New Materials for Wound and Skin Healing

Good research into healing — it leverages the body’s own natural resources.

Materials are widely used to help heal wounds: Collagen sponges help treat burns and pressure sores, and scaffold-like implants are used to repair bones. However, the process of tissue repair changes over time, so scientists are developing biomaterials that interact with tissues as healing takes place.

Now, Dr Ben Almquist and his team at Imperial College London have created a new molecule that could change the way traditional materials work with the body. Known as traction force-activated payloads (TrAPs), their method lets materials talk to the body’s natural repair systems to drive healing.

The researchers say incorporating TrAPs into existing medical materials could revolutionise the way injuries are treated. Dr Almquist, from Imperial’s Department of Bioengineering, said: “Our technology could help launch a new generation of materials that actively work with tissues to drive healing.”

The findings are published today in Advanced Materials.

Cellular call to action

After an injury, cells ‘crawl’ through the collagen ‘scaffolds’ found in wounds, like spiders navigating webs. As they move, they pull on the scaffold, which activates hidden healing proteins that begin to repair injured tissue.

The researchers designed TrAPs as a way to recreate this natural healing method. They folded the DNA segments into three-dimensional shapes known as aptamers that cling tightly to proteins. Then, they attached a customisable ‘handle’ that cells can grab onto on one end, before attaching the opposite end to a scaffold such as collagen.

During laboratory testing of their technique, they found that cells pulled on the TrAPs as they crawled through the collagen scaffolds. The pulling made the TrAPs unravel like shoelaces to reveal and activate the healing proteins. These proteins instruct the healing cells to grow and multiply.

The researchers also found that by changing the cellular ‘handle’, they can change which type of cell can grab hold and pull, letting them tailor TrAPs to release specific therapeutic proteins based on which cells are present at a given point in time. In doing so, the TrAPs produce materials that can smartly interact with the correct type of cell at the correct time during wound repair.

This is the first time scientists have activated healing proteins using different types of cells in human-made materials. The technique mimics healing methods found in nature. Dr Almquist said: “Using cell movement to activate healing is found in creatures ranging from sea sponges to humans. Our approach mimics them and actively works with the different varieties of cells that arrive in our damaged tissue over time to promote healing.”

From lab to humans

This approach is adaptable to different cell types, so could be used in a variety of injuries such as fractured bones, scar tissue after heart attacks, and damaged nerves. New techniques are also desperately needed for patients whose wounds won’t heal despite current interventions, like diabetic foot ulcers, which are the leading cause of non-traumatic lower leg amputations.

TrAPs are relatively straightforward to create and are fully human-made, meaning they are easily recreated in different labs and can be scaled up to industrial quantities. Their adaptability also means they could help scientists create new methods for laboratory studies of diseases, stem cells, and tissue development.

Aptamers are currently used as drugs, meaning they are already proven safe and optimised for clinical use. Because TrAPs take advantage of aptamers that are currently optimised for use in humans, they may be able to take a shorter path to the clinic than methods that start from ground zero.

Dr Almquist said: “The TrAP technology provides a flexible method to create materials that actively communicate with the wound and provide key instructions when and where they are needed. This sort of intelligent, dynamic healing is useful during every phase of the healing process, has the potential to increase the body’s chance to recover, and has far-reaching uses on many different types of wounds. This technology has the potential to serve as a conductor of wound repair, orchestrating different cells over time to work together to heal damaged tissues.”

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Joy of Giving Found to Last Longer Than the Joy of Getting

It’s rather striking that this is recent research with how important human happiness is (becoming happy may be the most important thing in life) and with how much focus there’s been on happiness. The research is incomplete, but it is part of a growing series of evidence demonstrating the value of kindness.

The happiness we feel after a particular event or activity diminishes each time we experience that event, a phenomenon known as hedonic adaptation. But giving to others may be the exception to this rule, according to research forthcoming in Psychological Science, a journal of the Association for Psychological Science.

In two studies, psychology researchers Ed O’Brien (University of Chicago Booth School of Business) and Samantha Kassirer (Northwestern University Kellogg School of Management) found that participants’ happiness did not decline, or declined much slower, if they repeatedly bestowed gifts on others versus repeatedly receiving those same gifts themselves.

“If you want to sustain happiness over time, past research tells us that we need to take a break from what we’re currently consuming and experience something new. Our research reveals that the kind of thing may matter more than assumed: Repeated giving, even in identical ways to identical others, may continue to feel relatively fresh and relatively pleasurable the more that we do it,” O’Brien explains.

In one experiment, university student participants received $5 every day for 5 days; they were required to spend the money on the exact same thing each time. The researchers randomly assigned participants to spend the money either on themselves or on someone else, such as by leaving money in a tip jar at the same café or making an online donation to the same charity every day. The participants reflected on their spending experience and overall happiness at the end of each day.

The data, from a total of 96 participants, showed a clear pattern: Participants started off with similar levels of self-reported happiness and those who spent money on themselves reported a steady decline in happiness over the 5-day period. But happiness did not seem to fade for those who gave their money to someone else. The joy from giving for the fifth time in a row was just as strong as it was at the start.

O’Brien and Kassirer then conducted a second experiment online, which allowed them to keep the tasks consistent across participants. In this experiment, 502 participants played 10 rounds of a word puzzle game. They won $0.05 per round, which they either kept or donated to a charity of their choice. After each round, participants disclosed the degree to which winning made them feel happy, elated, and joyful.

Again, the self-reported happiness of those who gave their winnings away declined far more slowly than did the happiness reported by those who kept their winnings.

Further analyses ruled out some potential alternative explanations, such as the possibility that participants who gave to others had to think longer and harder about what to give, which could promote higher happiness.

“We considered many such possibilities, and measured over a dozen of them,” says O’Brien. “None of them could explain our results; there were very few incidental differences between ‘get’ and ‘give’ conditions, and the key difference in happiness remained unchanged when controlling for these other variables in the analyses.”

Adaptation to happiness-inducing experiences can be functional to the extent that it motivates us to pursue and acquire new resources. Why doesn’t this also happen with the happiness we feel when we give?

The researchers note that when people focus on an outcome, such as getting paid, they can easily compare outcomes, which diminishes their sensitivity to each experience. When people focus on an action, such as donating to a charity, they may focus less on comparison and instead experience each act of giving as a unique happiness-inducing event.

We may also be slower to adapt to happiness generated by giving because giving to others helps us maintain our prosocial reputation, reinforcing our sense of social connection and belonging.

These findings raise some interesting questions for future research — for example, would these findings hold if people were giving or receiving larger amounts of money? Or giving to friends versus strangers?

The researchers have also considered looking beyond giving or receiving monetary rewards, since prosocial behavior includes a wide range of experiences.

New Bandage Speeds Skin Healing By Using Electric Stimulation

It’s cool that the bandage worked well on rats (which are used in scientific experiments due to having some important similarities to humans) by using electric stimulation created by an electric field.

Skin has a remarkable ability to heal itself. But in some cases, wounds heal very slowly or not at all, putting a person at risk for chronic pain, infection and scarring. Now, researchers have developed a self-powered bandage that generates an electric field over an injury, dramatically reducing the healing time for skin wounds in rats. They report their results in ACS Nano.

Chronic skin wounds include diabetic foot ulcers, venous ulcers and non-healing surgical wounds. Doctors have tried various approaches to help chronic wounds heal, including bandaging, dressing, exposure to oxygen and growth-factor therapy, but they often show limited effectiveness. As early as the 1960s, researchers observed that electrical stimulation could help skin wounds heal. However, the equipment for generating the electric field is often large and may require patient hospitalization. Weibo Cai, Xudong Wang and colleagues wanted to develop a flexible, self-powered bandage that could convert skin movements into a therapeutic electric field.

To power their electric bandage, or e-bandage, the researchers made a wearable nanogenerator by overlapping sheets of polytetrafluoroethylene (PTFE), copper foil and polyethylene terephthalate (PET). The nanogenerator converted skin movements, which occur during normal activity or even breathing, into small electrical pulses. This current flowed to two working electrodes that were placed on either side of the skin wound to produce a weak electric field. The team tested the device by placing it over wounds on rats’ backs. Wounds covered by e-bandages closed within 3 days, compared with 12 days for a control bandage with no electric field. The researchers attribute the faster wound healing to enhanced fibroblast migration, proliferation and differentiation induced by the electric field.

Infections During Childhood Increase Risks of Mental Disorders Developing

The connection between mind and body is further emphasized.

A new study from iPSYCH shows that the infections children contract during their childhood are linked to an increase in the risk of mental disorders during childhood and adolescence. This knowledge expands our understanding of the role of the immune system in the development of mental disorders.

High temperatures, sore throats and infections during childhood can increase the risk of also suffering from a mental disorder as a child or adolescent. This is shown by the first study of its kind to follow all children born in Denmark between 1 January 1995 and 30 June 2012. The researchers have looked at all infections that have been treated from birth and also at the subsequent risk of childhood and adolescent psychiatric disorders.

“Hospital admissions with infections are particularly associated with an increased risk of mental disorders, but so too are less severe infections that are treated with medicine from the patient’s own general practitioner,” says Ole Köhler-Forsberg from Aarhus University and Aarhus University Hospital’s Psychoses Research Unit. He is one of the researchers behind the study.

The study showed that children who had been hospitalised with an infection had an 84 per cent increased risk of suffering a mental disorder and a 42 per cent increased risk of being prescribed medicine to treat mental disorders. Furthermore, the risk for a range of specific mental disorders was also higher, including psychotic disorders, OCD, tics, personality disorders, autism and ADHD.

“This knowledge increases our understanding of the fact that there is a close connection between body and brain and that the immune system can play a role in the development of mental disorders. Once again research indicates that physical and mental health are closely connected,” says Ole Köhler-Forsberg.

Highest risk following an infection

The study has just been published in JAMA Psychiatry and is a part of the Danish iPSYCH psychiatry project.

“We also found that the risk of mental disorders is highest right after the infection, which supports the infection to some extent playing a role in the development of the mental disorder,” says Ole Köhler-Forsberg.

It therefore appears that infections and the inflammatory reaction that follows afterwards can affect the brain and be part of the process of developing severe mental disorders. This can, however, also be explained by other causes, such as some people having a genetically higher risk of suffering more infections and mental disorders.

The new knowledge could have importance for further studies of the immune system and the importance of infections for the development of a wide range of childhood and adolescent mental disorders for which the researchers have shown a correlation. This is the assessment of senior researcher on the study, Research Director Michael Eriksen Benrós from the Psychiatric Centre Copenhagen at Copenhagen University hospital.

“The temporal correlations between the infection and the mental diagnoses were particularly notable, as we observed that the risk of a newly occurring mental disorder was increased by 5.66 times in the first three months after contact with a hospital due to an infection and were also increased more than twofold within the first year,” he explains.

Michael Eriksen Benrós stresses that the study can in the long term lead to increased focus on the immune system and how infections play a role in childhood and adolescent mental disorders.

“It can have a consequence for treatment and the new knowledge can be used in making the diagnosis when new psychiatric symptoms occur in a young person. But first and foremost it corroborates our increasing understanding of how closely the body and brain are connected,” he says.

AI System Shows Somewhat Human-Like Creativity In Chess, In a Possible Landmark AI Moment

Artificial intelligence’s power brings with it the possibility of doing immense good or immense harm to humanity, and it is going to be up to society to ensure that AI functions in benevolent ways. Stockfish has also been the most dominant chess engine for quite some time, and to see it defeated consistently by a human-like, dynamic chess engine is both amazing and unsettling.

DeepMind’s artificial intelligence programme AlphaZero is now showing signs of human-like intuition and creativity, in what developers have hailed as ‘turning point’ in history.

The computer system amazed the world last year when it mastered the game of chess from scratch within just four hours, despite not being programmed how to win.

But now, after a year of testing and analysis by chess grandmasters, the machine has developed a new style of play unlike anything ever seen before, suggesting the programme is now improvising like a human.

Unlike the world’s best chess machine – Stockfish – which calculates millions of possible outcomes as it plays, AlphaZero learns from its past successes and failures, making its moves based on, a ‘nebulous sense that it is all going to work out in the long run,’ according to experts at DeepMind.

When AlphaZero was pitted against Stockfish in 1,000 games, it lost just six, winning convincingly 155 times, and drawing the remaining bouts.

Yet it was the way that it played that has amazed developers. While chess computers predominately like to hold on to their pieces, AlphaZero readily sacrificed its soldiers for a better position in the skirmish.

Speaking to The Telegraph, Prof David Silver, who leads the reinforcement learning research group at DeepMind said: “It’s got a very subtle sense of intuition which helps it balance out all the different factors.

“It’s got a neural network with millions of different tunable parameters, each learning its own rules of what is good in chess, and when you put them all together you have something that expresses, in quite a brain-like way, our human ability to glance at a position and say ‘ah ha this is the right thing to do’.

“My personal belief is that we’ve seen something of turning point where we’re starting to understand that many abilities, like intuition and creativity, that we previously thought were in the domain only of the human mind, are actually accessible to machine intelligence as well. And I think that’s a really exciting moment in history.”

AlphaZero started as a ‘tabula rasa’ or blank slate system, programmed with only the basic rules of chess and learned to win by playing millions of games against itself in a process of trial and error known as reinforcement learning.

It is the same way the human brain learns, adjusting tactics based on a previous win or loss, which allows it to search just 60 thousand positions per second, compared to the roughly 60 million of Stockfish.

[…]

The new analysis was published yesterday in the journal Science, and the DeepMind team are now hoping to use their system to help solve real world problems, such as why proteins become misfolded in diseases such as Parkinson’s and Alzheimer’s.

The new results suggest that it could come up with new solutions that humans might miss or take far longer to discover.

Past Successes of Teams in Sports Increases Their Chances of Future Victories

A study showing the power of teamwork, with implications for cooperative efforts outside of sports, such as in business or communities.

What makes a team successful? This is not only a crucial question for football coaches, it plays a role in almost all areas of life, from corporate management to politics. It goes without saying that a team can only win if the team members have the necessary skills. But there is another important element: joint successes in the past increase the chances of winning. This effect shows up in a similar way in completely different team sports.

A research team from TU Wien (Vienna), Northwestern University (Evanston, USA), and the Indian Institute of Management (Udaipur) were able to statistically prove this phenomenon by analyzing large amounts of data in physical sports (football, baseball, cricket and basketball), and also in e-sports (namely the multiplayer online game “Dota 2”). The results have now been published in the journal Nature Human Behaviour.

Skills are not everything

The research team collected extensive data on numerous teams from several sports. The strength of individual players was quantified using different parameters — for example in basketball, the number of points scored and the number of assists was taken into account. The strength of the team can then be calculated as the average strength of the players.

“This gives us a value that can predict the outcome of a game reasonably well,” says Julia Neidhardt of the E-Commerce research unit (Institute for Information Systems Engineering, TU Wien, Vienna). She conducts research in the areas of team performance, user modeling and recommender systems. She does not only consider individuals, but also models their relationships, for example with the help of social network analysis. “Teams with better individual players have of course a higher chance of winning — but that’s not the end of the story,” says Neidhardt.

The team effect

In all the sports studied, the actual results of the games can be predicted even better by not only considering the average strength of the team members, but also taking into account how often they have been victorious together in the past. It is therefore not only important to bring the best possible stars to the field, they also have to gain experience together as a team by celebrating joint victories.

Especially in elite sports, where the skills of all involved professionals are extremely high, individual differences do not necessarily play the key role. As the differences in the skill levels decrease, common experience becomes more important.

It is particularly interesting that the effect was to be seen in very different sports: In football or in the e-sport “Dota 2,” the team members permanently depend on each other. Most actions are performed by several players at the same time. In baseball, on the other hand, throwing and hitting the ball are individual actions that have nothing to do with the rest of the team. Nevertheless, the team effect can be seen in all these sports.

Robust result

There are different possible explanations for this: By training and playing together for a long time, the players become better at coordinating their actions and predicting their teammates’ reactions, but there may also be strong psychological effects, when there is a strong emotional bond between the team players. The statistical data cannot conclusively answer the question which effect is more important. “We can see clearly that in the case of similar skill levels, prior shared success is a good predictor of which team is going to win,” says Julia Neidhardt. “This effect is very robust, in a variety of sports. This leads us to suspect that similar effects also occur in other areas.”

Research Into Pain Shows That When People Expect More Pain, They Feel More Pain

A good study that’s needed to be done for a while.

Expect a shot to hurt and it probably will, even if the needle poke isn’t really so painful. Brace for a second shot and you’ll likely flinch again, even though — second time around — you should know better.

That’s the takeaway of a new brain imaging study published in the journal Nature Human Behaviour which found that expectations about pain intensity can become self-fulfilling prophecies. Surprisingly, those false expectations can persist even when reality repeatedly demonstrates otherwise, the study found.

“We discovered that there is a positive feedback loop between expectation and pain,” said senior author Tor Wager, a professor of psychology and neuroscience at the University of Colorado Boulder. “The more pain you expect, the stronger your brain responds to the pain. The stronger your brain responds to the pain, the more you expect.”

For decades, researchers have been intrigued with the idea of self-fulfilling prophecy, with studies showing expectations can influence everything from how one performs on a test to how one responds to a medication. The new study is the first to directly model the dynamics of the feedback loop between expectations and pain and the neural mechanisms underlying it.

Marieke Jepma, then a postdoctoral researcher in Wager’s lab, launched the research after noticing that even when test subjects were shown time and again that something wouldn’t hurt badly, some still expected it to.

“We wanted to get a better understanding of why pain expectations are so resistant to change,” said Jepma, lead author and now a researcher at the University of Amsterdam.

The researchers recruited 34 subjects and taught them to associate one symbol with low heat and another with high, painful heat.

Then, the subjects were placed in a functional magnetic resonance imaging (fMRI) machine, which measures blood flow in the brain as a proxy for neural activity. For 60 minutes, subjects were shown low or high pain cues (the symbols, the words Low or High, or the letters L and W), then asked to rate how much pain they expected.

Then varying degrees of painful but non-damaging heat were applied to their forearm or leg, with the hottest reaching “about what it feels like to hold a hot cup of coffee” Wager explains.

Then they were asked to rate their pain.

Unbeknownst to the subjects, heat intensity was not actually related to the preceding cue.

The study found that when subjects expected more heat, brain regions involved in threat and fear were more activated as they waited. Regions involved in the generation of pain were more active when they received the stimulus. Participants reported more pain with high-pain cues, regardless of how much heat they actually got.

“This suggests that expectations had a rather deep effect, influencing how the brain processes pain,” said Jepma.

Surprisingly, their expectations also highly influenced their ability to learn from experience. Many subjects demonstrated high “confirmation bias” — the tendency to learn from things that reinforce our beliefs and discount those that don’t. For instance, if they expected high pain and got it, they might expect even more pain the next time. But if they expected high pain and didn’t get it, nothing changed.

“You would assume that if you expected high pain and got very little you would know better the next time. But interestingly, they failed to learn,” said Wager.

This phenomenon could have tangible impacts on recovery from painful conditions, suggests Jepma.

“Our results suggest that negative expectations about pain or treatment outcomes may in some situations interfere with optimal recovery, both by enhancing perceived pain and by preventing people from noticing that they are getting better,” she said. “Positive expectations, on the other hand, could have the opposite effects.”

The research also may shed light on why, for some, chronic pain can linger long after damaged tissues have healed.

Whether in the context of pain or mental health, the authors suggest that it may do us good to be aware of our inherent eagerness to confirm our expectations.

“Just realizing that things may not be as bad as you think may help you to revise your expectation and, in doing so, alter your experience,” said Jepma.