Active Learning Environment Until 5 Years Old Found to Shape the Brain 4 Decades Later

The development children have until 5 years old is an especially important time of brain development.

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An enhanced learning environment during the first five years of life shapes the brain in ways that are apparent four decades later, say Virginia Tech and University of Pennsylvania scientists writing in the June edition of the Journal of Cognitive Neuroscience.

The researchers used structural brain imaging to detect the developmental effects of linguistic and cognitive stimulation starting at six weeks of age in infants. The influence of an enriched environment on brain structure had formerly been demonstrated in animal studies, but this is the first experimental study to find a similar result in humans.

“Our research shows a relationship between brain structure and five years of high-quality, educational and social experiences,” said Craig Ramey, professor and distinguished research scholar with Fralin Biomedical Research Institute at VTC and principal investigator of the study. “We have demonstrated that in vulnerable children who received stimulating and emotionally supportive learning experiences, statistically significant changes in brain structure appear in middle age.”

The results support the idea that early environment influences the brain structure of individuals growing up with multi-risk socioeconomic challenges, said Martha Farah, director of the Center for Neuroscience and Society at Penn and first author of the study.

“This has exciting implications for the basic science of brain development, as well as for theories of social stratification and social policy,” Farah said.

The study follows children who have continuously participated in the Abecedarian Project, an early intervention program initiated by Ramey in Chapel Hill, North Carolina, in 1971 to study the effects of educational, social, health, and family support services on high-risk infants.

Both the comparison and treatment groups received extra health care, nutrition, and family support services; however, beginning at six weeks of age, the treatment group also received five years of high quality educational support, five days a week, 50 weeks a year.

When scanned, the Abecedarian study participants were in their late 30s to early 40s, offering the researchers a unique look at how childhood factors affect the adult brain.

“People generally know about the potentially large benefits of early education for children from very low resource circumstances,” said co-author Sharon Landesman Ramey, professor and distinguished research scholar at Fralin Biomedical Research Institute. “The new results reveal that biological effects accompany the many behavioral, social, health, and economic benefits reported in the Abecedarian Project. This affirms the idea that positive early life experiences contribute to later positive adjustment through a combination of behavioral, social, and brain pathways.”

During follow-up examinations, structural MRI scans of the brains of 47 study participants were conducted at the Fralin Biomedical Research Institute Human Neuroimaging Lab. Of those, 29 individuals had been in the group that received the educational enrichment focused on promoting language, cognition, and interactive learning.

The other 18 individuals received the same robust health, nutritional, and social services supports provided to the educational treatment group, and whatever community childcare or other learning their parents provided. The two groups were well matched on a variety of factors such as maternal education, head circumference at birth and age at scanning.

Analyzing the scans, the researchers looked at brain size as a whole, including the cortex, the brain’s outermost layer, as well as five regions selected for their expected connection to the intervention’s stimulation of children’s language and cognitive development.

Those included the left inferior frontal gyrus and left superior temporal gyrus, which may be relevant to language, and the right inferior frontal gyrus and bilateral anterior cingulate cortex, relevant to cognitive control. A fifth, the bilateral hippocampus, was added because its volume is frequently associated with early life adversity and socioeconomic status.

The researchers determined that those in the early education treatment group had increased size of the whole brain, including the cortex.

Several specific cortical regions also appeared larger, according to study co-authors Read Montague, professor and director of the Human Neuroimaging Lab and Computational Psychiatry Unit at the Fralin Biomedical Research Institute, and Terry Lohrenz, research assistant professor and member of the institute’s Human Neuroimaging Laboratory.

The scientists noted the group intervention treatment results for the brain were substantially greater for males than for females. The reasons for this are not known, and were surprising, since both the boys and girls showed generally comparable positive behavioral and educational effects from their early enriched education. The current study cannot adequately explain the sex differences.

“When we launched this project in the 1970s, the field knew more about how to assess behavior than it knew about how to assess brain structure,” Craig Ramey said. “Because of advances in neuroimaging technology and through strong interdisciplinary collaborations, we were able to measure structural features of the brain. The prefrontal cortex and areas associated with language were definitely affected; and to our knowledge, this is the first experimental evidence on a link between known early educational experiences and long-term changes in humans.”

“We believe that these findings warrant careful consideration and lend further support to the value of ensuring positive learning and social-emotional support for all children — particularly to improve outcomes for children who are vulnerable to inadequate stimulation and care in the early years of life,” Craig Ramey said.

Eating Fruits and Vegetables Linked to Less Stress

Too much stress has a detrimental effect on one’s health.

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Eating a diet rich in fruit and vegetables is associated with less stress, according to new research from Edith Cowan University (ECU).

The study examined the link between fruit and vegetable intake and stress levels of more than 8,600 Australians aged between 25 and 91 participating in the Australian Diabetes, Obesity and Lifestyle (AusDiab) Study from Baker Heart and Diabetes Institute.

The findings revealed people who ate at least 470 grams of fruit and vegetables daily had 10 per cent lower stress levels than those who consumed less than 230 grams. The World Health Organization (WHO) recommends eating at least 400 grams of fruit and vegetables per day.

Lead researcher, PhD candidate Simone Radavelli-Bagatini from ECU’s Institute for Nutrition Research, said the study strengthens the link between diets rich in fruit and vegetables and mental wellbeing.

“We found that people who have higher fruit and veggie intakes are less stressed than those with lower intakes, which suggests diet plays a key role in mental wellbeing,” said Ms Radavelli-Bagatini.

A growing issue

Mental health conditions are an increasing problem in Australia and around the world. Around one in two Australians will experience a mental health issue in their lifetime. Globally, approximately 1 in 10 people live with a mental health disorder.

According to Ms Radavelli-Bagatini, some stress is considered normal, but long-term exposure can significantly impact mental health.

“Long-term and unmanaged stress can lead to a range of health problems including heart disease, diabetes, depression and anxiety so we need to find ways to prevent and possibly alleviate mental health problems in the future,” said Ms Radavelli-Bagatini.

The benefits of a healthy diet are well known, but only 1 in 2 Australians eat the recommended two serves of fruit per day and fewer than 1 in 10 eat the recommended five serves of vegetables each day.

“Previous studies have shown the link between fruit and vegetable consumption and stress in younger adults, but this is the first time we’re seeing similar results across adults of all ages,” said Ms Radavelli-Bagatini.

“The study’s findings emphasise that it’s important for people to have a diet rich in fruit and vegetables to potentially minimise stress.”

Food and mood

While the mechanisms behind how fruit and vegetable consumption influences stress are still unclear, Ms Radavelli-Bagatini said key nutrients could be a factor.

“Vegetables and fruits contain important nutrients such as vitamins, minerals, flavonoids and carotenoids that can reduce inflammation and oxidative stress, and therefore improve mental wellbeing,” she said.

“Inflammation and oxidative stress in the body are recognised factors that can lead to increased stress, anxiety and lower mood.”

“These findings encourage more research into diet and specifically what fruits and vegetables provide the most benefits for mental health.”

The research is part of ECU’s recently launched Institute for Nutrition Research, which aims to investigate how nutrition can help prevent and treat chronic health conditions.

‘Fruit and vegetable intake is inversely associated with perceived stress across the adult lifespan’ was published in Clinical Nutrition.

Experimental Drug Has Potential Against Alzheimer’s Disease

The drug reversed Alzheimer’s in mice through removing garbage from their brain cells. The research seems like a notable milestone against Alzheimer’s disease.

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Researchers at Albert Einstein College of Medicine have designed an experimental drug that reversed key symptoms of Alzheimer’s disease in mice. The drug works by reinvigorating a cellular cleaning mechanism that gets rid of unwanted proteins by digesting and recycling them. The study was published online today in the journal Cell.

“Discoveries in mice don’t always translate to humans, especially in Alzheimer’s disease,” said co-study leader Ana Maria Cuervo, M.D., Ph.D., the Robert and Renée Belfer Chair for the Study of Neurodegenerative Diseases, professor of developmental and molecular biology, and co-director of the Institute for Aging Research at Einstein. “But we were encouraged to find in our study that the drop-off in cellular cleaning that contributes to Alzheimer’s in mice also occurs in people with the disease, suggesting that our drug may also work in humans.” In the 1990s, Dr. Cuervo discovered the existence of this cell-cleaning process, known as chaperone-mediated autophagy (CMA) and has published 200 papers on its role in health and disease.

CMA becomes less efficient as people age, increasing the risk that unwanted proteins will accumulate into insoluble clumps that damage cells. In fact, Alzheimer’s and all other neurodegenerative diseases are characterized by the presence of toxic protein aggregates in patients’ brains. The Cell paper reveals a dynamic interplay between CMA and Alzheimer’s disease, with loss of CMA in neurons contributing to Alzheimer’s and vice versa. The findings suggest that drugs for revving up CMA may offer hope for treating neurodegenerative diseases.

Establishing CMA’s Link to Alzheimer’s

Dr. Cuervo’s team first looked at whether impaired CMA contributes to Alzheimer’s. To do so, they genetically engineered a mouse to have excitatory brain neurons that lacked CMA. The absence of CMA in one type of brain cell was enough to cause short-term memory loss, impaired walking, and other problems often found in rodent models of Alzheimer’s disease. In addition, the absence of CMA profoundly disrupted proteostasis — the cells’ ability to regulate the proteins they contain. Normally soluble proteins had shifted to being insoluble and at risk for clumping into toxic aggregates.

Dr. Cuervo suspected the converse was also true: that early Alzheimer’s impairs CMA. So she and her colleagues studied a mouse model of early Alzheimer’s in which brain neurons were made to produce defective copies of the protein tau. Evidence indicates that abnormal copies of tau clump together to form neurofibrillary tangles that contribute to Alzheimer’s. The research team focused on CMA activity within neurons of the hippocampus — the brain region crucial for memory and learning. They found that CMA activity in those neurons was significantly reduced compared to control animals.

What about early Alzheimer’s in people — does it block CMA too? To find out, the researchers looked at single-cell RNA-sequencing data from neurons obtained postmortem from the brains of Alzheimer’s patients and from a comparison group of healthy individuals. The sequencing data revealed CMA’s activity level in patients’ brain tissue. Sure enough, CMA activity was somewhat inhibited in people who had been in the early stages of Alzheimer’s, followed by much greater CMA inhibition in the brains of people with advanced Alzheimer’s.

“By the time people reach the age of 70 or 80, CMA activity has usually decreased by about 30% compared to when they were younger,” said Dr. Cuervo. “Most peoples’ brains can compensate for this decline. But if you add neurodegenerative disease to the mix, the effect on the normal protein makeup of brain neurons can be devastating. Our study shows that CMA deficiency interacts synergistically with Alzheimer’s pathology to greatly accelerate disease progression.”

A New Drug Cleans Neurons and Reverses Symptoms

In an encouraging finding, Dr. Cuervo and her team developed a novel drug that shows potential for treating Alzheimer’s. “We know that CMA is capable of digesting defective tau and other proteins,” said Dr. Cuervo. “But the sheer amount of defective protein in Alzheimer’s and other neurodegenerative diseases overwhelms CMA and essentially cripples it. Our drug revitalizes CMA efficiency by boosting levels of a key CMA component.”

In CMA, proteins called chaperones bind to damaged or defective proteins in cells of the body. The chaperones ferry their cargo to the cells’ lysosomes — membrane-bound organelles filled with enzymes, which digest and recycle waste material. To successfully get their cargo into lysosomes, however, chaperones must first “dock” the material onto a protein receptor called LAMP2A that sprouts from the membranes of lysosomes. The more LAMP2A receptors on lysosomes, the greater the level of CMA activity possible. The new drug, called CA, works by increasing the number of those LAMP2A receptors.

“You produce the same amount of LAMP2A receptors throughout life,” said Dr. Cuervo. “But those receptors deteriorate more quickly as you age, so older people tend to have less of them available for delivering unwanted proteins into lysosomes. CA restores LAMP2A to youthful levels, enabling CMA to get rid of tau and other defective proteins so they can’t form those toxic protein clumps.” (Also this month, Dr. Cuervo’s team reported in Nature Communications that, for the first time, they had isolated lysosomes from the brains of Alzheimer’s disease patients and observed that reduction in the number of LAMP2 receptors causes loss of CMA in humans, just as it does in animal models of Alzheimer’s.)

The researchers tested CA in two different mouse models of Alzheimer’s disease. In both disease mouse models, oral doses of CA administered over 4 to 6 months led to improvements in memory, depression, and anxiety that made the treated animals resemble or closely resemble healthy, control mice. Walking ability significantly improved in the animal model in which it was a problem. And in brain neurons of both animal models, the drug significantly reduced levels of tau protein and protein clumps compared with untreated animals.

“Importantly, animals in both models were already showing symptoms of disease, and their neurons were clogged with toxic proteins before the drugs were administered,” said Dr. Cuervo. “This means that the drug may help preserve neuron function even in the later stages of disease. We were also very excited that the drug significantly reduced gliosis — the inflammation and scarring of cells surrounding brain neurons. Gliosis is associated with toxic proteins and is known to play a major role in perpetuating and worsening neurodegenerative diseases.”

Treatment with CA did not appear to harm other organs even when given daily for extended periods of time. The drug was designed by Evripidis Gavathiotis, Ph.D.,, professor of biochemistry and of medicine and a co-leader of the study.

Drs. Cuervo and Gavathiotis have teamed up with Life Biosciences of Boston, Mass., to found Selphagy Therapeutics, which is currently developing CA and related compounds for treating Alzheimer’s and other neurodegenerative diseases.

The study is titled, “Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome.” The study’s other co-leader and first author is Mathieu Bourdenx, Ph.D., a postdoctoral fellow in Dr. Cuervo’s lab and also a junior researcher at the Institute of Neurodegenerative Diseases, University of Bordeaux, France. Additional Einstein authors include: Adrián Martín-Segura, Aurora Scrivo, Susmita Kaushik, Ph.D., Inmaculada Tasset, Ph.D., Antonio Diaz and Yves R. Juste.

Study Shows Electrolytes Effective at Preventing Muscle Cramping

The study found that electrolyte-infused water is more effective than plain water.

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If you reach for water when a muscle cramp strikes, you might want to think again. New research from Edith Cowan University (ECU) has revealed drinking electrolytes instead of pure water can help prevent muscle cramps.

The study, published in the Journal of the International Society of Sports Nutrition, found that people who drank electrolyte enhanced water during and after exercise were less susceptible to muscle cramps than those who drank pure water.

Muscle cramps are a common painful condition affecting many people, including around 39 per cent of marathon runners, 52 per cent of rugby players and 60 per cent of cyclists.

Dilution solution

Lead researcher Professor Ken Nosaka, from ECU’s School of Medical and Health Sciences, said the study builds on the evidence that a lack of electrolytes contributes to muscle cramps, not dehydration.

“Many people think dehydration causes muscle cramps and will drink pure water while exercising to prevent cramping,” he said.

“We found that people who solely drink plain water before and after exercise could in fact be making them more prone to cramps.

“This is likely because pure water dilutes the electrolyte concentration in our bodies and doesn’t replace what is lost during sweating.”

When cramp strikes

Professor Nosaka began researching the causes of muscle cramps after regularly suffering from them while playing tennis.

The study involved 10 men who ran on a downhill treadmill in a hot (35ºC) room for 40 to 60 minutes to lose 1.5 to 2 per cent of their body weight through sweat in two conditions.

They drank plain water during and after exercise for one condition and took a water solution containing electrolytes in the other condition.

The participants were given an electrical stimulation on their calves to induce muscle cramp. The lower the frequency of the electrical stimulation required, the more the participant is prone to muscle cramp.

“We found that the electrical frequency required to induce cramp increased when people drank the electrolyte water, but decreased when they consumed plain water,” said Professor Nosaka.

“This indicates that muscles become more prone to cramp by drinking plain water, but more immune to muscle cramp by drinking the electrolyte water.”

Not all water is equal

Electrolytes are minerals including sodium, potassium, magnesium and chloride. They are essential for muscle health and help the body to absorb water.

Oral rehydration solutions contain electrolytes in specific proportions and can be made with water, salt and sugar. They are commonly found in supermarkets and pharmacies.

Professor Nosaka said electrolytes have many benefits for both athletes and the general population.

“Electrolytes are vital to good health — they help the body to absorb water more effectively than plain water and replace essential minerals lost through sweat or illness,” he said.

“People should consider drinking oral rehydration fluids instead of plain water during moderate to intense exercise, when it’s very hot or when you are sick from diarrhoea or vomiting.”

Professor Nosaka is planning further research to find out the optimal amount of electrolytes to prevent muscle cramps as well as how they could help the elderly and pregnant women.

Study of 670,450 American Women Shows Almost Half of Them Are Receiving the Wrong UTI Treatment

Many American healthcare professionals are still prescribing incorrect antibiotics treatments for too long of a duration.

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Across the United States, in both rural and urban settings, most women with private health insurance are receiving inappropriate treatment for their urinary tract infections (UTIs), according to a new study. 

Of the 670,450 women included in this research, all of whom had been diagnosed with uncomplicated UTIs between the ages of 18 and 44, nearly half received the wrong antibiotics and over three quarters were prescribed the medicine for too long. (A UTI is declared ‘uncomplicated’ when the patient has no abnormality or disease that could predispose them to more frequent infections.)

The results are largely consistent from location to location, although patients in more rural settings were more likely to be prescribed antibiotics for longer. 

Over the course of the study, from 2011 to 2015, there was only a slight improvement in proper antibiotic prescriptions based on current clinical guidelines.

“Inappropriate antibiotic prescriptions for uncomplicated urinary tract infections are prevalent and come with serious patient- and society-level consequences,” says epidemiologist Anne Mobley Butler from the Washington University School of Medicine, St. Louis.

“Our study findings underscore the need for antimicrobial stewardship interventions to improve outpatient antibiotic prescribing, particularly in rural settings.” 

The research was funded in part by several pharmaceutical companies, including Sanofi Pasteur, Pfizer, and Merck. The results were peer-reviewed and fall largely in line with the findings of previous studies, which suggest up to 60 percent of antibiotics prescribed in intensive care units are “unnecessary, inappropriate, or suboptimal”.

Nor is this just a problem in the US. Around the world, UTIs are one of the most common infections leading to emergency room visits. In the United Kingdom, it’s the second most common reason for prescribing antibiotics. 

Not only does taking the wrong antibiotic have worse outcomes for the individual patient, longer prescriptions are not necessarily better and can cause bacteria to grow resistant, making recurrence more likely and future infections harder to treat. 

Today, it’s estimated one in three uncomplicated UTIs in women are resistant to the popular combined antibiotic drug Bactrim (sulfamethoxazole and trimethoprim), and one in five are resistant to five other common antibiotics. 

An estimate of the number of deaths related to antibiotic-resistant UTIs is hard to establish due to a lack of research and monitoring, but some studies suggest that in US hospitals alone it could be around 13,000 lives lost per year. And some people suffer recurrent, resistant infections for years on end with little to no relief.

In light of these emerging concerns, in 2010 the Infectious Diseases Society of America (IDSA) and the European Society for Microbiology and Infectious Diseases updated their clinical practice guidelines. Based on results from various studies, they now recommend several first-line antibiotic agents and durations to best treat UTIs while minimizing the risk of antibiotic resistance.

That advice, however, is clearly not getting through to physicians and healthcare professionals. Many are still prescribing non-recommended antibiotics for improper durations.

Figuring out where the most inappropriate prescriptions are happening could help us target areas where we need to improve adherence to antibiotic guidelines. In the US, rural areas experience numerous health disparities compared to more urban areas, and yet this is the first large-scale study to evaluate how that impacts UTI treatment.

The authors are not sure why longer antibiotic treatments for UTIs are especially prevalent in rural areas, but suggest it could have to do with access to care and physician awareness. In rural areas, women may be given longer prescriptions to avoid future travel if that treatment fails.

Studies also show late-career physicians are more prevalent in rural locations and are more likely to prescribe antibiotics for longer, possibly because they have not heard of updated guidelines. 

“Accumulating evidence suggests that patients have better outcomes when we change prescribing from broad-acting to narrow-spectrum antibiotics and from longer to shorter durations,” explains Butler.

“Promoting optimal antimicrobial use benefits the patient and society by preventing avoidable adverse events, microbiome disruption, and antibiotic-resistant infections.”

When up to 60 percent of women can suffer from a UTI at some point in their life, it’s clearly vital that guidelines for treatment are better enforced, especially as antibiotic resistance increases.

This particular study was only based on commercially insured individuals, which means those who are uninsured or who receive public insurance were not considered. Rural areas were also loosely defined, including small towns as well as ‘exurbs’ on the edges of urban areas, and men, who also suffer from UTIs (albeit at a lower rate), were not included. 

Future research should focus on filling these gaps, but in the meantime, the trend reinforces the idea that clinicians need to periodically review clinical practice guidelines, even for common conditions that they have been treating for years.

“In recent years, little effective progress has been achieved to reduce inappropriate antibiotic prescribing for uncomplicated UTI,” the new paper concludes

“Given the large quantity of inappropriate prescriptions annually in the United States, as well as the negative patient- and society-level consequences of unnecessary exposure to antibiotics, antimicrobial stewardship interventions are needed to improve outpatient UTI antibiotic prescribing, particularly in rural settings.”

The study was published in Infection Control & Hospital Epidemiology.

Giraffes That Are More Social Live Longer

This study on giraffes might might mean something for human populations too.

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A research team led by Monica Bond, research associate at the Department of Evolutionary Biology and Environmental Studies of the University of Zurich (UZH), studied giraffes in Tanzania for five years. The biologists examined the relative effects of sociability, the natural environment, and human factors on survival of the mega-herbivore. They have now shown that adult female giraffes living in larger groups have higher survival chances than more socially isolated individuals.

Gregariousness leads to better survival

Giraffe group formations are dynamic and change throughout the day, but adult females maintain many specific friendships over the long term. “Grouping with more females, called gregariousness, is correlated with better survival of female giraffes, even as group membership is frequently changing,” says Bond. “This aspect of giraffe sociability is even more important than attributes of their non-social environment such as vegetation and nearness to human settlements.”

The benefits of many friends

Aside from poaching, the main causes of adult female giraffe mortality are likely to be disease, stress or malnutrition, all of which are interconnected stressors. “Social relationships can improve foraging efficiency, and help manage intraspecific competition, predation, disease risk and psychosocial stress,” says UZH professor Barbara König, senior author of the study. Female giraffes may seek out and join together with an optimal number of other females in order to share and obtain information about the highest-quality food sources. Other benefits to living in larger groups might be lowering stress levels by reducing harassment from males, cooperating in caring for young, or simply experiencing physiological benefits by being around familiar females. The study also finds that females living closer to towns had lower survival rates, possibly due to poaching.

Social habits similar to humans and primates

The team documented the social behaviors of the wild free-ranging giraffes using network analysis algorithms similar to those used by big-data social media platforms. According to the results, the giraffes are surprisingly similar in their social habits to humans and other primates, for whom greater social connectedness offers more opportunities. Chimpanzees and gorillas, for example, live in communities where ties between many individuals facilitate the flexibility of feeding strategies. “It seems to be beneficial for female giraffes to connect with a greater number of others and develop a sense of larger community, but without a strong sense of exclusive subgroup affiliation,” adds Monica Bond.

Study of a giraffe population in Tanzania

For the past decade the research team has been conducting the largest study to date of a giraffe population. The vast scale of their study area in the Tarangire region of Tanzania spans more than a thousand square kilometers and includes multiple social communities, each with about 60 to 90 adult female members. Thus, the study was able to disentangle individual from community-level influences on survival. The study is also unique in combining social network analysis and modeling of vital rates such as survival in a sample of hundreds of individuals.

Teaching Young Students Empathy Improves Their Creativity, University of Cambridge Finds

Having students become more skilled at looking at things from different perspectives may be what drove the increase in their creativity. The power of enhanced creativity can obviously be leveraged in many fields to boost levels of success.

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Teaching children in a way that encourages them to empathise with others measurably improves their creativity, and could potentially lead to several other beneficial learning outcomes, new research suggests.

The findings are from a year-long University of Cambridge study with Design and Technology (D&T) year 9 pupils (ages 13 to 14) at two inner London schools. Pupils at one school spent the year following curriculum-prescribed lessons, while the other group’s D&T lessons used a set of engineering design thinking tools which aim to foster students’ ability to think creatively and to engender empathy, while solving real-world problems.

Both sets of pupils were assessed for creativity at both the start and end of the school year using the Torrance Test of Creative Thinking: a well-established psychometric test.

The results showed a statistically significant increase in creativity among pupils at the intervention school, where the thinking tools were used. At the start of the year, the creativity scores of pupils in the control school, which followed the standard curriculum, were 11% higher than those at the intervention school. By the end, however, the situation had completely changed: creativity scores among the intervention group were 78% higher than the control group.

The researchers also examined specific categories within the Torrance Test that are indicative of emotional or cognitive empathy: such as ’emotional expressiveness’ and ‘open-mindedness’. Pupils from the intervention school again scored much higher in these categories, indicating that a marked improvement in empathy was driving the overall creativity scores.

The study’s authors suggest that encouraging empathy not only improves creativity, but can deepen pupils’ general engagement with learning. Notably, they found evidence that boys and girls in the intervention school responded to the D&T course in ways that defied traditional gender stereotypes. Boys showed a marked improvement in emotional expression, scoring 64% higher in that category at the end of the year than at the start, while girls improved more in terms of cognitive empathy, showing 62% more perspective-taking.

The research is part of a long-term collaboration between the Faculty of Education and the Department of Engineering at the University of Cambridge called ‘Designing Our Tomorrow’ (DOT), led by Bill Nicholl and Ian Hosking. It challenges pupils to solve real-world problems by thinking about the perspectives and feelings of others.

The particular challenge used in the study asked pupils at the intervention school to design an asthma-treatment ‘pack’ for children aged six and under. Pupils were given various creative and empathetic ‘tools’ in order to do so: for example, they were shown data about the number of childhood asthma fatalities in the UK, and a video which depicts a young child having an attack. They also explored the problem and tested their design ideas by role-playing various stakeholders, for example, patients, family-members, and medical staff.

Nicholl, Senior Lecturer in Design and Technology Education, who trains teachers studying on the University’s D&T PGCE course, said: “Teaching for empathy has been problematic despite being part of the D&T National Curriculum for over two decades. This evidence suggests that it is a missing link in the creative process, and vital if we want education to encourage the designers and engineers of tomorrow.”

Dr Helen Demetriou, an affiliated lecturer in psychology and education at the Faculty of Education with a particular interest in empathy, and the other researcher involved in the study, said: “We clearly awakened something in these pupils by encouraging them to think about the thoughts and feelings of others. The research shows not only that it is possible to teach empathy, but that by doing so we support the development of children’s creativity, and their wider learning.”

The gender differences charted in the study indicate that the intervention enabled students to overcome some of the barriers to learning that assumed gender roles often create. For example, boys often feel discouraged from expressing emotion at school, yet this was one of the main areas where they made significant creative gains according to the tests.

In addition to the Torrance Tests, the researchers conducted in-depth interviews with pupils at both the intervention school and a third (girls-only) school who also undertook the asthma challenge. This feedback again suggested that pupils had empathised deeply with the challenges faced by young asthma-sufferers, and that this had influenced their creative decisions in the classroom.

Many, for example, used phrases such as ‘stepping into their shoes’ or ‘seeing things from another point of view’ when discussing patients and their families. One boy told the researchers: “I think by the end of the project I could feel for the people with asthma… if I was a child taking inhalers, I would be scared too.”

Another responded: “Let’s say you had a sister or brother in that position. I would like to do something like this so we can help them.”

Overall, the authors suggest that these findings point to a need to nurture ’emotionally intelligent learners’ not only in D&T classes, but across subjects, particularly in the context of emerging, wider scientific evidence that our capacity for empathy declines as we get older.

“This is something that we must think about as curricula in general become increasingly exam-based,” Demetriou said. “Good grades matter, but for society to thrive, creative, communicative and empathic individuals matter too.”

Nicholl added: “When I taught Design and Technology, I didn’t see children as potential engineers who would one day contribute to the economy; they were people who needed to be ready to go into the world at 18. Teaching children to empathise is about building a society where we appreciate each other’s perspectives. Surely that is something we want education to do.”

The study is published in the journal, Improving Schools.

Teenagers With Better Childhoods Drink Less and Do Drugs Less

If we structured a system where there was less poverty and despair, more people would have better childhoods, and less people would end up with damaging drug addictions.

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Teenagers with happy childhood memories are likely to drink less, take fewer drugs and enjoy learning, according to research published in the peer-reviewed journal Addiction Research & Theory.

The findings, based on data from nearly 2,000 US high school students, show a link between how pupils feel about the past, present and future and their classroom behavior. This in turn influences their grades and risk of substance misuse, according to the study.

The authors say action is needed now because Covid-19 has left many teenagers struggling with online study, suffering mentally and turning to drink and drugs.

They are calling on teachers — and parents — to help students develop more positive mindsets and become motivated to learn so they are less likely to binge drink or use marijuana.

“School often seems a source of stress and anxiety to students,” says John Mark Froiland from Purdue University in Indiana, US.

“This puts them at greater risk of not participating in lessons, getting lower grades and of substance misuse.

“Many teenagers also aren’t engaging with online learning during Covid or have lower engagement levels.

“But they’re more likely to be enthusiastic learners and not use drink and drugs if teachers take time to build more positive relationships with them. They can help students see that everything they’re learning is truly valuable. Parents have a role to play too.”

Teenagers with a balanced attitude towards their childhoods and other time periods have already been shown by studies to be more likely to abstain from drink and drugs and achieve academically. This is compared to those with a pessimistic outlook.

The aim of this study was to establish how substance misuse and behaviors towards learning are affected by students’ feelings about the past, present and future.

The data was based on assessments and questionnaires completed by 1,961 students at a high school in the San Francisco Bay Area. More than half (53%) of the pupils included in the study were female.

The study authors looked at responses from pupils where they rated how nostalgic they were towards their childhood, current happiness levels in life and how much they look forward to future happiness.

They also analysed marijuana and alcohol habits over the past 30 days including binge drinking, and average academic grades. They analysed motivation levels, and behavior in lessons such as how much teenagers paid attention and listened.

Statistical techniques were used by the researchers to assess the associations between all these different factors and establish the key predictors for alcohol and marijuana misuse.

In general, the study found that positive attitudes towards the past, present and future put adolescents at lower risk for alcohol use, binge drinking, and marijuana.

The opposite was true for those displaying pessimistic or negative ways of thinking or feeling about their life in the past, now or ahead of them.

The reason for this was that a content and optimistic outlook increased the likelihood they would be motivated and behave in a focused way on the chance to learn.

Other findings include girls having stronger levels of behavioral engagement than boys, and students who drank being most likely to use cannabis.

Experimental Drug Quickly Reduces Age-Related Mental Decline

The compound, known as ISRIB, holds potential for reversing numerous cognitive problems in humans. Mice are used in scientific studies due to having genes that are approximately 85 percent similar to the genes of humans.

Just a few doses of an experimental drug can reverse age-related declines in memory and mental flexibility in mice, according to a new study by UC San Francisco scientists. The drug, called ISRIB, has already been shown in laboratory studies to restore memory function months after traumatic brain injury (TBI), reverse cognitive impairments in Down Syndrome, prevent noise-related hearing loss, fight certain types of prostate cancer, and even enhance cognition in healthy animals.

In the new study, published December 1, 2020 in the open-access journal eLife, researchers showed rapid restoration of youthful cognitive abilities in aged mice, accompanied by a rejuvenation of brain and immune cells that could help explain improvements in brain function.

“ISRIB’s extremely rapid effects show for the first time that a significant component of age-related cognitive losses may be caused by a kind of reversible physiological ‘blockage’ rather than more permanent degradation,” said Susanna Rosi, PhD, Lewis and Ruth Cozen Chair II and professor in the departments of Neurological Surgery and of Physical Therapy and Rehabilitation Science.

“The data suggest that the aged brain has not permanently lost essential cognitive capacities, as was commonly assumed, but rather that these cognitive resources are still there but have been somehow blocked, trapped by a vicious cycle of cellular stress,” added Peter Walter, PhD, a professor in the UCSF Department of Biochemistry and Biophysics and a Howard Hughes Medical Institute investigator. “Our work with ISRIB demonstrates a way to break that cycle and restore cognitive abilities that had become walled off over time.”

Could Rebooting Cellular Protein Production Hold the Key to Aging and Other Diseases?

Walter has won numerous scientific awards, including the Breakthrough, Lasker and Shaw prizes, for his decades-long studies of cellular stress responses. ISRIB, discovered in 2013 in Walter’s lab, works by rebooting cells’ protein production machinery after it gets throttled by one of these stress responses — a cellular quality control mechanism called the integrated stress response (ISR; ISRIB stands for ISR InhiBitor).

The ISR normally detects problems with protein production in a cell — a potential sign of viral infection or cancer-promoting gene mutations — and responds by putting the brakes on cell’s protein-synthesis machinery. This safety mechanism is critical for weeding out misbehaving cells, but if stuck in the on position in a tissue like the brain, it can lead to serious problems, as cells lose the ability to perform their normal activities, Walter and colleagues have found.

In particular, recent animal studies by Walter and Rosi, made possible by early philanthropic support from The Rogers Family Foundation, have implicated chronic ISR activation in the persistent cognitive and behavioral deficits seen in patients after TBI, by showing that, in mice, brief ISRIB treatment can reboot the ISR and restore normal brain function almost overnight.

The cognitive deficits in TBI patients are often likened to premature aging, which led Rosi and Walter to wonder if the ISR could also underlie purely age-related cognitive decline. Aging is well known to compromise cellular protein production across the body, as life’s many insults pile up and stressors like chronic inflammation wear away at cells, potentially leading to widespread activation of the ISR.

“We’ve seen how ISRIB restores cognition in animals with traumatic brain injury, which in many ways is like a sped-up version of age-related cognitive decline,” said Rosi, who is director of neurocognitive research in the UCSF Brain and Spinal Injury Center and a member of the UCSF Weill Institute for Neurosciences. “It may seem like a crazy idea, but asking whether the drug could reverse symptoms of aging itself was just a logical next step.”

ISRIB Improves Cognition, Boosts Neuron and Immune Cell Function

In the new study, researchers led by Rosi lab postdoc Karen Krukowski, PhD, trained aged animals to escape from a watery maze by finding a hidden platform, a task that is typically hard for older animals to learn. But animals who received small daily doses of ISRIB during the three-day training process were able to accomplish the task as well as youthful mice, much better than animals of the same age who didn’t receive the drug.

The researchers then tested how long this cognitive rejuvenation lasted and whether it could generalize to other cognitive skills. Several weeks after the initial ISRIB treatment, they trained the same mice to find their way out of a maze whose exit changed daily — a test of mental flexibility for aged mice who, like humans, tend to get increasingly stuck in their ways. The mice who had received brief ISRIB treatment three weeks before still performed at youthful levels, while untreated mice continued to struggle.

To understand how ISRIB might be improving brain function, the researchers studied the activity and anatomy of cells in the hippocampus, a brain region with a key role in learning and memory, just one day after giving animals a single dose of ISRIB. They found that common signatures of neuronal aging disappeared literally overnight: neurons’ electrical activity became more sprightly and responsive to stimulation, and cells showed more robust connectivity with cells around them while also showing an ability to form stable connections with one another usually only seen in younger mice.

The researchers are continuing to study exactly how the ISR disrupts cognition in aging and other conditions and to understand how long ISRIB’s cognitive benefits may last. Among other puzzles raised by the new findings is the discovery that ISRIB also alters the function of the immune system’s T cells, which also are prone to age-related dysfunction. The findings suggest another path by which the drug could be improving cognition in aged animals, and could have implications for diseases from Alzheimer’s to diabetes that have been linked to heightened inflammation caused by an aging immune system.

“This was very exciting to me because we know that aging has a profound and persistent effect on T cells and that these changes can affect brain function in the hippocampus,” said Rosi. “At the moment, this is just an interesting observation, but it gives us a very exciting set of biological puzzles to solve.

ISRIB May Have Wide-Ranging Implications for Neurological Disease

It turns out that chronic ISR activation and resulting blockage of cellular protein production may play a role in a surprisingly wide array of neurological conditions. Below is a partial list of these conditions, based on a recent review by Walter and colleague Mauro Costa-Mattioli of Baylor College of Medicine, which could potentially be treated with an ISR-resetting agent like ISRIB:

  • Frontotemporal Dementia
  • Alzheimer’s Disease
  • Amyotrophic Lateral Sclerosis (ALS)
  • Age-related Cognitive Decline
  • Multiple Sclerosis
  • Traumatic Brain Injury
  • Parkinson’s Disease
  • Down Syndrome
  • Vanishing White Matter Disorder
  • Prion Disease

ISRIB has been licensed by Calico, a South San Francisco, Calif. company exploring the biology of aging, and the idea of targeting the ISR to treat disease has been picked up by other pharmaceutical companies, Walter says.

One might think that interfering with the ISR, a critical cellular safety mechanism, would be sure to have serious side effects, but so far in all their studies, the researchers have observed none. This is likely due to two factors, Walter says. First, it takes just a few doses of ISRIB to reset unhealthy, chronic ISR activation back to a healthier state, after which it can still respond normally to problems in individual cells. Second, ISRIB has virtually no effect when applied to cells actively employing the ISR in its most powerful form — against an aggressive viral infection, for example.

Naturally, both of these factors make the molecule much less likely to have negative side effects — and more attractive as a potential therapeutic. According to Walter: “It almost seems too good to be true, but with ISRIB we seem to have hit a sweet spot for manipulating the ISR with an ideal therapeutic window.

Researchers Claim Oral Drug Blocks COVID-19 Transmission Within 24 Hours

This drug (MK-4482) is notable because it has the distinction of “MK,” as in, it was developed in part by the Merck pharmaceutical company. I’m one to often disparage the pharmaceutical companies but Merck has done notable things in its past drug research. The Merck development of MK-677 — an experimental growth hormone secretagogue that has been shown to increase hunger, increase bone density in the frail, and improve healing in humans — has shown significant potential in medicine. A former Head of the US Biomedical Advanced Research and Development Authority has said that drugs similar to MK-4482 cause birth defects, but the study authors claim that toxicity studies on MK-4482 have already been done, with the results already approved by regulators as a sign to continue with research into the drug in people.


Treatment of SARS-CoV-2 infection with a new antiviral drug, MK-4482/EIDD-2801 or Molnupiravir, completely suppresses virus transmission within 24 hours, researchers in the Institute for Biomedical Sciences at Georgia State University have discovered.

The group led by Dr. Richard Plemper, Distinguished University Professor at Georgia State, originally discovered that the drug is potent against influenza viruses.

“This is the first demonstration of an orally available drug to rapidly block SARS-CoV-2 transmission,” said Plemper. “MK-4482/EIDD-2801 could be game-changing.”

Interrupting widespread community transmission of SARS-CoV-2 until mass vaccination is available is paramount to managing COVID-19 and mitigating the catastrophic consequences of the pandemic.

Because the drug can be taken by mouth, treatment can be started early for a potentially three-fold benefit: inhibit patients’ progress to severe disease, shorten the infectious phase to ease the emotional and socioeconomic toll of prolonged patient isolation and rapidly silence local outbreaks.

“We noted early on that MK-4482/EIDD-2801 has broad-spectrum activity against respiratory RNA viruses and that treating infected animals by mouth with the drug lowers the amount of shed viral particles by several orders of magnitude, dramatically reducing transmission,” said Plemper. “These properties made MK-4482/EIDD/2801 a powerful candidate for pharmacologic control of COVID-19.”

In the study published in Nature Microbiology, Plemper’s team repurposed MK-4482/EIDD-2801 against SARS-CoV-2 and used a ferret model to test the effect of the drug on halting virus spread.

“We believe ferrets are a relevant transmission model because they readily spread SARS-CoV-2, but mostly do not develop severe disease, which closely resembles SARS-CoV-2 spread in young adults,” said Dr. Robert Cox, a postdoctoral fellow in the Plemper group and a co-lead author of the study.

The researchers infected ferrets with SARS-CoV-2 and initiated treatment with MK-4482/EIDD-2801 when the animals started to shed virus from the nose.

“When we co-housed those infected and then treated source animals with untreated contact ferrets in the same cage, none of the contacts became infected,” said Josef Wolf, a doctoral student in the Plemper lab and co-lead author of the study. By comparison, all contacts of source ferrets that had received placebo became infected.

If these ferret-based data translate to humans, COVID-19 patients treated with the drug could become non-infectious within 24 hours after the beginning of treatment.

MK-4482/EIDD-2801 is in advanced phase II/III clinical trials against SARS-CoV-2 infection.

Flavanols Found in Cocoa, Fruits and Vegetables Shown to Boost Cognition and Brain Oxygenation

This study shows the benefits of good nutrition.

The brains of healthy adults recovered faster from a mild vascular challenge and performed better on complex tests if the participants consumed cocoa flavanols beforehand, researchers report in the journal Scientific Reports. In the study, 14 of 18 participants saw these improvements after ingesting the flavanols.

Previous studies have shown that eating foods rich in flavanols can benefit vascular function, but this is the first to find a positive effect on brain vascular function and cognitive performance in young healthy adults, said Catarina Rendeiro, a researcher and lecturer in nutritional sciences at the University of Birmingham who led the research with University of Illinois at Urbana-Champaign psychology professors Monica Fabiani and Gabriele Gratton.

“Flavanols are small molecules found in many fruits and vegetables, and cocoa, too,” Rendeiro said. “They give fruits and vegetables their bright colors, and they are known to benefit vascular function. We wanted to know whether flavanols also benefit the brain vasculature, and whether that could have a positive impact on cognitive function.”

The team recruited adult nonsmokers with no known brain, heart, vascular or respiratory disease, reasoning that any effects seen in this population would provide robust evidence that dietary flavanols can improve brain function in healthy people.

The team tested the 18 participants before their intake of cocoa flavanols and in two separate trials, one in which the subjects received flavanol-rich cocoa and another during which they consumed processed cocoa with very low levels of flavanols. Neither the participants nor researchers knew which type of cocoa was consumed in each of the trials. This double-blind study design prevents researchers’ or participants’ expectations from affecting the results.

About two hours after consuming the cocoa, participants breathed air with 5% carbon dioxide — about 100 times the normal concentration in air. This is a standard method for challenging brain vasculature to determine how well it responds, Gratton said.

The body typically reacts by increasing blood flow to the brain, he said.

“This brings in more oxygen and also allows the brain to eliminate more carbon dioxide,” he said.

With functional near-infrared spectroscopy, a technique that uses light to capture changes in blood flow to the brain, the team measured oxygenation in the frontal cortex, a brain region that plays a key role in planning, regulating behavior and decision-making.

“This allows you to measure how well the brain defends itself from the excess carbon dioxide,” Fabiani said.

Researchers also challenged participants with complex tasks that required them to manage sometimes contradictory or competing demands.

Most of the participants had a stronger and faster brain oxygenation response after exposure to cocoa flavanols than they did at baseline or after consuming cocoa lacking flavanols, the researchers found.

“The levels of maximal oxygenation were more than three times higher in the high-flavanol cocoa versus the low-flavanol cocoa, and the oxygenation response was about one minute faster,” Rendeiro said.

After ingesting the cocoa flavanols, participants also performed better on the most challenging cognitive tests, correctly solving problems 11% faster than they did at baseline or when they consumed cocoa with reduced flavanols. There was no measurable difference in performance on the easier tasks, however.

“This suggests that flavanols might only be beneficial during cognitive tasks that are more challenging,” Rendeiro said.

Participants varied in their responses to cocoa flavanols, the researchers found.

“Although most people benefited from flavanol intake, there was a small group that did not,” Rendeiro said. Four of the 18 study subjects had no meaningful differences in brain oxygenation response after consuming flavanols, nor did their performance on the tests improve.

“Because these four participants already had the highest oxygenation responses at baseline, this may indicate that those who are already quite fit have little room for improvement,” Rendeiro said. “Overall, the findings suggest that the improvements in vascular activity after exposure to flavanols are connected to the improvement in cognitive function.”

App That Listens to Coughing Developed to Tell if People Have COVID-19

If this app works effectively, it will be very important in allowing people to group up more freely again.

As millions of people worldwide battle the symptoms of COVID-19, a group of “silent patients” may not even know they’re sick and spreading the virus. Asymptomatic people, by definition, have no physical symptoms of the illnesses they carry.

Researchers at the Massachusetts Institute of Technology (MIT) however, say they may be showing symptoms after all — in the sound of their cough. Their study has created an artificial intelligence program that can identify if someone has coronavirus by the way their coughing sounds. Researchers programmed their AI model with thousands of different recorded coughs from both healthy and sick volunteers. When they fed in recordings of new patients, the system accurately detected 98.5 percent of coughs coming from people with a confirmed case of COVID-19. AI also successfully picked out 100 percent of asymptomatic cases from volunteers who reported not having any symptoms but tested positive for the virus.

The team is now working on turning their model into a user-friendly app. If approved by the Food and Drug Administration, the app would give people a non-invasive and quick way to screen themselves during the pandemic daily.

“The effective implementation of this group diagnostic tool could diminish the spread of the pandemic if everyone uses it before going to a classroom, a factory, or a restaurant,” says co-author Brian Subirana in a university release.

The MIT team notes researchers have been working on audio-based medical screenings since before the coronavirus emergency began. Their group in particular originally created this AI model to screen for Alzheimer’s disease.

Although the degenerative neurological condition is mostly associated with memory loss, it also affects the muscles and vocal cords. With this knowledge, researchers trained a general machine-learning algorithm called ResNet50 to detect changes in vocal cord strength. Subirana taught the neural network using an audiobook collection with over 1,000 hours of speech files. The AI model could eventually tell the difference between similar worlds like “them” and “the” or “then.”

The system can also read the emotions of the speaker based on the tone of their voice. The team says this is a key in Alzheimer’s detection because patients tend to display more frustration when they try to get words out. The program learned to assess these moods and put them into categories including neutral, calm, happy, and sad.

Finally, the team turned to coughing. Using recordings of patients coughing, the AI model could analyze the lung and respiratory performance of the cougher. An algorithm to detect muscular degradation was also added to help AI distinguish strong coughs from weaker ones.

With all of this data, study authors discovered that the technology could effectively screen for Alzheimer’s based on a patient’s vocal cord strength, sentiment, lung performance, and muscular degradation.

Once the pandemic began, the team at MIT changed gears and started looking at their model to see if it could detect COVID. Researchers say there is growing evidence coronavirus patients also suffer from neurological symptoms and temporary muscular impairment.

“The sounds of talking and coughing are both influenced by the vocal cords and surrounding organs. This means that when you talk, part of your talking is like coughing, and vice versa. It also means that things we easily derive from fluent speech, AI can pick up simply from coughs, including things like the person’s gender, mother tongue, or even emotional state. There’s in fact sentiment embedded in how you cough,” Subirana explains. “So we thought, why don’t we try these Alzheimer’s biomarkers [to see if they’re relevant] for COVID.”

The team created a website to collect audio samples from volunteers, including many with coronavirus. From nearly 200,000 forced-cough audio samples, the group was able to find 2,500 recordings that came from confirmed COVID-19 patients. Many of these patients were also asymptomatic. After adding more random samples to act as a control, the team chose 4,000 coughing samples to train their AI model to screen for the virus.

Along with amazing accuracy in detecting coronavirus patients, researchers say the tests reveal “a striking similarity between Alzheimer’s and COVID discrimination.” They add that the same four biomarkers for detecting Alzheimer’s effectively screen out the virus as well.

“We think this shows that the way you produce sound, changes when you have Covid, even if you’re asymptomatic,” the research scientist in MIT’s Auto-ID Laboratory adds.

Subirana and his team stress that their AI system is not meant to diagnose what illness you may have; whether it be the flu, asthma, or COVID-19. The tool, instead, works by screening out who is healthy from who is asymptomatic but carrying an illness.

The MIT team is now partnering with several hospitals to collect more coughing samples to refine the system’s accuracy. Their hope is to introduce a free pre-screening app to the public which can cut down on clinical testing delays.

“Pandemics could be a thing of the past if pre-screening tools are always on in the background and constantly improved,” the study authors contend.

The study appears in the IEEE Journal of Engineering in Medicine and Biology.