Brain

Deep in a tropical forest in Borneo 15 years ago, Rutgers student Didik Prasetyo first encountered a young male orangutan that he named “Jerry.”

The great ape was one of several orangutans that Prasetyo and other researchers followed at the Tuanan Orangutan Research Station in the Mawas Conservation Area in Indonesia. Prasetyo was skeptical when colleagues said orangutans always remember faces. But five years later, he spotted Jerry again in the same forest and the primate recognized him.

“Orangutans are very smart,” said Prasetyo, a doctoral student in the Graduate Program in Ecology and Evolution in the School of Graduate Studies at Rutgers University. “Slowly, he came closer to me until we were about 6 feet apart. After that, I thought, ‘OK, we’re friends,’ and I kept following him without a problem.”

Prasetyo’s passion is learning more about the endangered apes and trying to conserve their habitats and populations, which face enormous pressure from deforestation from logging, palm oil and paper pulp production and hunting. He co-authored an alarming recent study in Current Biology – that was featured in the New York Times – on the estimated loss of more than 100,000 Bornean orangutans between 1999 and 2015. “To prevent further decline and continued local extinctions of orangutans, humanity must act now,” the study states. “Biodiversity conservation … must become a guiding principle in the public discourse and in political decision-making processes.”

“Orangutans can adapt to different situations,” Prasetyo said. “When the forest changes from primary (old growth) to secondary (regenerated), they can adapt. Why not protect them in that forest and they can survive? We just need to make sure there’s no hunting.”

Prasetyo’s interest in conservation began when was growing up on a small family farm in Nganjuk, near Mount Wilis in East Java, Indonesia. “People were always removing the top of mountains or opening the forest to agriculture,” he said. That inspired him to pursue a bachelor’s degree in biology, focusing on ecology and conservation, at Universitas Nasional, Jakarta, which he earned in 1998. He received a master's degree in conservation biology from the University of Indonesia in 2007 and began his doctoral studies at Rutgers in 2013 under the supervision of Erin R. Vogel, a faculty member of the Graduate Program in Ecology and Evolution and an associate professor in the Department of Anthropology at Rutgers–New Brunswick and Center for Human Evolutionary Studies.

“Didik has been in the forefront of a lot of the orangutan conservation efforts in Indonesia,” Vogel said. “He’s been very involved on the ground in many surveys that led to these recent population estimates. If he’s not already, he will be one of the future leaders of orangutan conservation.”

Prasetyo became interested in the apes when he mapped the genome of orangutans in East Kalimantan in eastern Borneo, Indonesia. Orangutans weigh about 90 to 180 pounds and are quite shy. They’re the most solitary of the great apes and they live about 45 years in the wild. They spend nearly all their time in trees, but Borneo orangutans also spend time on the ground, according to Prasetyo.

His research has included the nesting behavior of wild orangutans. Every night, they build strong nests, or beds, in trees, with branches they lock together. They also make blankets using big leaves and pillows from small branches with leaves. In the rainy season, they make better blankets that double as umbrellas.

Prasetyo’s doctoral research focuses on the development of flanges – the large facial disks, or cheek pads, composed largely of muscle and fat that surround their faces – in male orangutans, touting their social status to attract females. Males will also develop a large, muscle-covered throat patch and long hair, and double their body mass, according to Vogel. But scientists know very little about bimaturism in adult male orangutans, and why flange development is delayed in some of them.

“Flanged orangutans put on a ton of fat and muscle, they look very different and they start acting very differently in the forest,” Vogel said. “They give really amazing long-call vocalizations that travel as far as a kilometer. They tend to attract females to them.”

Prasetyo is trying to gain a better understanding of what triggers the transition of adult males from unflanged to flanged and why some males delay their transition. He’s studying the diet of captive orangutans, competition among males and the hormones testosterone and cortisol, which is released during stress and inhibits testosterone production and may delay flange development.

Long-term studies show males eventually become flanged, but scientists are not 100 percent sure, Vogel said.

“Didik is a great student, a really hard worker and a great collaborator,” she said. “I feel like when he’s done with his Ph.D., he will be an excellent professor in Indonesia and will one of my collaborators in all my research efforts in Indonesia.”

Despite widespread availability of morning meal programs, a large number of Canadian students are still skipping breakfast, according to a study from the University of Waterloo.

The study looked at the eating habits of 42,000 students from 87 secondary schools in Alberta and Ontario during the 2014/15 school year. It found that 39 percent of students reported eating breakfast fewer than three days in a typical school week.

The findings were consistent with national data that showed nationwide, 48.5 percent of adolescents skipped breakfast at least once a week.

"In spite of the widely-acknowledged value of youth having a healthy morning meal, breakfast skipping is highly prevalent among Canadian adolescents," said Katelyn Godin, a doctoral candidate at Waterloo and lead author of the study. "While we do know that breakfast programs are having a positive impact, with one-fifth of adolescents reporting eating breakfast at school once-a-week, there is still room for improvement."

Godin said breakfast programs are not reaching their full potential in Canada due to a lack of social awareness about their diverse benefits, lingering social stigma and limited economic support for the programs.

"Canadian breakfast programs are currently supported by a patchwork of funding and would benefit from something more consistent," said Godin.

A comprehensive new study looking at variations in Ichthyosaurus, a common British Jurassic ichthyosaur (sea-going reptile) also known as 'Sea Dragons', has provided important information into recognizing new fossil species.

Professor Judy Massare (SUNY College at Brockport, NY, USA) and Dean Lomax (The University of Manchester) have studied hundreds of specimens of Ichthyosaurus. After their latest research project the pair urge caution in naming new fossil species on the basis of just a few fragmentary or isolated remains.

For their research Prof Massare and Lomax focused on one particular part of the Ichthyosaurus skeleton, the hindfin (or back paddle). The purpose was to evaluate the different forms among the six-known species of Ichthyosaurus. They examined 99 specimens which could provide useful information.

Early in their research, they found different types of hindfin that initially appeared to represent different species. However, the more specimens they examined the more 'variation' they uncovered, such as differences in the size and number of bones. They determined that a single hindfin alone could not be used to distinguish among species of Ichthyosaurus, but that a particular variation was more common in certain species.

Lomax explains: "As we have such a large, complete sample size, which is relatively unique among such fossil vertebrates, our study can help illustrate the limitations that palaeontologists face when dealing with few or even just one specimen".

Their findings show that with only a few specimens, features can be found that differ substantially from one specimen to the next and thus appear as if there are several species. Whereas, in reality, with a much larger sample size the gaps in the 'unique' variations are filled in, showing that differences are simply the result of individual variation and a lack of the full picture.

Prof Massare said: "We described a few hindfins, which might have been called a new species if they were found in isolation. Instead, we had enough specimens to determine that it was just an extreme variation of a common form."

Palaeontologists fall into one of two camps when it comes to naming species, 'lumpers' and 'splitters'. The former 'lump' groups of similar specimens together, whereas the latter opt to split-up specimens and distinguish new species. However, in this new study, if the team opted to split-up the specimens based on the variation found, it would suggest a huge number of species.

"If we considered the variation as unique, it would mean we would be naming about 30 new species. This would be similar to what was done in the 19th Century when any new fossil find, from a new location or horizon, was named as a new species if it differed slightly from previously known specimens.

"As lots of new fossil species are named every year, in some cases, such as with fragmentary or limited remains, the decision to name a new species should be considered very carefully." Added Lomax.

The new study has been published today in the scientific journal, Geological Magazine: https://doi.org/10.1017/S0016756818000146.

According to a panel of international experts, clinical trials of multimorbidity should measure and report, at minimum, quality of life, mortality, and mental health outcomes. Twenty-six multimorbidity researchers, clinicians, and patients from 13 countries participated in a Delphi Panel and reached consensus on 17 core outcomes for multimorbidity research. The highest ranked outcomes were health related quality of life, mental health outcomes and mortality. Other outcomes were grouped into overarching themes of patient-reported impacts and behaviors (treatment burden, self-rated health, self-management behavior, self-efficacy, adherence); physical activity and function (activities of daily living, physical function, physical activity); outcomes related to the medical visit (communication, shared decision making, prioritization); and health systems outcomes (healthcare utilization, costs, quality of healthcare). The authors suggest that, when designing studies to capture important domains in multimorbidity, researchers consider the full range of outcomes based on study aims and interventions.

A Core Outcome Set for Multimorbidity Research (COSmm)
Susan Smith, MD, MSc, et al
HRB Centre for Primary Care Research, Royal College of Surgeons, Dublin, Ireland
http://www.annfammed.org/content/16/2/132.full

ATLANTA-Exposure to psychological stress in the form of social conflict alters gut bacteria in Syrian hamsters, according to a new study by Georgia State University.

It has long been said that humans have "gut feelings" about things, but how the gut might communicate those "feelings" to the brain was not known. It has been shown that gut microbiota, the complex community of microorganisms that live in the digestive tracts of humans and other animals, can send signals to the brain and vice versa.

In addition, recent data have indicated that stress can alter the gut microbiota. The most common stress experienced by humans and other animals is social stress, and this stress can trigger or worsen mental illness in humans. Researchers at Georgia State have examined whether mild social stress alters the gut microbiota in Syrian hamsters, and if so, whether this response is different in animals that "win" compared to those that "lose" in conflict situations.

Hamsters are ideal to study social stress because they rapidly form dominance hierarchies when paired with other animals. In this study, pairs of adult males were placed together and they quickly began to compete, resulting in dominant (winner) and subordinate (loser) animals that maintained this status throughout the experiment. Their gut microbes were sampled before and after the first encounter as well as after nine interactions. Sampling was also done in a control group of hamsters that were never paired and thus had no social stress. The researchers' findings are published in the journal Behavioural Brain Research.

"We found that even a single exposure to social stress causes a change in the gut microbiota, similar to what is seen following other, much more severe physical stressors, and this change gets bigger following repeated exposures," said Dr. Kim Huhman, Distinguished University Professor of Neuroscience at Georgia State. "Because 'losers' show much more stress hormone release than do 'winners,' we initially hypothesized that the microbial changes would be more pronounced in animals that lost than in animals that won."

"Interestingly, we found that social stress, regardless of who won, led to similar overall changes in the microbiota, although the particular bacteria that were impacted were somewhat different in winners and losers. It might be that the impact of social stress was somewhat greater for the subordinate animals, but we can't say that strongly."

Another unique finding came from samples that were taken before the animals were ever paired, which were used to determine if any of the preexisting bacteria seemed to correlate with whether an animal turned out to be the winner or loser.

"It's an intriguing finding that there were some bacteria that seemed to predict whether an animal would become a winner or a loser," Huhman said.

"These findings suggest that bi-directional communication is occurring, with stress impacting the microbiota, and on the other hand, with some specific bacteria in turn impacting the response to stress," said Dr. Benoit Chassaing, assistant professor in the Neuroscience Institute at Georgia State.

This is an exciting possibility that builds on evidence that gut microbiota can regulate social behavior and is being investigated by Huhman and Chassaing.

Glioblastoma - a universally fatal form of brain cancer - is known for its ability to hijack immune checkpoints and evade detection and destruction by the body's immune defenses. But many of the details underlying this feat remain unknown. A new study by investigators from Brigham and Women's Hospital finds that some types of glioblastoma tumors may be able to shed extracellular vesicles (EVs) - small packages of biomaterial - that can help to suppress the body's ability to mount an immune response against the tumor. In addition, the team detected DNA levels from these EVs in blood samples from patients with glioblastoma, suggesting that they could potentially serve as a biomarker of the disease. The team's results are published online this week in Science Advances.

"This is the first time that anyone has observed that immune checkpoints can operate through extracellular vesicles and not just through the cell surface," said co-corresponding author Sean Lawler, PhD, of the BWH Department of Neurosurgery. "This is a new concept, suggesting that these vesicles can work more distantly from the tumor cells."

Immune checkpoint inhibitors are already in the clinic and in clinical trials for glioblastoma, but challenges remain. The current study identifies a new mechanism through which tumor cells may be able to suppress the activation of T cells, which have the ability to attack cancer cells. When tumors shed EVs, the vesicles can contain biological materials - including DNA and RNA - that can help tumor cells thrive. In the current study, researchers found that EVs derived from glioblastoma stem-like cells contained PDL-1 - a key component that tumor cells can use to deactivate T cells, protecting themselves from detection.

The research team then analyzed blood samples collected from healthy people and from patients with glioblastoma. They found that 14 of 21 patients tested showed enrichment of PDL-1 DNA in isolated EVs. They also correlated DNA abundance with glioblastoma tumor volume, finding a significant correlation between PDL-1 DNA abundance and tumor size, for tumors up to 60 cubic centimeters.

The authors acknowledge that due to the small sample size, follow up studies are needed to determine if their results are reproducible and if PDL-1 DNA on EVs can provide a viable biomarker for glioblastoma. They are continuing to follow up on these findings in the lab.

Researchers at The University of Manchester are using computer simulations of chimpanzees to improve not only our understanding of how the animals walk, but also the technology we use to do it.

The research, being published by the Royal Society Open Science Journal, shows how simple changes to 'machine learning' algorithms can produce better looking, more accurate computer-generated animal simulations.

It will also help researchers investigate the 'curious way' that all primates walk and how this might be linked to stability whilst moving through the trees.

Professor Bill Sellers, from the School of Earth and Environmental Sciences, says: 'Starting from an animal's skeleton, computers using machine learning can now reconstruct how the animal could have moved. However, they don't always do a good job.

'But with some simple changes to the machine learning goals we can now create much more accurate simulations. We've now used this process to generate chimpanzee locomotion to explore why they walk the way they do.

'The idea was to look at how much energy it costs to walk in a stable fashion compared to other movement patterns.'

The chimpanzee model was created from a full body CT scan of an adult male common chimpanzee. Using the scan the team generated a skeletal model and a skin outline. The skeletal model was then used to define joint positions, muscle paths and limb contact points for the simulation.

This was then used to analyse the chimpanzee's gait, the pattern of movement animals (including humans) make whilst walking.

In evolutionary biomechanics - the study of evolution through movement processes - it is often thought that gaits of all animals evolved to use the least amount energy whilst travelling.

However, using the chimpanzee model, the research team are proving that this is no longer the case.

Prof Sellers explains: 'As technology has advanced and with musculoskeletal models becoming increasingly sophisticated, previous simulation models are becoming extremely unrealistic in relation to gait patterns so we have to adapt the way we think and research.'

The researchers found that by increasing lateral stability in the simulation it increases the energetic cost, but also the realism of the generated walking gait in a chimpanzee musculoskeletal model.

Prof Sellers added: 'The realism of the gait produced by the chimpanzee model is considerably enhanced by including a lateral stability and it is highly likely that this is an important evolutionary development.

'This enhanced lateral stability comes at a moderate energetic cost however, and this cost would need to be outweighed by other adaptive advantages.'

AMHERST, Mass. - For many years, populations of a little red squirrel with cute ear tufts, a native of Great Britain, Ireland and Europe, have been in serious decline because of competition for food from an invasive North American gray squirrel and a pox it carries for which the native animal has no defense. Now, new research suggests that native pine martens, also once on the decline, are suppressing the invading squirrels' numbers.

An international research team including Christopher Sutherland of the University of Massachusetts Amherst, Xavier Lambin and Emma Sheehy of the University of Aberdeen, Scotland, and others at the Waterford Institute of Technology, Ireland, report in the current issue of Proceedings of the Royal Society B that native pine marten suppression of the invasive gray squirrels in Scotland is helping recovery of native red squirrel populations.

Sheehy says, "Our study has confirmed that exposure to pine martens has a strong negative effect on grey squirrel populations, whereas the opposite effect was observed in red squirrel populations who actually benefitted from exposure to martens."

UMass Amherst's Sutherland, who did his doctoral work at the University of Aberdeen with Lambin, adds, "Our state-of-the-art analysis suggests that we can achieve conservation objectives twice over by allowing a native species, the pine marten, to spread naturally while conserving our precious red squirrel."

"There has been a vigorous effort to eradicate the gray squirrel at the same time pine martens had retreated north, but the evidence is, that is changing," he points out. "Pine martens are now turning up in areas where they used to be and are suppressing gray squirrel populations just through the natural order. They keep the invasive squirrel in check, if not in decline, and we are seeing a recolonization of the red squirrel. We've potentially found an answer that doesn't require the high cost of eradication."

In their paper with its title beginning, "The enemy of my enemy is my friend," the authors point out that most studies of this kind "mostly consider the impact of a single enemy, despite species being embedded in complex networks of interactions." By contrast, they modeled not only the two squirrel species "linked by resource and disease-mediated apparent competition," but also a second enemy-mediated relationship, with the native marten.

They used DNA forensics and state-of-the-art analyses by combining spatial techniques to estimate pine marten density and squirrel site-occurrence and found that the occurrence of non-native grey squirrels is strongly negatively affected by exposure to pine martens. On the other hand, exposure had a positive effect on red squirrel populations, reversing the previous trends of squirrel interactions.

Sutherland, an expert in ecological and population modelling who carried out the connectivity and spatial capture-recapture analyses for this work, says the researchers deployed feeders in the field that had sticky tabs to capture hair samples of both squirrel species and pine martens. Using DNA from the hair samples, they were able to identify individual pine martens in each study area and map where they were spending most of their time.

Sheehy and colleagues state, "Our evidence that, in addition to their intrinsic value, pine martens provide an ecosystem service by suppressing invasive grey squirrel populations is good news for both red squirrel conservation efforts and the timber growing industry, due to the detrimental impact of the invasive grey squirrel on both."

The current study, which took place between 2014 and 2017, built on evidence from a 2014 investigation by Sheehy which suggested that pine martens may be responsible for the decline of gray squirrels in Ireland. Kenny Kortland, a species ecologist for Forest Enterprise Scotland, notes, "The findings of this research are extremely encouraging. It seems we have a very welcome ally in our efforts to protect red squirrel populations on the national forest estate. The research demonstrates that the return of native predators can have beneficial impacts for other native species."

Technology has a massive impact on our day-to-day lives, right down to the cellular level within our own bodies. Texas A&M University chemists are using it to determine how lipids talk to each other when they interact with membrane proteins, one of the primary targets for drug discovery and potential treatments for any number of different diseases.

By capitalizing on their technological expertise to "see" membrane proteins as they interact with different lipids, Texas A&M chemist Dr. Arthur Laganowsky's research group has discovered compelling evidence that these proteins may be capable of recruiting their own lipid microenvironments through allostery, a biological phenomenon first observed in the 1900s and identified in numerous biological processes, including cellular signaling, transcriptional control and disease.

The team's work, published today (Monday, Mar. 5) in Proceedings of the National Academy of Sciences and led by Texas A&M chemistry postdoctoral researchers Christopher Boone and John W. Patrick, shows that allostery extends to lipid-membrane protein interactions, enabling these proteins to alter their remote binding sites to accept lipids of different types and opening up new possibilities for pharmaceutical drug design and delivery.

From Protection to Communication

Protective membranes exist on the surface of all living cells and contain many of our cells' most important proteins, many of which have unique and specialized functions, such as safeguarding the cargo going into and out of the cell that is necessary for cell survival. These membranes are largely composed of lipids, which themselves play key roles in maintaining membrane integrity and ensuring that these specialized membrane proteins function properly.

"From this work and our previous work, it is becoming increasingly clear that membrane proteins are exquisitely sensitive to the chemistry of the lipid," Laganowsky says. "Given that lipid composition differs throughout the organs of the body, understanding how the lipid environment in these areas influences protein structure will be critical to opening new possibilities for pharmaceutical drugs designed to affect how these lipids bind with one another."

Membrane proteins represent one of the most important targets for pharmaceutical drug discovery, with a staggering 60 percent of drugs on the current market targeting them for their integral role in cellular processes. The crucial role of lipids in the folding, structure and function of membrane proteins is emerging through multiple research reports and channels -- findings that are uncovering the intimate roles lipid-protein interactions play in controlling protein structure and function.

"In a cell, molecular interactions with molecules are exploited to carry out cellular processes," Laganowsky explains. "For example, when you eat a chili pepper, you feel a hot sensation as a result of a molecule in the pepper binding to a specific membrane protein that, in turn, elicits this response. In a similar fashion, our study has demonstrated that the membrane protein can influence its surrounding lipid environment, and this environment may influence, for example, how molecules are sensed."

Barriers to a Breakthrough

Membrane proteins carry out essential cellular functions, including signaling and transport of molecules across the blood-brain bilayer, which most drugs have a difficult time crossing. These proteins are embedded in the chemically complex lipid environment of the biological membrane, which presents unique challenges in deciphering the roles that lipids play in modulating membrane protein structure and function.

To date, technology, or lack thereof, has been the primary barrier to such investigations. Beyond their expertise in using X-ray crystallography to determine the atomic structure of proteins, Laganowsky's lab was one of first in the U.S. to perfect the use of cutting-edge native ion mobility mass spectrometry -- a technique he helped develop as a postdoctoral researcher at the University of Oxford -- that has enabled his group to decipher the language lipids and membrane proteins use to communicate. By shedding new light on how lipid-protein interactions can enhance or weaken binding of other lipid types, their research is changing our understanding of the structural dynamics of proteins at cellular membrane levels and providing novel insights with the power to transform drug design, development and delivery.

"There is a critical need to expand our fundamental knowledge in this emerging field by applying and developing innovative approaches to elucidate how lipids modulate the structure function of membrane proteins," Laganowsky says. "To this end, we continue to study a number of ion channels, receptors and other types of membrane proteins."

Wen Liu, Yang Liu and Xiao Cong, former members of Laganowsky's lab within the Texas A&M Health Science Center's Institute of Biosciences and Technology (IBT), also collaborated in the research, as did Dr. Gloria Conover, an assistant research scientist in Laganowsky's group since 2017.

The team's paper, "Allostery Revealed Within Lipid Binding Events to Membrane Proteins," can be viewed online along with related figures and captions. Their work was funded by Laganowsky's five-year, $2.2 million National Institutes of Health (NIH) New Innovator Award.

Laganowsky received his doctorate in biochemistry from the University of California, Los Angeles, in 2011, earning the Biochemistry Distinguished Dissertation Award for his doctoral work on structural studies of amyloid-related proteins. He completed three years of postdoctoral study at Oxford as the Nicholas Kurti Junior Research Fellow in world-renowned Dame Carol Robinson's laboratory prior to coming to the IBT within Houston's Texas Medical Center as an assistant professor and director of the Waters Collaboratory for the Analysis of Membrane Proteins. He also held a joint appointment in Texas A&M Department of Chemistry, which he joined full-time in January 2017.

NEW YORK, NY--March 6, 2018--From 2014 to 2017, private insurance claim lines with a diagnosis of sleep apnea--a potentially serious disorder in which a person repeatedly stops and starts breathing while asleep--increased by 911 perc

NEW YORK, NY--March 6, 2018--From 2014 to 2017, private insurance claim lines with a diagnosis of sleep apnea--a potentially serious disorder in which a person repeatedly stops and starts breathing while asleep--increased by 911 percent in rural America, according to FAIR Health, a national, independent, nonprofit organization dedicated to bringing transparency to healthcare costs and health insurance information. In contrast, urban areas recorded an increase of 839 percent in the same time frame. In the nation overall, claim lines with a diagnosis of sleep apnea grew 850 percent.

Rural diagnoses of sleep apnea grew from 0.2 percent of all rural medical claim lines to 1.98 percent. In urban settings, the increase was from 0.13 percent of all urban medical claim lines to 1.24 percent, and in the nation overall, from 0.14 percent of all national medical claim lines to 1.33 percent.

FAIR Health's study was based on data from its database of over 25 billion privately billed healthcare claims, the nation's largest repository of private healthcare claim records. The study is particularly timely in light of the recent finding by the National Transportation Safety Board that engineer fatigue resulting from sleep apnea caused a Long Island Rail Road crash in Brooklyn and a New Jersey Transit train crash in Hoboken, New Jersey, the latter of which killed one person.

Other findings from FAIR Health's study:

Males are much more likely than females to be diagnosed with sleep apnea. In the period 2016-2017, males accounted for 65 percent of sleep apnea claim lines, females 35 percent.

The age group 51 to 60 years accounted for 31 percent of sleep apnea claim lines--the largest share of eight age groups studied. Patients 61 to 70 years old represented 23 percent of claim lines, while those 41 to 50 years old accounted for 20 percent.

In 2017, the states with the most sleep apnea claim lines as a percent of all medical claim lines by state were (ranked from most to least) Maryland, Idaho, Utah, Arkansas and Iowa. The states with the lowest proportion of sleep apnea claim lines were (from least to most) New Hampshire, Minnesota, Massachusetts, Vermont and Hawaii.

In 2016-2017, the most common diagnoses associated with sleep apnea on claim lines were diabetes, hypertension, respiratory and chest symptoms, dorsalgia, high cholesterol, general fatigue, joint pain and cardiac dysrhythmias.

The three most common (and costly) devices associated with sleep apnea diagnoses were (ranked from most to least): continuous positive airway pressure (CPAP) devices, disposable filters used with positive airway pressure devices and headgear used with positive airway pressure devices.

"Sleep apnea is a public health issue of increasing interest and concern," said FAIR Health President Robin Gelburd. "FAIR Health is ready to contribute its data resources and analytical capabilities to help researchers, policy makers and others address this issue."

Researchers at the University of Colorado Anschutz Medical Campus are working to develop statistical models to better predict which patients will be prescribed opioid medications long-term following discharge from a hospital stay. Opioids are commonly prescribed in the hospital but little is known about which patients will progress to chronic opioid therapy following discharge.

In the U.S. last year, more than 63,000 people died of a drug overdose, with opioids involved in 75 percent of those deaths. According to the 2015 National Survey of Drug Use and Health, over 2 million people in the US had a prescription opioid use disorder.

"Doctors and patients are increasingly aware of the dangers associated with overprescribing of opioids," said Susan Calcaterra, a fellow in addiction medicine at theCU School of Medicine. "We can assist physicians in making informed decisions about opioid prescribing by identifying patient characteristics which put them at risk progressing to chronic opioid use."

The study was published online in the February issue of the Journal of General Internal Medicine.

Calcaterra, lead author, said, "Physicians are moving away from using prescription opioids as the primary treatment of chronic, nonmalignant pain. For the hospitalized patient, our ultimate goal is to provide adequate pain control by using a variety of pain management modalities, in addition to, or in place of, opioid medications. In doing so, we may be able to limit the number of patients who progress to long-term opioid use."

Researchers aimed to develop a prediction model to identify hospitalized patients at highest risk of progressing to chronic opioid use following hospital discharge. To develop the prediction model, they accessed data available in the electronic health record from Denver Health Medical Center, an urban, safety net hospital. Researchers defined chronic opioid therapy (COT) as either receiving a 90-day or greater supply of oral opioids with less than a 30-day gap in supply over a 180-day period, or filling ten or more opioid prescriptions over one year.

By accessing electronic health record data, researchers identified patient-specific variables which were highly associated with the progression to COT. These variables included having a history of substance use disorder, past year receipt of a benzodiazepine, an opioid medication or a non-opioid analgesic, receipt of an opioid at hospital discharge and high opioid requirements during hospitalization. Having a surgical procedure during the hospitalization was not associated with progression to COT. The model correctly predicted chronic opioid therapy (COT) in 79% of the patients and no COT correctly in 78% of the patients.

According to the authors, no prediction model has been published to identify hospitalized patients at high-risk of future COT. There are useful prediction tools to assess the patient's risk of opioid misuse including the Screener and Opioid Assessment for Patients with Pain (SOAPP-R) and the Opioid Risk Tool (ORT). However, these tools have not been validated in the hospital setting and they can be too time-consuming to consistently administer in a busy clinical setting.

"This prediction model could be incorporated into the electronic health record and would activate when a physician orders opioid medication. It would inform the physician of their patient's risk for developing COT and may impact their prescribing practices," Calcaterra said.

She continues: "All of the data required to assess risk are already available in the electronic health record, the physician would not need to input additional information. This tool would be inexpensive to implement and helpful in busy hospital settings where physicians make important health care decisions on patients they may have only met the day before. Researchers plan to validate this model in other health care systems to tests its ability to predict COT in other patient populations."

Similar techniques are already used in medicine to help make predictions using electronic health data, including models that help predict development of diabetes, pancreatitis severity, heart failure readmissions and sepsis.

"Our goal is to manage pain in hospitalized patients, but also to better utilize effective non-opioid medications for pain control," Calcaterra said. "Ultimately, we hope to reduce the morbidity and mortality associated with long-term opioid use."

WEST LAFAYETTE, Ind. -- Purdue researcher Luis Solorio has helped create a lifelike cancer environment out of polymer to better predict how drugs might stop its course.

Previous research has shown that most cancer deaths happen because of how it spreads, or metastasizes, in the body. A major hurdle for treating cancer is not being able to experiment with metastasis itself and knock out what it needs to spread.

Studies in the past have used a 3-D printer to recreate a controlled cancer environment, but these replicas are still not realistic enough for drug screening.

"We need a much finer resolution than what a 3-D printer can create," said Solorio, an assistant professor of biomedical engineering.

Rather than 3-D printing, Solorio and a team of researchers have proposed 3-D writing. The device that they developed, a 3-D jet writer, acts like a 3-D printer by producing polymer microtissues as they are shaped in the body, but on a smaller, more authentic scale with pore sizes large enough for cells to enter the polymer structure just as they would a system in the body.

3-D jet writing is a fine-tuned form of electrospinning, the process of using a charged syringe containing a polymer solution to draw out a fiber, and then deposit the fiber onto a plate to form a structure. This structure is a scaffold that facilitates cell activity.

Solorio has so far used the device to write a structure that drew in cancer cells to sites in mice where cancer would not normally develop, confirming that the device could create a feasible cancer environment. Solorio's other studies have increased cancer cells in human samples for better analysis and maintained receptors on these cells that drugs would need to find.

"Ideally, we could use our system as an unbiased drug screening platform where we could screen thousands of compounds, hopefully get data within a week, and get it back to a clinician so that it's all within a relevant time frame," Solorio said.

Initial findings published on Feb. 27 in Advanced Materials based on Solorio's work as part of a team at the University of Michigan Biointerfaces Institute. He completed data analysis and writing while on faculty at Purdue.

AUGUSTA, Ga. (March 5, 2018) - Antibiotic use is known to have a near-immediate impact on our gut microbiota and long-term use may leave us drug resistant and vulnerable to infection.

Now there is mounting laboratory evidence that in the increasingly complex, targeted treatment of cancer, judicious use of antibiotics also is needed to ensure these infection fighters don't have the unintended consequence of also hampering cancer treatment, scientists report.

Any negative impact of antibiotics on cancer treatment appears to go back to the gut and to whether the microbiota is needed to help activate the T cells driving treatment response, says Dr. Gang Zhou, immunologist at the Georgia Cancer Center and the Department of Biochemistry and Molecular Biology at the Medical College of Georgia at Augusta University.

"It likely depends on what types of therapy physicians are giving to patients and how often they also are giving them antibiotics," says Zhou, corresponding author of the study in the journal Oncotarget.

They have some of the first evidence that in some of the newest therapies, the effect of antibiotics is definitely mixed.
Infections are typically the biggest complication of chemotherapy, and antibiotics are commonly prescribed to prevent and treat them.

"We give a lot of medications to prevent infections," says Dr. Locke Bryan, hematologist/oncologist at the Georgia Cancer Center and MCG.

"White blood cell counts can go so low that you have no defense against bacteria, and that overwhelming infection can be lethal," says Bryan, a study co-author.

In this high-stakes arena, where chemotherapy is increasingly packaged with newer immunotherapies, Bryan, Zhou and their colleagues have more evidence that antibiotics' impact on the microbiota can mean that T cells, key players of the immune response, are less effective and some therapies might be too.

They report that antibiotic use appears to have a mixed impact on an emerging immunotherapy called adoptive T-cell therapy, in which a patient's T cells are altered in a variety of ways to better fight cancer.

They found that one of the newest of these - CAR T-cell therapy - is not affected by antibiotics, likely because it is not so reliant on the innate immune system.

"These infused T cells can pretty much act on their own to kill cancer cells," Zhou says.

With this approach, physicians retrieve T cells from a patient's blood, engineer them to express a tumor-finding receptor - called chimeric antigen receptor, or CAR - and give them back to the patient. These patients typically will receive a conditioning chemotherapy regimen, which often includes the common agent cyclophosphamide, or CTX, to intentionally wipe out some of their normal T cells and make room for the engineered super-fighters. This emerging treatment is often used in patients who have failed multiple other treatments, including chemotherapy.

Even long-term antibiotic use does not seem to hinder the efficacy of CAR T-cell therapy against systemic lymphoma in their animal model. While they could see the impact of antibiotics on the microbiota, mice with CAR T-cell therapy continued to respond well to cancer treatment.

But the efficacy of another mode of adoptive T-cell therapy was impacted. This model mimics therapy in which receptors that target the patient's tumor are put onto their T cells. In this case, the researchers transferred tumor-specific CD4+T cells to treat mice with colorectal cancer.

One key difference here is that, unlike the CAR T-cell therapy, these engineered T cells still need help from the innate immune system to fight the tumor, now that they can better target it, Zhou says.

Mice with colorectal cancers that did not receive antibiotics were cured after being treated with the chemotherapy CTX followed by CD4+T-cell therapy. However, with antibiotics on board, this curative effect was lost in three out of five mice three weeks after treatment.

Their studies also confirmed that antibiotic use impacts the efficacy of the widely used CTX, when it's used alone, in this case to treat B-cell lymphoma. In addition to directly killing rapidly dividing cancer cells, CTX gets the attention and help of endogenous T cells, and antibiotics reduced that T-cell response, the scientists report.

Their findings in lab animals confirmed the recent work of others that the altered intestinal microbiota impacts CTX's ability to fight sarcoma, a rare cancer of our connective tissue. Bigger picture, it suggests that some chemotherapy regimens rely on the gut bacteria to stir the immune system to fight cancer, the scientists write.

"It is clear in animal models that if you wipe out the intestinal microbiota, like you do with antibiotics, it will attenuate the chemotherapy efficacy," says Zhou. "There is also emerging clinical evidence showing that for CTX-based chemotherapy, some patients who also get antibiotics for a longer period of time, seem to have less optimal outcomes."

Human studies are needed to see whether antibiotics affect the outcomes of adoptive T-cell therapy and to give clinicians and their patients better information about how best to maneuver treatment, Zhou notes.

The microbiota is comprised of trillions of bacteria, viruses and funguses and the biggest population resides in our gut, where they help us digest food and protect us from other invaders. Anyone who has taken an antibiotic also knows it can wreak havoc with the gut, causing severe diarrhea and other discomfort as it alters the natural - and healthful - complement of our microbiota.

While even a single course of antibiotics has been shown to disrupt the microbiota in humans, Zhou has shown in mice that it is protracted use that likely also impacts the immune response.
And, when mice, at least, have a weakened immune system their microbiota literally looks different and there is evidence that antibiotics suppress their immune response.

Even with antibiotics out of the equation, there can be conflicting crosstalk between chemotherapy and immunotherapy. If/when chemotherapy hampers the immune response it could obviously impact the efficacy of some immunotherapies. So scientists and clinicians alike also are trying to figure out how best to combine these different therapies, to achieve optimal synergy.

MADISON -- Not all smiles are expressions of warmth and joy. Sometimes they can be downright mean. And our bodies react differently depending on the message a smile is meant to send.

Research led by Jared Martin, a psychology graduate student at the University of Wisconsin-Madison, shows that smiles meant to convey dominance are associated with a physical reaction -- a spike in stress hormones -- in their targets. On the other hand, smiles intended as a reward, to reinforce behavior, appear to physically buffer recipients against stress.

"Facial expressions really do regulate the world. We have that intuition, but there hasn't been a lot of science behind it," says Martin, whose study was published today by the journal Scientific Reports. "Our results show that subtle differences in the way you make facial expressions while someone is talking to you can fundamentally change their experience, their body, and the way they feel like you're evaluating them."

Martin works in the lab of UW-Madison psychology professor -- and co-author on the study -- Paula Niedenthal, whose research on emotions has established three major types of smiles: dominance (meant to convey status), affiliation (which communicates a bond and shows you're not a threat), and reward (the sort of beaming, toothy smile you'd give someone to let them know they're making you happy).

The researchers stressed out 90 male college students by giving them a series of short, impromptu speaking assignments judged over a webcam by a fellow student who was actually in on the study. Throughout their speeches, the participants saw brief video clips they believed were their judge's reactions. In fact, each video was a prerecorded version of a single type of smile -- reward, affiliation or dominance.

Meanwhile, the researchers were monitoring the speakers' heart rates and periodically taking saliva samples to measure cortisol, a hormone associated with stress.

"If they received dominance smiles, which they would interpret as negative and critical, they felt more stress, and their cortisol went up and stayed up longer after their speech," says Niedenthal. "If they received reward smiles, they reacted to that as approval, and it kept them from feeling as much stress and producing as much cortisol."

The effect of affiliative smiles was closer to that of reward smiles -- interesting, but hard to interpret, Niedenthal says, because the affiliative message in the judging context was probably hard for the speakers to understand.

Other research has shown that people with greater variation in the rate at which their hearts beat are better able to understand social cues such as facial expressions.

"People vary in how tolerant or capable they are at sitting with and understanding or engaging with social information," says Niedenthal, whose research is supported by the National Institutes of Health and National Science Foundation and U.S.-Israeli Binational Science Foundation. "The thing about your body that permits you to take in the information and process it fully, or make sense of it, is the functioning of your parasympathetic nervous system, which manages your breathing and heart rate and allows you to be calm in the face of social information."

Smile study participants with high heart-rate variability did indeed show stronger physiological reactions to the different smiles.

But, Martin says, heart-rate variability is not innate and unalterable. In fact, a long list of disorders -- obesity, cardiovascular disease, autism, and anxiety and depression among them -- can drag down heart-rate variability. That may, in turn, make people worse at recognizing and reacting to social signals such as dominance and reward smiles.

"We are all individuals walking around in the world with different bodies. You may be really anxious. You may be in really good shape," Martin says. "Those things that we carry around with us change the way we perceive the world in very sensitive and personal ways."

A new paper on fieldwork in rural Belize serves as a case study for how an established anthropology fieldwork model can be used to both develop site-specific cultural and historical exhibits and train a new generation of public history scholars. The paper also highlights the importance of diversity to research teams when engaging in research - especially community-based scholarship.

"Public history, as a field, focuses on both sharing information about history and working with the public to place history in context - and understand how people already relate to their cultural and regional history," says Alicia McGill, an assistant professor of history at North Carolina State University and author of the paper.

"For this project, we worked with two Belizean villages - Crooked Tree and Biscayne - that are in close proximity to the Mayan ruins of Chau Hiix," McGill says. "Most of the residents in both villages are Belizean Kriol, of African descent. Our goal was to develop exhibits and educational materials that could be used by the villages to foster tourism and support educational efforts."

To that end, McGill led a team of public history graduate students from NC State and undergraduates from the University of New Hampshire (UNH) and Galen University, in Belize, as well as collaborating with archaeological researchers from UNH. The team worked closely with residents of Crooked Tree and Biscayne to ensure that the exhibits and related materials addressed not only the Mayan civilization, but the importance of Kriol culture to the region.

"We learned several things over the course of the project that I think are broadly applicable to other public history efforts," McGill says.

First, that the methodology of anthropological fieldwork can easily be adapted to the field of public history, particularly in regard to community engagement.

"It works so well because you are engaging in cultural immersion, which offers unique insights into the subject matter," McGill says.

Second, identifying local and regional partners is critical to success.

"We worked with national, regional and local partners, who provided us with resources, access and cultural and political insights that we may otherwise have missed," McGill says.

Lastly, the project also drove home the importance of having an ethnically diverse research team.

"For example, we found that local residents of African descent raised different topics when talking with African American members of our research team than when talking with other members of the research team," McGill says. "It gave us more insight and different perspectives on the subjects we were studying and the nature of our community engagements.

"And while I think all of these observations hold true for public history fieldwork in the U.S., they may be particularly valuable for public historians interested in international work," McGill says.