Culture

With an estimated 10-15% of adults over the age of 60 having some degree of osteoarthritis, otherwise known as degenerative joint disease (DJD), many people will be familiar with, or will know someone who suffers from, this painful and debilitating condition. What is not well recognised is that DJD, where the protective cartilage that cushions the end of the bones wears down over time, affects a high proportion of pet cats of all age groups, but particularly those 10 years of age and over. A study published today in the Journal of Feline Medicine and Surgery (JFMS)1 provides a screening checklist to help veterinarians and owners to identify cats experiencing DJD-associated pain.

The team of researchers that developed the new tool are based at North Carolina State University (NCSU) in the USA, and led by Margaret Gruen and Duncan Lascelles. They were concerned that feline DJD remains underdiagnosed and undertreated in veterinary practice despite its high prevalence; earlier research has revealed, for example, that 90% of cats are likely to have radiographic signs of DJD, with at least 40% showing related signs of pain. The authors suggest that one possible reason for this is that while many people may associate limping with joint pain, this is actually a less common sign of DJD in cats. Meanwhile other, more typical behavioral signs of DJD (such as difficulty navigating stairs) may be misinterpreted as normal aging.

In their study, the authors collated questionnaire data from five studies previously carried out at the Translational Research in Pain Program at NCSU. This enabled them to compare 249 cats with, and 53 cats without, DJD-associated pain, and, via a multistep process of analysis, develop a set of questions that can be answered with a straightforward 'yes' or 'no'. After some further refinement, they came up with a final checklist comprising six questions. These ask whether a cat can jump up and down normally, climb up and down stairs normally and run normally, and whether it chases moving objects such as toys and prey. The checklist can also be used for owners and cats living in a single-storey home by excluding the questions about stairs.

In developing this new tool, referred to as the 'Feline Musculoskeletal Pain Screening Checklist', the researchers compared the scoring of owners who were both aware or unaware of the link between DJD and pain in cats. Unsurprisingly, they found a gap in the responses between the groups, with a higher percentage of 'DJD-informed' owners scoring their cats as impaired for every question. The authors suggest that, given the high prevalence of feline DJD, many cats with undiagnosed DJD would nonetheless still be identified using the checklist; and, when coupled with owner education and engagement in watching for behavioural changes in their cats, the detection of DJD should improve even more.

The authors conclude that this checklist not only provides a clinically expedient tool likely to increase vets' ability to screen for DJD pain in cats, but it may also further provide a foundation for increasing awareness of DJD pain among cat owners. Cats being cats are more likely to display behavioural signs of DJD-associated pain at home compared with in the veterinary clinic, meaning owners are well placed to help in the diagnosis of this condition. The idea is that the checklist can be completed quickly by owners, and if 'no' is selected for any question, this will prompt further evaluation by the vet and treatment to improve the cat's comfort levels.

Scientists have made a breakthrough in the search for a new, sustainable permanent magnet.

Most permanent magnets are made from alloys of rare earth metals - but the mining and processing of these materials produces toxic by-products, leading to ecological challenges around rare-earth mines and refineries. At the same time, demand for permanent magnets is increasing as they are a common component in renewable energy, consumer electronics and electric-powered vehicles.

A team of scientists, led by the University of Leeds, has made a breakthrough in a new advanced material which may eventually replace rare-earth-based permanent magnets. The researchers have developed a hybrid film from a thin layer of cobalt, which is naturally magnetic, covered with molecules of Buckminsterfullerene, a form of carbon.

The presence of the carbon dramatically boosted cobalt's magnetic energy product, a measure of the strength of a magnet, by five times at low temperatures.

The findings have been published in Physical Review B, produced by the American Physical Society. Available at: https://journals.aps.org/prb/pdf/10.1103/PhysRevB.101.060408

The research team observed the increase in magnetic strength at minus 195 degrees Centigrade, but they hope by chemically manipulating the carbon molecules, they will be able to get the same effect at room temperature.

Dr Tim Moorsom, co-principal investigator from the School of Physics and Astronomy at Leeds, said: "This is the first indication I have seen that a rare-earth-free magnet could compare to something like samarium cobalt, a rare-earth-based permanent magnet.

"While we have only seen this effect at low temperatures thus far, I am hopeful that a hybrid magnetic material similar to this will one day replace rare earth permanent magnets, helping to mitigate the environmental damage they cause."

Although carbon is not magnetic, the way the molecules bond to the cobalt surface causes a magnetic pinning effect, which prevents the magnetism in the cobalt from changing direction, even in strong opposing fields. This surface interaction is the key to the unusually high magnetic energy of the hybrid material.

While it may be a long time before hybrid magnets are ready to be used in wind turbines or electric cars, there are other applications which are closer at hand.

Dr Oscar Cespedes, co-principal investigator, who is also at Leeds, said "Although room temperature applications in bulk permanent magnetism may be a long way off, the use of molecular coupling to tune the magnetic properties of thin films, for example in magnetic memories, is a tantalising prospect that is within easy reach."

Researchers at Western University are studying a molecule found in sweet oranges and tangerines called nobiletin, which they have shown to drastically reduce obesity and reverse its negative side-effects.

But why it works remains a mystery.

New research published in the Journal of Lipid Research demonstrates that mice fed a high-fat, high-cholesterol diet that were also given nobiletin were noticeably leaner and had reduced levels of insulin resistance and blood fats compared to mice that were fed a high-fat, high-cholesterol diet alone.

"We went on to show that we can also intervene with nobiletin," said Murray Huff, PhD, a Professor at Western's Schulich School of Medicine & Dentistry who has been studying nobiletin's effects for over a decade. "We've shown that in mice that already have all the negative symptoms of obesity, we can use nobelitin to reverse those symptoms, and even start to regress plaque build-up in the arteries, known as atherosclerosis."

But Huff says he and his team at Robarts Research Institute at Western still haven't been able to pinpoint exactly how nobiletin works. The researchers hypothesized that the molecule was likely acting on the pathway that regulates how fat is handled in the body. Called AMP Kinase, this regulator turns on the machinery in the body that burns fats to create energy, and it also blocks the manufacture of fats.

However, when the researchers studied nobiletin's effects on mice that had been genetically modified to remove AMP Kinase, the effects were the same.

"This result told us that nobiletin is not acting on AMP Kinase, and is bypassing this major regulator of how fat is used in the body," said Huff. "What it still leaves us with is the question - how is nobiletin doing this?"

Huff says while the mystery remains, this result is still clinically important because it shows that nobiletin won't interfere with other drugs that act on the AMP Kinase system. He says current therapeutics for diabetes like metformin for example, work through this pathway.

The next step is to move these studies into humans to determine if nobiletin has the same positive metabolic effects in human trials.

"Obesity and its resulting metabolic syndromes are a huge burden to our health care system, and we have very few interventions that have been shown to work effectively," said Huff. "We need to continue this emphasis on the discovery of new therapeutics."

CHAPEL HILL -- The five-year survival rate for adolescents and young adults with cancer has significantly improved from 1975 to 2005 in the United States overall, but this was not the case for all cancers, according to a report in the Journal of the National Cancer Institute.

"We are making improvements in survival for adolescents and young adults with cancer over time, but adolescents and young adults are a heterogeneous group, and we have to make sure that overall improvements don't hide the fact that there are specific cancer types that haven't had equivalent advances, and we need to do more," said Hazel B. Nichols, PhD, member of the University of North Carolina Lineberger Comprehensive Cancer Center and associate professor in the UNC Gillings School of Global Public Health.

Chelsea Anderson, PhD, MPH, postdoctoral fellow at the American Cancer Society, was the study's corresponding author.

The researchers identified substantial improvements in five-year mortality rates for adolescents and young adults (AYA) diagnosed with leukemia, non-Hodgkin lymphoma, Hodgkin lymphoma, central nervous system tumors, melanoma and other skin cancers, breast cancer or kidney cancer.

However, five-year mortality rates for AYA patients with bone tumors, soft tissue sarcomas, bladder cancer, cervical and uterine cancers or colorectal cancer did not improve across the more than 30-year time period.

Researchers compared mortality rates in the five to 10 years beyond diagnosis for people ages 15 to 39. They compared mortality rates for young people in the U.S. who were first diagnosed between 1975 and 1984 with rates for people diagnosed in more recent time periods, including from 1985-1994, 1995-2004 and 2005-2011. The study drew on data from the National Cancer Institute's Surveillance, Epidemiology and End Results database.

They found that all-cause mortality rates in the five to 10 years after diagnosis fell from 8.3 to 5.4 percent between 1975-1984 and 2005-2011. That decline was driven by a drop in the number of deaths from the patients' primary cancer, Nichols said, although deaths from other causes declined as well.

"Some of the most dramatic improvements were for leukemia and non-Hodgkin lymphoma," Nichols said. "In those groups, we saw that if you were diagnosed with leukemia, for example, in 1975, the mortality between five and 10 years was almost 30 percent. If you were diagnosed with that same disease in 2005, the mortality rate was only 7 percent. That's pretty dramatic over a 30-year interval."

UNC Lineberger's Andrew B. Smitherman, MD, MSc, assistant professor and medical director of the UNC Adolescent and Young Adult Oncology Program, said the results were encouraging.

"With improved cancer-directed therapies and enhanced supportive care, survival outcomes are improving among many AYA cancers, including for leukemia, lymphoma and central nervous system cancers," Smitherman said. "Also, improvements in non-cancer mortality were observed that speak to refinements in cancer treatment to limit treatment-related late effects, such as cardiopulmonary disease. The authors also report small decreases in mortality related to secondary cancers. More time will be needed to fully understand how changes in therapy over the past few decades will impact rates of secondary cancers, as these may develop much later."

However, while mortality rates improved overall, there was no major improvement in five-year mortality rates for AYA patients with bone tumors, soft tissue sarcomas, bladder cancer, cervical and uterine cancers, or colorectal cancer.

"This highlights areas where more work needs to be done," Nichols said.

Cancers among adolescents and young adults make up only about 4 percent of all cancers diagnosed in the U.S., researchers reported. However, previous studies indicated that survival improvement has been less dramatic in this age group.

"Cancer risk is still very low overall before 40," Nichols said. "However, we haven't seen strong representation of adolescents and young adults in clinical trials, which may be contributing to the fact that patients with certain cancer types in this age group haven't made big advancements over this time period."

To improve outcomes and provide support for adolescents and young adults, UNC Lineberger and the North Carolina Cancer Hospital launched a program for patients with cancer between the ages of 13 and 40.

The program, which is under the direction of Smitherman and Lauren Lux, LCSW, is designed to recognize that teenagers and young adults have unique cancer biology and have different needs than other patients. Cancer treatment can impact relationships, career, independence, fertility and other aspects of life.

"This study underscores the importance of clinical trials in advancing cutting-edge treatments and cures for cancer," Smitherman said. "Many of the improvements that have been seen in pediatric, adolescent and young adult cancers are due to the work of cooperative research groups. More work is needed to develop new treatments for the AYA cancers that are not seeing equivalent survival improvements. These results can help inform clinical researchers regarding where we need to focus energy to develop new trials, and hopefully improve outcomes."

CHAMPAIGN, Ill. -- A study that relied on citizen scientists to monitor the health of corals on Turks and Caicos Islands in the Caribbean from 2012 to 2018 found that 35 key coral species remained resilient during a 2014-17 global coral-bleaching event that harmed coral reefs around the world. Even corals that experienced bleaching quickly recovered, the researchers found. Some corals appeared healthier in 2017 than they were in 2014.

The researchers report their findings in the Springer Nature journal Applied Sciences.

"Boulder-type corals on the Turks and Caicos Islands demonstrated no significant bleaching as a result of the peak thermal stress in late 2015," said Abby Knipp, who conducted the research while an undergraduate student at the University of Illinois at Urbana-Champaign. Knipp is the first author of a paper detailing the findings. "Plate-type corals did suffer bleaching, but they quickly rebounded. Their pigmentation levels were back to normal within months of the anomalously high thermal stress."

Coral bleaching is a common response to extreme heat stress, and global coral-bleaching events are becoming more frequent as the oceans warm. The 2014-17 bleaching event occurred as record-breaking sea-surface temperatures pushed some corals past their physiological limits. Scientists call it "the most severe, widespread and longest-lasting" global coral-bleaching event on record.

Pigmentation in corals comes from photosynthetic algae, on which the corals depend for nutrients, said U. of I. geology professor and study co-author J. Cory Pettijohn.

"The algae colonize the corals and feed on the byproducts of their metabolism," he said. "When sea-surface temperatures are too high, corals will expel the algae. Corals that experience prolonged bleaching usually die, leaving only a white calcium-carbonate skeleton behind."

In Turks and Caicos Islands, pigmentation of the boulder corals was darker in 2017 than in 2014, suggesting these corals were even healthier after rebounding from the heat stress, Knipp said.

"We were surprised that apparent healing and darkening could happen so fast," she said.

The scientists say more studies are needed to explain the unusual hardiness of the corals at Turks and Caicos Islands, but previous research offers clues to factors that promote coral health. For example, some algal types appear to confer added resilience to corals experiencing heat stress. Ocean salinity and acidity likely play a role. Turks and Caicos Islands tend to have lower water temperatures than other, more thermally stressed regions of the Caribbean. And the massive 2017 hurricanes Irma and Maria cooled surface waters and likely contributed to the corals' recovery, the researchers said.

SEATTLE – Seeing a physician or other health specialist for low back and neck pain? You’re not alone, according to a new scientific study.

Americans in 2016 spent an estimated $380 billion on low back and neck pain, as well as on joint and limb pain, and other musculoskeletal disorders.

In total, $3.1 trillion – or $9,655 per person, about 17.9% of the US GDP – was spent on health care by a combination of individuals and public and private insurance. In 1996, that percentage was 13.3% of GDP, with a total amount of $1.4 trillion, or $5,259 per person.

“The vast costs associated with health care represent one of the most important and contentious issues facing Americans today,” said Dr. Joseph Dieleman of the Institute for Health Metrics and Evaluation (IHME) at the University of Washington’s School of Medicine and lead author of the study. “Our study provides comprehensive estimates over a 20-year period that highlight how health care and prescription drugs are paid for, what they are spent on, and how such payments have changed over time.”

Among 154 conditions included in today’s study, low back and neck pain generated the highest expenditures at $134.5 billion. When combined with all other musculoskeletal disorders, such as joint and limb pain, osteoarthritis, and rheumatoid arthritis, the total exceeds $380 billion, or 14.1% of the $2.7 trillion included in this study for 2016.

Other health conditions with substantial spending in 2016 were diabetes ($111.2 billion), ischemic heart disease ($89.3 billion), and falls ($87.4 billion).

As expected, a combination of private and public insurance paid for the majority of those expenditures:

Low back and neck pain – $76.9 billion paid by private insurance, $45.2 billion paid by public insurance, and $12.3 billion paid by individuals out-of-pocket

Other musculoskeletal disorders – $73.3 billion paid by private insurance, $46.9 billion paid by public insurance, and $9.7 billion paid by individuals out-of-pocket

Diabetes – $55.4 billion paid by public insurance; $49.1 billion paid by private insurance, and $6.7 billion paid by individuals out-of-pocket

Ischemic heart disease – $48.2 billion paid by public insurance, $37.9 billion paid by private insurance, and $3.2 billion paid by individuals out-of-pocket

Falls – $40.7 billion paid by public insurance, $34.8 billion paid by private insurance, and $11.9 billion paid by individuals out-of-pocket

The majority of public insurance spending (58.6%) in 2016 was earmarked for patients aged 65 or older. After adjusting for changes in the population size and age, spending by public insurance increased faster than private insurance, although this is driven at least partially by expansions of Medicaid.

Other findings include:

Spending in 2016 on prescription pharmaceuticals totaled $336.0 billion, with 45.4% paid by private insurance; spending by public insurance has increased from 19.1% in 1996 to 40.6% in 2016, with an increase in 2006 associated with Medicare Part D.

Spending on dementia increased substantially, from $38.6 billion in 1996 to $79.2 billion in 2016.

Data behind the study included 5.9 billion unique insurance claims, information regarding an additional 150.4 million ambulatory care visits, dental procedures, and emergency department visits; 1.5 billion inpatient and nursing facility bed-days; and 5.9 million prescribed pharmaceuticals.

The spread of antibiotic resistance is partly due to the ability of bacteria to pick up DNA from their surroundings. A new study, which started at the University of Groningen, showed that drugs blocking this ability (which is called 'competence') in the bacterium Streptococcus pneumoniae can indeed stop the spread of resistance in mice. As competence is blocked without affecting cell growth, it will be difficult for the bacteria to evolve resistance to the blockade. The study was published online by the journal Cell Host & Microbe on 3 March.

The bacterium Streptococcus pneumoniae is often present in our nose or throat and is usually harmless. However, it can migrate to other parts of the body, causing severe diseases. The only way to treat these infections is with antibiotics, but with this treatment, acquisition of antibiotic resistance is a cause for concern. In order to pick up these resistance genes, a chain of events is needed that brings the bacteria in a state called 'competence'. During competence, bacteria express all the machinery required to 'catch' and incorporate the resistance genes into their own genomes.

Growth stress

In a project that started at the University of Groningen in the Netherlands and was finished at the Swiss University of Lausanne, Arnau Domenech and colleagues figured out how to stop the cells from becoming competent. 'We collaborated with scientists from Heidelberg, who developed a high-throughput assay to simultaneously test cells for competence and growth,' says Domenech. In this assay, 1366 approved drugs were screened. It turned out that 46 of them blocked the induction of competence, without negatively affecting growth.

'When cells are under growth stress, for instance in the presence of antibiotics, they try to find a solution and become resistant to these drugs,' explains Domenech. 'Importantly, we did not observe resistance to the drugs found here as they do not cause growth stress.' The 46 drugs could be divided into two groups: drugs affecting ion homeostasis, and antipsychotics. Several candidates were selected for further exploration. 'This showed that they all acted through the same mechanism,' says Domenech. They disrupted the proton-motive force: the electrochemical gradient that moves protons across the bacterial membrane and powers various processes.

Resistance

'The result is that the cells fail to secrete a peptide called CSP,' explains Domenech. The CSP concentration outside the cells induces competence through a process called quorum sensing: if enough cells secrete CSP, the concentration will reach a threshold that activates competence genes.

Domenech: 'In the lab, we observed that our competence-blocking drugs could prevent the transfer of antibiotic resistance genes to susceptible strains of Streptococcus pneumoniae and we obtained the same results in cultures of human lung epithelial cells.' The drugs also reduced the transmission of bacterial resistance genes in a mouse model of infection.

Antibiotics

The concentrations blocking the induction of competence were lower than those inhibiting growth. However, they may still not be safe to treat patients, as human cells also rely on the proton-motive force for some vital functions. 'Nevertheless, we discovered a general pathway that we can block to prevent the spread of antibiotic resistance,' says Domenech. Future studies must show whether it is feasible to use this approach in humans. If that is the case, the finding could be a breakthrough: competence blockers are anti-evolution drugs, which could be given together with antibiotics. This combination would be a very powerful weapon in the fight against infections and could extend the lifespan of current antibiotics.

An explanimation of the study can be found on YouTube: https://youtu.be/WlAoEbNcOFY

What The Study Did: Data from annual financial reports were used to compare the profitability of 35 large pharmaceutical companies with 357 companies in the S&P 500 Index from 2000 to 2018. This study is part of a theme issue from JAMA on drug pricing.

Authors: Fred D. Ledley, of Bentley University in Waltham, Massachusetts, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(doi:10.1001/jama.2020.0442)

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

What The Study Did: Researchers estimated the cost to bring 63 new drugs or biologics to market between 2009 and 2018 using publicly available data on research and development expenditures for these medicines. This study is part of a theme issue from JAMA on drug pricing.

Authors: Olivier J. Wouters, Ph.D., of the London School of Economics and Political Science, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(doi:10.1001/jama.2020.1166)

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

What The Study Did: This study describes changes in list and net prices for 600 branded drugs in the U.S. from 2007 to 2018 and estimated the extent to which price increases were offset by increases in discounts. This study is part of a theme issue from JAMA on drug pricing.

Authors: Inmaculada Hernandez, Pharm.D., Ph.D. of the University of Pittsburgh School of Pharmacy, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(doi:10.1001/jama.2020.1012)

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

Large pharmaceutical companies are more profitable than most companies in the S&P 500 according to a study published in the Journal of the American Medical Association (JAMA) titled "Profitability of Large Pharmaceutical Companies Compared with Other Large Public Companies." Pharmaceutical profits were closer to those of other research-based companies within the S&P 500 and were not higher than companies in the technology sector.

The study from the Center for Integration of Science and Industry at Bentley University is the first to critically examine the profitability of the companies that are responsible for the development, manufacturing, marketing and sale of most medicines. The results may inform policies to ensure both the affordability and availability of essential medicines now and in the future.

The study was undertaken in the context of public opinion surveys showing that 80% of respondents believe the profits made by pharmaceutical companies are a major factor contributing to the price of prescription drugs. "While there is extensive research on the health impacts of unaffordable drugs, there has been little research on the profitability of pharmaceutical companies," said Dr. Fred Ledley, director of the Center for Integration of Science and Industry, and the senior author of the study. "Developing policies to assure the affordability of essential medicines will also require an understanding of how reducing drug prices may impact the industry that makes these drugs available."

The Bentley University study compared the profits of 35 large pharmaceutical companies with those of 347 companies from the S&P 500 Index. During the period from 2000 through 2018, the pharmaceutical companies had a cumulative revenue of $11.5 trillion and cumulative net income of $1.9 trillion. Net income, also called "earnings," reflects the difference between all revenues and expenses and is a company's "bottom line" used in calculating earnings per share. Over this same period, the median net income margin (the percentage of revenue remaining after deducting all expenses) for pharmaceutical companies was 13.7% compared to 7.7% for S&P 500 companies, a difference of 6.1%. However, when comparing pharmaceutical companies to those S&P 500 companies reporting research and development expenses and considering the effects of company size and time trends, the difference in median profits was 3.6%, and pharmaceutical companies were not more profitable than those companies in the technology sector or healthcare companies developing non-pharmaceutical products. Over the past five years, from 2014-2018, there was no significant difference in net income margin between pharmaceutical and S&P 500 companies.

These estimates of pharmaceutical profit margins were lower than those used by the National Academies of Science in their 2017 report, Making Medicines Affordable: a National Imperative.

The Bentley study focused explicitly on large pharmaceutical companies, which provide the large majority of all medicines. In 2018, these companies had a combined market value of $2.4 trillion, directly employed 992 thousand people, and expensed $120 billion for research & development of new medicines. Pharmaceutical companies represent only one element of the pharmaceutical distribution system, which also includes pharmacy benefit managers, wholesalers, pharmacies, and healthcare providers as well as academic laboratories and biotechnology companies involved in basic and applied research leading to the development of new medicines.

What The Study Did: What the pharmaceutical and health product industry spent on lobbying and contributions to political campaigns in the U.S. from 1999 to 2018 was the focus of this observational study that used federal- and state-level data. This study is part of a theme issue from JAMA on drug pricing.

Author: Olivier J. Wouters, Ph.D., of the London School of Economics and Political Science, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamainternmed.2020.0146)

Editor's Note: Please see the articles for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

What The Study Did: A variety of data were used to estimate annual health care spending in the U.S. from 1996 through 2016 by payer (public insurance, private insurance and out-of-pocket payments) and by health conditions, including low back pain and musculoskeletal disorders, diabetes and ischemic heart disease. This study is part of a theme issue from JAMA on drug pricing.

Authors: Joseph L. Dieleman, Ph.D., of the Institute for Health Metrics and Evaluation in Seattle, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jama.2020.0734)

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

You just finished a good meal and are feeling full? Researchers from the CNRS, Inrae, University of Burgundy, Université de Paris, Inserm, and University of Luxembourg (1) have just revealed the mechanisms in our brains that lead to this state. They involve a series of reactions triggered by a rise in blood glucose levels. This study, which was conducted on mice, is published in Cell Reports on 3 March 2020.

The neuronal circuits in our brain governing feelings of hunger and satiety can modify their connections, thereby adjusting feeding behaviour to living conditions and maintaining a balance between food intake and calorie expenditure. Scientists suspect that this plasticity could be altered for obese subjects.

In a new study conducted on mice, a team led by Alexandre Benani, a CNRS researcher at the Centre for Taste and Feeding Behavior (CNRS/Inrae/University of Burgundy/AgroSup Dijon), has shown that these circuits are activated on the time scale of a meal, subsequently regulating feeding behaviour. However, this activation does not occur through a change in the circuit's "connections."

Scientists focused on POMC neurons in the hypothalamus, located at the base of the brain, which are known for limiting food intake. They are connected to a large number of neurons from other parts of the brain, with the connections of this circuit being malleable: they can be made and unmade very quickly based on hormonal fluctuations. Researchers observed that this neuronal circuit is not modified after a balanced meal, but that other nerve cells associated with POMC neurons, known as astrocytes, actually change form.

Astrocytes are star-shaped nerve cells that were first studied for their supporting role with respect to neurons. Under usual conditions, they sheathe POMC neurons and act somewhat like brake pads by limiting their activity. After a meal, blood glucose levels (glycaemia) temporarily increase, with astrocytes detecting this signal and retracting in less than one hour: once this "brake" is released, POMC neurons are activated, ultimately promoting the feeling of satiety.

Surprisingly, a meal that is high in fats does not lead to this remodelling. Does this mean that lipids are less effective in satisfying hunger? The scientists are trying to determine whether they trigger satiety through another circuit. It also remains to be seen whether sweeteners have the same effects, or whether they lure the brain by providing an addictive sensation of sweetness without satisfying hunger.

The historic economies of Mongolia are among the least understood of any region in the world. The region's persistent, extreme winds whisk away signs of human activity and prevent the buildup of sediment which archaeologists rely on to preserve the past. Today crop cultivation comprises only a small percent of Mongolia's food production, and many scholars have argued that Mongolia presents a unique example of dense human populations and hierarchical political systems forming without intensive farming or stockpiling grains.

The current study, led by Dr. Shevan Wilkin of the Max Planck Institute for the Science of Human History provides, for the first time, a detailed glimpse into the diets and lives of ancient Mongolians, underscoring the importance of millets during the formation of the earliest empires on the steppe.

Isotopic analysis and the imperial importance of millets

Collaborating with archaeologists from the National University of Mongolia and the Institute of Archaeology in Ulaanbaatar, Dr. Wilkin and her colleagues from the MPI SHH sampled portions of teeth and rib bones from 137 previously excavated individuals. The skeletal fragments were brought back to the ancient isotope lab in Jena, Germany, where researchers extracted bone collagen and dental enamel to examine the ratios of stable nitrogen and carbon isotopes within. With these ratios in hand, scientists were able to reconstruct the diets of people who lived, ate, and died hundreds to thousands of years ago.

Researchers tracked the trends in diet through the millennia, creating a "dietscape" which clearly showed significant differences between the diets of Bronze Age peoples and those who lived during the Xiongnu and Mongol Empires. A typical Bronze Age Mongolian diet was based on milk and meat, and was likely supplemented with small amounts of naturally available plants. Later, during the Xiongnu Empire, human populations displayed a larger range of carbon values, showing that some people remained on the diet common in the Bronze Age, but that many others consumed a high amount of millet-based foods. Interestingly, those living near the imperial heartlands appear to have been consuming more millet-based foods than those further afield, which suggests imperial support for agricultural efforts in the more central political regions. The study also shows an increase in grain consumption and increasing dietary diversity through time, leading up to the well-known Mongolian Empire of the Khans.

Rethinking Mongolian prehistory

The new discoveries presented in this paper show that the development of the earliest empires in Mongolia, like in other parts of the world, was tied to a diverse economy that included the local or regional production of grain. Dr. Bryan K. Miller, a co-author who studies the historical and archaeological records of Inner Asian empires, remarks that "these regimes were like most empires, in that they directed intricate political networks and sought to amass a stable surplus - in this case a primarily pastoral one that was augmented by other resources like millet."

"In this regard," Dr. Miller adds, "this study brings us one step closer to understanding the cultural processes that led humanity into the modern world."

The view that everyone in Mongolian history was a nomadic herder has skewed discussions concerning social development in this part of the world. Dr. Wilkin notes that "setting aside our preconceived ideas of what prehistory looked like and examining the archaeological record with modern scientific approaches is forcing us to rewrite entire sections of humanity's past." Dr. Spengler, the director of the archaeobotany labs at the MPI SHH, emphasizes the importance of this discovery, noting that "this study pulls the veil of myth and lore off of the real people who lived in Mongolia millennia ago and lets us peak into their lives."