Culture

If you are an introvert, force yourself to be an extravert. You'll be happier.

That's the suggestion of the first-ever study asking people to act like extraverts for a prolonged period. For one week, the 123 participants were asked to - in some cases - push the boundaries of their willingness to engage, by acting as extraverts. For another week, the same group was asked to act like introverts.

The benefits of extraversion have been reported before, including those of "forced extraversion," but usually only for brief intervals. In one study, train-riders were asked to talk to strangers; a control group was directed to remain silent. The talkers reported a more positive experience.

UC Riverside researcher Sonja Lyubomirsky wanted to extend the faux extraversion to see if it would result in better well-being.

"The findings suggest that changing one's social behavior is a realizable goal for many people, and that behaving in an extraverted way improves well-being," said Lyubomirsky, a UCR psychologist and co-author of the study, published in the Journal of Experimental Psychology: General. Psychologists favor "extravert" to the more commonly used "extrovert," due to its historic use in academia, and the Latin origins of "extra," meaning "outside."

An initial challenge for this study was the presumption that extraversion--as a trait rewarded in U.S. culture--is best. Many of the adjectives associated with extraversion are more flattering than those tied to introversion. Most people would rather be associated with words like "dynamic" than with words like "withdrawn."

So Lyubomirsky's team went for words agreed upon as most neutral. The adjectives for extraversion were "talkative," "assertive," and "spontaneous"; for introversion, "deliberate," "quiet," and "reserved."

Researchers next told participants -- both the Act Introvert group and the Act Extravert group -- that previous research found each set of behaviors are beneficial for college students.

Finally, the participants were told to go forth, and to be as talkative, assertive, and spontaneous as they could stand. Later, the same group was told to be deliberate, quiet, and reserved, or vice versa. Three times a week, participants were reminded of the behavioral change via emails.

According to all measures of well-being, participants reported greater well-being after the extraversion week, and decreases in well-being after the introversion week. Interestingly, faux extraverts reported no discomfort or ill effects.

"It showed that a manipulation to increase extraverted behavior substantially improved well-being," Lyubomirsky said. "Manipulating personality-relevant behavior over as long as a week may be easier than previously thought, and the effects can be surprisingly powerful."

The researchers suggest that future experiments addressing this question may switch up some variables. The participants were college students, generally more malleable in terms of changing habits. Also, Lyubomirsky said, effects of "faking" extroversion could surface after a longer study period.

Parents will be pleased to know that more is not always better when it comes to play equipment for their children.

A study by researchers at The University of Queensland found children who have access to fixed play equipment like swings and slides and fewer electronic devices were more likely to meet national physical activity guidelines.

UQ School of Public Health researcher Dr Katrina Moss said it was good news for parents, who can implement the findings at home.

"In this study, we found the type of play equipment that children have at home is directly related to the amount of physical activity they do," Dr Moss said.

"This is good news because play equipment at home is modifiable, and in lots of cases, it can be easily changed.

"It's also not about having the most equipment; it's about having the right equipment.

"Parents don't have to go out and buy every toy, they just need to have the right combination of play equipment to support their child's physical activity."

The study identified four combinations of play equipment, categorised as Plenties, Sliders, Batters and Techies.

Plenties averaged eight different types of active play equipment compared to Sliders with six, yet there was no difference in their physical activity.

"This shows kids can be just as active with less equipment," Dr Moss said.

Batters averaged five different types of play equipment and Techies seven, but these groups were the least physically active.

The difference was that their play equipment was mostly portable items such as bats and skipping ropes, instead of fixed. The Techies also had double the electronic devices in the bedroom.

"The findings should be reassuring for parents - they don't have to buy everything, but they do need the right combination of equipment to support the development of gross motor skills and physical activity," she said.

Fewer than 20 per cent of children aged 5-17 meet the physical activity guidelines of one hour of moderate to vigorous physical activity per day, putting them at risk of diseases like diabetes and obesity.

"If we can support children to be more active now, it protects their future health and reduces the risk of lifestyle diseases," she said.

Urban density was another contributing factor, with diminishing backyards and playgrounds eroding children's playtime.

"It is important to note that having this bigger, fixed equipment does require a bigger backyard.

"Increasingly, children's play is going inside as the size of our backyards is decreasing.

"If parents can't provide fixed equipment in their own backyard due to limited spaces, then we need to be designing public spaces that can."

Scientists at Washington University School of Medicine in St. Louis appear to have solved a decades-long mystery regarding the precise biochemical pathway leading to a fatal genetic disorder in children that results in seizures, developmental regression and death, usually around age 3. Studying a mouse model with the same human illness -- called Krabbe disease -- the researchers also identified a possible therapeutic strategy.

The research is published Sept. 16 in the Proceedings of the National Academy of Sciences.

Patients with infantile globoid cell leukodystrophy, also known as Krabbe disease, gradually lose the protective covering that insulates axons, the wiring of the nervous system. The rare condition -- affecting about 1 in 100,000 births -- is typically diagnosed before age 1 and progresses rapidly.

Scientists long have suspected that nerve insulation is destroyed in this disorder because of a buildup of a toxic compound called psychosine. Patients with the inherited disorder are missing an important protein involved in breaking down psychosine. But the source of psychosine in Krabbe disease has been elusive, making the problem impossible to correct.

"Krabbe disease in infancy is invariably fatal," said senior author Mark S. Sands, PhD, a professor of medicine. "It's a heartbreaking neurodegenerative disease first described more than a century ago, but we still have no effective treatments. For almost 50 years, we have assumed the psychosine hypothesis was correct -- that a toxic buildup of psychosine is the cause of all the problems. But we've never been able to prove it."

Surprisingly, Sands and his team, led by graduate student Yedda Li, proved the psychosine hypothesis correct by, essentially, giving the mice another lethal genetic disease.

The scientists showed that mice harboring genetic mutations resulting in Krabbe disease and Farber disease, a lethal condition that results from the loss of a different protein, have no signs of Krabbe disease. The missing protein in Farber disease is called acid ceramidase, and when it is gone, psychosine does not build up, effectively curing Krabbe disease in mice that otherwise would have it.

"We did not expect these mice to survive through embryonic development with the genetic alterations that cause both Farber disease and Krabbe disease," Sands said. "We felt it was likely that the combination of these genetic problems would be lethal to the mouse embryo, or at least cause some combination of the problems characteristic of both diseases. Not only were the mice alive, we found that they did not have Krabbe disease -- despite having the causal genetics -- and we tested them for it in every way imaginable. It was shocking."

Without the toxic buildup of psychosine, Krabbe disease did not develop in these mice, proving the 50-year-old hypothesis.

After identifying acid ceramidase as the trigger of the toxic buildup of psychosine, Sands and his colleagues gave mice with Krabbe disease a drug known to be an acid ceramidase inhibitor. The drug, carmofur, is a common chemotherapy used to treat cancer. The drug modestly extended the lives of mice with a model of Krabbe disease.

"Carmofur is quite toxic by itself, so it would never be used as a treatment for this disease, but we did show a modest therapeutic benefit," Sands said. "The research demonstrates a proof-of-concept that we can inhibit acid ceramidase with a drug and it will relieve some of the symptoms of Krabbe disease. We will need to strike a balance, though, because inhibiting it too much will cause Farber disease."

Sands said he hopes researchers specializing in drug development will begin working toward a safe and effective acid ceramidase inhibitor for this disorder.

LA JOLLA, CA – For decades, chemists have tested theories for how life began on Earth. One hypothesis has caught the scientific imagination for years: RNA World. This theory proposes that prebiotic molecules joined up early on to form RNA, the molecules that carry instructions from DNA in organisms today. RNA World posits that once RNA formed on Earth, it began replicating itself and later gave rise to molecules like DNA.

RNA World is a fascinating theory, says Ramanarayanan Krishnamurthy, PhD, an associate professor of chemistry at Scripps Research, but it may not hold true. The problem is that the ingredients, such as enzymes, to make RNA World work just didn’t exist on early Earth.

"RNA World has given rise to the idea that if you somehow synthesize RNA, which can replicate and catalyze reactions, everything else automatically follows,” says Krishnamurthy, who is a member of the Simons Collaboration on the Origins of Life and holds a joint appointment with the Center for Chemical Evolution, co-funded by the NASA Astrobiology program and the National Science Foundation. “That's not the case, because RNA World relies on RNA replicating itself, which is very difficult."

Part of the challenge is that RNA molecules form stable structures called duplexes. These structures have what’s known as a strong binding affinity. This means the RNA molecules have difficulty separating from each other and acting as templates for replicating further in the absence of enzymes.

Krishnamurthy now has experimental evidence to demonstrate that life’s process on Earth could have actually started with molecules that looked like a mixture of RNA and DNA. In the latest issue of Nature Chemistry, he and the study’s first author, Subhendu Bhowmik, PhD, also of Scripps Research, report that these mixed molecules form unstable duplexes and have lesser affinity for themselves. Surprisingly, these “chimeras” have stronger affinity for RNA and DNA, which allows them to act as templates for making RNA or DNA.

In fact, the researchers were able to form these chimeras under lab conditions and show that they have the potential to replicate RNA and DNA, and the thus formed RNA and DNA are able to reproduce the chimeras. This behavior could lead to a cross-catalytic amplification of RNA and DNA—a key step toward the evolution of complex organisms.

“A provocative implication of this study is that RNA and DNA could have appeared simultaneously instead of the widely accepted RNA World theory, where RNA appears first and then gives rise to DNA,” says Krishnamurthy. “This means mixtures of RNA and DNA could have co-existed.”

In organisms today, DNA and RNA perform very different roles in our cells. The new project experimentally supports the idea that life could have arisen from a much messier system, where “pure” RNA and DNA did not exist yet. As Krishnamurthy says: “It's OK not to have clean chemistry.”

In work spearheaded by Bhowmik, a research associate in Krishnamurthy’s Scripps Research laboratory, the team also created “heterogeneous” mixed molecules made of RNA and a synthetic molecule called TNA, which has been proposed to be a plausible ancestor of RNA (“pre-RNA”). TNA is very similar to RNA, but scientists have replaced one type of sugar molecule (ribose) with another (threose). This allows TNA to cross-pair with RNA and DNA. Krishnamurthy and Bhowmik say a molecule like TNA could have performed this cross-pairing at the very beginning of evolution, leading to the side-by-side formation of TNA and RNA.

By mixing RNA-DNA, the researchers showed that it could have been possible to form a mixed molecule that could work as templates for RNA and DNA. This mixed molecule is also a high-energy system in the sense that it forms unstable duplexes. The new research shows that these unstable duplexes (higher energy systems) are capable of giving rise to RNA and DNA, which form more stable duplexes (lower energy systems). Thus, there is a thermodynamically favorable movement from chimeric systems (less-stable, higher-energy) to homogeneous systems (more-stable, lower-energy).

“Hybrid system like these could have helped in the evolution of homogeneous systems,” says Bhowmik.

We’ll never know exactly how early life formed, but the experiments at least show chemical reactions that could have eventually led to the pure RNA and DNA sequences that support life today. The work also supports the findings of a 2018 Scripps Research study, which showed how an engineered bacterium can function with a mixed RNA-DNA genome.

Krishnamurthy says research going forward should focus on which ingredients needed for RNA-DNA chimeras would have been available on prebiotic Earth. The scientists used several molecules that were likely not available back then, though similar ingredients should have existed. The new study gives researchers a “proof of principle” that these reactions can work, and Krishnamurthy plans to follow up with further experiments to explore the pathways for how life’s molecules could have come together. “This study is the first step in that direction,” he says.

Krishnamurthy is also interested in how RNA-DNA chimeras might be used in medicinal chemistry studies. He says these mixed systems may help researchers overcome some challenges in genetic sequencing.

Human red blood cells (RBCs) are extremely resilient and have the capacity to undergo cellular deformation as they navigate across various micro-vessels and capillaries. Over their 120-day normal lifespan, RBCs must undergo significant cyclic deformation through large elastic stretching and relaxation. Pathological deformations in RBCs are associated with various diseases such as malaria, sickle cell anemia, diabetes, myocardial infarction and various hereditary disorders.

Mechanical fatigue that arises from cyclic straining in RBCs also is a key factor in the degradation of engineered materials and structures. This fatigue can damage and fracture natural biomaterials like bone as well as synthetic biomaterials used in implant devices such as dental implants and synthetic heart valves. However, the mechanisms responsible for the degradation of circulating biological cells due to mechanical fatigue are not well-understood, especially in human RBCs. Measuring the complex and clinically relevant mechanical fatigue behavior of biological cells in health and disease has challenged scientists for decades.

Researchers from Florida Atlantic University's College of Engineering and Computer Science, in collaboration with Massachusetts Institute of Technology, and the Nanyang Technological University in Singapore, have developed a novel way to measure how mechanical fatigue affects biological cells. Furthermore, they have established the important role of this effect in influencing physical properties of biological cells such as RBCs.

Results of the study, published in the Proceedings of the National Academy of Sciences, also provide insights into the accumulated membrane damage during blood circulation, paving the way for further investigations of the eventual failure of RBCs and the mechanism that causes their destruction in various blood disorder pathologies such as sickle cell anemia.

This new technique assesses the mechanical integrity and fatigue behavior of RBCs using a general microfluidics method that incorporates amplitude-modulated electro-deformation. It induces static and cyclic mechanical deformation of RBCs and measures systematic changes in morphological and biomechanical characteristics of healthy human RBCs and their membrane mechanical properties. This method also is capable of subjecting cells to static loads for prolonged periods of time or to large numbers of controlled mechanical fatigue cycles.

"The fatigue testing platform that we have developed features multiple and distinctive advantages for the quantitative characterization of mechanical fatigue behavior of single biological cells," said Sarah Du, Ph.D., a senior author and an associate professor in FAU's Department of Ocean and Mechanical Engineering. "The strengths of our method lie in its simplicity and flexibility to impose controlled mechanical loads at selected frequencies and waveforms, and its capability to probe a number of single cells over thousands of fatigue cycles."

The researchers wanted to better understand the effect of fluctuations in stresses or deformation of a healthy biological cell on its mechanical and physical characteristics, structural integrity and performance. They also wanted to identify the function of factors such as the maximum intensity, amplitude and rate of strain, frequency of cyclic deformation, and number of cycles as well as whether or not this effect is specific to cyclic variations in deformation.

Results from the study further indicate that loss of deformability of RBCs during cyclic deformation is much faster than that under static deformation at same maximum load over same accumulated loading time. Such fatigue-induced deformability loss is more pronounced at higher amplitudes of cyclic deformation.

"This cutting-edge technique developed by Professor Du and her group will be a game changer, which will help scientists to better understand the biological functions of red blood cells and other cells that impact many aspects of human health," said Stella Batalama, Ph.D., dean of FAU's College of Engineering and Computer Science. "In addition, this unique method has important applications for mechanical fatigue studies in conjunction with other microenvironments related to health and materials engineering."

Obesity is linked to a nearly 6-fold increased risk of developing type 2 diabetes (T2D), with high genetic risk and unfavorable lifestyle also increasing risk but to a much lesser extent. These are the conclusions of new research presented at this year's Annual Meeting of the European Association for the Study of Diabetes in Barcelona, Spain (16-20 Sept), by Hermina Jakupovi?, University of Copenhagen, Novo Nordisk Foundation Center for Basic Metabolic Research, Copenhagen, Denmark, and colleagues.

Genetic predisposition, obesity, and unfavorable lifestyle have an important role in the development of type 2 diabetes, an increasingly common disorder that contributes majorly to the global burden of disease. According to the International Diabetes Federation, approximately 425 million adults (20-79 years) were living with diabetes in 2017; by 2045 this is expected rise above 600 million.

The current strategy to prevent T2D is underlined by the maintenance of normal body weight and the promotion of a healthy lifestyle. Lifestyle interventions designed for weight loss have been shown to delay the onset of T2D among high-risk subjects. However, the effects of lifestyle factors and obesity on T2D risk may vary between individuals depending on genetic variation. Thus, it is important to understand the interplay between genetic predisposition, obesity, and unfavorable lifestyle in the development of T2D. In this new research, the authors aimed to study whether the genetic risk for T2D is accentuated by obesity and unfavorable lifestyle.

They applied statistical modelling to a case-cohort sample of 9,556 men and women from the Danish prospective Diet, Cancer and Health cohort (49.6% women, 50.4% men, mean age 56.1 (range 50-65)). Almost half (49.5%) of the participants developed T2D during an average 14.7 years of follow-up. A favourable lifestyle was defined as having at least three of the following healthy lifestyle factors: no current smoking, moderate alcohol consumption, regular physical activity, and a healthy diet. An unfavorable lifestyle was defined as zero or only one healthy lifestyle factor while the remaining participants were defined as having an intermediate lifestyle. Genetic risk was assessed by a genetic risk score (GRS) comprising 193 genetic variants known to be strongly associated with T2D. The GRS was stratified into low (lowest 20%), intermediate (middle 60%) and high risk (top 20%) groups.

The researchers found that having an unfavorable lifestyle and obesity are associated with a greater risk of developing T2D regardless of their genetic risk. Obesity (defined as a body mass index of 30 kg/m2 or higher) increased T2D-risk by 5.8-fold compared to individuals with normal weight. The independent effects of high (vs. low) genetic risk and unfavourable (vs. favourable) lifestyle were relatively modest by comparison, with the highest genetic risk group having a 2-fold increased risk of developing T2D compared with the lowest group; and unfavourable lifestyle was associated with a 20% increased risk of developing T2D compared with favourable lifestyle.

The authors conclude: "The effect of obesity on type 2 diabetes risk is dominant over other risk factors, highlighting the importance of weight management in type 2 diabetes prevention."

While overall, the numbers (prevalence) of people with type 2 diabetes continue to grow at an alarming rate, new research presented at this year's annual meeting of the European Association for the Study of Diabetes (EASD) in Barcelona, Spain (16-20 September) shows that recent studies suggest the rate at which new cases develop (incidence) may be falling. The study is by Professor Dianna Magliano and Professor Jonathan Shaw, Baker Heart and Diabetes Institute, Melbourne, Australia, and colleagues.

According to the International Diabetes Federation, approximately 425 million adults (aged 20-79 years) were living with diabetes in 2017; by 2045 this is expected rise above 600 million. However, because care is improving and people are surviving longer, the number of people with diabetes does not accurately show population-level risk of new cases developing. Diabetes incidence (the number of new cases per year) is a better way to understand the population risk of diabetes.

The authors searched the MEDLINE, EMBASE and CINAHL databases for publications between January 1980 and August 2018. Studies were included if they were of population-based cohorts, occupational groups, and health examination or primary care cohorts, with at least 2 years of follow-up, reported incidence of diabetes or type 2 diabetes in adults, and published in English.

A mid-point was estimated in each study's follow-up period to categorise the study into one of five time periods (1970-79, 1980-89, 1990-99, 2000-09, and 2010 onwards). Diabetes incidence was modelled by age group and adjusted for mid-point of baseline year, ethnicity, and method used in the diagnosis of diabetes at follow-up using statistical modelling.

A total of 275 articles met the inclusion criteria, mostly from high-income countries. The overall crude annualised diabetes incidence rose from 0.53% (5.3 new cases per 1000 population per year) in the 1970s to 1.0% (10 new cases per 1000 persons per year) in the 2010s. Compared to persons aged 35 years and under, the incidence rate was around double in those aged 35-44 years and 45-54 years; trebled in those aged 55-65 years, and increased 4-fold in people aged 65 years and older.

Compared to studies with a mid-point of baseline year in 1990s, the incidence rate was 20% was higher in studies with a mid-point in 2000-2009; however, when looking at studies from 2010 onwards, diabetes incidence was no longer increasing -- there was a 5% decrease in incidence that did not reach statistical significance. The authors say: "It therefore appears that following the rise in incidence from 1990s there was a flattening or even a possible decline in the rate of new cases of type 2 diabetes in the last few years."

Compared to studies with people of predominantly European ancestry, the incidence was higher in studies of Africans, Asians, Hispanics/Mexicans, and in Indigenous populations. In Africans, diabetes incidence was 60% higher; in Asian populations, incidence was 30% higher, and in Hispanic populations, it was 80% higher. For Middle Eastern and Pacific Islander populations, there was no statistically significant increased incidence, but the authors suggest this could be due to low overall numbers of studies measuring incidence in these populations included in the review.

The authors say: "The rate of new cases (incidence) of diabetes, mainly type 2 diabetes, continued to rise among people aged 35 years and above over the last four decades, with the highest rate observed in studies beginning around 2000-04. Studies that began in 2010 and later suggested a possible downturn in incidence. Further investigations are required to establish the trends in different region/ethnic subgroups."

They add: "If these trends continue, it may mean that incidence is starting to stabilise and this could indicate that prevention and public health activities may have had an effect. Lower levels of screening for diabetes may have played a role, and it is also possible that depletion of susceptible people may be involved. In reality, it is probably a combination of all these factors."

Regarding the pool of susceptible people, the authors explain: "It has been suggested that we might have depleted the pool of susceptible people who could have developed diabetes and that is why we are not diagnosing as many new cases now. This assumes that there is a group of people who are at risk of diabetes and that some people, despite what they do, won't ever get diabetes. This is a very difficult concept to test and we have not worked out how to explore this."

And on the overall findings in this work, the authors conclude: "We need to be clear that although incidence may be decreasing, prevalence is still increasing and we cannot be complacent. This work tells us have we may be cautiously optimistic about the global diabetes epidemic and we should continue implementing strategies for diabetes prevention to ensure incidence does not increase again."

A new study presented at this year's Annual Meeting of the European Association for the Study of Diabetes (EASD) in Barcelona, Spain (16-20 Sept) shows that men and women experience different comorbidities (other diseases at the same time) as having diabetes or prediabetes, as well as an unexpectedly high rate of prediabetes among children aged 6-10 years.

The study, by Dr Alina Ofenheimer, Sigmund Freud University, Medical School, Vienna, Austria and colleagues, analysed the sex and gender differences in the prevalence of co-morbidities in subjects with prediabetes and diabetes, as well as determining the prevalence of prediabetes and diabetes in the study population.

A number of additional disease processes (comorbidities) are known to occur alongside prediabetes and/or diabetes including congestive heart failure, high blood pressure, cardiac arrhythmia (abnormal heart rate), osteoporosis (weaker bones), kidney dysfunction, and even severe anxiety and depression. Gender may affect the incidence of these comorbidities through differences in biology as well as differences in lifestyle and behaviour.

The authors conducted an observational population-based cohort study of 11,014 subjects aged 6 to 80 years who underwent a detailed examination. This included taking blood samples, measuring ankle-brachial index, performing an electrocardiogram (ECG), assessing body composition using a dual energy X-ray absorptiometry (DEXA) scan, and an interviewer-administered questionnaire. Prediabetes and diabetes were defined by one or all of fasting plasma glucose levels (prediabetes: 100-125mg/dl, diabetes: 126mg/dl or higher), glycated haemoglobin (HbA1c) levels (prediabetes: 5.7-

The team found that for the study population as a whole, the prevalence of prediabetes was 20.2% (male 23.6%; female 17.1%) and 5.4% for diabetes (male 7.3%; female 3.7%). Prediabetes occurrence varied from 4.4% in male subjects age 6-tony@tonykirby.com as some figures do not copy to Eurekalert).

The authors say: "Angina, heart attack and calcification (hardening) of the arteries were more prevalent in diabetic men than diabetic women, as well as mild anxiety and reduced cognitive processing speed. Similar to the comorbidity profile of prediabetic females, women with diabetes had a higher prevalence of irregular heartbeat (arrhythmia), and elevated signs of systemic inflammation compared with diabetic men. Prediabetic women also showed a higher prevalence of osteoporosis and depression compared with prediabetic men."

They add: "The unexpected 4.6% prevalence of prediabetes in children aged 6-10 underscores the need for population-based studies across all ages and the importance of starting diabetes prevention efforts at a young age, through a healthy lifestyle and diet for all, including children."

Antibiotic resistance is one of the biggest public health challenges in the world today since many common bacterial infections are developing resistance to the drugs once used to treat them, and new antibiotics aren't being developed fast enough to combat the problem.

Once primarily confined to health care settings, these resistant strains of bacteria are now commonly found in other places, especially marine environments. To date, few studies have looked at long-term trends in antibiotic resistance in pathogens isolated from wildlife populations.

Researchers from Florida Atlantic University's Harbor Branch Oceanographic Institute in collaboration with Georgia Aquarium , the Medical University of South Carolina and Colorado State University, conducted a unique, long-term study (2003 to 2015) of antibiotic resistance among pathogens isolated from bottlenose dolphins (Tursiops truncatus) in Florida's Indian River Lagoon. This lagoon has a large coastal human population and significant environmental impacts.

"In 2009, we reported a high prevalence of antibiotic resistance in wild dolphins, which was unexpected," said Adam M. Schaefer, MPH, lead author and an epidemiologist at FAU's Harbor Branch. "Since then, we have been tracking changes over time and have found a significant increase in antibiotic resistance in isolates from these animals. This trend mirrors reports from human health care settings. Based on our findings, it is likely that these isolates from dolphins originated from a source where antibiotics are regularly used, potentially entering the marine environment through human activities or discharges from terrestrial sources."

Using 13-years of data and the Multiple Antibiotic Resistance (MAR) index, researchers obtained a total of 733 pathogen isolates from 171 individual bottlenose dolphins. Several of the organisms isolated from these animals are important human pathogens.

Results of the study, published in the journal Aquatic Mammals, shows that the overall prevalence of resistance to at least one antibiotic for the 733 isolates was 88.2 percent. The prevalence of resistance was highest to erythromycin (91.6 percent), followed by ampicillin (77.3 percent) and cephalothin (61.7 percent). This is one of the few studies to use the MAR index for bacterial isolates from a marine mammal species.

Resistance to ciprofloxacin among E. coli isolates more than doubled between sampling periods, reflecting recent trends in human clinical infections. Pseudomonas aeruginosa, responsible for respiratory system infections, urinary tract infections, among others, were the highest recorded for any organism and increased during the study period.

The MAR index increased significantly between the periods 2003-2007 and 2010-2015 for P. aeruginosa and Vibrio alginolyticus, a common pathogenic marine Vibrio species found to cause serious seafood-poisoning. For all bacterial isolates, resistance to cefotaxime, ceftazidime and gentamicin increased significantly between sampling periods.

"The Health and Environmental Risk Assessment or HERA Project has helped discover that the emerging bacterial resistance to antibiotics in bottlenose dolphins is prevalent. Bottlenose dolphins are a valuable sentinel species in helping us understand how this affects human and environmental health. Through HERA we've been able to provide a large database of information in order to continue learning from these impressive animals," said Gregory D. Bossart, V.M.D., Ph.D., co-author, senior vice president and chief veterinary officer at Georgia Aquarium. "Antibiotic resistance is one of the most significant risks to public health. As resistance increases, the probability of successfully treating infections caused by common pathogens decreases."

The sampling for the study was conducted and funded in part by the Florida Specialty License Plate fund and Georgia Aquarium with Bossart serving as the HERA lead and permit holder. Swab samples for microbiology were taken from the blowhole, gastric fluid and feces and cultured on standard media under aerobic conditions. The most frequently isolated pathogens were Aeromonas hydrophila, E. coli, Edwardsiella tarda, V. alginolyticus, and S. aureus, pathogens frequently associated with aquatic environments. The dolphins were captured and released back into the Indian River Lagoon as a part of the HERA Project. Sampling took place during June and July each year.

"The nationwide human health impact of the pathogen Acinetobacter baumannii is of substantial concern as it is a significant nosocomial pathogen with increasing infection rates over the past 10 years," said Peter McCarthy, Ph.D., co-author, a research professor and an associate director for education at FAU's Harbor Branch. "In addition to nosocomial infections, resistant strains associated with fish and fish farming have been reported globally. The high MAR index for this bacteria isolated from dolphins in the Indian River Lagoon represents a significant public health concern."

Each year in the United States, at least 2 million people get an antibiotic-resistant infection, and at least 23,000 people die.

What role does fate play when it comes to the 145,000 people diagnosed with cancer each year in Australia and 125,000 people in Vietnam?

Smoking, sun exposure, poor diet, alcohol consumption and inadequate exercise are proven risk factors for many types of cancer, but new research shows this message is not getting through to many patients.

According to an international study led by the University of Newcastle and Vietnam Cancer Institute, and involving the University of South Australia (UniSA), Australian cancer patients identified 'bad luck' or fate as the third most common perceived cause of their cancer - behind age and family history.

The study compared the perceptions between 585 cancer patients in Australia and Vietnam, analysing differences across 25 possible beliefs about what may have caused their cancer.

Almost half of the Australian cancer patients believed "getting older" was the main cause of their cancer, while most Vietnamese patients cited "poor diet" as the main contributing factor of their cancer.

Overall, smoking was ranked the 5th most likely cause and alcohol the 9th most likely cause. This is despite repeated health messages that many cancers are preventable, and alcohol and smoking are both high risk factors for many cancer types.

UniSA Research Chair of Cancer Epidemiology and Population Health, Professor David Roder, says there are many misconceptions about what causes cancer.

"Unfortunately, people's understanding of many cancer-related risk factors is modest to low. People's beliefs about what may have caused their cancer are complex and likely to be impacted by multiple factors, including cultural beliefs," he says.

The survey revealed some significant differences between Australian and Vietnamese cancer patients, including:

"Getting older" was listed as the main cause of cancer by the Australian patients; the Vietnamese cancer patients ranked it a lot lower, in 10th place;

"Poor diet" was the top perceived cause of cancer among the Vietnamese patients, while Australian patients ranked diet in 11th place;

"Air pollution" was listed as the second main cause of cancer by Vietnamese participants, whereas Australian patients listed it in 10th place;

Australians ranked "alcohol" as the 12th contributing factor to causing cancer and "lack of exercise" as the 17th. Vietnamese listed "alcohol" in 7th place and "lack of exercise" in 12th place.

The two cultures gave similar rankings in just four areas: smoking (5th overall), mental illness (20), prescribed medication (23) and injury or physical trauma (25).

HMRI researcher Dr Alix Hall, one of the study leaders, says a substantial proportion of both Australian (27 per cent) and Vietnamese (47 per cent) patients held fatalistic views about the possible causes of their cancer.

"In the Australian sample, "bad luck" was ranked third and in the Vietnamese sample it was ranked fifth.

"This is concerning because it suggests they believe they have little control over their health. That may affect their willingness to change their behaviour when it comes to diet and lifestyle, and influence their decisions relating to treatment and/or care," Hall says.

The researchers say the study findings underline why public health campaigns need to highlight accurate information about the possible causes of cancer.

Scientists have revealed close-up details of a vital molecule involved in the mix and match of genetic information within cells - opening up the potential to target proteins of this family to combat cancer's diversity and evolution.

A team at The Institute of Cancer Research, London, has discovered the three-dimensional structure and function of this 'mix n match' protein, which helps control a process linked to cancer's progression and drug resistance.

The researchers believe the study opens up a potentially exciting new way to tackle drug-resistant cancers and will be exploring the possibility further within the pioneering £75 million new Centre for Cancer Drug Discovery.

The study is published in the Biochemical Journal today (14th September) and was funded by Cancer Research UK with additional support from the Faringdon Fund, which was created by The Institute of Cancer Research (ICR) to get high-risk projects off the ground following a generous philanthropic donation.

Researchers at the ICR investigated the structure and function of a molecule known as DHX8. This belongs to a class of proteins involved in a fundamental process in life called 'alternative splicing', which affects 95 per cent of human genes.

Splicing takes place once the DNA code has been copied into RNA, with certain pieces cut out and the rest stuck together to create a final code that is translated into protein.

In alternative splicing, the bits of RNA that are cut out, or kept in, can be varied to create multiple proteins from a single gene - increasing the diversity of proteins available to cells.

When alternative splicing goes wrong, it can generate changes to the proteins within cells - which can lead to cancer, or fuel cancer's diversity, evolution and drug resistance.

Splicing is carried out by a complex made up of proteins and RNA, which constantly changes during the cutting and gluing of the RNA. DHX8 is a crucial member of this complex and helps to release the finished RNA into the cell so it can be translated into protein.

In this new study, the researchers examined how the human DHX8 protein binds to RNA and acts to unravel RNA from the rest of the splicing machinery.

They also determined the first high-resolution X-ray crystal structures of DHX8 with and without RNA - allowing them not only to visualise the protein's molecular structure but also to gain key clues about its function.

In particular, the study shed light on the roles of specific structural regions of DHX8, including the so-called 'DEAH motif', 'hook loop' and 'hook turn' regions, which were all shown to be vital for DHX8's function.

The researchers next want to study in greater detail how DHX8 can contribute to cancer - and believe their study will open up ways of blocking members of the protein family as a promising new approach to treatment.

Attempting to combat cancer's diversity is one of the central strategies the ICR is pursuing as part of a pioneering research programme to overcome the ability of cancers to adapt, evolve and become drug resistant.

The ICR - a charity and research institute - is raising the final £14 million of a £75 million investment in the new Centre for Cancer Drug Discovery to house a world-first programme of 'anti-evolution' therapies.

Study leader Dr Rob van Montfort, Team Leader in Hit Discovery and Structural Design at The Institute of Cancer Research, London, said:

"Our study has shed new light on the structure and function of a crucial protein involved in the process of alternative splicing, in which genetic information is mixed and matched to create multiple protein molecules from a single gene.

"Cancer cells take advantage of alternative splicing to diversify, evolve and escape the body's regulatory mechanisms. By determining the detailed molecular structure of one of the key protein molecules involved in alternative splicing, we have opened up potentially exciting new avenues for cancer treatment."

Study co-author Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:

"We are excited to study these 'mix and match' proteins further, because we think our findings open up a new route to help block cancer's evolutionary pathways, and potentially overcome drug resistance.

"This is exactly the sort of approach we plan to take within our pioneering new Centre for Cancer Drug Discovery, which once completed will house the world's first 'Darwinian' drug discovery programmed dedicated to overcoming the twin challenges of cancer evolution and drug resistance."

Dr Emily Farthing, research information manager at Cancer Research UK, said:

"This research provides valuable information about how cancer cells hijack a process in our cells to make them more diverse and enables them to evade treatment. Although more work is needed to build on these findings, this research could open up the possibility of novel cancer therapies in the future."

PITTSBURGH, Sept. 13, 2019 - Among teen boys in urban neighborhoods with low resources, the presence of adult social support is linked to significantly fewer occurrences of sexual violence, youth violence and bullying, and to more positive behaviors, including school engagement and future aspirations, according to a new study from researchers at UPMC Children's Hospital of Pittsburgh and the University of Pittsburgh School of Medicine.

The study, published today in JAMA Network Open, suggests that prevention efforts that focus on adult support can mitigate patterns of co-occurring violent behavior.

"Teen boys in urban neighborhoods are disproportionately exposed to violence and consequently are at higher risk of violence perpetration and victimization," said the study's senior author Alison Culyba, M.D., Ph.D., M.P.H., a physician at UPMC Children's Hospital and assistant professor of pediatrics at Pitt's School of Medicine. "Historically, research often has focused on a single type of violence, but our study shows that there are complex co-occurring behavior patterns and shared protective factors that we need to pay attention to."

The researchers analyzed survey data from a recently completed sexual violence prevention trial that enrolled 866 adolescent boys aged 13- to 19-years-old from lower-resource neighborhoods in the Pittsburgh region. More than three fourths of the participants self-identified as black and six percent self-identified as Hispanic.

The survey included data on 40 "risk" and 18 "protective" behaviors that were classified into one of seven categories -- youth violence, bullying, sexual and/or dating violence, violence exposure and adversities, substance use, school engagement, and career and future aspirations. The participants also rated their personal level of dependable adult social support.

When it came to the data analysis, Culyba and her colleagues took a less conventional approach. "We borrowed methods that have proven effective for large scale genetic analyses," she said.

The analysis revealed interesting patterns. Teen boys with high social support engaged in approximately eight of the 40 risk behaviors -- significantly fewer than those with low social support who engaged in around 10 risky behaviors. Those who had high social support and reported more career and future aspirations were less likely to report all types of violent behavior. In contrast, among those with low social support, school engagement was an important protective factor. Feeling happy at a school that promoted diversity was strongly correlated with fewer instances of both physical and sexual partner violence and dating abuse.

The researchers also found patterns in how different violent behaviors co-occurred. The strongest correlations were between different types of sexual violence perpetration behaviors. For example, teens who endorsed posting sexual pictures of partners were 14 times more likely to also report having coerced someone who they were going out with to have sex. On the other hand, while gang involvement was infrequently associated with violence perpetration, it was more frequently reported among those who had been exposed to sexual violence, bullying or substance use.

"Our analysis revealed how interconnected these behaviors are," said Culyba. "By creating programs that help parents and mentors support teen boys, we may be able to reduce multiple types of violence at once."

The authors caution that the study is limited in that the findings don't demonstrate causative links, and further analysis of the associations is required. "It's a starting point for beginning to understand detailed patterns of violence at a much deeper level -- and for offering new opportunities for prevention," said Culyba.

Culyba notes that the findings align with the recommendations of the Centers for Disease Control and Prevention's Connecting the Dots Initiative, which encourages prevention programs that identify and address these common underlying factors through community involvement to keep kids safe.

Bottom Line: This observational study of adolescent men in urban neighborhoods examined associations between social support, patterns of violence, and violence-related risk behaviors or protective factors that might mitigate them. The analysis included data from a recently completed randomized clinical trial that included 866 male adolescents from lower-resource neighborhoods in Pittsburgh who were enrolled at community agencies. Participants were surveyed on issues including violence, bullying, sexual and dating violence, substance use and involvement in school. The authors report that a high level of social support was associated with fewer risk behaviors among young people, and high social support and mentoring were both associated with a lower likelihood of being involved in a gang. The results suggest understanding the associations between different types of violence and their related risk and protective factors may help in prevention efforts. A limitation of the study was that it was conducted in urban neighborhoods in a single city, which may limit its generalizability to other communities.

Authors: Alison J. Culyba, M.D., Ph.D., M.P.H., University of Pittsburgh School of Medicine, and coauthors

(doi:10.1001/jamanetworkopen.2019.11375)

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

An international team of researchers has observed that local thermal perturbations of spins in a solid can convert heat to energy even in a paramagnetic material - where spins weren't thought to correlate long enough to do so. This effect, which the researchers call "paramagnon drag thermopower," converts a temperature difference into an electrical voltage. This discovery could lead to more efficient thermal energy harvesting - for example, converting car exhaust heat into electric power to enhance fuel-efficiency, or powering smart clothing by body heat.

The research team includes scientists from North Carolina State University, the Department of Energy's Oak Ridge National Laboratory (ORNL), the Chinese Academy of Sciences and the Ohio State University.

In solids with magnetic ions (e.g., manganese), thermal perturbations of spins either can align with each other (ferromagnets or antiferromagnets), or not align (paramagnets). However, spins are not entirely random in paramagnets: they form short-lived, short-range, locally ordered structures - paramagnons - which exist for only a millionth of a billionth of a second and extend over only two to four atoms. In a new paper describing the work, the researchers show that despite these shortcomings, even paramagnons can move in a temperature difference and propel free electrons along with them, creating paramagnon drag thermopower.

In a proof-of-concept finding, the team observed that paramagnon drag in manganese telluride (MnTe) extends to very high temperatures and generates a thermopower that is much stronger than what electron charges alone can make.

The research team tested the concept of paramagnon drag thermopower by heating lithium-doped MnTe to approximately 250 degrees Celsius above its Néel temperature (34 degrees Celsius) - the temperature at which the spins in the material lose their long-range magnetic order and the material becomes paramagnetic.

"Above the Néel temperature, one would expect the thermopower being generated by the spin waves to drop off," says Daryoosh Vashaee, professor of electrical and computer engineering and materials science at NC State and co-corresponding author of the paper describing the work. "However, we didn't see the expected drop off, and we wanted to find out why."

At ORNL the team used neutron spectroscopy at the Spallation Neutron Source to determine what was happening within the material. "We observed that even though there were no sustained spin waves, localized clusters of ions would correlate their spins long enough to produce visible magnetic fluctuations," says Raphael Hermann, a materials scientist at ORNL and co-corresponding author of the paper. The team showed that the lifetime of these spin waves - around 30 femtoseconds - was long enough to enable the dragging of electron charges, which requires only about one femtosecond, or one quadrillionth of a second. "The short-lived spin waves, therefore, could propel the charges and create enough thermopower to prevent the predicted drop off," Hermann says.

"Before this work, it was believed that magnon drag could exist only in magnetically ordered materials, not in paramagnets," says Joseph Heremans, professor of mechanical and aerospace engineering at the Ohio State University and co-corresponding author of the paper. "Because the best thermoelectric materials are semiconductors, and because we know of no ferromagnetic semiconductor at room temperature or above, we never thought before that magnon drag could boost the thermoelectric efficiency in practical applications. This new finding changes that completely; we can now investigate paramagnetic semiconductors, of which there are a lot."

"When we observed the sudden rise of Seebeck coefficient below and near the Néel temperature, and this excess value extended to high temperatures, we suspected something fundamentally related to spins must be involved," says Huaizhou Zhao, a professor at the Chinese Academy of Science in Beijing and co-corresponding author of the paper. "So we formed a research team with complementary expertise which laid the groundwork for this discovery."

"Spins enable a new paradigm in thermoelectricity by alleviating the fundamental tradeoffs imposed by Pauli exclusion on electrons," Vashaee says. "Just as in the discovery of the spin-Seebeck effect, which led to the new area of spincaloritronics, where the spin angular momentum is transferred to the electrons, both the spin waves (i.e., magnons) and the local thermal fluctuations of magnetization in the paramagnetic state (i.e., paramagnons) can transfer their linear momentum to electrons and generate thermopower."

The research appears in Science Advances and is supported by the National Science Foundation, the Air Force Office of Scientific Research, and the U.S. Department of Energy Office of Science, Basic Energy Sciences, Materials Sciences and Engineering Division. Graduate students and co-first authors Yuanhua Zheng of the Ohio State University, Tianqi Lu of the Chinese Academy of Sciences and Mobarak H. Polash of NC State contributed equally to the work. The Spallation Neutron Source at ORNL is a DOE Office of Science User Facility.

Research into why adolescent drivers are involved in motor vehicle crashes, the leading cause of injury and death among 16- to 19-year-olds in the United States, has often focused on driving experience and skills. But a new study suggests that development of the adolescent brain may play a critical role in whether a teenager is more likely to crash.

The study finds that slower growth in the development of working memory is associated with motor vehicle crashes, which points to cognitive development screening as a potential new strategy for identifying and tailoring driving interventions for teens at high risk for crashes.

The study, led by researchers at the Annenberg Public Policy Center of the University of Pennsylvania (APPC) and Children's Hospital of Philadelphia (CHOP), is the first longitudinal study of working memory development in relation to vehicle crashes. The paper "Working Memory Development and Motor Vehicle Crashes in Young Drivers" was published today in JAMA Network Open.

The research examines data from 118 youth in Philadelphia who were part of a larger group that participated in a six-wave survey from when they were 10- to 12-year-olds, in 2005, until they were 18- to 20-year-olds, in 2013-14. The survey measured working memory development, as well as associated risk-related traits and behaviors. This group later participated in a follow-up survey on driving experience.

"We found that teens who had slower development in working memory were more likely to report being in a crash," said the lead author, Elizabeth A. Walshe, Ph.D., who is a postdoctoral fellow at the Annenberg Public Policy Center and at the Center for Injury Research and Prevention at CHOP.

Driving and working memory

Working memory, which develops through adolescence into the twenties, is a frontal lobe process associated with complex, moment-to-moment tasks essential to driving. "Safe driving involves scanning, monitoring, and updating information about the vehicle and environment while managing multiple subtasks (e.g., adjusting speed, steering, in-vehicle controls) and distractors (e.g., peer passengers and cell phones)," the researchers said in their paper. All of these tasks challenge working memory, especially when a young driver has not yet fully learned to automate many basic driving routines.

Adolescent drivers have the highest rate of crashes, injuries, and mortality. While poor skills and inexperience explain some of the risk shortly after a new driver receives a license, crash risk is inversely related to age during the early years of driving. In other words, among equally new drivers, those who are 17 years old have a higher crash rate than those who are 20 years old, which suggests a possible developmental link.

"Not all young drivers crash," Walshe said. "So we thought, what is it about those who are crashing? It could be related to variability in working memory development."

Findings

Prior research has shown a link between lower working memory capacity and reckless and inattentive driving, crashes, and poor performance on simulated driving tasks. For the current study, the researchers recruited participants from the Philadelphia Trajectory Study, a broad six-wave study conducted by researchers at APPC and CHOP. Across seven years - when the adolescents were 11-13 years old to 18-20 years old - this study measured the change in working memory and other characteristics. Subsequently, in 2015, 118 young adults, including 84 drivers and 34 non-drivers, took the follow-up survey on driving. Among the drivers, 25 reported having a crash history and 59 reported no crash history.

The drivers who reported crashes and those who didn't started from about the same point in working memory capacity though the trends diverged from there. The researchers found that the relative growth of working memory was associated with car crashes within three years after starting to drive. Young drivers whose trajectory of working memory growth was less-than-average in the group were more likely to report being in a crash; drivers with greater-than-average growth in working memory were more likely to say they had not been in a crash.

The analysis controlled for other risk-related factors including reckless driving and drug use.

Driving crashes: "Predictable and preventable"

The researchers say the results have important policy implications. While all 50 states have some type of graduated driver licensing (GDL) program that gradually lifts restrictions for young new drivers, the research suggests that individual assessments of adolescents' cognitive development may play an important part, too.

"If our findings hold up in larger samples with diverse youth, we will need to start assessing cognitive abilities, such as working memory, to see if some adolescents are less ready for independent driving," said Daniel Romer, Ph.D., research director of the Annenberg Public Policy Center and a senior fellow at the Center for Injury Research and Prevention at CHOP. "There is considerable variation in working memory development during the teen years, and some teens may not be as ready to drive on their own without additional assistance."

Flaura K. Winston, M.D., Ph.D., founder and scientific director of the Century for Injury Research and Prevention at CHOP, said that enabling teens to become safe drivers is a health concern for physicians. Prior research has focused on driving skills and experience, but this study examines cognitive development in typical adolescents and suggests that individual variation plays a critical role.

"This research points to the fact that crashes are predictable and preventable," said Winston, who also is an APPC distinguished research fellow. "It focuses attention more on the role of the driver and the driver's clinician. A clinician could identify teens who will be at an increased risk and use 'precision prevention' to tailor anticipatory guidance so that young drivers achieve independent mobility in a safe way."

Precision prevention, Winston said, could provide different types of driver training or a release from driving restrictions at different times based on their development.

The researchers said that some form of standardized screening or testing during adolescence could determine which teens have slower development of working memory. "Ideally, we'd be able to offer interventions like driver training or technologies like in-vehicle alert systems to assist new drivers who need it," Walshe said.

In addition to Walshe, Romer, and Winston, the study was conducted by Laura M. Betancourt, Ph.D., and Kristin Arena, B.S., at CHOP, and Atika Khurana, Ph.D., of the College of Education, University of Oregon, who is also an APPC distinguished research fellow.