Culture

Gold leaf -- gold metal hammered into thin sheets -- is used by artists and crafters to gild picture frames, artwork and clothing. Despite its luxurious appearance, the material is affordable and available at most craft stores. Now, researchers reporting in ACS Central Science have developed gold leaf electrodes that, in combination with a CRISPR-based assay, could sensitively detect human papillomavirus (HPV) DNA in human samples. The method also could be modified to diagnose other viral infections.

Previous research indicates that about 80% of new cases of sexually transmitted infections, such as HPV and human immunodeficiency virus (known as HIV), take place in low-resource settings. In addition, over 90% of cervical cancer deaths, which are caused mainly by HPV, occur in these regions, according to the World Health Organization. But people in low-resource settings lack the facilities, trained personnel and money to conduct common diagnostic tests, including polymerase chain reaction (PCR) or antibody detection. Therefore, Ariel Furst, Catherine Klapperich and colleagues wanted to develop a simple, affordable point-of-care test.

Using a sheet of 24K gold leaf, an adhesive, a stencil and a razor blade, the researchers made a three-electrode system that provided a readout in the presence of HPV DNA. On the surface of the electrodes, they attached DNA strands tagged with a dye. Then, they amplified DNA from cervical swab samples with a technique called loop-mediated isothermal amplification, which doesn't require expensive PCR machines. They added the amplified DNA, along with a CRISPR Cas12a enzyme engineered to recognize an HPV sequence, to the surface of the electrode. In the presence of HPV DNA, Cas12a became activated, causing the enzyme to cut the dye-tagged DNA sequence, which changed the electrochemical signal. The assay, which costs only about $2.30 total per test (compared with $30-75 for existing tests), accurately detected HPV in cervical swabs from patients. The technology could be adapted to detect any viral infection, including SARS-CoV-2, the researchers say.

The authors acknowledge funding from the Dorf-Ebner Distinguished Faculty Fellow Award, the Boston University Precision Diagnostics Center, the Defense Advanced Research Projects Agency and the National Science Foundation.

The paper with be freely available as an ACS AuthorChoice article on May 12 at 8 a.m. Eastern time here: http://pubs.acs.org/doi/abs/10.1021/acscentsci.1c00186

The American Chemical Society (ACS) is a nonprofit organization chartered by the U.S. Congress. ACS' mission is to advance the broader chemistry enterprise and its practitioners for the benefit of Earth and all its people. The Society is a global leader in promoting excellence in science education and providing access to chemistry-related information and research through its multiple research solutions, peer-reviewed journals, scientific conferences, eBooks and weekly news periodical Chemical & Engineering News. ACS journals are among the most cited, most trusted and most read within the scientific literature; however, ACS itself does not conduct chemical research. As a leader in scientific information solutions, its CAS division partners with global innovators to accelerate breakthroughs by curating, connecting and analyzing the world's scientific knowledge. ACS' main offices are in Washington, D.C., and Columbus, Ohio.

To automatically receive news releases from the American Chemical Society, contact newsroom@acs.org.

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Coal combustion by power plants and industry pollutes the air, causing many governments to implement mitigation actions and encourage cleaner forms of energy. Now, a new study in ACS' Environmental Science & Technology indicates that in China, indoor air pollution from residential coal burning causes a disproportionate number of premature deaths from exposure to tiny, inhalable pollutants known as PM2.5.

In China, coal is still the largest source of energy, although recent mitigation actions have replaced some coal-fired power plants with petroleum- or natural gas-powered plants. Also, many coal-fired power plants and industrial boilers have installed equipment that reduces emissions. However, some households continue to use coal for heating and cooking, especially in rural areas, and the health impacts of this indoor PM2.5 exposure compared with other forms of indoor and outdoor exposure are largely unknown. Therefore, Shu Tao and colleagues wanted to quantify health risks of exposure to indoor and outdoor PM2.5 from coal used in the power, industrial and residential sectors in China from 1974 to 2014.

The researchers compiled data on coal consumption by power plants, industry, and rural and urban residences over the 40-year period. Using atmospheric chemical transport and statistical models, they calculated outdoor and indoor PM2.5 levels. Then, the team used exposure response functions -- mathematical relationships that calculate health effects resulting from specific exposures -- to estimate premature deaths caused by five diseases associated with PM2.5, including lung cancer and heart disease. From 1974 to 2014, the contribution of indoor residential coal use to overall PM2.5 exposure decreased in urban populations but remained steady in rural populations. The researchers calculated that in 2014, residential coal accounted for 2.9% of total energy use in China but 34% of premature deaths associated with PM2.5. The number of premature deaths caused by unit coal consumption in the residential sector was 40 times higher than that in the power and industrial sectors. These results indicate that efforts to reduce residential coal use should be a key focus of future air pollution mitigation actions in China, the researchers say.

The authors acknowledge funding from the Chinese Academy of Sciences and the National Natural Science Foundation of China.

The article will be freely available as an ACS AuthorChoice article on May 12 at 8 a.m. Eastern time here: http://pubs.acs.org/doi/abs/10.1021/acs.est.1c01148.

The American Chemical Society (ACS) is a nonprofit organization chartered by the U.S. Congress. ACS' mission is to advance the broader chemistry enterprise and its practitioners for the benefit of Earth and all its people. The Society is a global leader in promoting excellence in science education and providing access to chemistry-related information and research through its multiple research solutions, peer-reviewed journals, scientific conferences, eBooks and weekly news periodical Chemical & Engineering News. ACS journals are among the most cited, most trusted and most read within the scientific literature; however, ACS itself does not conduct chemical research. As a leader in scientific information solutions, its CAS division partners with global innovators to accelerate breakthroughs by curating, connecting and analyzing the world's scientific knowledge. ACS' main offices are in Washington, D.C., and Columbus, Ohio.

To automatically receive news releases from the American Chemical Society, contact newsroom@acs.org.

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Trained to see patterns by analyzing thousands of chest X-rays, a computer program predicted with up to 80 percent accuracy which COVID-19 patients would develop life-threatening complications within four days, a new study finds.

Developed by researchers at NYU Grossman School of Medicine, the program used several hundred gigabytes of data gleaned from 5,224 chest X-rays taken from 2,943 seriously ill patients infected with SARS-CoV-2, the virus behind the infections.

The authors of the study, publishing in the journal npj Digital Medicine online May 12, cited the "pressing need" for the ability to quickly predict which COVID-19 patients are likely to have lethal complications so that treatment resources can best be matched to those at increased risk. For reasons not yet fully understood, the health of some COVID-19 patients suddenly worsens, requiring intensive care, and increasing their chances of dying.

In a bid to address this need, the NYU Langone team fed not only X-ray information into their computer analysis, but also patients' age, race, and gender, along with several vital signs and laboratory test results, including weight, body temperature, and blood immune cell levels. Also factored into their mathematical models, which can learn from examples, were the need for a mechanical ventilator and whether each patient went on to survive (2,405) or die (538) from their infections.

Researchers then tested the predictive value of the software tool on 770 chest X-rays from 718 other patients admitted for COVID-19 through the emergency room at NYU Langone hospitals from March 3 to June 28, 2020. The computer program accurately predicted four out of five infected patients who required intensive care and mechanical ventilation and/or died within four days of admission.

"Emergency room physicians and radiologists need effective tools like our program to quickly identify those COVID-19 patients whose condition is most likely to deteriorate quickly so that health care providers can monitor them more closely and intervene earlier," says study co-lead investigator Farah Shamout, PhD, an assistant professor in computer engineering at New York University's campus in Abu Dhabi.

"We believe that our COVID-19 classification test represents the largest application of artificial intelligence in radiology to address some of the most urgent needs of patients and caregivers during the pandemic," says Yiqiu "Artie" Shen, MS, a doctoral student at the NYU Data Science Center.

Study senior investigator Krzysztof Geras, PhD, an assistant professor in the Department of Radiology at NYU Langone, says a major advantage to machine-intelligence programs such as theirs is that its accuracy can be tracked, updated and improved with more data. He says the team plans to add more patient information as it becomes available. He also says the team is evaluating what additional clinical test results could be used to improve their test model.

Geras says he hopes, as part of further research, to soon deploy the NYU COVID-19 classification test to emergency physicians and radiologists. In the interim, he is working with physicians to draft clinical guidelines for its use.

The 'missing link' that helped our ancestors to begin communicating with each other through language may have been iconic sounds, rather than charades-like gestures - giving rise to the unique human power to coin new words describing the world around us, a new study reveals.

It was widely believed that, in order to get the first languages off the ground, our ancestors first needed a way to create novel signals that could be understood by others, relying on visual signs whose form directly resembled the intended meaning.

However, an international research team, led by experts from the University of Birmingham and the Leibniz-Centre General Linguistics (ZAS), Berlin, have discovered that iconic vocalisations can convey a much wider range of meanings more accurately than previously supposed.

The researchers tested whether people from different linguistic backgrounds could understand novel vocalizations for 30 different meanings common across languages and which might have been relevant in early language evolution.

These meanings spanned animate entities, including humans and animals (child, man, woman, tiger, snake, deer), inanimate entities (knife, fire, rock, water, meat, fruit), actions (gather, cook, hide, cut, hunt, eat, sleep), properties (dull, sharp, big, small, good, bad), quantifiers (one, many) and demonstratives (this, that).

The team published their findings in Scientific Reports, highlighting that the vocalizations produced by English speakers could be understood by listeners from a diverse range of cultural and linguistic backgrounds. Participants included speakers of 28 languages from 12 language families, including groups from oral cultures such as speakers of Palikúr living in the Amazon forest and speakers of Daakie on the South Pacific island of Vanuatu. Listeners from each language were more accurate than chance at guessing the intended referent of the vocalizations for each of the meanings tested.

Co-author Dr Marcus Perlman, Lecturer in English Language and Linguistics at the University of Birmingham, commented: "Our study fills in a crucial piece of the puzzle of language evolution, suggesting the possibility that all languages - spoken as well as signed - may have iconic origins.

"The ability to use iconicity to create universally understandable vocalisations may underpin the vast semantic breadth of spoken languages, playing a role similar to representational gestures in the formation of signed languages."

Co-author Dr Bodo Winter, Senior Lecturer in Cognitive Linguistics at the University of Birmingham, commented: "Our findings challenge the often-cited idea that vocalisations have limited potential for iconic representation, demonstrating that in the absence of words people can use vocalizations to communicate a variety of meanings - serving effectively for cross-cultural communication when people lack a common language."

An online experiment allowed researchers to test whether a large number of diverse participants around the world were able to understand the vocalisations. A field experiment using 12 easy-to-picture meanings, allowed them to test whether participants living in predominantly oral societies were also able to understand the vocalisations.

They found that some meanings were consistently guessed more accurately than others. In the online experiment, for example, accuracy ranged from 98.6% for the action 'sleep' to 34.5% for the demonstrative 'that'. Participants were best with the meanings 'sleep', 'eat', 'child', 'tiger', and 'water', and worst with 'that', 'gather', 'dull', 'sharp' and 'knife'.

The researchers highlight that while their findings provide evidence for the potential of iconic vocalisations to figure in the creation of original spoken words, they do not detract from the hypothesis that iconic gestures also played a critical role in the evolution of human communication, as they are known to play in the modern emergence of signed languages.

Everyone has at some point been charmed by the sound of a person's voice: but can we believe our ears? What can a voice really reveal about our character? Now an international research team led by the University of Göttingen has shown that people seem to express at least some aspects of their personality with their voice. The researchers discovered that a lower pitched voice is associated with individuals who are more dominant, extrovert and higher in sociosexuality (more interested in casual sex). The findings were true for women as well as for men. The results were published in the Journal of Research in Personality.

The researchers analysed data from over 2,000 participants and included information from four different countries. Participants filled in questionnaires about themselves to measure personality and provided recordings of their voice so that the pitch could be measured using a computer programme. This is the first time that an objective digital measure of voice pitch has been used in a study of this kind, rather than subjective ratings of how "high" or "deep" a voice might sound. The researchers measured "sociosexuality" by collecting responses about sexual behaviour, attitude and desire. They also collected data to provide ratings of dominance and other character traits such as neuroticism, extraversion, openness to experience, agreeableness and conscientiousness. The number of participants helps to confirm the robustness of the findings: the study involves the largest number to date compared to similar research in this theme.

The researchers found that people with lower pitched voices were more dominant, extroverted and higher in sociosexuality (eg were more interested in sex outside a relationship). However, the relationship between voice pitch and other personality traits (such as agreeableness, neuroticism, conscientiousness or openness) seems less clear. It is possible that these traits are not expressed in the pitch of voices. The researchers found no difference between men and women.

"People's voices can make a huge and immediate impression on us," explains Dr Julia Stern, at the University of Göttingen's Biological Personality Psychology Group. "Even if we just hear someone's voice without any visual clues - for instance on the phone - we know pretty soon whether we're talking to a man, a woman, a child or an older person. We can pick up on whether the person sounds interested, friendly, sad, nervous, or whether they have an attractive voice. We also start to make assumptions about trust and dominance." This led Stern to question whether these assumptions were justified. "The first step was to investigate whether voices are, indeed, related to people's personality. And our results suggest that people do seem to express some aspects of their personality with their voice."

This study was conducted as a "registered report" which means it benefits from peer review from other researchers at a very early stage and was accepted for publication independent of the results. It is one of the new indicators of quality being developed to make science more transparent and reliable.

The gopher tortoise (Gopherus polyphemus) is declining because of habitat loss and fragmentation, human interaction including collisions with vehicles, predation by domestic animals, and disease. These long-lived reptiles are found throughout Florida and are affected by various diseases including upper respiratory tract disease. A number of pathogens such as Mycoplasma spp., Herpesvirus, and Ranavirus are known to cause upper respiratory tract disease in gopher tortoises. Chronic disease resulting from these pathogens can lead to reduced reproduction, abnormal growth and development, increased susceptibility to secondary infections and, in some cases, a shorter life span. To date, little is known about the prevalence of these microorganisms in wild tortoises.

This lack of knowledge creates a dilemma for wildlife biologists, conservationists and public policy makers seeking to uphold and improve protections for this threatened species.

Researchers from Florida Atlantic University's Harbor Branch Oceanographic Institute and the Harriet L. Wilkes Honors College in collaboration with Loggerhead Marinelife Center and the University of Florida College of Veterinary Medicine, conducted a comprehensive health assessment of previously unstudied gopher tortoise aggregations at two sites in southeastern Florida.

Results of the study, published in the journal Conservation Physiology, showed that overall, 42.9 percent of all tortoises tested had circulating antibodies to Mycoplasma agassizii, an infectious bacterium that causes upper respiratory tract disease. Researchers detected antibodies to M. agassizii in 29 percent of tortoises at one of the sites and 70 percent at the other site, suggesting that at least one of these tortoise aggregations may be experiencing an outbreak of M. agassizii.

In contrast, none of the tortoises tested positive for Ranavirus or Herpesvirus via polymerase chain reaction (PCR), which represents important baseline data, since these viruses are thought to be emerging pathogens of other tortoise and turtle species.

For the study, researchers collected samples of blood and nasal, oral, and cloacal swabs (digestive, reproductive, and urinary tract openings) from 91 tortoises (48 adults, 35 juveniles and eight hatchlings) captured at FAU Harbor Branch in Fort Pierce in 2019, and Loggerhead Park in Juno Beach during 2018-2019. The samples were analyzed for hematology, plasma protein electrophoretic profiles, and infectious disease testing including Mycoplasma spp. serology and PCR assays for Ranavirus, Herpesvirus, and Anaplasma spp., a tick-borne bacteria of medical importance.

At both study sites, adult tortoises were significantly more likely to have clinical signs of upper respiratory tract disease than juveniles. There was a significant relationship between tortoise size and M. agassizii antibody test results. Physical examination revealed that 19.8 percent of the tortoises had clinical signs consistent with upper respiratory tract disease, including nasal discharge, asymmetrical nares, wheezing, eyelid/conjunctival swelling, and ocular discharge. In addition, 13.2 percent of tortoises had some other form of physical abnormality noted during physical examination, including limb, eye and shell abnormalities or extra scutes on the tortoise's shell.

"The full effect of chronic disease on a long-lived species such as the gopher tortoise may take months to years to manifest in a population," said Annie Page-Karjian, D.V.M., Ph.D., lead author, clinical veterinarian and an assistant research professor, FAU Harbor Branch. "Because the gopher tortoise is one of the most commonly translocated species in North America, it is important to understand pathogen distributions within their populations and to monitor them using standardized techniques so that any changes associated with health problems may be detected over time."

Researchers also found that adult tortoises were significantly more likely than juvenile tortoises to have ticks as well as hemogregarine parasites in their red blood cells. Tortoises with ticks were significantly more likely to have the hemogregarine parasites. Ticks were found on 59 percent and hemoparasites were identified in 30 percent of the tortoises sampled at FAU Harbor Branch, while only a single tick was found, and no hemoparasites were identified in tortoises sampled at Loggerhead Park. These findings are noteworthy because hemogregarines in tortoises are thought to be transmitted by ticks.

"Free-ranging animals typically have higher internal and external parasite burdens and are likely exposed to pathogens more frequently than captive animals, which often are regularly treated with parasiticides and also receive supportive care such as anti-microbials when they are sick," said Page-Karjian. "Long-term studies of these animals and other populations will help us to better understand the consequences of disease and various stressors that impact their behavior and reproductive potential. Additional health assessments and surveillance of pathogens in southeastern Florida's gopher tortoises are warranted."

The study conducted by the University of Turku and the Finnish Institute for Health and Welfare together with an international research team is so far the largest population-level study in the world examining the connection between human gut microbiota and health and mortality in the following decades.

The composition of the research subjects' gut microbiota was analysed from stool samples collected in 2002. The researchers had access to follow-up data on the subjects' mortality until 2017, i.e., close to the present day.

"Many bacterial strains that are known to be harmful were among the enterobacteria predicting mortality, and our lifestyle choices can have an impact on their amount in the gut. By studying the composition of the gut microbiota, we could improve mortality prediction, even while taking into account other relevant risk factors, such as smoking and obesity. The data used in this research make it possible for the first time to study the long-term health impact of the human gut microbiota on a population level," says Teemu Niiranen, Professor of Medicine at the University of Turku, Finland.

Everyone has a unique microbiota

Human microbiota is highly individual and consists of a vast amount of different bacteria and other microorganisms. The bacteria predicting a shorter lifespan were discovered when the researchers compared health records and billions of DNA strands retrieved from the research subjects' microbiota.

"We developed a machine learning algorithm that screened the data for microbial species having a significant association with mortality among the research subjects in the following two decades after the sample was taken," describes Associate Professor Leo Lahti from the University of Turku.

"Finnish population studies are unique in their extent and scope even on a global scale. With new data science methods, we are now able to study more closely the specific connections between microbiota and, for example," ageing and incidence of common diseases, Lahti continues.

Even though the connection between gut microbiota and lifestyle has lately been studied extensively in cross-sectional studies, there are only a few long-term follow-up studies available. Therefore, only a small amount of information has been gained about the connection between microbiota and health in the long term.

The study was based on a sample of over 7,000 Finnish adults. The data are part of the FINRISK 2002 study conducted by the Finnish Institute for Health and Welfare. The research article was published in Nature Communications.

Philadelphia, May 12, 2021 - In recent years there has been an increased interest in the consumption of kefir, a fermented dairy beverage, because there is some evidence that it has health benefits and its affordability. A new study by researchers from the University of Illinois and The Ohio State University, published in JDS Communications, found that 66 percent of the commercial kefir products studied overstated microorganism density and 80 percent contained bacterial species that were not included on the label, potentially misleading consumers.

Senior author Kelly S. Swanson, PhD, University of Illinois, Urbana, IL, USA, believes better quality control of kefir products is required to demonstrate and understand their potential health benefits. "It is important for consumers to know the accurate contents of the fermented foods they consume," Swanson said.

Swanson and his team of researchers bought five kefir products from online vendors and stores in the Urbana, IL area and analyzed two lots of each. Although all five guaranteed specific bacterial species used in fermentation, the team found that no product completely matched its label. All products contained Streptococcus salivarius, and four out of five products contained Lactobacillus paracasei, although they were not included on the labels.

According to Dr. Swanson, classification as a "cultured milk product" by the FDA requires disclosure of added microorganisms. "Regulatory agencies and consumers must continue to scrutinize these products and demand a higher level of accuracy and quality," he explained.

The authors hope this and future studies will call attention to the effect of inaccurate kefir product labeling.

A new study led by the Centre for Nutraceuticals in the University of Westminster shows that pink drinks can help to make you run faster and further compared to clear drinks.

The researchers found that a pink drink can increase exercise performance by 4.4 per cent and can also increase a 'feel good' effect which can make exercise seem easier.

The study, published in the journal Frontiers in Nutrition, is the first investigation to assess the effect of drink colour on exercise performance and provides the potential to open a new avenue of future research in the field of sports drinks and exercise.

During the study participants were asked to run on a treadmill for 30 minutes at a self-selected speed ensuring their rate of exertion remained consistent. Throughout the exercise they rinsed their mouths with either a pink artificially sweetened drink that was low in calories or a clear drink which was also artificially sweetened and low in calories.

Both drinks were exactly the same and only differed in appearance - the researchers added food dye to the pink drink to change the colour.

The researchers chose pink as it is associated with perceived sweetness and therefore increases expectations of sugar and carbohydrate intake.

Previous studies have also shown that rinsing the mouth with carbohydrates can improve exercise performance by reducing the perceived intensity of the exercise, so the researchers wanted to assess whether rinsing with a pink drink that had no carbohydrate stimulus could elicit similar benefits through a potential placebo effect.

The results show that the participants ran an average 212 metres further with the pink drink while their mean speed during the exercise test also increased by 4.4 per cent. Feelings of pleasure were also enhanced meaning participants found running more enjoyable.

Future exploratory research is necessary to find out whether the proposed placebo effect causes a similar activation to the reward areas of the brain that are commonly reported when rinsing the mouth with carbohydrates.

Talking about the study, Dr Sanjoy Deb, corresponding author on the paper from the University of Westminster, said: "The influence of colour on athletic performance has received interest previously, from its effect on a sportsperson's kit to its impact on testosterone and muscular power. Similarly, the role of colour in gastronomy has received widespread interest, with research published on how visual cues or colour can affect subsequent flavour perception when eating and drinking.

"The findings from our study combine the art of gastronomy with performance nutrition, as adding a pink colourant to an artificially sweetened solution not only enhanced the perception of sweetness, but also enhanced feelings of pleasure, self-selected running speed and distance covered during a run."

For college students under pressure, a dog may be the best stress fighter around.

Programs exclusively focused on petting therapy dogs improved stressed-out students' thinking and planning skills more effectively than programs that included traditional stress-management information, according to new Washington State University research.

The study was published today in the journal AERA Open, a peer-reviewed journal of the American Educational Research Association. The paper demonstrated that stressed students still exhibited these cognitive skills improvements up to six weeks after completion of the four-week-long program.

"It's a really powerful finding," said Patricia Pendry, associate professor in WSU's Department of Human Development. "Universities are doing a lot of great work trying to help students succeed academically, especially those who may be at risk due to a history of mental health issues or academic and learning issues. This study shows that traditional stress management approaches aren't as effective for this population compared with programs that focus on providing opportunities to interact with therapy dogs."

The researchers measured executive functioning in the 309 students involved in the study. Executive function is a term for the skills one needs to plan, organize, motivate, concentrate, memorize: "all the big cognitive skills that are needed to succeed in college," Pendry said.

Pendry conducted this study as a follow up to previous work, which found that petting animals for just 10 minutes had physiological impacts, reducing students' stress in the short-term.

In the three-year study, students were randomly assigned to one of three academic stress-management programs featuring varying combinations of human-animal interaction and evidenced-based academic stress management. The dogs and volunteer handlers were provided through Palouse Paws, a local affiliate of Pet Partners, a national organization with over 10,000 therapy teams.

"The results were very strong," Pendry said. "We saw that students who were most at risk ended up having most improvements in executive functioning in the human-animal interaction condition. These results remained when we followed up six weeks later."

Many universities, including WSU, have provided academic stress management programs and workshops for many years. These are traditionally very similar to college classes, where students listen to an expert, watch slideshows and take notes. They're often evidence-based courses that talk about ways to get more sleep, set goals, or manage stress or anxiety.

"These are really important topics, and these workshops are helping typical students succeed by teaching them how to manage stress," Pendry said. "Interestingly though, our findings suggest that these types of educational workshops are less effective for students that are struggling. It seems that students may experience these programs as another lecture, which is exactly what causes the students to feel stressed."

Human-animal interaction programs help by letting struggling students relax as they talk and think about their stressors. Through petting animals, they are more likely to relax and cope with these stressors rather than become overwhelmed. This enhances students' ability to think, set goals, get motivated, concentrate and remember what they are learning, Pendry said.

"If you're stressed, you can't think or take up information; learning about stress is stressful!" she said.

Animal sessions aren't just about changing behavior; they help students engage in positive thoughts and actions.

"You can't learn math just by being chill," Pendry said. "But when you are looking at the ability to study, engage, concentrate and take a test, then having the animal aspect is very powerful. Being calm is helpful for learning especially for those who struggle with stress and learning."

INDIANAPOLIS -- Artificial intelligence (AI)-driven healthcare has the potential to transform medical decision-making and treatment, but these algorithms must be thoroughly tested and continuously monitored to avoid unintended consequences to patients.

In a JAMA Network Open Invited Commentary, Regenstrief Institute President and Chief Executive Officer and Indiana University School of Medicine Associate Dean for Informatics and Health Services Research Peter Embí, M.D., M.S., strongly stated the importance of algorithmovigilance to address inherent biases in healthcare algorithms and their deployment. Algorithmovigilance, a term coined by Dr. Embí, can be defined as the scientific methods and activities relating to the evaluation, monitoring, understanding, and prevention of adverse effects of algorithms in healthcare.

"We wouldn't think of treating patients with a new pharmaceutical or device without first ensuring its efficacy and safety," said Dr. Embí. "In the same way, we must recognize that algorithms have the potential for both great benefit and harm and, therefore, require study. Also, compared with drugs or devices, algorithms often have additional complexities and variations, such as how they are deployed, who interacts with them, and the clinical workflows where interactions with algorithms take place."

The commentary was in response to a study from IBM scientists evaluating different approaches to debiasing healthcare algorithms developed to predict postpartum depression. Dr. Embí stated the study suggests that debiasing methods can help address underlying disparities represented in the data used to develop and deploy the AI approaches. He also said the study demonstrates that the evaluation and monitoring of these algorithms for effectiveness and equity is necessary and even ethically required.

"Algorithmic performance changes as it is deployed with different data, different settings and different human-computer interactions. These factors could turn a beneficial tool into one that causes unintended harm, so these algorithms must continually be evaluated to eliminate the inherent and systemic inequities that exist in our healthcare system," Dr. Embí continued. "Therefore, it's imperative that we continue to develop tools and capabilities to enable systematic surveillance and vigilance in the development and use of algorithms in healthcare."

ROCHESTER, Minn. ­­­-- Patients diagnosed with post-COVID-19 syndrome, also known as "PCS," "COVID-19 long-haul syndrome" and "Post-Acute Sequelae of SARS COV-2," experience symptoms such as mood disorders, fatigue and perceived cognitive impairment that can negatively affect returning to work and resuming normal activities, according to a Mayo Clinic study published in Mayo Clinic Proceedings.

The study reports on the first 100 patients to participate in Mayo Clinic's COVID-19 Activity Rehabilitation program (CARP), one of the first multidisciplinary programs established to evaluate and treat patients with post-COVID-19 syndrome. The patients were evaluated and treated between June 1 and Dec. 31, 2020. They had a mean age of 45, and 68% were female. They were evaluated a mean of 93 days after infection.

The most common symptom of patients seeking evaluation for post-COVID-19 syndrome was fatigue. Of the patients in the study, 80% reported unusual fatigue, while 59% had respiratory complaints and a similar percentage had neurologic complaints. More than one-third of patients reported difficulties performing basic activities of daily living, and only 1 in 3 patients had returned to unrestricted work activity.

"Most patients in the study had no preexisting comorbidities prior to COVID-19 infection, and many did not experience symptoms related to COVID-19 that were severe enough to require hospitalization," says Greg Vanichkachorn, M.D., medical director of Mayo Clinic's COVID-19 Activity Rehabilitation program and first author of the study. "Most of the patients had normal or nondiagnostic lab and imaging results, despite having debilitating symptoms. That's among the challenges of diagnosing PCS in a timely way and then responding effectively."

Nonetheless, the symptoms often resulted in significant negative effects as patients tried to return to normal daily activities, including work. "Most patients with whom we worked required physical therapy, occupational therapy or brain rehabilitation to address the perceived cognitive impairment," says Dr. Vanichkachorn. "While many patients had fatigue, more than half also reported troubles with thinking, commonly known as 'brain fog.' And more than one-third of patients had trouble with basic activities of life. Many could not resume their normal work life for at least several months."

Mayo Clinic developed the COVID-19 Activity Rehabilitation program at Mayo Clinic in Rochester in June 2020 to care for patients experiencing persistent symptoms after COVID-19 infection. In addition to Dr. Vanichkachorn, Mayo Clinic staff from many specialty fields are involved in diagnostics and treatment. Among services provided are psychosocial support for patients who frequently report feelings of abandonment, guilt and frustration during initial evaluation.

Mayo Clinic is conducting intensive research on post-COVID-19 syndrome, in part to better define how the condition presents across different socioeconomic groups and ethnicities. Prolonged symptoms, such as those experienced with post-COVID-19 syndrome, have been reported in prior epidemics.

"As the pandemic continues, we expect to see more patients who experience symptoms long after infection, and health care providers need to prepare for this, know what to look for, and know how to best provide for their patients' needs," says Dr. Vanichkachorn.

Patients who have recovered from acute infection shouldn't wait to be evaluated if they are experiencing prolonged symptoms, though Dr. Vanichkachorn says providers should be judicious in recommending expensive diagnostic tests, which often aren't covered by insurance and don't reveal significant information.

Environmental enrichment -- with infrastructure, unfamiliar odors and tastes, and toys and puzzles -- is often used in zoos, laboratories, and farms to stimulate animals and increase their wellbeing. Stimulating environments are better for mental health and cognition because they boost the growth and function of neurons and their connections, the glia cells that support and feed neurons, and blood vessels within the brain. But what are the deeper molecular mechanisms that first set in motion these large changes in neurophysiology? That's the subject of a recent study in Frontiers in Molecular Neuroscience.

Here, a multinational team of scientists used a large molecular toolbox to map, in unprecedented detail, how environmental enrichment leads to changes in the 3D organization of chromosomes in neurons and glia cells of the mouse brain, resulting in the activation or deactivation of a minority of genes within the genome. They show that genes which in humans are important for cognitive mental health are especially affected. This finding could inspire the search for novel therapies.

Enrichment first causes the 3D structure of chromosomes to 'open up'

"Here we show for the first time, with large-scale data from many state-of-the-art methods, that young adolescent mice that grew up in an extra stimulating environment have highly specific 'epigenetic' changes -- that is, molecular changes other than in DNA sequence -- to the chromosomes within the cells of the brain cortex," says corresponding author Dr Sergio Espeso-Gil from the Center for Genomic Regulation in Barcelona, Spain.

He continues: "These increase the local 'openness' and 'loopiness' of the chromosomes, especially around DNA stretches called enhancers and insulators, which then finetune more 'downstream' genes. This happens not only in neurons but also in the supportive glia cells, too often ignored in studies about learning."

Espeso-Gil and colleagues raised laboratory mice for the first month after birth in social groups inside housing with Lego blocks, ladders, balls, and tunnels that were frequently changed and moved around. As a control, mice were raised in smaller groups inside standard housing. The authors then used a swathe of complementary tools to look for molecular changes in neurons and glia cells within the brain cortex. These included changes in the 3D structure of chromosomes, in particular the local 'chromatin accessibility' (openness) and 'chromatin interactions' (where distant genes are brought together through loops, to coordinate activity).

Epigenetic 'master' switches

They show that one 'master' switch operational after environmental enrichment is a locally increased activity of the protein CTCF, which stimulates chromatin interactions within and between chromosomes. A second master switch works by locally increasing chromatin accessibility, especially within the pyramidal neurons that are important for cognition. A third is the highly localized adding of CH3- (methyl) groups to the important chromosomal protein histone H3, a change which activates nearby genes.

These switches mainly occur around genomic regions that contain enhancers, regulatory DNA that (when bound to proteins called transcription factors) can activate neighboring genes. Also affected were genomic regions with insulators, regulatory DNA that can override the gene-activating effect of neighboring enhancers.

The authors conclude that growing up in an enriched environment causes highly local and specific epigenetic changes in neurons and glia cells. These then change the activity -- predominantly by activation rather than inhibition -- of a minority of genes within the genome. Overall, 0.2-0.4% of all enhancers and 2-5% of all promoters (i.e. start sites for the first step of gene expression, where DNA is transcribed into protein-coding or regulatory RNA) are affected.

Link to mental health in humans

"Our results show that many of the genes involved are known to play a role in the growth and differentiation of neurons, the development of blood vessels, the formation and patterning of new synaptic connections on neurons, and molecular pathways implicated in memory and learning in mice," says Espeso-Gil.

"And when we look for parallel regions in the human genome, we find many regions that are statistically associated with differences in complex traits such as insomnia, schizophrenia, and Alzheimer's in humans, which means that our study could inform future research on these disorders. This points to the potential of environmental enrichment in therapies for mental health. Our research could also help to guide future research on chromatin interactions and the poorly known importance of glial cells for cognitive mental health."

Researchers used genetic engineering tools to create a virus that can enter specific neurons and insert into the prefrontal cortex a new genetic code that induces the production of modified proteins. In tests with mice, the alteration of these proteins was sufficient to modify brain activity, indicating a potential biomarker for the diagnosis of psychiatric disorders such as schizophrenia and autism.

Sometimes referred to as the “executive brain”, the prefrontal cortex is the region that governs higher-level cognitive functions and decision making. Studies of tissue from this brain region in patients with schizophrenia have detected alterations in two proteins: BDNF (brain-derived neurotrophic factor) and trkB (tyrosine receptor kinase B).

The relationship between BDNF and trkB is important during brain development. When these proteins bind to each other, they trigger a cascade of intracellular signals that are essential to neuronal maturation and growth. Imbalances in this kind of signaling may be associated with the manifestation of certain disorders.

A group of researchers affiliated with the Federal University of Minas Gerais (UFMG) and the University of São Paulo’s Ribeirão Preto Medical School (FMRP-USP) in Brazil, and with Sweden’s Karolinska Institute, have created a virus capable of carrying the genetic code for a mutant form of trkB. When the modified trkB binds to BDNF, the intracellular signaling cascade is blocked, reproducing characteristics observed in brain tissue from schizophrenia patients.

The research, conducted with funding from FAPESP and the Ministry of Education’s Coordination for the Improvement of Higher Education Personel (CAPES), involved parvalbumin-expressing inhibitory interneurons, or PV interneurons for short. Interneurons connect spinal motor and sensory neurons, and can also communicate with each other, forming circuits of various complexity. Firing at relatively high frequencies in the gamma range (30-80 Hertz), they resemble the conductor of an orchestra, regulating excitation and inhibition in the central nervous system. 

PV is a protein that plays a role in many processes, such as cell-cycle regulation and muscle contraction, among others. PV interneurons are the most common interneurons in the cortex, and are involved in attention, social memory, and more. Dysfunction of PV interneurons disrupting cortical information processing and cognitive behavior has been detected in psychiatric patients.

The neurons and interneurons in the human brain communicate via electrical and chemical signals to activate or inhibit nearby neurons as well as circuits in distant brain regions. The organized activity of these different circuits gives rise to consciousness, feelings and behavior.

“Using a novel viral strategy for cell-type-specific and spatially restricted expression of a dominant-negative trkB (trkB.DN), we show that BDNF/trkB signaling is essential to the integrity and maintenance of prefrontal PV interneurons in adult male and female mice,” the researchers write in an article published in February in the Journal of Neuroscience.

In the study, the genetically modified virus was introduced into the brain tissue of adult transgenic mice using Cre-Lox recombination, a site-specific recombinase technology for inserting or deleting target DNA sequences. The researchers then recorded electrical activity in the prefrontal cortex and found alterations in the excitation-inhibition balance, as well as changes in brain waves and neuronal activity resulting in more aggressive behavior and anxiety.

Specific circuits in the cortex were manipulated in an innovative manner using the technique, explained Cleiton Lopes Aguiar, a professor at UFMG’s Institute of Biological Sciences and co-principal investigator for the study alongside Marie Carlén, a professor at Karolinska Institute.

“The results show that manipulating BDNF/trkB in adults can alter not only brain activity but also complex behaviors that depend on the prefrontal cortex,” Aguiar said. “It can be inferred that BDNF/trkB signaling is necessary to development, and to maintain mature neural networks.”

According to Leonardo Rakauskas Zacharias, a co-author of the article and a researcher at FMRP-USP’s Epilepsy Research Laboratory, the new technique enhances the study of the developed adult brain.

The role of interneurons

In the same issue of the Journal of Neuroscience, the group published another article on synchronous activity of cortical inhibitory interneurons expressing parvalbumin. “Brain oscillations are fundamental to the coordination of neuronal activity across neurons and structures. Gamma oscillations (30-80 Hz) have received particular attention through their association with perceptual and cognitive processes. (...) [Here we] show how deficient PV inhibition can lead to increased and asynchronous excitatory firing, contaminating the local field potential and manifesting as increased gamma power. Thus, increased gamma power does not always reflect a genuine rhythm. Further, we show that ketamine-induced gamma increases are caused by separate network mechanisms,” the authors explain.

According to Nicolas Gustavo Guyon, a member of the group and a researcher at Karolinska Institute, their analysis of brain oscillations in genetically modified mice detected asynchronous activity due to the inability of PV interneurons to respond to all excitatory stimuli generated by other neurons.

For Aguiar, what both articles have in common is the search for a deeper understanding of the role played by interneurons in the prefrontal cortex and how the brain organizes the excitation-inhibition balance. “We’re exploring the normal brain in order to achieve a deeper understanding of psychiatric disorders such as schizophrenia,” he said. “We show that if there are alterations in certain specific aspects of these normal animals, they display symptoms that could be initial clues to the mechanisms underlying the disorders.”

According to the Pan American Health Organization (PAHO-WHO), mental illness accounts for more than a third of total disability in the Americas, yet investment in mental health programs falls well short of what is required to address the needs of psychiatric patients. The term covers mental disorders such as dementia and schizophrenia, as well as depression. Over 300 million people live with depression, 60 million with bipolar disorders, and 23 million with schizophrenia-related disorders (including 1.5 million Brazilians), the WHO estimates.

Zacharias points out that the group’s research projects have been in progress for more than seven years and their results could contribute to the development of potential treatments. “We work with basic science to understand the mechanisms of the brain, and our findings can help all those concerned understand psychiatric disorders a little better,” he said.

A new study by the University of Georgia revealed that more college students change majors within the STEM pipeline than leave the career path of science, technology, engineering and mathematics altogether.

Funded by a National Institutes of Health grant and a National Science Foundation Postdoctoral Fellowship and done in collaboration with the University of Wisconsin, the study examined interviews, surveys and institutional data from 1,193 students at a U.S. midwestern university for more than six years to observe a single area of the STEM pipeline: biomedical fields of study.

Out of 921 students who stayed in the biomedical pipeline through graduation, almost half changed their career plans within the biomedical fields.

"This was almost double the number of students who left biomedical fields altogether," said Emily Rosenzweig, co-author of the study and assistant professor in the Mary Frances Early College of Education's department of educational psychology. "This suggests that if we want to fully understand why there are shortages in certain STEM careers, we need to look at those who change plans within the pipeline, not just those who leave it."

Rosenzweig examined students' motivations for changing career plans and found that students were more often inspired to make a change because a new field seemed more attractive.

This finding pointed to an underexplored research area that educators, policymakers and administrators should devote more attention to in the future. Rather than focusing only on what makes students disenchanted with a particular career, factors that make alternative career paths seem valuable to students need to be considered.

"The sheer number of changes made by students who remained in the biomedical pipeline highlights the divergence of paths students take in their career decision-making," Rosenzweig said. "We should not simply assume that students are staying on course and progressing smoothly toward intended careers just because they have not left the [STEM] pipeline."

Ultimately, the research provides new insights about students' motivations for choosing various careers inside the STEM pipeline and demonstrates the importance of understanding this group if schools are to promote retention in particular STEM careers.