreams serves to help our brains better generalize our day-to-day experiences.

"There's obviously an incredible number of theories of why we dream," says Hoel. "But I wanted to bring to attention a theory of dreams that takes dreaming itself very seriously--that says the experience of dreams is why you're dreaming."

A common problem when it comes to training AI is that it becomes too familiar with the data it's trained on--it starts to assume that the training set is a perfect representation of anything it might encounter. Data scientists fix this by introducing some chaos into the data; in one such regularization method, called "dropout," some data is randomly ignored. Imagine if black boxes suddenly appeared on the internal screen of a self-driving car: the car that sees the random black boxes on the screen and focuses on overarching details of its surroundings, rather than the specifics of that particular driving experience, will likely better understand the general experience of driving.

"The original inspiration for deep neural networks was the brain," Hoel says. And while comparing the brain to technology is not new, he explains that using deep neural networks to describe the overfitted brain hypothesis was a natural connection. "If you look at the techniques that people use in regularization of deep learning, it's often the case that those techniques bear some striking similarities to dreams," he says.

With that in mind, his new theory suggests that dreams happen to make our understanding of the world less simplistic and more well-rounded--because our brains, like deep neural networks, also become too familiar with the "training set" of our everyday lives. To counteract the familiarity, he suggests, the brain creates a weirded version of the world in dreams, the mind's version of dropout. "It is the very strangeness of dreams in their divergence from waking experience that gives them their biological function," he writes.

Hoel says that there's already evidence from neuroscience research to support the overfitted brain hypothesis. For example, it's been shown that the most reliable way to prompt dreams about something that happens in real life is to repetitively perform a novel task while you are awake. He argues that when you over-train on a novel task, the condition of overfitting is triggered, and your brain attempts to then generalize for this task by creating dreams.

But he believes that there's also research that could be done to determine whether this is really why we dream. He says that well-designed behavioral tests could differentiate between generalization and memorization and the effect of sleep deprivation on both.

Another area he's interested to explore is on the idea of "artificial dreams." He came up with overfitted brain hypothesis while thinking about the purpose of works of fiction like film or novels. Now, he hypothesizes that outside stimuli like novels or TV shows might act as dream "substitutions"--and that they could perhaps even be designed to help delay the cognitive effects of sleep deprivation by emphasizing their dream-like nature (for instance, by virtual reality technology).

While you can simply turn off learning in artificial neural networks, Hoel says, you can't do that with a brain. Brains are always learning new things--and that's where the overfitted brain hypothesis comes in to help. "Life is boring sometimes," he says. "Dreams are there to keep you from becoming too fitted to the model of the world."

Credit: 
Cell Press

Bio-inspired scaffolds help promote muscle growth

image: Aligned myotubes formed on electrospun extracellular matrix scaffolds produced at Rice University. The staining with fluorescent tags shows cells' expression of myogenic marker desmin (green), actin (red) and nuclei (blue) after seven days of growth.

Image: 
Mikos Research Group/Rice University

HOUSTON - (May 14, 2021) - Rice University bioengineers are fabricating and testing tunable electrospun scaffolds completely derived from decellularized skeletal muscle to promote the regeneration of injured skeletal muscle.

Their paper in Science Advances shows how natural extracellular matrix can be made to mimic native skeletal muscle and direct the alignment, growth and differentiation of myotubes, one of the building blocks of skeletal muscle. The bioactive scaffolds are made in the lab via electrospinning, a high-throughput process that can produce single micron-scale fibers.

The research could ease the burden of performing an estimated 4.5 million reconstructive surgeries per year to repair injuries suffered by civilians and military personnel.

Current methods of electrospinning decellularized muscle require a copolymer to aid in scaffold fabrication. The Rice process does not.

"The major innovation is the ability to prepare scaffolds that are 100% extracellular matrix," said Rice bioengineer and principal investigator Antonios Mikos. "That's very important because the matrix includes all the signaling motifs that are important for the formation of the particular tissue."

The scaffolds leverage bioactive cues from decellularized muscle with the tunable material properties afforded through electrospinning to create a material rich with biochemical signals and highly specific topography. The material is designed to degrade as it is replaced by new muscle within the body.

Experiments revealed that cells proliferate best when the scaffolds are not saturated with a crosslinking agent, allowing them access to the biochemical cues within the scaffold matrix.

Electrospinning allowed the researchers to modulate crosslink density. They found that intermediate crosslinking led to better retention of fiber alignment during cell culture.

Most decellularized matrix for muscle regeneration comes from such thin membranes as skin or small intestine tissue. "But for muscle, because it's thick and more complex, you have to cut it smaller than clinically relevant sizes and the original material properties are lost," said Rice graduate student and lead author Mollie Smoak. "It doesn't resemble the original material by the time you're done.

"In our case, electrospinning was the key to make this material very tunable and have it resemble what it once was," she said.

"It can generate fibers that are highly aligned, very similar to the architecture that one finds in skeletal muscle, and with all the biochemical cues needed to facilitate the creation of viable muscle tissue," Mikos said.

Mikos said using natural materials rather than synthetic is important for another reason. "The presence of a synthetic material, and especially the degradation products, may have an adverse effect on the quality of tissue that is eventually formed," he said.

"For eventual clinical application, we may use a skeletal muscle or matrix from an appropriate source because we're able to very efficiently remove the DNA that may elicit an immune response. We believe that may make it suitable to translate the technology for humans."

Smoak said the electrospinning process can produce muscle scaffolds in any size, limited only by the machinery.

"We're fortunate to collaborate with a number of surgeons, and they see promise in this material being used for craniofacial muscle applications in addition to sports- or trauma-induced injuries to large muscles," she said. "These would include the animation muscles in your face that are very fine and have very precise architectures and allow for things like facial expressions and chewing."

Credit: 
Rice University

Crowdsourcing for university community engagement COVID-19 safety strategies

What The Study Did: This is a qualitative study that evaluates a crowdsourcing open call to gather community input for engaging the university community in COVID-19 safety strategies.

Authors: Suzanne Day, Ph.D., of the University of North Carolina at Chapel Hill, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2021.10090)

Editor's Note: This article includes funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Credit: 
JAMA Network

Availability of US hospital price data

What The Study Did: Researchers evaluated the compliance of hospitals with a Centers for Medicare & Medicaid Services ruling mandating that a list of charges for services, procedures and items be publicly available and in a machine-readable file.

Authors: David Hsiehchen, M.D., of the University of Texas Southwestern Medical Center in Dallas, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2021.10109)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Credit: 
JAMA Network

Fruit flies and mosquitos are 'brainier' than most people suspect, say scientists

image: (Left) Whole brain of a fruit fly. (Right) Nuclei of neurons in fruit fly brain tissue.

Image: 
Joshua Raji and Christopher Potter, Johns Hopkins Medicine.

In research made possible when COVID-19 sidelined other research projects, scientists at Johns Hopkins Medicine meticulously counted brain cells in fruit flies and three species of mosquitos, revealing a number that would surprise many people outside the science world.

The insects' tiny brains, on average, have about 200,000 neurons and other cells, they say. By comparison, a human brain has 86 billion neurons, and a rodent brain contains about 12 billion. The figure probably represents a "floor" for the number needed to perform the bugs' complex behaviors.

"Even though these brains are simple [in contrast to mammalian brains], they can do a lot of processing, even more than a supercomputer," says Christopher Potter, Ph.D., associate professor of neuroscience at the Johns Hopkins University School of Medicine. "They enable the insects to navigate, find food and perform other complicated tasks at the same time, and our study offers one answer to the question of how many brain cells come together to conduct these behaviors," Potter adds.

Results of the research are summarized May 14 in PLOS ONE.

Those who study insect behavior and brain function have long suspected these insects must have hundreds of thousands of brain cells, says Potter, but when he and postdoctoral fellow Joshua Raji, Ph.D., followed chains of scientific papers that referenced the count, they did not find proof for it.

In response, they report, they set out to find proof using a relatively simple counting method called an isotropic fractionator, a technique familiar to pathologists when they tally the number of any type of cell in a tissue.

First, Raji used a plastic pestle to break down all the brain tissue of the individual insects. Then, he used a pipette to break apart the tissue and distribute the cells evenly through a buffered solution.

Knowing the precise total volume of the solution, they could then count cells within a small fraction of the solution, and scale it up to account for and estimate the total number of cells in the entire solution.

To make the actual count, the small amount of solution was spread on a microscope slide and placed on top of a small grid. With painstaking precision, Raji counted the cells on each slide, one by one.

The researchers concluded that the total sum of brain cells was 199,380 plus or minus 3,400 for the fruit fly Drosophila melanogaster. For three species of mosquito, the researchers found 217,910 plus or minus 6,180 in Aedes aegypti; 223,020 plus or minus 4,650 in Anopheles coluzzii; and 225,911 plus or minus 7,220 in Culex quinquefasciatus.

Raji and Potter found that the brain cells in each species contained mostly neurons -- about 90%. The rest are most likely supportive cells called glia, they say.

Potter says that researchers have determined the number of brain cells in only a few species of insects, including wasps and ants. "It would be interesting to apply this approach to social insects like bees, and see if there are differences between queens and drones," he says.

Potter also notes that the counting technique is a simple one that most researchers could perform, and it's an opportunity for any researcher to perform the counts and contribute them to scientific literature.

Raji noted that he did most of the work for the study as a side project during times when COVID-19 restrictions halted his main research projects.

The most challenging part of the technique, says Potter, was the microdissection of a brain that is smaller than the tip of a pencil. "It takes a really steady hand and lots of practice," he says.

Credit: 
Johns Hopkins Medicine

Fairness 'important - but not enough'

Being treated fairly is important - but fairness alone isn't enough to make people feel valued in a workplace or other groups, new research suggests.

Researchers found that "distinctive treatment" - where a person's talents and qualities are recognised - provides this sense of value while also reinforcing their sense of inclusion. It also promotes mental health.

The findings suggest there is no conflict between "fitting in" and "standing out" in groups - in fact, they complement each other.

But while the importance of fairness is widely accepted, the researchers say distinctive treatment is often overlooked.

The research was carried out by the University of Exeter, UCLA and Sonoma State University.

"Organisations and other groups often recognise the importance of members treating each other fairly - with dignity and without bias," said lead author Dr Christopher Begeny, of the University of Exeter.

"In six studies of workplaces and other groups, we find that this is indeed key to fostering individuals' sense of belonging.

"However, individuals also need to be shown that they have some distinct value to the group.

"When colleagues or fellow group members show interest and appreciation for an individual's more distinguishing qualities, that individual benefits.

"This kind of distinctive treatment has real benefits for mental health too, including less anxiety and depression.

"To be clear, fair treatment is a must - but our studies show it's also woefully insufficient on its own.

"Individuals need to feel more than inclusion. As well as 'fitting in', they need to 'stand out' - to feel that they have some distinct value and worth that they bring to the group."

Asked how organisations could embed distinctive treatment in their workplace, Dr Begeny said: "It helps to have supervisors with the time and energy to recognise and tap into the particular skills and knowledge of the different people they supervise.

"Another method is to create well-developed systems of mentorship, allowing people to share their experience and expertise.

"This can also foster a workplace culture that is not just inclusive, but value-affirming - where people regularly seek each other out for advice, which is beneficial to both parties."

Dr Begeny added: "Expressing distinctive treatment does not simply mean sending out a mass email saying 'if anyone has any ideas about this project, please let me know'.

"It's about going to an individual, or small group of individuals, and saying, 'hey, I really think your insights and perspectives could be an asset to this project. Would you be willing to offer your thoughts?'

"It's not a passive process of hearing people when they have ideas to share.

"It involves actively seeking them out - taking the initiative to learn what an individual has to offer -and showing recognition and appreciation for it."

Of the six studies, four were based in workplaces, while the others examined fair and distinctive treatment in student communities, and in racial/ethnic minority communities.

In all cases, distinctive treatment provided clear benefits.

Credit: 
University of Exeter

Ventilating the rectum to support respiration

image: Based on the fact that loaches have intestinal respiration under hypoxic conditions, the efficacy of the EVA method was examined in mammals such as mice and pigs. The EVA method may be effective for patients with respiratory failure.

Image: 
Institute of Research,TMDU

Tokyo, Japan - Oxygen is crucial to many forms of life. Its delivery to the organs and tissues of the body through the process of respiration is vital for most biological processes. Now, researchers at Tokyo Medical and Dental University (TMDU) have shown that oxygen can be delivered through the wall of the intestine to compensate for the reduced availability of oxygen within the body that occurs in lung diseases that cause respiratory failure.

To breathe is to live; for higher animals, respiration involves absorbing oxygen and excreting carbon dioxide at gills or in the lungs. However, some animals have evolved alternative ventilatory mechanisms: loaches, catfish, sea cucumbers and orb-weaving spiders can absorb oxygen through their hindgut to survive in situations where the availability of oxygen is limited. Inspired by these unique adaptations, the team at TMDU devised strategies to allow gas exchange through the lining of the intestine, a process termed as enteral ventilation or EVA.

"The rectum has a mesh of fine blood vessels just beneath the surface of its lining, which means that drugs administered through the anus are readily absorbed into the bloodstream," first author Ryo Okabe explains. "This made us wonder whether oxygen could also be delivered into the bloodstream in the same way. We used experimental models of respiratory failure in mice, pigs and rats to try out two methods: delivering oxygen into the rectum in gas form, and infusing an oxygen-rich liquid via the same route."

The researchers prepared the lining of the rectum by rubbing it to cause inflammation and increase blood flow; these changes were confirmed by increased genetic markers and improved the effectiveness of the oxygen delivery. However, because such a preparation requirement would be unacceptable for human patients, the researchers also tried using oxygenated perfluorodecalin (PFD), a liquid that can be safely used in the human body and is already in selective clinical use, and that can carry large amounts of oxygen and carbon dioxide.

The team demonstrated that delivery of oxygen both as a gas and in liquid form was beneficial: oxygenation levels increased and behavior normalized, while survival was prolonged. The team also confirmed the improvement in oxygenation at the cellular level by immunochemical staining. Furthermore, they found that the minimal amount of PFD that was absorbed along with the oxygen caused no harm, and gut bacteria were not disrupted, indicating the safety of these methods in the animal models.

"Patients in respiratory distress can have their oxygen supply supported by this method to reduce the negative effects of oxygen deprivation while the underlying condition is being treated," foresees Takanori Takebe, corresponding author. "Enteral ventilation showed great promise in our asphyxia-like experimental model. The next steps will be to test safety of the EVA approach with more profound mechanistic understanding by which it works; and to establish effectiveness in humans in a clinical setting."

Conventional therapeutic respiratory support comprises complex technological protocols such as ventilators and artificial lungs. The current SARS-CoV-2 pandemic has highlighted the high need for development of less invasive alternatives such as EVA for short-term support of respiratory function. These new findings from the researchers at TMDU may pave the way for new ventilation strategies in the future.

Credit: 
Tokyo Medical and Dental University

Yoga and breathing exercises aid children with ADHD to focus

image: Sergey Kiselev is a head at Laboratory of Brain and Neurocognitive Development UrFU

Image: 
UrFU / Karina Golovanova.

Yoga and breathing exercises have a positive effect on children with attention deficit hyperactivity disorder (ADHD). After special classes, children improve their attention, decrease hyperactivity, they do not get tired longer, they can engage in complex activities longer. This is the conclusion reached by psychologists at Ural Federal University who studied the effect of exercise on functions associated with voluntary regulation and control in 16 children with ADHD aged six to seven years. The results of the study are published in the journal Biological Psychiatry.

"For children with ADHD, as a rule, the part of the brain that is responsible for the regulation of brain activity - the reticular formation - is deficient," said Sergey Kiselev, head of the Laboratory of Brain and Neurocognitive Development at UrFU, head of the study. "This leads to the fact that they often experience states of inadequate hyperactivity, increased distraction and exhaustion, and their functions of regulation and control suffer a second time. We used a special breathing exercise based on the development of diaphragmatic rhythmic deep breathing - belly breathing. Such breathing helps to better supply the brain with oxygen and helps the reticular formation to better cope with its role. When the reticular formation receives enough oxygen, it begins to better regulate the child's state of activity".

In addition to breathing exercises, psychologists used body-oriented techniques, in particular, exercises with polar states "tension-relaxation". The trainings took place three times a week for two to three months (depending on the program).

"Exercise has an immediate effect that appears immediately, but there is also a delayed effect. We found that exercise has a positive effect on regulation and control functions in children with ADHD and one year after the end of the exercise. This happens because the child's correct breathing is automated, it becomes a kind of assistant that allows better supply of oxygen to the brain, which, in turn, has a beneficial effect on the behavior and psyche of a child with ADHD," says Sergey Kiselev.

This technique was developed by the Russian neuropsychologist Anna Semenovich as part of a neuropsychological correction technique. UrFU psychologists tested how well this approach helps children with ADHD. But the study is pilot, says Kiselev. It showed that these exercises have a positive effect. However, more work needs to be done, involving more children with ADHD. This will also take into account factors such as gender, age, severity of the disease, concomitant problems in children (speech, regulatory, etc.).

Note

Attention deficit hyperactivity disorder is a disorder associated with impaired development of the child's nervous system. Most often it manifests itself at the age of seven or at the beginning of regular education. ADHD is characterized by inattention, excessive activity, and impulsive behavior.

Since 2013, the Laboratory of the Brain and Neurocognitive Development of UrFU has been conducting research on the maturation of the brain and mental processes in typically developing children, as well as in children with deviant development, in particular, those at risk of developing autism and ADHD, children with moderate traumatic brain injury severity. The laboratory is one of the leading Russian centers for the study of brain development and neurocognitive processes in children.

Credit: 
Ural Federal University

Lockdown led to positive lifestyle changes in older people

image: Professor Anna Whittaker

Image: 
University of Stirling

The COVID-19 lockdown was a catalyst for many older people to embrace technology, reconnect with friends and build new relationships with neighbours, according to University of Stirling research.

Understanding the coping mechanisms adopted by some over 60s during the pandemic will play a key role in developing interventions to help tackle loneliness, isolation and wellbeing in the future.

The study, led by the Faculty of Health Sciences and Sport, surveyed 1,429 participants - 84 percent (1,198) of whom were over 60 - and found many had adapted to video conferencing technology to increase online contact with existing social networks, while others reconnected with previous networks. Participants reported that lockdown had led them to engage with neighbours and other members of their communities for the first time, while several said social distancing had brought an additional meaning to life, by highlighting what was important to them.

Published in the International Journal of Environmental Research and Public Health, the paper comes six months after the study - funded under the Scottish Government Chief Scientist Office's Rapid Research in COVID-19 programme - reported in its preliminary findings that social distancing had increased feelings of loneliness in older people.

Professor of Behavioural Medicine, Anna Whittaker, who led the study, said: "Our research found that the COVID-19 lockdown triggered feelings of loneliness in older people - with many experiencing less social contact and support. However, the study also highlighted positive outcomes, for example, lockdown encouraged some older people to embrace and engage with technology - such as Zoom, Whatsapp or FaceTime - to stay in touch with loved-ones or participate in exercise classes or religious groups. Those who engaged in such activity were able to prevent high levels of loneliness, therefore, helping older adults to increase their digital literacy and use of remote social interactions could be a really important tool for addressing loneliness.

"Participants also reported actively looking for new social contact while restrictions were in place - such as contacting friends who they had not spoken to in years and increasing interactions with neighbours and other members of their communities. Significantly, many of our participants reported that social distancing has actually led them to find new sources of satisfaction in life.

"Our study also highlighted that encouraging safe social contact through physical activity and engaging with people in the community may be an effective way to reduce loneliness, improve wellbeing, increase social activity, and improve social support."

The study - which involved a survey conducted between May and July 2020 - examined the impact of social distancing during the pandemic on loneliness, wellbeing and social activity, including social support, in Scottish older adults.

Participants were asked about the strategies they adopted to increase social interaction during this time and reported that the way they interacted with their friends and family, faith, chosen group activities and, to a lesser extent, their employer and colleagues, had changed. More than 300 participants mentioned 'Zoom' - the video conferencing tool - in their answers.

More than 150 participants reported that their religious gatherings had moved online - replacing face-to-face gatherings - while 91 said that social gatherings with family and friends had changed in favour of online 'games nights'. New activities included bingo and quiz nights, while other activities moved online - such as bridge nights, book clubs, choir rehearsals, and dance and exercise classes.

The role of community - particularly neighbours - was mentioned by more than 300 participants and some reported the common experience of getting to know previously unknown neighbours and increase interaction with others in the community at local shops or parks. A pleasant Scottish summer also supported such interactions, several said.

At least 100 people said social interactions were linked to their physical activities - such as time spent outdoors while walking for exercise, walking the dogs or active commuting.

Professor Whittaker added: "Our research underlines the importance of addressing loneliness and social support in older adults - but particularly during situations where risk of isolation is high. Although specific to the pandemic, this study has wider implications of helping us to understand the impact of social distancing and social isolation on older people.

"The findings may be applicable in the future - both in and outwith pandemic situations. In Scotland, the recommendations for improvement may be through encouraging older adults to get to know their neighbours better, getting involved with local buddying systems and community initiatives, including via digital means, and engaging in physical activity, such as daily walks in the community."

Brian Sloan, Chief Executive of Age Scotland, said: "While it may prove difficult to consider any aspect of the pandemic positive as such, it is important and worthwhile to reflect on what it has taught us, both about ourselves and society and about the necessary tools to tackle Scotland's increased levels of loneliness and isolation.

"For example, we've seen first-hand how important the community response has been in terms of supporting older people throughout lockdown and it has been inspiring to witness how people across the country stepped in and stepped forward to help those in need around them. Even as restrictions ease, we hope to see this sense of community spirit continue.

"The ongoing impact of COVID-19 has also demonstrated just how important increased digital inclusion is and how easily those without access to technology can feel out of the loop. It's reassuring to see so many older people reporting that they have been able to embrace and engage with technology to stay connected and active.

"However, it's equally important to ensure those who are unable or do not wish to use the internet have alternative ways to stay connected to their communities and support networks.

"As we take steps towards recovery together, it is vital that no one is left behind and those most impacted are supported to play a full part in society again.

"We know we will be living with the ongoing effects of lockdown loneliness for a long time to come, and this research will be incredibly valuable when considering how best to tackle loneliness and isolation and to improve the wellbeing of older people going forward."

Credit: 
University of Stirling

New perspective on stress pandemics and human resilience from the analysis of COVID-19

A new analysis of the effects of SARS-CoV-2, the virus causing the current pandemic, on the human body has provided novel insights into the nature of resilience and how we deal with stressful situations. Using COVID-19 as an example, the findings provide a new framework that may be central to managing this disease, minimise the likelihood of ferocious viral outbreaks in the future and deal with other major stresses.

"COVID-19 has been a huge burden on society at all levels. Whilst the prospects are improving in countries with efficient vaccination schemes like the UK, the virus is still present, and new variants continue to pose considerable risks. Moreover, there are sustained effects such as Long COVID and the mental health burden of the pandemic to overcome," Martin Feelisch, Professor of Experimental Medicine and Integrative Biology at the University of Southampton explained.

"By analysing and re-ordering the information available in the literature we aimed to offer a systems-level view on the disease within a single framework that provides a coherent picture about the way this infection stresses the human body."

The research team involving physicians, chemical biologists and an authority on human nutrition, looked at COVID from a higher level than just a disease affecting the lungs and considered how the whole body deals with the various stresses the virus causes when viewed through the lens of electron exchange (also known as 'redox') processes. Electron exchange reactions are the foundation of all Life on Earth, underpinning human physiology and our ability to react to changes in demand and environmental conditions. While change is healthy in principle, some people experience unfavourable consequences when a major stress such as a viral infection is added to the stresses of daily life. What happens when such stresses act together is not yet fully understood, and COVID-19 was used as an example to look at the consequences of those interactions.

"COVID can present as a severe lung infection in one person while producing only minor symptoms in others, although it may have affected several other organs by then already. Arriving at a better understanding of how the body deals with different stresses while maintaining an appropriate redox balance would put us in a better position to treat patients acutely, protect the rest of the population and control disease spread. While the current vaccination success story is encouraging, emerging virus mutants show the threat continues, and we need to be better prepared in the future." Prof Feelisch continued.

Their analysis, published in the leading journal Antioxidants & Redox Signaling, revealed three key areas in the body's ability to cope with the stress of viral infections:

Firstly, nutrition emerges to be of utmost importance in maintaining the necessary redox balance and provide one's metabolism with the flexibility to adjust and combat the damaging effects of viral infection on cells and tissues. It also explains the greater susceptibility to disease in more deprived areas of the country because low income increases the risk for poor nutrition.

The second key finding was the importance of the endothelium - the inner lining of blood vessels that provides organs with oxygen and nutrients - in particular, a highly fragile layer on its surface that regulates nutrient/fluid exchange and protects blood cells from coming into close contact with the vessel wall. The research team have found that the crucial regulatory function performed by the endothelium has not been fully recognised in existing research and may also be essential to understanding the effects of Long COVID, where the body does not get back to its normal balance. They advise that routine monitoring of this cell layer in a non-invasive fashion, such as from under the tongue, may provide valuable insight into this and other stressful process and guide therapeutic approaches.

The final key observation was the role played by small molecules known as 'gasotransmitters'. These are used by all cells to sense changes in their environment and adapt. These molecules are part of a body-wide system that uses circulating blood as a communication highway to inform other organs how to best respond to the mixture of stresses experienced by other parts of the body, for example how to ramp up the metabolism in the liver to deal with an infection of the lung. Of all the molecules involved, nitric oxide appears to be fundamental in protecting the overall redox system.

Professor Feelisch concluded, "We need to make best use of the opportunity the current crisis has given us to learn more about how the body and individual cells deal with stresses. Our holistic framework should be interpreted as a 'call to action' and encourage investigators around the world to study whole-body redox regulation, find ways to monitor redox status and identify factors that are critical for health and resilience. The next pandemic could be just around the corner and if we do not learn from current events, chances are we will face the same problems all over again."

Credit: 
University of Southampton

Maternal stress during pregnancy may shorten lifespans of male lizard offspring

image: Mother fence lizards that experience stress during pregnancy give birth to male offspring with shortened telomeres, which is associated with shortened life spans, according to new research.

Image: 
Tracy Langkilde, Penn State

UNIVERSITY PARK, Pa. -- Mother fence lizards that experience stress during pregnancy give birth to male offspring with shortened telomeres, or bits of non-coding DNA that cap the ends of chromosomes, according to a Penn State-led study. Shorter telomeres are associated with decreased lifespan in humans; therefore, the team's findings may have implications for human longevity.

"Human men have shorter telomeres than women, which may partly explain why they have shorter lifespans of about seven years," said Tracy Langkilde, professor and Verne M. Willaman dean of the Eberly College of Science. "Our study shows that stress experienced by mothers during gestation could further shorten the telomeres, and therefore the lifespans, of their sons, thereby exacerbating these sex differences."

According to Langkilde, telomeres are short sections of non-coding DNA that cap the ends of chromosomes, like the plastic tips at the ends of shoelaces, and are responsible for protecting genomic integrity. They are known to decrease in length as an organism ages. Stressors, she added, can speed up this process.

"Stressors cause concentrations of the hormone corticosterone to rise; this is supposed to help an organism cope and respond appropriately," she said. "However, corticosterone can also induce oxidative stress [an imbalance between the body's free radicals and antioxidants] and decrease telomerase activity, both of which are known to exacerbate telomere shortening. What hasn't been known is how increased corticosterone in mothers affects telomere length, and thus lifespan, in offspring."

To examine the effects of maternal corticosterone and offspring telomere length, the researchers captured 22 pregnant female eastern fence lizards (Sceloporus undulatus) from Tennessee and Kentucky and randomly assigned them to one of two groups: those receiving a transdermal treatment of corticosterone or a control group. The team applied the corticosterone in amounts that are similar to those generated by lizards after exposure to a non-lethal attack by a predator or a heat challenge.

From the eggs laid by the mothers, 21 hatchlings were used for the project. The researchers collected blood from these hatchlings at 4-7 days of age. They isolated the DNA from the blood samples and measured telomere length using a quantitative PCR method. Their findings appeared on April 29 in the journal Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology.

The team found that the male offspring of corticosterone-treated mothers had telomeres that were more than 20% shorter than those from control mothers. In contrast, the telomere lengths of the mothers were unaffected by the mothers' exposure to corticosterone. Similarly, the telomere lengths of the female offspring were unaffected.

Estrogen may buffer the telomeres of mothers and daughters from the negative effects of increased corticosterone through its protective effect against oxidative stress and its promotion of telomerase activity, noted Langkilde.

"The connection between corticosterone concentration and telomere length has rarely been examined between generations," said David Ensminger, National Science Foundation postdoctoral research fellow in biology at UC Berkeley, future assistant professor of physiology at San Jose State University, and former graduate student in ecosystem science and management and in biology, Penn State. "We found a sex-specific effect of maternal corticosterone on offspring telomeres, explained by a tendency for a decrease in offspring telomere length of sons but not daughters."

Sue Siegel, research professor, Biomarker Core Lab, Department of Biobehavioral Health, said the findings are robust even though the sample size was small.

"Although care must be taken in drawing conclusions from this study due to the small sample size, the results are still statistically significant and suggest a negative impact of maternal corticosterone on the telomere length of sons," she said. "Further studies would help elucidate the underlying mechanism of corticosterone on telomere length."

Credit: 
Penn State

Businesses have a moral duty to explain how algorithms make decisions that affect people

Increasingly, businesses rely on algorithms that use data provided by users to make decisions that affect people. For example, Amazon, Google, and Facebook use algorithms to tailor what users see, and Uber and Lyft use them to match passengers with drivers and set prices. Do users, customers, employees, and others have a right to know how companies that use algorithms make their decisions? In a new analysis, researchers explore the moral and ethical foundations to such a right. They conclude that the right to such an explanation is a moral right, then address how companies might do so.

The analysis, by researchers at Carnegie Mellon University, appears in Business Ethics Quarterly, a publication of the Society for Business Ethics.

"In most cases, companies do not offer any explanation about how they gain access to users' profiles, from where they collect the data, and with whom they trade their data," explains Tae Wan Kim, Associate Professor of Business Ethics at Carnegie Mellon University's Tepper School of Business, who co-wrote the analysis. "It's not just fairness that's at stake; it's also trust."

In response to the rise of autonomous decision-making algorithms and their reliance on data provided by users, a growing number of computer scientists and governmental bodies have called for transparency under the broad concept of algorithmic accountability. For example, the European Parliament and the Council of the European Union adopted the General Data Protection Regulation (GDPR) in 2016, part of which regulates the use of automatic algorithmic decision systems. The GDPR, which launched in 2018, affects businesses that process the personally identifiable information of residents of the European Union.

But the GDPR is ambiguous about whether it involves a right to explanation regarding how businesses' automated algorithmic profiling systems reach decisions. In this analysis, the authors develop a moral argument that can serve as a foundation for a legally recognized version of this right.

In the digital era, the authors write, some say that informed consent--obtaining prior permission for disclosing information with full knowledge of the possible consequences--is no longer possible because many digital transactions are ongoing. Instead, the authors conceptualize informed consent as an assurance of trust for incomplete algorithmic processes.

Obtaining informed consent, especially when companies collect and process personal data, is ethically required unless overridden for specific, acceptable reasons, the authors argue. Moreover, informed consent in the context of algorithmic decision-making, especially for non-contextual and unpredictable uses, is incomplete without an assurance of trust.

In this context, the authors conclude, companies have a moral duty to provide an explanation not just before automated decision making occurs, but also afterward, so the explanation can address both system functionality and the rationale of a specific decision.

The authors also delve into how companies that run businesses based on algorithms can provide explanations of their use in a way that attracts clients while maintaining trade secrets. This is an important decision for many modern start-ups, including such questions as to how much code should be open source, and how extensive and exposed the application program interface should be.

Many companies are already tackling these challenges, the authors note. Some may choose to hire "data interpreters," employees who bridge the work of data scientists and the people affected by the companies' decisions.

"Will requiring an algorithm to be interpretable or explainable hinder businesses' performance or lead to better results?" asks Bryan R. Routledge, Associate Professor of Finance at Carnegie Mellon's Tepper School of Business, who co-wrote the analysis. "That is something we'll see play out in the near future, much like the transparency conflict of Apple and Facebook. But more importantly, the right to explanation is an ethical obligation apart from bottom-line impact."

Credit: 
Carnegie Mellon University

Access to overdose-reversing drugs declined during pandemic, researchers find

Boston - While overall emergency department visits have decreased during the pandemic, nonfatal opioid overdose visits have more than doubled. However, few patients who overdosed on opioids had received a prescription for naloxone, a medication designed to block the effects of opioids on the brain and rapidly reverse opioid overdose.

In a new study, clinician-researchers at Beth Israel Deaconess Medical Center (BIDMC) analyzed naloxone prescription trends during the COVID-19 pandemic in the United States and compared them to trends in opioid prescriptions and to overall prescriptions. The team's findings, published in the journal JAMA Health Forum, suggest patents with opioid misuse disorders may be experiencing a dangerous decrease in access to the overdose-reversing drug.

"In March of 2020, we saw a sharp reduction in the average number of individuals filling naloxone prescriptions each week, which far exceeded the decline in the number of people filling prescriptions for any medication," said corresponding author Ashley O'Donohue, PhD, an economist in the Center for Healthcare Delivery Science at BIDMC. "And since March 2020, there's been no statistically significant recovery in naloxone prescriptions, indicating that the number of individuals filling naloxone prescriptions has remained low throughout the pandemic."

Using data from a national pharmacy insurance claims database that includes claims from national retail pharmacies, mail-order pharmacies and specialty pharmacies, O'Donoghue and colleagues analyzed weekly trends in the number of patients filling naloxone prescriptions, opioid prescriptions and all prescriptions between May 2019 and December 2020.

The team found that the number of individuals filling prescriptions for any medication fell by 14 percent in the early months of the COVID-19 pandemic, while the number of individuals filling opioid prescriptions fell by just 9 percent. However, the number of people filling naloxone prescriptions fell by more than 25 percent, and the number of individuals with Medicare and commercial coverage filling naloxone prescriptions declined by nearly a third. Meanwhile, among patients with Medicaid coverage or patients who paid in cash, there was no statistically significant change in the number of individuals filling naloxone prescriptions.

"Our study identifies an urgent gap in necessary access to lifesaving medication for individuals covered by Medicare and commercial insurance during the pandemic," said senior author Jennifer P. Stevens, MD, MS, Director of the Center for Healthcare Delivery Science at BIDMC. "Continuing to distribute naloxone in densely populated areas and through community-based organizations could help mitigate some of the reductions in naloxone distribution via pharmacies and could also reduce some of the increases in fatal opioid overdose is during the COVID-19 pandemic."

Credit: 
Beth Israel Deaconess Medical Center

Sensors developed at URI can identify threats at the molecular level

image: URI doctoral student Peter Ricci (left) and Professor Otto Gregory test the Digital Dog Nose sensors platform in Gregory's Thin Film Sensors Laboratory at URI. The blue devices on the table represent the two latest versions of the Digital Dog Nose.

Image: 
Photo by Mike Platek

KINGSTON, R.I. - May 14, 2021 - We are frequently reminded of how vulnerable our health and safety are to threats from nature or those who wish to harm us.

New sensors developed by Professor Otto Gregory, of the College of Engineering at the University of Rhode Island, and chemical engineering doctoral student Peter Ricci, are so powerful that they can detect threats at the molecular level, whether it's explosive materials, particles from a potentially deadly virus or illegal drugs entering the country.

"This is potentially life-saving technology," said Gregory. "We have detected things at the part-per-quadrillion level. That's really single molecule detection."

Broad-Based Applications

Because Gregory's sensors are so small and so powerful, there is a wide range of applications.

"The platform is broad-based, so you can apply it to lots of different venues, with lots of different end users," said Gregory.

While his research is largely funded by the Department of Homeland Security, other government agencies have taken notice of Gregory's sensors.

The Department of Defense may be interested in using it to monitor wounds in soldiers and to detect roadside improvised explosive devices (IEDs).

If a soldier or first responder suffered an open wound from shrapnel, Gregory's sensors could help determine if the wound became infected.

"Hydrogen peroxide generated by the human body for wounds is an indication of how good or how bad antibiotics are working to fight the wound," said Ricci. "Our sensor could be used as a wearable device to sniff out peroxide coming from the wound at the part-per-billion level."

At Miami Heat basketball games, dogs have been used to sniff traces of COVID-19 coming from the pores in people's skin. In an article published in the prestigious journal Nature, Gregory stated that his sensors could be used for the same purpose.

"Where dogs are detecting it from the skin, our sensors would detect it from biomarkers in people's breath," Ricci said, who is from West Warwick.

The Coast Guard has shown an interest in using the technology to "sniff out" illegal drugs being smuggled into the United State aboard ships.

Shrinking the 'Digital Dog Nose'

"Anything that can typically be sniffed out by a dog we can do," said Gregory. "That's why we've called it the Digital Dog Nose."

The Digital Dog Nose was featured on shows such as CBS This Morning in November 2019, but what was once the size of a toolbox has been reduced to a quarter of the size of a pack of cigarettes.

"By decreasing the thermal mass of the sensor, we've decreased the amount of power required to run the sensor," said Gregory. "We started with a thermal mass on the order of grams. Now the thermal mass of our sensor is on the order of micrograms."

One of the keys to making a device as small and powerful as Gregory's is to find the right battery.

"We have partnered with a company that makes very thin, low-mass batteries in Colorado called ITN Energy Systems," Gregory said. "They make lithium batteries that are no thicker than a piece of paper. The process has been about finding the right partners, which helps us improve our catalysts and improve our sensor platform."

Passing the Test

In March 2021, the Naval Research Laboratory brought its mobile testing unit to URI's W. Alton Jones Campus to put Gregory's explosives sensors and others to the test.

"They set up a field test outside using their vapor test bed," said Ricci. "They were able to select an explosive molecule and deliver it to the sensor system. Knowing what the level was, they wanted to see how our sensor would respond. One of the tests was at the part-per-quadrillion level."

Staying a Step Ahead

As bad guys have developed new explosives or new ways to improvise on existing explosives, the good guys have tried to stay a step ahead.

"The Department of Homeland Security has asked us to be flexible enough to anticipate and adapt to emerging threats that may come several years down the road," said Gregory. "We can tweak our catalysts for a specific molecule that is the current threat. That's what we do with biomarkers. That's what we do with drugs. What's nice about this platform is that it's flexible."

Coming a Long Way

The sensors Gregory and Ricci have developed have been tested and improved upon over a long period of time. The professor's research was originally funded 20 years ago by the Defense Advanced Research Projects Agency (DARPA), a research and development agency of the United States Department of Defense that is responsible for the development of emerging technologies for use by the military.

After two years of DARPA funding, the Army funded the project for a year. The Department of Homeland Security has provided funding ever since.

"At the time, this research was very novel and very different," said Gregory. "DARPA funds projects that are high risk, high reward. We've demonstrated that the gamble they took on our concept back then has paid off."

Michael Silevitch, the Robert D. Black Distinguished Professor of Engineering at Northeastern University, has collaborated with Gregory on his research for more than 10 years.

"This is breakthrough technology," said Silevitch. "Otto's work on chemical detectors has evolved to the point of being ready for use in many applications, including the deployment of his sensors on a drone-based platform to help protect soft targets such as schools, shopping malls or places of worship."

Taking the New Steps

Now that the sensors are very small and lightweight, they could be attached to drones, leading to many new applications.

"We've been talking to drone companies about using our sensors on their drones," said Gregory. "Drones need very lightweight, portable power supplies and you have to tap into their wireless communication. It's a much different set of engineering conditions than using a robot arm that the Army is looking to use for roadside IEDs."

Gregory and Ricci are also working on sensor arrays, to differentiate one explosive, or threat, from another.

"We'll need an array of sensors to detect a specific explosive in the presence of other explosives or precursors," said Ricci. "If there's a plume of three different explosives, we may need to identify one from the others."

Ready to Use

Now that the sensors have proven to be effective, implementing them in real-world situations is just a matter of funding.

"Our sensor is not an off-the-shelf commercial product yet, but we have a potential partner," Gregory said. "We just need a customer to step up to the plate and say here's an order for 1,000 of these, can you deliver them?"

Credit: 
University of Rhode Island

New benefit increases Veterans' access to urgent care in the community

May 14, 2021 - Two years ago, the Veterans Affairs healthcare system (VA) began rolling out a new benefit, enabling Veterans to receive urgent care from a network of community providers - rather than visiting a VA emergency department or clinic. Progress toward expanding community care services for Veterans is the focus of a special supplement to the May issue of Medical Care. The journal is published in the Lippincott portfolio by Wolters Kluwer.

The urgent care benefit "provides a new way to deliver unscheduled, low-acuity acute care to Veterans," according to the new research by Anita Vashi, MD, MPH, MHS, of VA Palo Alto Health Care System and colleagues. The study is one of 12 research papers and commentaries on "Innovations in Community Care Programs, Policies, and Research" - focusing on Veterans' use of healthcare services in the community, and how VA centers interact with community care providers.

What's the best balance of VA and community care? That's the 'billion-dollar question'

Dr. Vashi and colleagues analyzed initial data on how Veterans are using the community urgent care benefit, which was implemented starting in June 2019. Eligible Veterans were able to receive urgent care from providers in VA's community network, without prior authorization. Focusing on minor illnesses and injuries that might otherwise lead to emergency department (ED) visits, the program was part of VA's "Maintaining Internal Systems and Strengthening Integrated Outside Networks" (MISSION) Act, designed to increase Veterans' access to health care in VA facilities and the community.

Through the first nine months of the program, 138,305 Veterans made a total of 175,821 urgent care visits to VA community network providers. That accounted for 2.4 percent of a cohort of 5.9 million potentially eligible Veterans. By comparison, 7.3 percent of Veterans visited a VA ED or clinic for lower-acuity (non-emergency) conditions during the same period.

Dr. Vashi and colleagues examined trends in community urgent care use, including factors associated with urgent care rather than ED visits. Urgent care visits generally increased over time and varied between regions. Most Veterans using urgent care lived in urban areas - more than 80 percent lived within 30 minutes of a VA primary care site. Most had no copays for urgent care visits.

Upper respiratory infections, back pain, and bronchitis were the most frequent reasons for community urgent care visits. Common procedures and treatments included chest x-rays, influenza or strep testing, and urinalysis. Average cost to VA for urgent care visits was $132, with total costs of about $23 million.

On analysis adjusting for other factors, women and younger Veterans were more likely to take advantage of the urgent care benefit. Driving time was a key factor: Veterans who lived more than 60 minutes from a VA ED or VA urgent care center were twice as likely to choose community urgent care services.

The study provides key information on how "early adopters" are taking advantage of the urgent care benefit. "As the program continues to expand and evolve, impacts on care coordination, medication safety, outcomes, and shifts in utilization of VA primary and emergency services must be evaluated," Dr. Vashi and coauthors write.

While most care is still provided at VA Medical Centers and outpatient sites, initiatives including the MISSION Act have greatly expanded Veterans' ability to seek care at private health care providers, clinics, and hospitals in the community. The papers in the new open-access supplement offer "a broad examination of the first two years of MISSION Act implementation, and highlights areas where additional research is needed to understand Veterans' perceptions, satisfaction and use of VA Community Care," according to an introductory guest editorial by Kristin Mattocks, PhD, of VA Central Western Massachusetts and colleagues.

The supplement papers are an important step toward providing the best experience for Veterans in choosing among their healthcare options. Dr. Mattocks and coauthors conclude: "The enduring challenge for VA - literally the 'billion dollar question' - is to determine what balance of in-person VA care, virtual VA care, and care in the community offers the optimal balance of timely, patient-centered and high-quality care."

Credit: 
Wolters Kluwer Health