Culture

Many people have experienced stressful situations that trigger a particular mood and also change certain feelings toward food. An international team led by researchers at Baylor College of Medicine looked into the possibility of crosstalk between eating and mood and discovered a brain circuit in mouse models that connects the feeding and the mood centers of the brain. Published in the journal Molecular Psychiatry, these findings may help explain some of the observations between changes in mood and metabolism and provide insights into future solutions to these problems by targeting this circuit.

"This study was initiated by first author Dr. Na Qu, a psychiatrist of Wuhan Mental Health Center, China, when she was visiting my lab," said corresponding author Dr. Yong Xu, associate professor of pediatrics and of molecular and cellular biology at Baylor College of Medicine.

Qu, a practicing psychiatrist who also conducts basic brain research, was interested in investigating whether there was a neurological basis for the association between depression and other psychiatric disorders and alterations in metabolism, such as obesity or lack of appetite, she had observed in a number of her patients.

Xu, Qu and their colleagues worked with a mouse model of depression induced by chronic stress and observed that depressed animals ate less and lost weight. Then, they applied a number of experimental techniques to identify the neuronal circuits that changed activity when the animals were depressed.

"We found that POMC neurons in the hypothalamus, which are essential for regulating body weight and feeding behavior, extend physical connections into another region of the brain that has numerous dopamine neurons that are implicated in the regulation of mood," said Xu, who also is a researcher at the USDA/ARS Children's Nutrition Research Center at Baylor and Texas Children's Hospital. "We know that a decrease in dopamine may trigger depression."

In addition to the physical connection between the feeding and the mood centers of the brain, the researchers also discovered that when they triggered depression in mice, the POMC neurons were activated and this led to inhibition of the dopamine neurons. Interestingly, when the researchers inhibited the neuronal circuit connecting the feeding and the mood centers, the animals ate more, gained weight and looked less depressed.

"We have discovered that a form of chronic stress triggered a neuronal circuit that starts in a population of cells that are known to regulate metabolism and feeding behavior and ends in a group of neurons that are famous for their regulation of mood," Xu said. "Stress-triggered activation of the feeding center led to inhibition of dopamine-producing neurons in the mood center."

Although more research is needed, Xu, Qu and their colleagues propose that their findings provide a new biological basis that may explain some of the connections between mood alterations and changes in metabolism observed in people, and may provide solutions in the future.

"Our findings only explain one scenario, when depression is associated with poor appetite. But in other cases depression has been linked to overeating. We are interested in investigating this second association between mood and eating behavior to identify the neuronal circuits that may explain that response," Xu said.

Study shows ground floor-based businesswomen doubled their income, narrowed the gender earnings gap by more than half.

Toronto - The gender earnings gap has proven to be a hard nut to crack around the world and it's just as prevalent in strategies designed to lift women out of poverty in developing countries.

New research however is a reminder that solutions to seemingly intractable problems aren't necessarily complicated. A study of 1800 working-aged residents in a public apartment complex in Colombia found that women were more likely to run a home-based business when their randomly-assigned unit was on the ground floor. They earned a lot more at it too.

Female home-based entrepreneurs in ground-floor units of the four- storey complex earned twice as much as women running businesses from the other three floors. They also earned triple what their female neighbours made in other occupations.

While no such differences were seen for men, they continued to outpace women, earning an average of $241 a month in their home-based businesses, compared to $64 for upper-floor female entrepreneurs. But the ground-floor women narrowed that gap by 58.5 percent, earning $167 a month. The research highlights the importance of "micro-geographic space" and how subtle differences in location can make a big difference to people's access to and exchange of resources, especially for women.

"What really stood out for me was the strength of the effect, given how small the spatial distance was," said researcher Laura Doering, an assistant professor of strategic management at the University of Toronto's Rotman School of Management.

Prof. Doering co-wrote the paper with her former colleague Christopher Liu, now an assistant professor at the University of Oregon's Lundquist College of Business.

Self-employment and associated training supports are often promoted as tools for improving low-income women's economic prospects in places where their labour market options are much more limited and poorly paid compared to men. Yet Dr. Doering points out the strategy "hasn't moved the needle very much."

The study's results underline the importance of visibility for female entrepreneurs, who are typically overlooked and less likely to promote their businesses as aggressively as men, according to other research. Ground-floor female entrepreneurs in the Colombian housing complex used their windows and terraces as informal storefronts, almost exclusively selling food and drinks. Women on the upper floors tended towards beauty or other services, such as ice vending or laundry machine rental.

While Prof. Doering cautions that the findings are preliminary, "the real takeaway for me is when we think about programs and policies for economic development, we have to be thinking about space as a resource," says Prof. Doering. "It might be as important as financial capital."

Medicare often spends $3,590 for an individual's 30-day prescription after adjusting for all rebates, and prices continue to rise.

Dr. Richard G. Frank of the Harvard Medical School and Dr. Len M. Nichols of George Mason University's College of Health and Human Services offer a perspective published today in the New England Journal of Medicine that balances prescription drug costs and incentives for innovation.

"The problem is lack of competition, and consumers and taxpayers are left picking up the check," explains Nichols. "Giving Medicare the ability to negotiate prices with pharmaceutical companies is critical to bring down the cost of health care."

Medicare spending for prescription drugs is growing at higher rates than other Medicare spending (9% for Medicare Part B drug spending and 7.3% for Medicare Part D, annually). Specialty drugs--those for a smaller number of patients that cost more and require clinical supervision--were responsible for 63% of the spending growth in Medicare Part D from 2010 to 2015.

"We need carefully designed Medicare prescription drug negotiations," says Frank. "We've proposed specific criteria to guide negotiations and maximize savings while preserving incentives for innovation."

To optimize negotiations, Frank and Nichols recommend two guiding principles: (1) targeting the right drugs and (2) establishing reference prices for negotiations. Medicare would begin negotiations on drug pricing when one of two criteria are met: (1) little competition with high markups and (2) high levels of annual Medicare spending or more than $500 million.

However, negotiations need to meet 3 items for success. First, Medicare will need the power to penalize manufacturers if a reasonable price could not be obtained. Second, upper and lower limits of drug pricing would be set in advance by using the dollars per quality-adjusted life-year (QALY) gained or a similar index. This step will allow higher prices for drugs providing more clinical value and, thereby, provide incentive for developing medications needed most by populations. Third, a neutral third-party arbitrator would become involved if negotiations could not be reached between Medicare and a manufacturer.

Implementing these criteria, which are administratively feasible, would foster exchange and voluntary agreements between Medicare and pharmaceutical manufacturers to balance power amongst consumers and manufacturers while preserving incentives to innovate. This process would reduce the cost of prescription medications for taxpayers and consumers and slow accelerating Medicare expenses.

BIRMINGHAM, Ala. - Beta cells in pancreatic islets produce insulin to exquisitely regulate blood glucose levels and, thus, provide energy to cells throughout the body. Loss or dysfunction of the beta cells results in diabetes, a major public health threat that can lead to heart disease, neuropathy, blindness and kidney failure.

The future points to several possible therapies for diabetes -- including transplantation of functional beta cells grown in culture into patients, or finding strategies to promote regeneration of a patient's own beta cells. Either of those potential therapies requires basic knowledge of the complex genetic programs that produce and maintain functional beta cells.

Chad Hunter, Ph.D., associate professor in the University of Alabama at Birmingham Comprehensive Diabetes Center and Department of Medicine's Division of Endocrinology, Diabetes and Metabolism, has added a key piece to that basic research in a study published online ahead of print in the Journal of Biological Chemistry.

Hunter studies a protein complex in the nucleus of beta cells that functions something like a molecular Swiss Army knife -- different proteins in the complex have different functions, and yet they work together to regulate genes important for the development and maintenance of functional beta cells. The key protein in the complex is the Islet-1 transcription factor, and Hunter, in a series of previous discoveries, has tracked down other proteins that join with Islet-1 to form the complex.

This complex, in addition to the so-far known protein members, now has been shown to also associate with enzymes RNF20 and RNF40, which are two related ubiquitin ligases. The researchers showed that these RNF enzymes are also key proteins in the complex because disruption of either RNF20 or RNF40 reduced insulin release from cultured beta cells.

"The RNF enzymes can act as transcriptional co-regulators," Hunter said. "They can help change how tightly DNA is wrapped around histone proteins, which is important for packaging genomic DNA within a cell's nucleus. You need to loosen the histone association with the DNA to make the gene accessible, so it can be expressed."

Hunter and colleagues reported that the RNF enzymes and Islet-1 are required for the appearance of the ubiquitin modification on histone 2B proteins in beta cells, which is involved in gene transcription and aids with loosening of the DNA at particular genetic sites.

"This histone modification and RNF proteins are associated with gene expression in multiple cell types, but this is the first time they have been studied in beta cells," Hunter said. "The more we know about how beta cells develop and maintain function, the closer we can come to freeing patients from insulin injections or pharmacological intervention."

Research by an international team of scientists shed new light to the nutritional quality of whitefish and revealed that the tasty fish is best to eat in late summer. Whitefish growth and spawning cycles lead to differences in both fish condition and nutritional quality. The measurements done in the research showed that European whitefish muscle omega-3 fatty acid concentration declined by 60 percent from the end of the growing season to the spawning time in winter. The research was completed in University of Jyväskylä, Finland, and was published in Freshwater Biology in August 2019.

The team studied changes in nutritional quality of European whitefish muscle in a year-round study in subarctic Lake Kilpisjärvi, located at 69°N Finnish Lapland. This high-latitude lake is covered from November to mid-summer, but is followed by brief, very intensive productive period in summer.

During this short period when growth is possible (July-August), whitefish have to eat and accumulate enough energy for spawning at December before surviving the long and severe winter.
Professor Kimmo Kahilainen from Inland Norway University oversaw the study as part of a larger research program in the region:

"We found that whitefish muscle omega-3 fatty acid concentration declined by 60 percent from the end of the growing season to the spawning time in winter. At the same time, parental fish avoid storing harmful mercury in their gonads and thus muscle mercury level reach year-round maximum level just after the winter spawning, although even then they did not exceed the 0.5 ppm health limit", professor Kahilainen says.

Local people fish for their winter whitefish supplies in a right time

Whitefish growth and spawning cycles lead to differences in both fish condition and nutritional quality. Local people fish for their winter whitefish supplies just after the main growing season in autumn when the fish condition and nutritional quality is optimal.

"People eating wild fish might have observed decreasing fish condition and muscle quality during spawning time. This reflects the fact that spawning is an extremely energy-demanding time for fish, as they transfer nutritionally valuable compounds into eggs and milt to improve chance of success for their offspring", says Ossi Keva, a PhD student from Jyvaskyla University, who led the study.

Mr. Keva noted:

"Our research on the fatty acid and mercury levels provides scientific background to this traditional knowledge regarding whitefish and should be confirmed for other species and regions. However, we have strong evidence that fishing for food fish should be done during their main growth season and on the other hand leave spawning fish in peace".

University of Arizona ecology and evolutionary biology processor Brian Enquist and former doctoral student Vanessa Buzzard trekked across the Americas: from moist, tropical jungles in Panama to the frigid boreal forests in Colorado to the wet temperate forests of the Pacific Northwest. Along the way, they collected soil samples, enveloped trees in belts to measure growth on a fine scale, and planted sensors that continue to collect data on soil moisture and temperature, which varies widely between forests.

"Temperature influences many ecological processes and has been used to explain patterns of biodiversity for over a century; however, we still don't have a clear understanding of how temperature influences the functioning of ecosystems," Buzzard said.

But by measuring and comparing the traits of diverse species to understand how they function in their environment across a range of temperatures, the team uncovered how temperature influences an ecosystem. They found that temperature drives coordinated shifts in the functional traits between plants and microbes that influence ecosystems, according to Buzzard, who is the lead author on the paper published in Nature Ecology and Evolution on Aug. 19.

"The work represents an unprecedented monitoring of soils and forests from hot tropical forests to the cold boreal forests and fills important gaps in our ecological understanding of how organisms within different levels of an ecosystem's food chain are linked via temperature," Enquist said of the project that began in 2011. "The work involved much field work in remote locations, lab work associated with analyzing soil microbial DNA and computer analyses using large datasets."

As an example, bacteria within certain communities have genes tailored by evolution for cycling the nutrients that are naturally available within their ecosystem. The team saw a shift in the genes tied to nutrient cycling for bacteria as temperatures differed across sites.

"As you increase the latitude - so, cooler temperatures - we have a nitrogen limitation. We expect that to influence the structuring of these communities, both plants and microbes," Enquist said.

In tropical forests, on the other hand, trees quickly grow and shed very broad leaves. That means these "throw-away leaves," as Buzzard put it, constantly fall to the floor for microbes to consume. The research team saw a lower abundance of genes in the local microbes for processing carbon. In forests with pine trees that sprout and drop dense, narrow leaves, the local bacteria had different functional traits: They have a greater abundance of carbon-cycling genes to handle the complex-difficult to access large pools of carbon that is available in temperate regions. It's like eating lettuce (tropics) verse eating bark (temperate regions), according to Buzzard.

"We can use this understanding to make predictions about how we expect soil microbial communities to function as climate changes," Buzzard said. "If temperature drives the observed shift in plant and bacterial functioning, ecosystems subjected to climate warming should also experience directional shifts in functional diversity and biogeochemistry."

That shift might happen too quickly for ecosystems to adapt. She also added that diversity is not solely driven by temperature. There could be other constraining factors that could be teased out in another study.

Next, Buzzard said the team will install more sites to collect more data. They also want to monitor how growth rates in plants vary across ecosystems with differing temperatures. This means much more time in the field, but that's no problem for Buzzard. She spent at least six months a year for the first three years of the study in the field: "I really enjoyed being in the field. There are long days. They're hard, but you get to go see these amazing places and have unique interactions with the wildlife."

BOSTON - Heart attacks and strokes are collectively the leading cause of death in most low- and middle-income countries (LMICs) worldwide. Treatment with four drugs - aspirin, a statin, an angiotensin converting-enzyme (ACE)-inhibitor, and a beta blocker - improves survival and quality of life among patients who have had a heart attack or stroke in the past; however, fewer than a quarter of eligible patients in LMICs receive these medications due to concerns about pill burden and cost.

To address this gap, a team of researchers led by Dhruv S. Kazi, MD, MSc, MS, Associate Director of the Smith Center for Outcomes Research at Beth Israel Deaconess Medical Center (BIDMC) evaluated whether it would be cost-effective to combine several medications into a single "cardiovascular polypill" for patients who have had a previous heart attack or stroke, instead of prescribing the four drugs individually. The findings were published on August 30 in Lancet Global Health.

The researchers built a mathematical model that simulated all adults with a prior heart attack or stroke in five LMICs across a wide range of economic development: India, China, Mexico, Nigeria, and South Africa. These countries were chosen because they have a large burden of cardiovascular disease in their population. Kazi and colleagues used real-world data to model each country's current rates of medication use and cardiovascular outcomes, and then examined what would happen if patients currently receiving one or more of the evidence-based therapies for cardiovascular disease were switched to the polypill instead. In this simulation model, the researchers followed individuals for their entire lifetime, keeping track of heart attacks, strokes, and deaths, as well as all health care costs. They also estimated patients' survival and quality-of-life, allowing them to estimate, for each country, a metric called the incremental cost-effectiveness ratio (or ICER). The ICER indicates how much money it would cost to prevent the loss of one disability-adjusted life year.

Overall, the team found that the polypill may represent an unprecedented public health opportunity. "In cardiovascular disease, we seldom identify interventions that have the potential to save a lot lives and, over the short term, also save money," said Kazi. "LMICs that adopt the cardiovascular polypill for secondary prevention are likely to receive excellent clinical and health economic returns on investment - an important consideration when health care budgets are extremely tight."

The study generated three compelling findings. First, the polypill was projected to be cost-effective compared with the standard of care in each of the countries studied. Because using a polypill results in downstream savings from prevented heart attacks and strokes, adopting the polypill in some settings was projected to save money while also saving lives.

Second, most of the benefit of the polypill would be derived from the fact that doctors, instead of prescribing four separate pills, would only need to prescribe a single pill. Because a single prescription would ensure that patients receive all four life-saving therapies, more patients would receive these drugs. This is a novel finding, as it was previously believed that the polypill primarily works by improving patient adherence: since patients prefer taking fewer pills, they are more likely to take the polypill instead of individual medications. While the effect of the polypill on patient adherence is important, this study shows that the effect on physician prescriptions delivers much of the polypill's benefit in LMICs.

Finally, because very few eligible patients in LMICs are receiving any of the evidence-based treatments at all, maximizing the public health impact of the polypill will require that many more patients with a history of a heart attack or stroke are diagnosed in a timely manner and initiated on the cardiovascular polypill to prevent recurrent events.

The researchers caution that their work shows that the polypill is not a panacea for the epidemic of cardiovascular disease facing these countries. "In order to achieve meaningful improvements in health outcomes, LMICs adopting the polypill must also make strategic investments in high-quality health infrastructure and effective supply chains to ensure that patients with a prior history of heart disease or stroke have reliable access to an affordable cardiovascular polypill," said Kazi.

Microbes are well-known among biologists as master engineers of useful small molecules, and there are many tricks of their trade. When researchers at the University of Illinois took a closer look at how a known microbe makes a known so-called natural product, they were rewarded with the discovery of a completely unknown biochemical trick.

G. William Arends Professor of Molecular and Cellular Biology at the University of Illinois William Metcalf led the study with then-postdoctoral researcher Elizabeth (Betsy) Parkinson. Parkinson is now an assistant professor of chemistry at Purdue University. Metcalf, Parkinson and coauthors reported their work, which was supported by NIH, in Nature Chemical Biology.

The work began with a surprise: the researchers set out to explore how their microbe of interest, Streptomyces lavendulae, creates a chemical called fosmidomycin. The team was interested in how this compound is created in part because it's an antimicrobial that is effective against malaria, a mosquito-borne illness that kills hundreds of thousands of people each year. As expected, S. lavendulae did produce a compound that killed microbes--but it wasn't fosmidomycin.

"The most interesting stuff research is where you ask a question and you get a completely unexpected answer," Metcalf said. "Something turn out as we expected; that's great!"

More surprises quickly followed. The team traced the bacterium's killing powers to production of a closely related molecule, dehydrofosmidomycin, a known natural product that may even be slightly better than fosmidomycin for treating malaria. However, the genes that S. lavendulae was using to make dehydrofosmidomycin were completely unlike those seen in other microbes.

"It's very similar to another class of molecule that we've worked on in the past, virtually identically, chemically and structurally, but the biosynthetic pathway and the genes are completely different," Metcalf said. "Which if you think about evolution and how you got there, that's fascinating, that these molecules are so good that nature independently discovered it multiple times."

Microbes evolve the capability to make natural products like fosmidomycin and dehydrofosmidomycin to help them outcompete neighboring microbes for space and resources. Each natural product is chemically crafted by a series of proteins called enzymes, which take turns tweaking the growing molecule by adding or removing atoms to change its shape and activity. Microbial genomes are scattered with clusters of genes encoding these enzymes, with one cluster typically containing all the genes necessary for making one natural product.

Metcalf's laboratory and other researchers at the Carl R. Woese Institute for Genomic Biology at the University of Illinois want to explore the relationship between microbial natural products and the gene clusters that enable their production. By learning to recognize what genes lead to what types of products, they hope to use genome sequencing to speed discovery of new natural products that, like fosmidomycin and related molecules, may have key therapeutic properties.

Metcalf was particularly excited to see a familiar type of molecule being made by an unfamiliar gene cluster.

"The technical term is convergent evolution towards a chemical product," Metcalf said. "And that tells you . . . that it's a really good molecule. It does what nature wants it to do: it's an antibacterial and it also kills parasites, like malaria and plants, like weeds, it's really got a lot of uses. It's utterly non-toxic to human beings, which is nice."

The researchers delved deeper into the details of the new gene cluster and the chemical reactions facilitated by its enzymes. They reconstructed and experimentally confirmed a series of steps leading from the starting "ingredients" to the finished product.

"So why do you care about how molecules like this are made? . . . A really good bioengineered pathway, it's the cheapest way to make anything," Metcalf said. "This offers another route to the same molecule, which might be a more efficient route, might be a cheaper route, that has yet to be explored."

The highlight of the newly discovered pathway was an enzyme encoded by the gene dfmD. Its name, reminiscent of a library call number and chosen by the researchers to indicate its position in the dehydrofosmidomycin-producing gene cluster, belies the novelty of the chemical reaction the enzyme facilitates.

"You break two carbon-nitrogen bonds, you reform one carbon-carbon bond, and you oxidize another carbon-carbon bond. And you do that all in one step," Metcalf said. In other words, the enzyme breaks a piece off the larger molecule, flips it around, reattaches it, and tweaks the resulting product, all in the single continuous action, analogous to a person changing seat configurations in a minivan commercial.

"In simplest terms, what dfmD is doing is a chemical reaction that's not easy to envision, number one, just based on first principles of chemistry; and number two, that's never been observed in nature before," Metcalf said. "Because this is doing something radically different, it adds to that body of knowledge so that when we look at new pathways, we can think about how they might work."

Aurora-watchers gazing at spectacular displays over the Labor Day weekend may have been seeing more than the northern lights. They may have been dazzled by STEVE as well.

STEVE is short for the Strong Thermal Emissions Velocity Enhancement, a celestial phenomenon auroral researchers, citizen-scientists and photography enthusiasts first introduced to the world in 2016.

STEVE's narrow ribbon of light, to the naked eye, looks strikingly similar to aurora. However, there are distinct differences. First, its pinkish mauve color is not aurora-like. In addition, the phenomenon is often associated with "picket fence" emissions, which look like green columns of light passing through the ribbons at lower altitudes. Lastly, STEVE appears in areas farther south than auroral lights typically do.

Scientists thought something didn't add up.

This summer, researchers confirmed that STEVE is not aurora, but is instead a unique phenomenon. Their findings were published in the journal Geophysical Research Letters.

"The big thing is, we can clearly say now it's not regular aurora," said University of Alaska Fairbanks researcher Don Hampton, a co-author on the paper. "It's a new phenomenon, that's pretty exciting."

The project, led by University of Calgary researcher D.M. Gillies, used a spectrograph to examine the light from the phenomenon and identify what kind of emissions it gives and in what patterns and wavelengths. Hampton and his colleagues designed and built the spectrograph at the UAF Geophysical Institute.

"We need to understand what the spectrum looks like and therefore understand the physics behind it," Hampton said. A spectrum acts as a definitive identification, like a DNA test or chemical formula for light.

When the scientists looked at STEVE's spectrum they saw something unique. Aurora has individual wavelengths and acts like a neon sign. In aurora, electrons from our magnetosphere fly down, bumping into atoms and molecules in our atmosphere, which excites them. Once the excited particles relax they emit photons, which can be seen as specific wavelengths of light. Depending on which colors you see, you know certain lights came from a nitrogen molecule and others came from oxygen.

"When we looked at the spectrum of STEVE, it had none of those distinct wavelengths," Hampton said. "Instead, it's a very broad band of light. So all wavelengths are basically equally as strong."

This means that the light is not coming from atoms and molecules colliding in the atmosphere but from something very warm -- maybe thousands of degrees warm.

"When you turn your electric stove on, those coils get red hot, right? If you look at it with a spectrograph, you would see broadband emissions," Hampton said. "So this is like very, very warm atmosphere emissions of some sort."

The research also concluded that the picket fence emissions are similar to a typical aurora structure. These are caused by the same kinds of particle precipitation usually seen with aurora.

Like auroras, STEVE's appearances vary greatly, showing up anywhere from weeks to months apart.

Scientists have studied the hot particles associated with STEVE since the 1970s. However, they did not realize until recently that they produced a visible feature.

Confirming the existence of a celestial phenomenon is exciting, Hampton said. The next, and more difficult step, is finding out what causes it and how it affects us.

Any disturbance to our upper atmosphere, like aurora, can affect radio communications between Earth and spacecraft. STEVE is especially interesting because it is a large local energy input, but clearly not normal aurora.

"As a new phenomenon we want to understand not just why and how it is created, but also how does it affect our infrastructure," Hampton said. "We don't expect that if we understand how STEVE is created that we will cure cancer, or produce warp drive (though one never knows), but we do want to understand how one bit of the ionosphere works, and that may help overall knowledge as well as provide some practical understanding to reduce the impact on other aspects of our daily life."

You are what you eat -- and sometimes what animals eat -- so much so that clues from ancient animal bones can be used to determine how and when humans began growing certain crops in earnest.

New research from Washington University in St. Louis and Kiel University in Germany uses DNA from the skeletal remains of sheep and goats to show that animals first domesticated in the Near East had reached eastern Kazakhstan, at the settlement of Dali, by 2700 B.C. The DNA also reveals that these animals were fed millet grain first domesticated in China to help them survive harsh winters.

The study draws upon field work and museum collections as part of a longstanding scientific partnership between Washington University, led by archaeologist Michael Frachetti of Arts & Sciences, and the Institute of Archaeology in Almaty, Kazakhstan.

The mountainous site of Dali is located near the crossroads of cultural and genetic change during the Early and Late Bronze Age in a region that Frachetti calls the Inner Asia Mountain Corridor.

"The most important finding for me is the presence of a well-developed pastoralist economy using Chinese millets at 2700 B.C.," said Taylor Hermes of Kiel University, co-lead author of the new study in Proceedings of the Royal Society B and a 2007 graduate of Washington University. "This is quite an early date for the domesticated animals to be present in the region, and it is also the earliest dated evidence that millets had spread out of China. This suggests that it took domesticated sheep and goats from the Near East to have spread all the way to China before millets began spreading widely."

The spread of domesticated plants and animals through the vast steppe grasslands of Inner Asia nearly 5,000 years ago marked the beginning of the ancient trade routes, later known as Asia's Silk Roads. However, the exact timing and circumstances of moving crops through this continental crossroads and the case for actual farming, have remained elusive.

"Our previous research showed archaeobotanical remains of both wheat and millet around 2300 B.C.E. in the highlands of Kazakhstan, but there was little concrete evidence to show whether these were trade items or farmed locally," Frachetti said. He is a co-author and co-director of the underlying archaeological fieldwork.

"We were left to speculate about the integration of intensive farming among Early Bronze Age herders in the region, and if these grains made it into their diet," he said.

Evidence of cereal consumption can be traced using isotopes found in human bones, but human skeletal remains dating to the third millennium BC are rare.

As a result, reconstructing the seasonal diets reflected in more abundant animal bones is a key approach to assess agricultural production and the scale of local production, the researchers said.

"The evidence we found of people foddering sheep, goats and cattle with millet at various intensities suggests a huge degree of flexibility in food production," Hermes said. "It may very well be the case that people who lived at Dali and Begash shifted their herding and farming strategies year-to-year depending on environment or social circumstances.

"For now, we can only tell that people were cultivating millet to support their animals' welfare in the harsh winters of central Asia."

This study clearly links the westward dispersal of millets -- a key indigenous crop of Chinese civilization -- to livestock herding by nomadic pastoralists who used farming to enhance their animal-focused worlds.

Expensive high-tech air mattresses are only marginally better at preventing pressure sores and ulcers than a specialist foam mattress, according to the results of a major study.

Known as an alternating-pressure mattress, the high-tech devices contain air pockets that inflate and deflate to constantly change pressure points on the skin. They cost at least £1,000 each (US $1,217).

In comparison, a specialist foam mattress is around £200 (US $243) and is made up of high-quality polyurethane and viscoelastic foam designed to cradle the patient to reduce pressure on the skin.

The specialist foam mattresses are in widespread use across the NHS (National Health Service). The high-tech air mattresses are found on approximately 10% of NHS hospital beds and given to patients considered to be at high risk of pressure ulcers even though there has been no independent evaluation of their effectiveness.

The UK Government's health regulator, the National Institute of Health and Care Excellence, had called for a scientific trial to investigate the benefits of the high-tech mattresses.

That study, led by nurse researchers at the University of Leeds, is published today (04/09/19) in the journal EClinicalMedicine.

Clinical benefit

The investigation showed that the gains from the use of the high-tech air mattresses were marginal. The paper concludes that for every 50 patients allocated to one of the high-tech air mattresses, only one would benefit from it.

The results showed that 6.9% of patients on the high-tech air mattresses developed a pressure sore that was grade two (ie blister or break in the skin) or worse compared with 8.9% on the specialist foam mattress. Ulcers are graded on a scale from one to four, with four being the most serious.

The median length of time it took for the ulcers to develop for the patients on a high-tech air mattress was 18 days compared to 12 days for those on the specialist foam mattress.

The paper - Pressure relieving support surfaces for pressure ulcer prevention: clinical and health economic results of a randomised controlled trial - also noted that the overall number of patients who developed pressure sores during the study was smaller than expected: the result, the researchers believe, of changes in nursing practice designed to reduce the burden of pressure sores.

This is the first large-scale study world-wide into the effectiveness of high-tech air and specialised foam mattresses to prevent pressure sores. It involved more than 2000 patients at high risk of developing pressure sores in hospital and NHS community units.

In 2018, NHS Improvement described pressure sores as a "concerning and avoidable harm" with the costs to the NHS of treating the condition running at more than £3.8 million every day.

Pressure sores are a major complication faced by people who are bedridden or immobile. The pressure that builds on soft tissue causes distortion to the tissues and/or an interruption to the blood supply - and that kills or damages skin leading to painful ulcers.

The study was led by Jane Nixon, Professor of Tissue Viability and Clinical Trials at the University of Leeds.

She said: "The professional guidelines tell healthcare staff that they should use specialist foam for all at-risk patients and high-tech air- mattresses for patients with an existing pressure ulcer when adequate pressure distribution cannot be achieved.

"But in practice, some nurses provide high-risk patients as well as those with existing pressure ulcers with the high-tech air mattresses and there has not been any evaluation of the effectiveness of one type of mattress over another.

"Some patients find the air mattress unsettling. They are kept awake by the noise of the pump, feel unsafe because the mattress is moving, or just find them uncomfortable.

"Rehabilitating patients also complain that they can't move around themselves or get in and out of bed - and that exacerbates already limited mobility."

Patients who agreed to take part were randomly allocated to either a high-tech air or specialised foam mattress for 2 months or until discharge, whichever came sooner. They were then assessed by a nurse for a final time 30 days after discharge. The majority of the patients were elderly, with the median age 81 and included a number of patients who were aged over 100.

The analysis suggested that the patients who benefitted most from the high-tech air mattresses were those who were completely immobile, confused, had nutritional deficits and very red skin on a pressure area.

Financial evaluation

The study found an economic advantage to using the high-tech air pressure mattresses. Although they cost more to buy, the patients who were nursed on them had, on average, a slightly shorter stay in hospital, and that reduced the overall cost of care.

More research is needed to fully understand the correlation between mattress type and length of hospital stay.

While acknowledging that there were benefits to using the high-tech air pressure mattresses, the researchers said that as the gains were small, the advice to nurses should be that most patients could be safely cared for on a specialised foam mattress.

Professor Nixon said: "The outcome of this study provides the evidence that specialist foam mattresses are appropriate for most patients who are at high risk of developing pressure ulcers.

"But staff should be free to exercise clinical discretion in provision of either mattress, informed by patient preference, comfort or rehabilitation needs as well as specific risk factors such as being completely immobile, being confused, having nutritional deficits or early signs of pressure damage."

Swedish and New Zealand scientists shed new light on demise of two extinct New Zealand songbirds

They may not have been seen for the past 50 and 110 years, but an international study into their extinction has provided answers to how the world lost New Zealand's South Island kokako and huia.

Lead author Dr Nicolas Dussex, of the University of Otago, New Zealand, and Swedish Museum of Natural History, says the team set out to investigate if it was external (habitat loss, mammalian predators) or internal (demography, genetic effects) factors which led to their extinction.

Very little was known about the forest songbirds he describes as "iconic and somehow mysterious", which were last seen in 1960s and 1907 respectively, but recent advances in the extraction and analysis of ancient DNA provided the opportunity scientists needed to find out more.

The study, just published in Biology Letters, produced what Dr Dussex calls "very surprising" results.

The researchers mapped the birds' complete genomes and saw a response to ice age climate change many thousands of years ago, but no signs of genetic problems common in small populations such as inbreeding. This suggests a rapid population decline possibly caused by habitat loss and new predators introduced by the Europeans.

"Because even the earliest Polynesian settlers more than 700 years ago had a significant impact on forest cover, we would have expected huia and South Island kokako populations to have survived at small population sizes for centuries and thus to have experienced an increase in inbreeding.

"However, our data did not show evidence for inbreeding and indicated that the two species still had quite a bit of genetic diversity close to the time of extinction. This means that their extinction was most likely not driven by genetic effects and inbreeding, but that further habitat loss and introduction of mammalian predators by European must have triggered a rapid extinction," he says.

Dr Dussex says this is the first study to generate high-quality genomes from historical specimens of extinct New Zealand species.

"Using complete genomes allowed us to reconstruct the birds' population history, and, more importantly, to determine whether genetic effects could have contributed to their extinction.

"While we focused here on two extinct species, understanding the role of genetic effects in the extinction process is extremely relevant to the study of declining and inbred populations, such as the kakapo, saddleback, and kiwi. This knowledge can thus contribute the conservation and recovery of endangered species potentially exposed to negative genetic effects."

Co-author Dr Michael Knapp, of Otago's Department of Anatomy, says the team hopes its work will stimulate similar research in other extinct or endangered endemic species from New Zealand.

"Recent advances in ancient DNA mean that it is the right time to study extinction from a genomics perspective. So far, very little is known about the role genetic effects play in the process of extinction. This research is thus very timely and extremely relevant to the understanding of the decline in biodiversity in New Zealand."

Humans use a snorkel and fish have gills. Now researchers have found a sea snake which uses a complex system of blood vessels in its head to draw in extra oxygen when it dives and swims underwater.

During submersion, the blue-banded sea snake (Hydrophis cyanocinctus) is now thought to use an extensive vascular network across the top of its head to absorb oxygen from the surrounding water.

"For the first time, we describe this modified cephalic vascular network (MCVN) that provides this sea snake with a complementary supply of oxygen to the brain during submersion," says lead researcher, Flinders University evolutionary researcher Dr Alessandro Palci, who is a visiting researcher at the University of Alberta, Canada.

"Basically we found that this sea snake uses the top of its head as a gill to breathe underwater," says Dr Palci.

The highly venomous blue-banded sea snakes, which live in tropical waters of Southeast Asia, are found on coral reefs and warm coastal waters. Sea snakes must surface regularly to breathe but are among the most completely aquatic of all air-breathing vertebrates.

The vascular network, located just under the skin of the snout and forehead of the snake, surprised researchers in their new study.

"While the MCVN is structurally very different from the gills of fish and amphibians, its function is nonetheless quite similar, in that it provides a large surface area packed with oxygen-depleted blood vessels that can efficiently take in oxygen from the surrounding water," Dr Palci says.

ARC Future Fellow Dr Kate Sanders, from the University of Adelaide School of Biological Sciences, says the latest study expands understanding of the unusual cutaneous respiratory anatomy of sea snakes.

"Sea snakes have been extremely successful at adapting to a fully marine lifestyle, including the ability to absorb oxygen through their skin," Dr Sanders says.

"Now we have discovered this interesting feature in H. cyanocinctus by using microCT scans and computer modelling.

"This feature probably allows these sea snakes to stay submerged for longer periods of time, which further research can test."

Mr Palci, with experts from the South Australian Museum, Vietnam Academy of Science and Technology, and University of Adelaide, modelled the snake's special feature.

As growing numbers of people are using cannabis to treat post-traumatic stress disorder (PTSD), a new UCL study reports that prescriptions are not backed up by adequate evidence.

The systematic review, published in the Journal of Dual Diagnosis, finds that the active components of cannabis, called cannabinoids, may hold promise as a treatment for PTSD, particularly for reducing nightmares and helping people sleep, but more research is needed to determine whether these drugs should be used in routine clinical practice.

"There has been a recent surge of interest in the use of cannabinoids to treat PTSD, particularly from military veterans, many of whom are already self-medicating or obtaining prescriptions in some American states," said the study's lead author, Dr Chandni Hindocha (UCL Clinical Psychopharmacology Unit).

"The lack of evidence supporting cannabis as a PTSD treatment is striking given the vast interest in it, and the large unmet need for better PTSD treatments," she said.

PTSD is a potentially debilitating condition affecting roughly 1% of the UK population, typically consisting of re-experiencing a traumatic event through intrusive memories, flashbacks or nightmares, and often involves hyper-reactivity (a state of constant vigilance) and insomnia.

Psychotherapies (talking therapies) including trauma-focussed cognitive-behavioural therapy have been shown to be effective for PTSD. However, not everyone can access talking therapies and they do not work for everyone, so many people still need to take prescribed medications. Existing drugs approved for PTSD do not work for everyone, and can have side effects, so researchers say there is an urgent need to identify new treatments.

A growing number of people have turned to cannabinoids, which is an approved treatment for PTSD in most states in the USA that permit medical cannabis.

Cannabinoids, the active ingredients of cannabis, which include tetrahydrocannabinol (THC) and cannabidiol (CBD), may be helpful at treating PTSD as they can change how the brain processes memories. The cannabinoids act on the brain's in-built endocannabinoid system which also regulates other brain functions that are affected by PTSD.

The research team conducted a systematic review of all studies where someone with a PTSD diagnosis has been using a cannabinoid to reduce their symptoms, and they assessed the quality of each study.

They found 10 studies that met their criteria, which cover a range of products including smoked cannabis, THC or CBD separately in oil or pill form, and a synthetic cannabinoid called nabilone.

Every study had medium to high risk of bias and all were assessed as low in quality due to limitations such as small sample size, retrospective study design, lack of a control group or placebo, short follow-up periods, and not reporting other medication use or addiction. Only one study was a randomised controlled trial, investigating nabilone, but it was in a small sample over a relatively short period of time.

The researchers say there are still many unanswered questions about the safety and efficacy of cannabis-based medications for PTSD, and potential long-term effects such as addiction or a risk of psychosis.

The existing evidence shows promise, however, as some studies showed that cannabis products appeared to reduce PTSD symptoms such as insomnia and nightmares.

"Based on the evidence, we cannot yet make any clinical recommendations about using cannabinoids to treat PTSD. Current prescribing of cannabinoids for PTSD is not backed up by high quality evidence, but the findings certainly highlight the need for more research, particularly long-term clinical trials," said the study's senior author, Dr Michael Bloomfield (UCL Psychiatry and the Traumatic Stress Clinic, St Pancras Hospital).

"Many of these studies have been conducted in military veterans, but we also need to be looking at other groups, as PTSD can vary depending on the nature of the trauma so different approaches may benefit different groups," he added.

Dr Hindocha added: "Unfortunately, medicinal uses of cannabis have historically been difficult to study due to legal restrictions, so it could take a long time before there is enough evidence to support clinical recommendations. New approaches are needed to make the most of existing evidence in the meantime."

States that require prescribers to register with and use prescription drug monitoring programs in most clinical circumstances saw notably fewer opioid prescriptions and reduced opioid-related hospital use by Medicaid patients compared to states with weak or no drug monitoring program mandates, according to a new study from investigators at Weill Cornell Medicine. The approximate annual reduction of about 12,000 inpatient stays and 39,000 emergency department visits could save an estimated $155 million a year in Medicaid spending.

Drug monitoring programs are statewide databases that collect and monitor prescribing and dispensing information of controlled prescription drugs. All states and the District of Columbia, except Missouri, have implemented prescription drug monitoring programs, a prominent tool to combat the opioid epidemic.

However, how these programs have been implemented has varied. Some states have comprehensive mandates that require all providers, regardless of practice setting or specialty, to register with and use the program on initial prescribing to a patient and at least every 12 months after that for continued prescriptions. Others have non-comprehensive mandates that only require registration, or have a weak use requirement, or both.

In the study, published Sept. 3 in the September issue of Health Affairs, the researchers found that states with comprehensive mandates saw an 8.92 percent reduction in population-adjusted number of opioid prescriptions, as well as 4.27 percent fewer hospital stays and 17.75 percent fewer emergency department visits related to opioid use. States with non-comprehensive mandates saw no reductions in these areas.

"Our findings contribute significant evidence in support of comprehensive mandates for reducing the use of opioid prescriptions by Medicaid patients, a population with an elevated risk for opioid misuse and overdose compared to patients with other insurance status," said senior author Dr. Yuhua Bao, an associate professor of healthcare policy and research at Weill Cornell Medicine.

The investigators used prescription drug utilization data reported by states to the Centers for Medicare and Medicaid Services and hospital discharge data from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project. They analyzed data from the first quarter of 2011 through the last quarter of 2016.

In a previous study using data until 2014, Dr. Bao and colleagues found that states requiring prescribers to register with prescription drug monitoring programs saw a reduction in the number of Schedule II opioids -- drugs associated with the highest risk of misuse and overdose -- by up to 10 percent among Medicaid enrollees. In the new study, which was conducted in collaboration with the University of Kentucky and Emory University, the reduction in opioid prescriptions also traced primarily to Schedule II opioids.

"This is one of a few studies that have examined the downstream effects of prescription drug monitoring mandates, using data that capture recent experience with comprehensive mandates," Dr. Bao said. "We hope our findings will inform state policy discussions for strengthening prescription drug monitoring programs to address the opioid crisis more effectively."