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http://bit.ly/2MFFwNyChagas disease, caused by a parasite, has spread

outside of Latin America and carries a high risk of heart disease

Chagas disease has spread to areas where it had not traditionally been seen

DALLAS -- Chagas disease, caused by infection with a parasite called Trypanosoma cruzi (T cruzi), causes chronic heart disease in about one third of those infected. Over the past 40 years, Chagas disease has spread to areas where it had not traditionally been seen, including the United States, according to a new American Heart Association scientific statement published in the American Heart Association journal Circulation.The statement. summarizes the most up-to-date information on diagnosis, screening and treatment of T cruzi infection. Infection occurs when feces from the infected blood sucking insect triatomine enters the skin through the bite site or in the eye. Triatomine insects are found in Central and South America, where they infest adobe houses and in the Southern United States.The disease can also be passed through contaminated food or drink, from pregnant mothers to their babies, and through blood transfusions and organ transplants.The health risks of Chagas disease are well-known in Latin America where most cases are found in countries that include Brazil, Argentina, Bolivia, Paraguay, Mexico and El Salvador. However, doctors outside of Latin America are largely unaware of the infection and its connection to heart disease. Countries where infected individuals have been diagnosed include the United States with an estimated 300,000 cases, Spain with at least 42,000 cases, Italy, France, Switzerland, the United Kingdom, Australia and Japan.

"This statement aims to increase global awareness among physicians who manage patients with Chagas disease outside of traditionally endemic environments," said Maria Carmo Pereira Nunes, M.D., Ph.D, co-chair of the committee that produced the statement. "This document will help healthcare providers and health systems outside of Latin America recognize, diagnose and treat Chagas disease and prevent further disease transmission," said Pereira Nunes, who is a cardiologist at the Federal University of Minas Gerais in Belo Horizonte, Brazil.Although 60-70 percent of people infected with T cruzi never develop any symptoms, those that do can develop heart disease, including heart failure, stroke, life threatening ventricular arrhythmias (heart rhythm abnormalities) and cardiac arrest. In the Americas, Chagas disease is responsible for more than seven times as many disability-adjusted life-years lost as malaria. However, if caught early, an infection can be cured with medications that have a 60 to 90 percent success rate, depending on when in the course of infection the patient is treated."Early detection of Chagas disease is critical, allowing prompt initiation of therapy when the evidence for cure is strong," said statement co-author Caryn Bern, M.D., M.P.H., professor of epidemiology and biostatistics at the University of California in San Francisco.The risk of infection is extremely low for most travelers and residents of endemic countries. To minimize risk, people should avoid sleeping in houses with un-plastered adobe walls and/or thatch roofs, and avoid unpasteurized sugar cane juice, açai fruit juice and other juices when visiting affected countries.Other co-authors are Andrea Beaton, M.D., Harry Acquatella, M.D.; Ann F. Bolger, M.D.; Luis E. Echeverría Correa, M.D.; Walderez O. Dutra, Ph.D.; Joaquim Gascon, M.D., Ph.D.; Carlos A. Morillo, M.D.; Jamary Oliveira-Filho, M.D., M.S., Ph.D.; Antonio Luiz Pinho Ribeiro, M.D., Ph.D.; and Jose Antonio Marin-Neto, M.D., Ph.D. Author disclosures are on the manuscript.

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http://bit.ly/2PonUEaA timescale for the origin and evolution of all of life

Combination of genomic and fossil data explain the history of life on Earth

A new study led by scientists from the University of Bristol has used a combination of genomic and fossil data to explain the history of life on Earth, from its origin to the present day. Palaeontologists have long sought to understand ancient life and the shared evolutionary history of life as a whole.However, the fossil record of early life is extremely fragmented, and its quality significantly deteriorates further back in time towards the Archaean period, more than 2.5 billion years ago, when the Earth's crust had cooled enough to allow the formation of continents and the only life forms were microbes.Holly Betts, lead author of the study, from the University of Bristol's School of Earth Sciences, said: "There are few fossils from the Archaean and they generally cannot be unambiguously assigned to the lineages we are familiar with, like the blue-green algae or the salt-loving archaebacteria that colours salt-marshes pink all around the world."The problem with the early fossil record of life is that it is so limited and difficult to interpret - careful reanalysis of the some of the very oldest fossils has shown them to be crystals, not fossils at all."Fossil evidence for the early history of life is so fragmented and difficult to evaluate that new discoveries and reinterpretations of known fossils have led to a proliferation of conflicting ideas about the timescale of the early history of life. Co-author Professor Philip Donoghue, also from Bristol's School of Earth Sciences, added: "Fossils do not represent the only line of evidence to understand the past. A second record of life exists, preserved in the genomes of all living creatures."

Co-author Dr Tom Williams, from Bristol's School of Biological Sciences, said: "Combining fossil and genomic information, we can use an approach called the 'molecular clock' which is loosely based on the idea that the number of differences in the genomes of two living species (say a human and a bacterium) are proportional to the time since they shared a common ancestor."

A timescale for the evolution of life on planet Earth summarising the findings of Betts et al. study. University of Bristol

By making use of this method the team at Bristol and Mark Puttick from the University of Bath were able to derive a timescale for the

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history of life on Earth that did not rely on the ever-changing age of the oldest accepted fossil evidence of life. Co-author Professor Davide Pisani said: "Using this approach we were able to show that the Last Universal Common Ancestor all cellular life forms, 'LUCA', existed very early in Earth's history, almost 4.5 Billion years ago - not long after Earth was impacted by the planet Theia, the event which sterilised Earth and led to the formation of the Moon. "This is significantly earlier than the currently accepted oldest fossil evidence would suggest. "Our results indicate that two "primary" lineages of life emerged from LUCA (the Eubacteria and the Archaebacteria), approximately one Billion years after LUCA. "This result is testament to the power of genomic information, as it is impossible, based on the available fossil information, to discriminate between the oldest eubacterial and archaebacterial fossil remains."The study confirms modern views that the eukaryotes, the lineage to which human life belongs (together with the plants and the fungi, for example), is not a primary lineage of life. Professor Pisani added: "It is rather humbling to think we belong to a lineage that is billions of years younger than life itself."This research was funded by the Natural Environment Research Council and the Biotechnology and Biological Sciences Research Council.

https://wb.md/2LfVvgpA Tradeoff Between Hypertension and Cognition?

Two interesting related studies examining links between hypertension and cognitive impairment

Charles P. Vega, MD August 20, 2018Hello. I'm Dr Charles Vega, and I am a clinical professor of family medicine at the University of California at Irvine. Welcome to

Medscape Morning Report, our 1-minute news story for primary care.Two interesting related studies examining links between hypertension and cognitive impairment were presented at the recent Alzheimer's Association International Conference.The first, a randomized controlled trial involving over 9000 adults with hypertension and at least one additional cardiovascular risk factor, concluded that patients who were aggressively treated to lower systolic blood pressure (BP) to 120 mm Hg had a statistically significant 19% relative risk reduction for mild cognitive impairment compared with those whose target was 140 mm Hg.The risk for dementia was also reduced by 15%, a result that was not significant.Patients in the aggressive-treatment arm took an average of 2.8 BP medications daily compared with 1.8 in the less-aggressive-treatment group.The second study was a meta-analysis of data from 31,000 adults with treated hypertension followed for up to 22 years and enrolled in one of six long-term prospective cohort studies. The researchers assessed associations between different classes of BP-lowering drugs and incident dementia or Alzheimer disease.They concluded that, compared with those who were not treated, use of any BP-lowering drug, regardless of drug class, was associated with a reduced hazard ratio for all-cause dementia of 0.88 and for Alzheimer's of 0.85. For both, however, the upper limit of the confidence interval approached 1.0.Taken together, the two studies support the notion that treating hypertension in older adults is associated with cognitive benefits, although the true clinical significance for an individual may be small. While the reductions in MCI and dementia certainly have important public health implications, the uncertain benefits to an

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individual may not outweigh the known risks for hypotension with therapy that is too aggressive.

http://bit.ly/2wbgrQ0Natural selection as karma: wasp parasitises tree, vine

parasitises waspResearchers find that an insect living off a tree is itself a target

for a very different type of predator.Tanya Loos reports.

A parasitic plant known as the love vine grows on oak trees, and also feeds upon gall wasps. The researchers who discovered this behaviour are calling it “botanical parasitism of an insect by a parasitic plant” – a peculiar type of interaction never previously recorded. The wasps induce the Sand live oak tree (Quercus geminata) to create tumour-like growths called galls, which protect their developing young.The love vine (Cassytha filiformis) actively seeks out these growths and attaches their specialised roots to their walls, leaching out the moisture and nutrients within. Inside a normal gall, a young wasp grows into an adult and exits through a small hole in the wall. When a love creeper feeds on a gall, the wasp still develops into an adult, but ends up a mummified corpse trapped inside.

Another vine mess: a gall wasp. Kim Taylor / Getty Images “I've been studying gall wasps and their interactions with their hosts and natural enemies from the southern tip of Florida to the southern edge of Texas for over a decade but had never observed

this interaction between the wasps and parasitic vine,” says lead author Scott Egan, from Rice University, Houston, US. “We have discovered a new interaction between plant and insect parasites when the two exist on a shared host. Most notably, the vine parasite is directly influencing the fitness and survival of the insect parasite.”The wasp most commonly attacked is a species called Belonocnema treatae, which forms spherical single-chambered galls, but the love creeper vine was also found attached to those of several other species, suggesting that the behaviour made be widespread. This means that the potential is global in scale. Parasitic species comprise 1% of flowering plants, or angiosperms, representing some 4500 species in 20 families. Gall formation is described in more than 13,000 species in six insect orders.The next goal for Egan and his colleagues is to establish how the love vine finds the galls. “We know that the vine's root structures are targeting the gall tissues specifically because they're attaching to galls located in regions of the tree the vine normally doesn't attach to,” he says. “This suggests that the vine may have some kind of searching mechanism or that there's something special about the gall that's drawing them in.” How the vines detect galls may have medical applications, particularly in cancer research.The research is published in the journal Current Biology.

https://bbc.in/2OQI4psHealth fear over rise in teens using protein supplements

Concerns raised over the potential harm protein supplements could have on teenagers

By Morgan Hammond BBC Wales

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When he was 14 years old Cerith Evans started using the same protein shakes as sports stars in a bid to bulk up.Now a personal trainer, he says social media was putting pressure on young people to use supplements to gain the perfect body quickly.A health expert and former Olympian have raised concerns over the potential harm they could have on teenagers.The European Specialist Sports Nutrition Alliance said supplements were never aimed at children.Recent research from marketing firm Mintel found 12% of people in the UK take supplements for exercise, rising to 23% of men aged 16-24 and 18% of women aged 16-24.Concerns have now been raised that while the products may be suitable for professional athletes, younger people could be putting their health at risk because of a lack of testing. Mr Evans, from Carmarthen, started weight training in his garage after his dad bought him a set of weights - and used the supplements to help him bulk up."I was extremely skinny, I was 6ft 2in (1.88m) but I was only 9 stone (57kg), so I wasn't far off being anorexic, so for my confidence, because I was bullied quite a lot in school, I started weight training," he said. "At that time that's when social media was all building up, so I was constantly following all kinds of athletes that were 15, 20 years older than me, they were taking these products and the fact that I was taking the same products as them made me feel like I had some sort of relationship with them," he added.Now a personal trainer he said while he had used the products safely to aid his fitness regime, there was an increasing pressure on young people to get a certain body type quickly.He said many were using supplements for a quick fix rather than focussing on exercise routines and nutrition.

"In the last five to six years when social media has gone so massive you can't really scroll through Facebook or Instagram without seeing a man with a top off or someone in great shape," he added."I think you have to look a certain way to be accepted which is a bad way of looking at it."Dr Ruth Fairchild, a nutritionist at Cardiff Metropolitan University, said that while protein supplements may be suitable for athletes they may not be right for the average person at the gym.She said: "They may have been tested amongst elite rowers for example but not within the general public."Any sport supplement isn't really suitable for children purely because we have never done any trials on children."Michaela Breeze, a former Olympic weightlifter who used to run a gym in Aberdare, Rhondda Cynon Taff, said some youngsters used the products because they saw sports stars using them.She said: "I think it needs to be made very clear, particularly to youngsters looking to take supplements to enhance their performance - it's a process of time. "There are quick fixes to getting there, but those are just simply not safe. The health effects and the risks are way too risky in my view to warrant doing it." The European Specialist Sports Nutrition Alliance insisted such products were governed by "very stringent regulation" - from production to labelling and marketing. Chairman Dr Adam Carey said: "These products are intended for use by sportspeople who have differing and more specific nutritional needs to the general public to help them perform to their best ability. "They do not represent a risk to one's general health as long as they are used for the correct reasons and in the correct dosages."

http://bit.ly/2nWNX9iGut bacteria provide key to making universal blood

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Gut enzymes can turn type A and B blood into O, as much as 30 times more efficiently than previously studied enzymes

BOSTON -- In January, raging storms caused medical emergencies along the U.S. East Coast, prompting the Red Cross to issue an urgent call for blood donations. The nation's blood supply was especially in need of O-type blood that can be universally administered in an emergency. Now, scientists say they have identified enzymes -- from the human gut -- that can turn type A and B blood into O, as much as 30 times more efficiently than previously studied enzymes.The researchers will present their results today at the 256th National Meeting & Exposition of the American Chemical Society (ACS). ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features more than 10,000 presentations on a wide range of science topics. A brand-new video on the research is available at http://bit.ly/acsblood."We have been particularly interested in enzymes that allow us to remove the A or B antigens from red blood cells," Stephen Withers, Ph.D., says. "If you can remove those antigens, which are just simple sugars, then you can convert A or B to O blood." He says scientists have pursued the idea of adjusting donated blood to a common type for a while, but they have yet to find efficient, selective enzymes that are also safe and economical.To assess potential enzyme candidates more quickly, Withers collaborated with a colleague at his institution, the University of British Columbia (UBC), who uses metagenomics to study ecology. "With metagenomics, you take all of the organisms from an environment and extract the sum total DNA of those organisms all mixed up together," Withers explains. Casting such a wide net allows Withers' team to sample the genes of millions of microorganisms without the need for individual cultures. The researchers then use E. coli to select for DNA containing genes that

code for enzymes that can cleave sugar residues. So instead of using metagenomics as a means of learning about microbial ecology, Withers uses it to discover new biocatalysts. "This is a way of getting that genetic information out of the environment and into the laboratory setting and then screening for the activity we are interested in," he says.Withers' team considered sampling DNA from mosquitoes and leeches, the types of organisms that degrade blood, but ultimately found successful candidate enzymes in the human gut microbiome. Glycosylated proteins called mucins line the gut wall, providing sugars that serve as attachment points for gut bacteria while also feeding them as they assist in digestion. Some of the mucin sugars are similar in structure to the antigens on A- and B-type blood. The researchers homed in on the enzymes the bacteria use to pluck the sugars off mucin and found a new family of enzymes that are 30 times more effective at removing red blood cell antigens than previously reported candidates. Withers is now working with colleagues at the Centre for Blood Research at UBC to validate these enzymes and test them on a larger scale for potential clinical testing. In addition, he plans to carry out directed evolution, a protein engineering technique that simulates natural evolution, with the goal of creating the most efficient sugar-removing enzyme."I am optimistic that we have a very interesting candidate to adjust donated blood to a common type," Withers says. "Of course, it will have to go through lots of clinical trails to make sure that it doesn't have any adverse consequences, but it is looking very promising."A press conference on this topic will be held Tuesday, Aug. 21, at 9:30 a.m. Eastern time in the Boston Convention & Exhibition Center. Reporters may check-in at t he press center, Room 102A, or watch live on YouTube http://bit.ly/ACSLive_Boston2018. To ask questions, sign in with a Google account.The researchers acknowledge support and funding from the Canadian Institutes of Health Research.

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http://bit.ly/2w32uo7Simple leg exercises could reduce impact of sedentary

lifestyle on heart and blood vesselsPerforming simple leg exercises whilst lying down might help to

prevent heart and blood vessel diseasesA sedentary lifestyle can cause an impairment of the transport of blood around the body, which increases the risk of disease in the heart and blood vessels. New research published in Experimental Physiology suggests that performing simple leg exercises whilst lying down might help to prevent these problems.Previous work has demonstrated that prolonged sitting for up to 6 hours results in a decline in both blood flow to the limbs and in our larger arteries' ability to widen to accommodate increased blood flow. This is the first study to demonstrate that sitting for just 10 minutes is sufficient to reduce blood flow to the legs and impairs the function of small blood vessels supplying muscles in the leg.This paper also demonstrates a reduction in the function of small blood vessels when lying down. However, this study suggests we might be able to somewhat reverse this impairment in function by performing simple leg exercises when lying down in bed or on the sofa. These findings are important in increasing our understanding of the negative impact of sitting and physical inactivity on blood vessel function and the supply of blood to the legs.The effects of sitting on blood circulation have been attributed to blood passing more sluggishly through arteries whilst sitting. The researchers who performed this study aimed to find out whether these reductions were caused by sustained sitting, or whether 10 minutes would be sufficient to have a negative effect.The research group used a Doppler ultrasound technique alongside the knee to measure blood flow and examined the extent to which blood vessels widened in 18 healthy, young males. These measurements were made prior to and following a 10-minute period

of sitting or during a period of rest whilst lying down, with or without leg exercises, which were performed by extending the foot back and forth every two seconds for a third of the time spent lying down. Results showed that a 10 minute period of sitting reduced participants' ability to rapidly increase blood flow to the lower legs via small blood vessels, but did not affect the widening of larger arteries in response to increased blood flow. These findings suggest that a brief period of inactivity affects an individual's ability to rapidly push blood to the lower limbs as efficiently as normal, but doesn't affect the ability of large blood vessels to widen. The results also suggest leg exercises can help maintain rapid increases in the blood supply to the limbs.The current study demonstrates changes in blood vessel function measured at the level of the knee. However, the researchers only tested healthy young males, and as such, their findings cannot be extended to females. It remains unknown as to how these responses may vary with age, or with people who have heart problems. Further research may investigate the impact of sitting and inactivity on blood vessels in other places in the body. For example, would sitting impact the function of blood vessels supplying the brain? Finally, studies designed to investigate the impact of repeated bouts of short-term sitting on blood vessel function are needed.Co-author Dr. Paul Fadel sheds light on his team's results: "These findings further our understanding of the negative impact of inactivity on blood vessel function and demonstrate the positive effects of simple leg exercises whilst lying down providing further insight into how inactivity affects vascular health of the lower legs".

http://bit.ly/2MzWoFtIce confirmed at the Moon's poles

Definitive evidence of water ice on the Moon's surface

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In the darkest and coldest parts of its polar regions, a team of scientists has directly observed definitive evidence of water ice on the Moon's surface. These ice deposits are patchily distributed and could possibly be ancient. At the southern pole, most of the ice is concentrated at lunar craters, while the northern pole's ice is more widely, but sparsely spread. A team of scientists, led by Shuai Li of the University of Hawaii and Brown University and including Richard Elphic from NASA's Ames Research Center in California's Silicon Valley, used data from NASA's Moon Mineralogy Mapper (M3) instrument to identify three specific signatures that definitively prove there is water ice at the surface of the Moon.M3, aboard the Chandrayaan-1 spacecraft, launched in 2008 by the Indian Space Research Organization, was uniquely equipped to confirm the presence of solid ice on the Moon. It collected data that not only picked up the reflective properties we'd expect from ice, but was able to directly measure the distinctive way its molecules absorb infrared light, so it can differentiate between liquid water or vapor and solid ice.

The image shows the distribution of surface ice at the Moon's south pole (left) and north pole (right), detected by NASA's Moon Mineralogy Mapper

instrument. Blue represents the ice locations, plotted over an image of the lunar surface, where the gray scale corresponds to surface temperature (darker representing colder areas and lighter shades indicating warmer

zones). The ice is concentrated at the darkest and coldest locations, in the shadows of craters. This is the first time scientists have directly observed

definitive evidence of water ice on the Moon's surface. Credits: NASAMost of the newfound water ice lies in the shadows of craters near the poles, where the warmest temperatures never reach above minus 250 degrees Fahrenheit. Because of the very small tilt of the Moon's rotation axis, sunlight never reaches these regions.Previous observations indirectly found possible signs of surface ice at the lunar south pole, but these could have been explained by other phenomena, such as unusually reflective lunar soil.With enough ice sitting at the surface—within the top few millimeters—water would possibly be accessible as a resource for future expeditions to explore and even stay on the Moon, and

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potentially easier to access than the water detected beneath the Moon's surface.Learning more about this ice, how it got there, and how it interacts with the larger lunar environment will be a key mission focus for NASA and commercial partners, as we endeavor to return to and explore our closest neighbor, the Moon.The findings were published in the Proceedings of the National Academy of Sciences on August 20, 2018. NASA's Jet Propulsion Laboratory, Pasadena, California, designed and built the moon mineralogy mapper instrument and was home to its project manager. More information: Shuai Li et al. Direct evidence of surface exposed water ice in the lunar polar regions, Proceedings of the National Academy of Sciences (2018). DOI: 10.1073/pnas.1802345115

http://bit.ly/2MEPcYGGenetic error led humans to evolve bigger, but more

vulnerable, brainsError in original NOTCH gene helped to expand brain size, but left greater risk of schizophrenia or autistic spectrum disorder

August 21, 2018 by Anthony King *Newly-discovered genes that helped supersize human brains along with DNA retrieved from extinct humans, which can still be found in people living today, are expanding scientists' understanding of how our species evolved.One of the major features that distinguish humans from other primates is the size of our brains, which underwent rapid evolution from about two to three million years ago in a group of our ancestors in Africa called the Australopithecines. During this period, the human brain grew almost three-fold to reach its

current size. Scientists know this from skull remains, but have puzzled over how it happened.

The skull of a Australopithecus sediba, a species of Australopithecines, who were our ancestors and whose brains started to grow two to three million

years ago. Australopithecus sediba by Brett Eloff, courtesy Profberger and Wits University is licensed under CC BY-SA 4.0

This year, the mystery was partially solved by Professor Pierre Vanderhaeghen at the Flanders Institute for Biotechnology in Belgium. Prof. Vanderhaeghen, who was conducting his work as part of the GENDEVOCORTEX project, went on a hunt for the genes that drove the growth of human brains.Scientists had suspected that brain expansion began in our human ancestors when they evolved genes that are switched on in the foetus, when a lot of key brain development occurs. Prof. Vanderhaeghen therefore looked for genes present in human foetal tissue, but missing from our closest living relatives, apes.His lab discovered 35 hominid—present only in apes and humans—genes that were active in foetal brain tissue. They then became intrigued by three specific genes—all similar to NOTCH genes, an ancient gene family involved in sending messages between cells and that are present in all animals. They found that the three new genes, collectively named NOTCH 2NL, were created by a copy and paste error of an original NOTCH gene.This error created entirely new proteins which likely helped our ancestors' cerebral cortex to balloon. This is the part of our brain responsible for our language, imagination and problem-solving abilities. Scientists at the University of California, Santa Cruz, have also identified the NOTCH 2NL genes in DNA from Homo sapiens' extinct cousins—the Neanderthals and Denisovans.'(The NOTCH 2NL) genes are only present in humans today. They were also present in Neanderthal DNA, but not in chimpanzees," Prof. Vanderhaeghen said.

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EvolutionThese genes control the growth rate and differentiation of brain stem cells—the starter cells that multiply and give rise to all neurons in our brain—causing them to seed more nerve cells, which in turn helped to expand brain size. The genes likely led to more neurons and brain tissue in our ancestor's descendants—including Neanderthals, Denisovans, and modern humans.Prof. Vanderhaeghen's research could also help to provide new insights into brain disorders. The US researchers linked genetic faults in DNA that were very similar to NOTCH 2NL, to children born with enlarged brains or small brains. Many of the new human-specific genes are located in a small area of our genome that plays an important role in brain size, according to Prof. Vanderhaeghen.As DNA in this area closely resembles another part of the genome where it was originally cut and pasted from millions of years ago, errors are more likely, said Prof. Vanderhaeghen. "Patients who have (inherited) deletions in this area tend to be at risk of developing schizophrenia, whereas patients with duplications are more at risk of autistic spectrum disorder," he said.Prof. Vanderhaeghen is now studying some 20 of the remaining human-only genes to see how they contributed to the evolution of the human brain.The use of genetics to study human evolution in this way is helping to transform our understanding of how our own species compared to our ancestors. Traditionally, scientists have studied extinct species by looking at the fossilised remains of their bones. This was how they discovered the existence of Neanderthals, the extinct human species that lived across Europe and much of Asia before vanishing around 40,000 years ago.In the last decade, however, scientists have begun to look at the DNA inside these bones. Professor Svante Pääbo, director of the Max Planck Institute for Evolutionary Anthropology in Leipzig,

Germany, has led the way in sequencing DNA of these extinct humans from small bone fragments.This allows scientists to compare modern human DNA with that of extinct humans, rather than just living relatives like chimps. Already, the work has revealed some surprising findings—our own species appears to have interbred with some of these ancient relatives during our history.Ancient humansScientists have found that the DNA of every person outside Africa is 1–2% Neanderthal, meaning that these extinct human relatives had offspring with our own ancestors.

That many people still retain Neanderthal DNA today could mean that it plays a role in our immune system. Frank Vinken for Max Planck Society

"Different people tend to carry different pieces of the Neanderthal genome," said Prof. Pääbo, who is undertaking a project called 100 Archaic Genomes to decipher the DNA of ancient human individuals."Something like 40–50% of the Neanderthal genome can still be found in people today," he said.According to Prof. Pääbo, we retained some of this DNA because it offered an advantage to our ancestors. "Some (of this retained DNA) has to do with the immune system, presumably helping us to fight off infectious diseases."The power of genetics to unravel the history of human evolution took a new twist in 2010 after Prof. Pääbo's lab sequenced DNA from a finger bone fragment found by a Russian archaeological team in a remote Siberian cave.The analysis revealed the bone belonged to a previously unknown human relative, now called Denisovans after Denisova Cave where

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the bone was found. This mysterious ancient human species lived at around the same time as Neanderthals, but further east into Asia.Last year, Prof. Pääbo's group published DNA sequences from a tooth found in the cave—the fourth ever Denisovan discovered. We now know Denisovan DNA carries more variation than Neanderthal DNA, leading scientists to conclude that they were more widespread than the better-known Neanderthals.Denisovans left a more impressive stamp on some of us than Neanderthals, according to Prof Pääbo. Their DNA can be found in people across Asia today, while indigenous peoples of Papua New Guinea and Australia may carry up to 5%. Tibetans also carry some Denisovan DNA in their genomes, which has helped them adapt to life at high altitudes where there is little oxygen in the atmosphere.Prof. Pääbo and his colleagues will soon publish their third high-quality genome—where almost the entire DNA sequence is intact—of a Neanderthal from Siberia. A deciphered genome of this quality allows for better DNA comparisons and could tell us more about the evolution of important genes—such as those linked to the development and function of the brain. It will add yet another puzzle piece to help us understand the history of our closest extinct relatives, according to Prof. Pääbo."There may even be other forms of extinct humans out there to be discovered by studying the DNA of the (ancient) bones we find," he said.* Horizon: The EU Research & Innovation MagazineMore information: Ira Espuny-Camacho et al. Hallmarks of Alzheimer's Disease in Stem-Cell-Derived Human Neurons Transplanted into Mouse Brain, Neuron (2017). DOI: 10.1016/j.neuron.2017.02.001

http://bit.ly/2MFbauwLaughing gas may have helped warm early Earth and

given breath to lifeNitrous oxide may have played a significant role in warming

early earth

More than an eon ago, the sun shone dimmer than it does today, but the Earth stayed warm due to a strong greenhouse gas effect, geoscience theory holds. Astronomer Carl Sagan coined this "the Faint Young Sun Paradox," and for decades, researchers have searched for the right balance of atmospheric gases that could have kept early Earth cozy.A new study led by the Georgia Institute of Technology suggests that nitrous oxide, known for its use as the dental sedative laughing gas, may have played a significant role.The research team carried out experiments and atmospheric computer modeling that in detail substantiated an existing hypothesis about the presence of nitrous oxide (N2O), a powerful greenhouse gas, in the ancient atmosphere. Established research has already pointed to high levels of carbon dioxide and methane, but they may not have been plentiful enough to sufficiently keep the globe warm without the help of N2O.Jennifer Glass, an assistant professor at Georgia Tech, and Chloe Stanton, formerly an undergraduate research assistant in the Glass lab at Georgia Tech, published the study in the journal Geobiology the week of August 20, 2018. Their work was funded by the NASA Astrobiology Institute. Stanton is now a graduate research assistant at the Pennsylvania State University.No 'boring billion'The study focused on the middle of the Proterozoic Eon, over a billion years ago. The proliferation of complex life was still a few hundred million years out, and the pace of our planet's evolution probably appeared deceptively slow."People in our field often refer to this middle chapter in Earth's history roughly 1.8 to 0.8 billion years ago as the 'boring billion' because we classically think of it as a very stable period," said Stanton, the study's first author. "But there were many important

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processes affecting ocean and atmospheric chemistry during this time."Chemistry in mid-Proterozoic ocean was heavily influenced by abundant soluble ferrous iron (Fe2+) in oxygen-free deep waters.Ancient iron key"The ocean chemistry was completely different back then," said Glass, the study's principal investigator. "Today's oceans are well-oxygenated, so iron rapidly rusts and drops out of solution. Oxygen was low in Proterozoic oceans, so they were filled with ferrous iron, which is highly reactive."In lab experiments, Stanton found that Fe2+ in seawater reacts rapidly with nitrogen molecules, especially nitric oxide, to yield nitrous oxide in a process called chemodenitrification. This nitrous oxide (N2O) can then bubble up into the atmosphere.When Stanton plugged the higher fluxes of nitrous oxide into the atmospheric model, the results showed that nitrous oxide could have reached ten times today's levels if mid-Proterozoic oxygen concentrations were 10 percent of those today. This higher nitrous oxide would have provided an extra boost of global warming under the Faint Young Sun.Breathing laughing gasNitrous oxide could have also been what some ancient life breathed.Even today, some microbes can breathe nitrous oxide when oxygen is low. There are many similarities between the enzymes that microbes use to breathe nitric and nitrous oxides and enzymes used to breathe oxygen. Previous studies have suggested that the latter evolved from the former two. The Georgia Tech model provides a plentiful source of nitrous oxide in ancient iron-rich seas for this evolutionary scenario. And prior to the Proterozoic, when oxygen was extremely low, early aquatic microbes could have already been breathing nitrous oxide.

"It's quite possible that life was breathing laughing gas long before it began breathing oxygen," Glass said. "Chemodenitrification might have supplied microbes with a steady source of it."The paper was co-authored by Chris Reinhard of Georgia Tech, James Kasting of the Pennsylvania State University, Nathaniel Ostrom and Joshua Haslun of Michigan State University, and Timothy Lyons of the University of California Riverside. The research was funded by grant NNA15BB03A from the NASA Astrobiology Institute. Findings, opinions, and conclusions are those of the authors and not necessarily of the NASA Astrobiology Program.

http://bit.ly/2MoZVHgRed or yellow? A simple paper test detects false or

substandard antibioticsResearchers have put chemistry to work on a simple, inexpensive way to identify counterfeit antibiotics - a serious problem in the

developing worldAntibiotics - medicines that treat bacterial infections - have saved millions of lives worldwide since their discovery in the early 20th century. When we fill a prescription at the doctor's office or pharmacy today, most of us take for granted that these commonly prescribed medicines are real, and of good quality.But in the developing world, the manufacture and the distribution of substandard, nonlegitimate medicines is widespread. The World Health Organization estimates that up to 10 percent of all drugs worldwide could be falsified, with up to 50 percent of those some form of antibiotics. A counterfeit or diluted antibiotic can not only endanger an unwitting patient, but can also contribute to the wider problem of antimicrobial resistance.

13 5/13/23 Name Student number A simple, paper-based test can quickly identify a falsified or substandard

antibiotic. John Eisele/Colorado State UniversityA Colorado State University laboratory is putting chemistry to work on a simple, inexpensive way to identify such falsified and substandard antibiotics, offering a practical solution to a very real problem. The researchers have created a paper-based test that can quickly determine whether an antibiotic sample is appropriate strength, or diluted with filler substances like baking soda. Similar to the mechanism of a home pregnancy test, a strip of paper turns a distinctive color if a falsified antibiotic is present.It's the latest paper-based chemical assay developed in the lab of Chuck Henry, professor in the Department of Chemistry. Researchers including first author Kat Boehle, a recently graduated Ph.D. student, describe the invention in ACS Sensors. "In this country, we take for granted that our antibiotics are good - we don't even think twice," Boehle said. "But counterfeit and substandard antibiotics are an extremely common thing in other parts of the world. The goal of this project has been to make a cheap detection device that is easy to use; our device costs literally a quarter to make."Here's how it works: Bacteria naturally produce an enzyme that can give them resistance to antibiotics by chemically binding to portions of the antibiotic molecule. The researchers used this very enzyme, called beta-lactamase, to empower their device to detect the presence of antibiotics in a given sample.For the test, the user dissolves the antibiotic in water, and adds the solution to a small paper device. The paper contains a molecule called nitrocefin that changes color when it reacts with the enzyme. In this setup, the antibiotic and the nitrocefin on the paper are in competition to bind with the enzyme in a detection zone.With a good antibiotic dose, there is little color change in the paper strip, because the antibiotic outcompetes the nitrocefin and

successfully binds with the beta-lactamase enzyme. But in a falsified or weakened antibiotic, the paper goes red, because the enzyme instead reacts with the nitrocefin. In short, yellow means good (appropriate strength antibiotic); red means bad (diluted antibiotic).The device also includes a pH indicator, to determine if a sample is acidic or alkaline. This extra information could further alert the user to whether a sample has been falsified with filler ingredients, which might otherwise confound the main test.It's simple, it's fast (about 15 minutes), and it can be used by an untrained professional - all key goals of the project, Henry said. Traditional approaches for testing drug purity rely on large, expensive analytical equipment in labs, including mass spectrometry, making it challenging or impossible for developing countries to access easily.To ensure the usability of the device, the researchers included in their experiment a blind test with five users who were unfamiliar with the device or the science behind it. They all successfully identified 29 out of 32 antibiotic samples as either legitimate or false.The test is effective for a broad spectrum of beta-lactam antibiotics, but there's room for refinement. The sample most misidentified by untrained users was acetylsalicylic acid -commonly known as aspirin - which did not turn as red as the other false samples because its acidic pH destabilized the reaction. Being able to more accurately distinguish such specific chemicals will be the subject of future optimization of the new test, the researchers say.

http://bit.ly/2PnqGd3Clay to fight bacteria in wounds: An old practice may

be a new solutionOne type of clay may help fight disease-causing bacteria in

wounds

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ROCHESTER, Minn. - The use of mud or wet clay as a topical skin treatment or a poultice is a common practice in some cultures and the concept of using mud as medicine goes back to earliest times. Now Mayo Clinic researchers and their collaborators at Arizona State University have found that at least one type of clay may help fight disease-causing bacteria in wounds, including some treatment-resistant bacteria. The findings appear in the International Journal of Antimicrobial Agents."We showed that this reduced iron-bearing clay can kill some strains of bacteria under the laboratory conditions used, including bacteria grown as biofilms, which can be particularly challenging to treat," says Robin Patel, M.D., a clinical microbiologist and infectious diseases specialist at Mayo Clinic and senior author of the study. Biofilms occur when bacteria attach to surfaces and develop a film or protective coating making them relatively resistant to antibiotics. They appear in two-thirds of the infections seen by physicians."This study is an important advance in understanding how clays, specifically blue clay from Oregon, have shown medicinal properties by attaching to pathogenic bacteria," says Enriqueta Barrera, program director in the National Science Foundation's Division of Earth Sciences, which funded the research.In laboratory tests the researchers found the clay has antibacterial effects against bacteria such as Escherichia coli, and Staphylococcus aureus, including resistant strains such as CRE and MRSA. The clay suspension was effective against a number of bacteria both in their planktonic and biofilm states.The research is preliminary and the authors caution that only one concentration of the clay suspension was tested, based on preliminary results. The lab tests are a first step in simulating the complex environment found in an actual infected wound. They also caution that not all types of clay are beneficial. Some may actually

help bacteria grow. More research is needed to identify and reproduce the properties of clays that are antibacterial, with the goal of possibly synthesizing a consistent compound of the key minerals under quality control.Others on the research team were Katherine Caflisch, Suzannah Schmidt-Malan, Jayawant Mandrekar, Ph.D., Melissa Karau, and Jonathan Nicklas of Mayo Clinic; and Lynda B. Williams, Ph.D., Arizona State University.

http://bit.ly/2NdpU0sAnnual pap test a 'thing of the past?'

Professor reviews new cervical cancer screening guidelines from US Preventive Services Task Force

The United States Preventive Services Task Force (USPSTF) has released new recommendations on screening for cervical cancer. These latest recommendations continue the trend of decreasing participant burden by lengthening screening intervals, making the "annual Pap" a historical artifact. Since its introduction 75 years ago, exfoliative cytology commonly known as the Pap test has been the "gold-standard" screening test for cervical cancer.In the current issue of the Journal of the American Medical Association (JAMA), the USPSTF, an independent panel of experts in primary care and prevention, updates its 2012 recommendations for cervical cancer screening with one important addition. This is the first time the USPSTF has recommended a method of cervical cancer screening that does not include the Pap test. A leading obstetrician/gynecologist Lee A. Learman, M.D., Ph.D., senior associate dean for Graduate Medical Education and Academic Affairs and professor at Florida Atlantic University's Schmidt College of Medicine, is lead author of an editorial in this JAMA issue. Learman and co-author Francisco A.R. Garcia, M.D., M.P.H., a distinguished professor at the University of Arizona Cancer Center, provide a history of cervical cancer screening and an overview of the new USPSTF recommendations, which open

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avenues for new tools and opportunities that benefit both clinicians and patients. The new USPSTF guidelines recommend that women ages 21 to 29 years be screened for cervical cancer every three years with the Pap test alone. This recommendation remains unchanged from 2012. For women ages 30 to 65 years, the USPSTF recommends screening for cervical cancer with primary high-risk human papillomavirus (hrHPV) test alone every five years. As an option, they also recommend the previous guideline of hrHPV test and Pap test together (co-testing) every three years. What was novel in the 2012 USPSTF recommendations was that women ages 30 to 65 years were given the option for the first time to be screened with hrHPV test and Pap test together every five years to lengthen their screening interval. The 2018 recommendations go one step further by including, for the first time, the option of hrHPV testing alone, without a Pap test, every five years. The table in the new USPSTF recommendations also acknowledges an important trade-off. Co-testing is slightly better than primary hrHPV testing at detecting precancerous lesions but is associated with increased tests and diagnostic procedures that may not benefit the patient and have real costs to the health care system. Pap tests detect changes in cervical cells that could indicate the presence of pre-cancer or cancer, while HPV tests detect the genetic material or DNA of the high-risk types in cervical samples. "The current guidelines preserve the greatest range of choices for practitioners and patients; in the sense that both will benefit," said Learman. "More efficient cervical cancer screening every three to five years will liberate time at the annual visit to discuss prevention of other cancers and chronic diseases that disproportionately burden women."

Because most high-risk HPV infections among healthy individuals are cleared spontaneously without intervention, over the years, screening and clinical management recommendations have become more conservative in general and for young women in particular. "Despite many advances such as the HPV prophylactic vaccine, for now, high-quality screening remains an essential tool in the prevention of cervical cancer," said Learman."With the new recommendations come new demands on patients, especially those who bear the greatest disease burden from cervical cancer: women from low socioeconomic backgrounds, women from communities of color, and other women with compromised access to timely and effective care." Nearly all cases of cervical cancer are caused by infection with oncogenic, or high-risk, types of HPV. Cervical cancer is the fourth most common cancer in women worldwide. In 2012, 10 percent of women in the United States ages 21 to 65 years (an estimated 8 million women) reported not being screened for cervical cancer in the past five years. From 2012 to 2016, there was a continued decline in the number of women receiving cervical cancer screening.In addition, 10 years after approval of the first HPV prophylactic vaccine in the U.S., only 43 percent of adolescents (50 percent of girls and 38 percent of boys) were up to date with the HPV vaccination guidelines, compared with 88 percent for tetanus, diphtheria, and acellular pertussis vaccine.

http://bit.ly/2MroGm7Can China, the world’s biggest pork producer, contain

a fatal pig virus? Scientists fear the worstHighly contagious, often fatal disease of domestic pigs and wild

boars, has appeared in China

16 5/13/23 Name Student number By Dennis Normile Aug. 21, 2018 , 3:30 PM

A nightmare is unfolding for animal health experts: African swine fever (ASF), a highly contagious, often fatal disease of domestic pigs and wild boars, has appeared in China, the world’s largest pork producer. As of today, ASF has been reported at sites in four provinces in China’s northeast, thousands of kilometers apart.Containing the disease in a population of more than 430 million hogs, many raised in smallholder farmyards with minimal biosecurity, could be a monumental challenge.China has millions of pig farms, many of them small, such as this one on the

outskirts of Beijing. Nicolas Asfouri/AFP/Getty Images “The entry of ASF into China is really a very serious issue,” says Yang Hanchun, a swine viral disease scientist at China Agricultural University in Beijing. Given the scale of China's pork sector, the economic impact could be devastating, Yang says, and the outbreak puts a crucial protein source at risk. From China, the virus could also spread elsewhere; if it becomes endemic, “it will represent a major threat for the rest of the world, including the American continent,” says François Roger, an animal epidemiologist at the Agricultural Research Center for International Development in Montpellier, France.The virus that causes ASF does not harm humans, but it spreads rapidly among domestic pigs and wild boars through direct contact or exposure to farm workers’ contaminated shoes, clothing, and equipment. It can survive heat and cold and persists for weeks in carcasses, feces, and fresh and semicured pork products, such as sausages. Ticks can also spread it. Infection causes a high fever, internal bleeding, and, often, death. There is no ASF vaccine and no treatment for infected animals.Endemic in most African countries, ASF jumped to the nation of Georgia in 2007 and later spread through Russia; it has also been reported in Poland and the Czech Republic, and scientists worry

about a jump to major pork producers such as Germany and Denmark.East Asia’s first confirmed outbreak occurred on 1 August in Shenyang, a city in Liaoning province, China’s Ministry of Agriculture says. Investigators have traced the disease back through sales of pigs and concluded the virus has been circulating in the area since at least March, says Wantanee Kalpravidh, a veterinarian at the Food and Agriculture Organization’s (FAO’s) Emergency Centre for Transboundary Animal Disease in Bangkok.A threat emerges As of 21 August, African swine fever had been reported in four provinces in northeastern China.A genetic analysis suggests the virus is closely related to the strain circulating in Russia, scientists from the Institute of Military Veterinary Medicine in Changchun, and other Chinese institutions reported on 13 August in Transboundary and Emerging Diseases. “The increasing demand for pork has resulted in a great increase in the volume of live pigs and pork products imported to China,” heightening the risk of introduction, they wrote. The virus probably arrived in imported pork products, Kalpravidh says, which

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then infected pigs that were fed contaminated table and kitchen scraps.A second outbreak occurred on 14 August at a slaughterhouse in Zhengzhou, the capital of Henan province; the afflicted pigs had been shipped from a market in Jiamusi, a town in Heilongjiang province, more than 2000 kilometers to the northeast. The virus struck again on 15 August at a farm in Lianyungang, in Jiangsu province. The Chinese government has responded by culling sick and exposed animals—nearly 9000 were killed in Shenyang alone—blockading outbreak areas; disinfecting farms, markets, and processing facilities; controlling the movement of live pigs and pork products; screening animals; and conducting epidemiological surveys.But there are serious challenges to containing the virus. Pig producers in China range from massive, sophisticated operations to small backyard farms; tailoring a response to suit them all “is the biggest challenge for China to control ASF,” Yang says. The complexity of the production chain makes tracing paths of infection “an incredible effort to tackle,” says Juan Lubroth, chief veterinarian at FAO’s headquarters in Rome. Kalpravidh says China is trying to earn the cooperation of producers by immediately compensating them for culled animals, in hopes of stopping them from slaughtering sick pigs and selling their meat. But ticks and wild boar could also spread the disease, although their role is poorly understood.So far, Lubroth says, China’s “very sophisticated and knowledgeable veterinary workforce” has operated aggressively, and the government has been transparent about ASF’s spread. But containing ASF “won’t happen overnight,” he warns.With reporting by Bian Huihui.

http://bit.ly/2MJXoqv

Flint water crisis: Michigan health director ordered to manslaughter trial

Michigan Health Director Nick Lyon is highest-ranking official charged for Flint water issues.

Beth Mole - 8/22/2018, 6:37 AMA judge on Monday ordered Michigan’s top health official, Nick Lyon, to stand trial for involuntary manslaughter charges in two deaths linked to the Flint water crisis.Genesee District Judge David Goggins determined that there was probable cause that Lyon committed involuntary manslaughter against Robert Skidmore and John Snyder in 2015. The two men died during an outbreak of Legionnaire’s disease, which researchers have connected to the devastating use of improperly treated water in Flint starting in 2014.Lyon, the director of Michigan’s Department of Health and Human Services, is the highest-ranking official in the state to stand trial in connection with the catastrophe. An additional 14 current or former state and local officials have been criminally charged in connection with the water issues.As Ars has reported previously, prosecutors allege that Lyon specifically had “willfully disregarded the deadly nature of the Legionnaires’ disease outbreak” and failed to warn the public in time to spare lives. He allegedly knew about the outbreak in early 2015 but waited until early 2016 to release a public advisory.According to NPR, Judge Goggins read from his opinion Monday:The victims’ deaths—that is Robert Skidmore and John Snyder—their deaths were caused by this neglect of the defendant, in [Nick Lyon’s] failure to act appropriately with regard to disseminating notices to the public."Involuntary manslaughter is a felony punishable by up to 15 years in prison. Lyon is also charged with felony misconduct in office for allegedly obstructing academic researchers from studying the

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outbreak, which carries a sentence of up to five years in prison. Last, he faces a misdemeanor charge of willful neglect in office.When the judge announced the decision that Lyon must face trial, a woman in the gallery let out a “yes, yes, yes,” according to the Associated Press.In comments to reporters after the hearing, Lyon’s defense attorney, John Bursch, said that they will “absolutely file a motion to quash” the judge’s decision. He was confident that the “circuit court, and if not there the court of appeals, are going to look at this, and they’re going to reverse [this] so fast it’ll make your head spin.”Deadly drinkThe trouble for Flint residents and Lyon all began in 2014, after state-appointed emergency managers switched the city’s water supply to save money. They went from buying treated water sourced from Lake Huron and the Detroit River to the less-expensive option of using water from Flint River. But they did not ensure that the water was properly treated to prevent corrosion in old plumbing. This caused lead and other metals to leach into the water, exposing residents and risking permanent neurological damage to local children.The improper water treatment also interfered with disinfectants and caused the release of iron and other bacterial nutrients into the water, which can spur the spread and growth of Legionella bacteria. When those germs are aerosolized and inhaled from sources such as hot showers, humidifiers, and water coolers, they can cause a deadly form of pneumonia called Legionnaire’s disease, so named for an outbreak at an American Legion convention in 1976.Flint experienced a surge in Legionnaire’s disease after the water switch, with cases totaling around 100 and leading to at least 12 deaths, including Skidmore and Snyder’s. Researchers with the Centers for Disease Control and Prevention genetically linked the bacteria infecting patients to those found in the city’s water.

State officials now say that the city’s water meets federal standards for lead and other contaminants. However, the water can still pick up toxic ingredients from contaminated pipes. For now, residents need to continue drinking bottled or filtered water until the city’s plumbing is replaced, which the city is working to do by 2020. In April, Michigan Governor Rick Snyder announced that the state will stop providing free bottled water to Flint residents.

https://go.nature.com/2PwBKo4Mum’s a Neanderthal, Dad’s a Denisovan: First

discovery of an ancient-human hybridGenetic analysis uncovers a direct descendant of two different

groups of early humans.Matthew Warren

A female who died around 90,000 years ago was half Neanderthal and half Denisovan, according to genome analysis of a bone discovered in a Siberian cave. This is the first time scientists have identified an ancient individual whose parents belonged to distinct human groups. The findings were published on 22 August in Nature1.“To find a first-generation person of mixed ancestry from these groups is absolutely extraordinary,” says population geneticist Pontus Skoglund at the Francis Crick Institute in London. “It’s really great science coupled with a little bit of luck.”

Denny inherited one set of chromosomes from her Neanderthal ancestors, depicted in this model. Christopher Rynn/University of Dundee

The team, led by palaeogeneticists Viviane Slon and Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, conducted the genome analysis on a single bone fragment recovered from Denisova Cave in the Altai Mountains of

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Russia. This cave lends its name to the ‘Denisovans’, a group of extinct humans first identified on the basis of DNA sequences from the tip of a finger bone discovered2 there in 2008. The Altai region, and the cave specifically, were also home to Neanderthals.

Given the patterns of genetic variation in ancient and modern humans, scientists already knew that Denisovans and Neanderthals must have bred with each other — and with Homo sapiens (See 'Tangled Tree'). But no one had previously found the first-generation offspring from such pairings, and Pääbo says that he questioned the data when his colleagues first shared them. “I thought they must have screwed up something.” Before the discovery of the Neanderthal–Denisovan individual, whom the team has affectionately named Denny, the best evidence for so close an association was found in the DNA of a Homo sapiens specimen who had a Neanderthal ancestor within the previous 4–6 generations 3 .A bone fragment was sequenced for its genome. Thomas Higham/University of

OxfordAncestry revealedPääbo’s team first uncovered Denny’s remains several years ago, by looking through a collection of more than 2,000 unidentified bone fragments for signs of human proteins. In a 2016 paper4, they used radiocarbon dating to determine that the bone belonged to a hominin who lived more than 50,000 years ago (the upper limit of the dating technique; subsequent genetic analysis has put the specimen at around 90,000 years old, according to Pääbo). They then sequenced the specimen’s mitochondrial DNA — the DNA found inside cells’ energy converters — and compared that data to sequences from other ancient humans. This analysis showed that the specimen’s mitochondrial DNA came from a Neanderthal.But this was only half of the picture. Mitochondrial DNA is inherited from the mother and represents just a single line of inheritance, leaving the identity of the father and the individual’s broader ancestry unknown. In the latest study, the team sought to get a clearer understanding of the specimen’s ancestry by sequencing its genome and comparing

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the variation in its DNA to that of three other hominins — a Neanderthal and a Denisovan, both found in Denisova Cave, and a modern-day human from Africa. Around 40% of DNA fragments from the specimen matched Neanderthal DNA — but another 40% matched the Denisovan. By sequencing the sex chromosomes, the researchers also determined that the fragment came from a female, and the thickness of the bone suggested she was at least 13 years old.With equal amounts of Denisovan and Neanderthal DNA, the specimen seemed to have one parent from each hominin group. But there was another possibility: Denny's parents could have belonged to a population of Denisovan–Neanderthal hybrids.A fascinating genomeTo work out which of these options was more likely, the researchers examined sites in the genome where Neanderthal and Denisovan genetics differ. At each of these locations, they compared fragments of Denny's DNA to the genomes of the two ancient hominins. In more than 40% of cases, one of the DNA fragments matched the Neanderthal genome, whereas the other matched that of a Denisovan, suggesting that she had acquired one set of chromosomes from a Neanderthal and the other from a Denisovan. That made it clear that Denny was the direct offspring of two distinct humans, says Pääbo. “We’d almost caught these people in the act.”The results convincingly demonstrate that the specimen is indeed a first-generation hybrid, says Kelley Harris, a population geneticist at the University of Washington in Seattle who has studied hybridization between early humans and Neanderthals. Skoglund agrees: “It’s a really clear-cut case,” he says. “I think it’s going to go into the textbooks right away.” Harris says that sexual encounters between Neanderthals and Denisovans might have been quite common. “The number of pure

Denisovan bones that have been found I can count on one hand,” she says — so the fact that a hybrid has already been discovered suggests that such offspring could have been widespread. This raises another interesting question: if Neanderthals and Denisovans mated frequently, why did the two hominin populations remain genetically distinct for several hundred-thousand years? Harris suggests that Neanderthal–Denisovan offspring could have been infertile or otherwise biologically unfit, preventing the two species from merging.Neanderthal-Denisovan pairings could also have had some advantages, even if there were other costs, says Chris Stringer, a palaeoanthropologist at the Natural History Museum in London. Neanderthals and Denisovans were less genetically diverse than modern humans, and so interbreeding might have provided a way of “topping up” their genomes with a bit of extra genetic variation, he says. The study also raises questions over how matings between different human groups happened, says Stringer — for example, whether or not they were consensual. A more detailed account of the gene flow between Neanderthals and Denisovans in the future might offer hints into ancient human behaviour.Missed connectionsPääbo agrees that Neanderthals and Denisovans would have readily bred with each other when they met - but he thinks that those encounters were rare. Most Neanderthal remains have been found across western Eurasia, whereas Denisovans have so far been discovered only in their eponymous Siberian cave. Although the two groups’ home turf overlapped in the Altai Mountains and possibly elsewhere, these areas would have been sparsely populated. “I think any Neanderthal that lived west of the Urals would never ever meet a Denisovan in their life,” Pääbo says, referring to the mountain range that slices through western Russia and Kazakhstan.

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But sometimes, Neanderthal populations might have travelled from western Eurasia to Siberia, or vice-versa. On the basis of the variation in the specimen’s genome, the team deduced that Denny’s Neanderthal mother was more closely related to a Neanderthal specimen found thousands of kilometres away, in Croatia, than to another found less than 1 metre away in the same cave.

Denny's remains were discovered in Denisova Cave in southern Siberia. Bence Viola/Max Planck Institute for Evolutionary Anthropology

The Croatian Neanderthal died died much more recently than Denny — about 55,000 years ago — while the Neanderthal from Denisova Cave is around 120,000 years old. That leaves two possibilities to explain the ancestry of Denny's mother: either a population of European Neanderthals came west to the Altai Mountains and partly replaced the region’s Neanderthals before the hybrid was born, or a group of Neanderthals could have left the Altai Mountains for Europe sometime after Denny’s birth. Either way, says Harris, Neanderthals “didn’t just stay in one place for thousands of years”.With a Neanderthal mother and a Denisovan father, what should we call the new specimen? “We shy away a little from the word ‘hybrid’,” says Pääbo. The term implies that the two groups are discrete species of human, whereas in reality the boundaries between them are blurry — as the new study shows. Defining a species in the natural world is not always clear-cut, says Harris, and it’s interesting to see long-running debates about how to categorize organisms start to be applied to humans.

Whatever scientists decide to call Denny, Skoglund says he would have loved to be able to meet her. “It’s probably the most fascinating person who’s ever had their genome sequenced.”Nature 560, 417-418 (2018) doi: 10.1038/d41586-018-06004-0

https://go.nature.com/2o2VFOWJapan must tighten up clinical trial of stem cells for

heart failureTwo aspects of the trial protocol need to be addressed before it

can be fast-trackedAkira Akabayashi, Eisuke Nakazawa & Nancy S. Jecker

A task force in Japan’s health ministry has conditionally approved the world’s first clinical trial to treat patients with heart failure, using sheets of heart-muscle cells derived from ‘reprogrammed’ adult stem cells (Nature 557 , 619–620; 2018 ). In our view, two aspects of the trial protocol need to be addressed before it can be fast-tracked (see also Nature 557 , 611–612; 2018 and Y. Yui npj Regen. Med . 3 , 7; 2018 ).First, we question the trial’s use of allogeneic induced pluripotent stem (iPS) cells, called iPS stock cells and prepared by Kyoto University’s Center for iPS Cell Research and Application. This use of heart-muscle cells from different donors could trigger transplant rejection by the patient. And using immunosuppressants to prevent rejection can cause unpleasant side effects, including a risk of promoting tumour development. We suggest that such risks be minimized by using autologous (that is, the patient’s own) iPS cells in the trial instead.Second, the task force has specified that the trial should involve three participants with “more serious” heart failure than was proposed in the submitted trial protocol. In our view, it would be better to recruit people who are less severely affected, given that the trial’s main goal is to establish the procedure’s safety. The intervention involves open heart surgery and is medically intensive,

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so by itself could kill those who are more vulnerable. This would also prevent proper evaluation of the stem-cell treatment. Addressing these scientific and ethical concerns will ensure that the clinical trial amounts to more than a compassionate rescue attempt. Nature 560, 431 (2018) doi: 10.1038/d41586-018-06015-x

http://bit.ly/2LmdzWpBreastfeeding may help protect mothers against stroke

Journal of the American Heart Association ReportDALLAS -- Breastfeeding is not only good for babies, there is growing evidence it may also reduce the risk for stroke in post-menopausal women who reported breastfeeding at least one child, according to new research in Journal of the American Heart Association, the Open Access Journal of the American Heart Association/American Stroke Association.Stroke is the fourth leading cause of death among women aged 65 and older, and is the third leading cause of death among Hispanic and black women aged 65 and older, according to the study."Some studies have reported that breastfeeding may reduce the rates of breast cancer, ovarian cancer and risk of developing Type 2 diabetes in mothers. Recent findings point to the benefits of breastfeeding on heart disease and other specific cardiovascular risk factors," said Lisette T. Jacobson, Ph.D., M.P.A., M.A., lead author of the study and assistant professor in the department of preventive medicine and public health at the University of Kansas School of Medicine-Wichita.This is among the first studies to examine breastfeeding and a possible relationship to stroke risk for mothers, as well as how such a relationship might vary by ethnicity.Researchers analyzed data on 80,191 participants in the Women's Health Initiative observational study, a large ongoing national study that has tracked the medical events and health habits of postmenopausal women who were recruited between 1993 and

1998. All women in this analysis had delivered one or more children and 58 percent reported ever having breastfed. Among these women, 51 percent breastfed for one-six months, 22 percent for seven-12 months and 27 percent for 13 or more months. At the time of recruitment, the average age was 63.7 years and the follow-up period was 12.6 years.After adjusting for non-modifiable stroke risk factors (such as age and family history), researchers found stroke risk among women who breastfed their babies was on average: 23 percent lower in all women, 48 percent lower in black women, 32 percent lower in Hispanic women, 21 percent lower in white women, and 19 percent lower in women who had breastfed for up to six months. A longer reported length of breastfeeding was associated with a greater reduction in risk."If you are pregnant, please consider breastfeeding as part of your birthing plan and continue to breastfeed for at least six months to receive the optimal benefits for you and your infant," Jacobson said."Our study did not address whether racial/ethnic differences in breastfeeding contribute to disparities in stroke risk. Additional research should consider the degree to which breastfeeding might alter racial/ethnic differences in stroke risk," Jacobson said.Because the study was observational, it couldn't establish a cause-and-effect relationship between breastfeeding and lower stroke risk, meaning that it is possible some other characteristic that distinguishes between women who breastfeed and those who don't is the factor changing the stroke risk. However, because the Women's Health Initiative is large, researchers were able to adjust for many characteristics, and the effects of breastfeeding remained strong, Jacobson said.

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"Breastfeeding is only one of many factors that could potentially protect against stroke. Others include getting adequate exercise, choosing healthy foods, not smoking and seeking treatment if needed to keep your blood pressure, cholesterol and blood sugar in the normal range," Jacobson said.The study was also limited by the relatively small number of strokes that occurred during the follow-up period (just 3.4 percent of the women experienced a stroke during the study period and 1.6 percent reported having had a stroke prior to the study) and by the Women's Health Initiative's exclusion of women who had already had severe strokes at the time of recruitment.Currently, the American Academy of Pediatrics and the World Health Organization recommend exclusive breastfeeding for six months, with continuation of breast feeding for one year or longer. For babies health, the American Heart Association recommends breastfeeding for 12 months with transition to other additional sources of nutrients beginning at about four - six months of age to ensure sufficient micronutrients in the diet.Frontiers: The Heartland Institute for Clinical and Translational Research and the Wichita Center for Graduate Medical Education-Kansas Bioscience Authority funded the study. The WHI was supported by the National Health, Lung, and Blood Institute.Co-authors are Erinn M. Hade, Ph.D.; Tracie C. Collins, M.D., M.P.H., M.H.C.D.S.; Karen L. Margolis, M.D., M.P.H.; Molly E. Waring, Ph.D.; Linda V. Van Horn, Ph.D., R.D.; Brian Silver, M.D.; Maryam Sattari, M.D., M.S.; Chloe E. Bird, Ph.D.; Kim Kimminau, Ph.D.; Karen Wambach, Ph.D.; and Marcia L. Stefanick, Ph.D. Author disclosures are on the manuscript.

https://bbc.in/2Mu41xUUse honey first for a cough, new guidelines say

Honey should be the first line of treatment for most people with coughs

By Alex Therrien Health reporter, BBC NewsHoney and over-the-counter medicines should be the first line of treatment for most people with coughs, new guidelines recommend.

Antibiotics should rarely be prescribed by doctors for coughs because in most cases they do little to improve symptoms, health officials say. Most of the time a cough will improve on its own within two to three weeks.The new recommendations for doctors are intended to help tackle the problem of antibiotic resistance. Overusing antibiotics is making infections harder to treat, by creating drug-resistant superbugs.'Huge problem'A hot drink with honey - and often with lemon and ginger as well - is a well-known home remedy for coughs and a sore throat. Now new proposed guidelines from the National Institute for Health and Care Excellence (NICE) and Public Health England (PHE) say there is some limited evidence that it can help improve cough symptoms. Cough medicines containing pelargonium, guaifenesin or dextromethorphan might also be beneficial, they say.Patients are being advised to use these treatments and wait for symptoms to improve on their own, before going to a GP.Most coughs are caused by viruses, which cannot be treated by antibiotics and will clear up on their own. Yet despite this, research has previously found that 48% of UK GP practices have prescribed antibiotics for a cough or bronchitis.Dr Susan Hopkins, a deputy director at PHE, said: "Antibiotic resistance is a huge problem, and we need to take action now to reduce antibiotic use... "These new guidelines will support GPs to reduce antibiotic prescriptions and we encourage patients to take their GP's advice about self-care."Check symptomsHowever, the guidelines recommend that antibiotics may be necessary for a cough when it is part of a more serious underlying

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illness, or when a person is at risk of further complications, such as those with chronic health conditions or weakened immune systems. Honey is not recommended for children under the age of one because it occasionally contains bacteria that can cause infant botulism. Dr Tessa Lewis, GP and chair of the antimicrobial prescribing guideline group, said: "People can check their symptoms on NHS Choices or NHS Direct Wales or ask their pharmacist for advice."If the cough is getting worse rather than better, or the person feels very unwell or breathless, then they would need to contact their GP."The draft recommendations are part of a raft of new antibiotic prescribing guidelines being developed jointly by PHE and NICE. England's chief medical officer, Prof Dame Sally Davies, has previously warned of a "post-antibiotic apocalypse".If the drugs fail, infections will become harder to treat and common medical procedures such as cancer treatments and transplants would be too risky, she said.The consultation on the new guidelines closes on 20 September.

http://bit.ly/2OXmkrWBaby poop may be source of beneficial probiotics

There are probiotics in dirty diapersWINSTON-SALEM, N.C- Probiotics seem to be everywhere these days - in yogurt, pickles, bread, even dog food. But there's one place that may surprise you: There are probiotics in dirty diapers. Yes, that's right - baby poop. Scientists at Wake Forest School of Medicine have developed a probiotic "cocktail" derived from gut bacteria strains found in infant feces that may help increase the body's ability to produce short-chain fatty acids (SCFAs). Why is that important?

"Short-chain fatty acids are a key component of good gut health," said the study's lead investigator, Hariom Yadav, Ph.D., assistant professor of molecular medicine at Wake Forest School of Medicine. "People with diabetes, obesity, autoimmune disorders and cancers frequently have fewer short-chain fatty acids. Increasing them may be helpful in maintaining or even restoring a normal gut environment, and hopefully, improving health."The study findings are reported in the Aug. 23 online edition of Scientific Reports, a Nature publication.Over the past decade, research has shown that specific probiotic strains can effectively prevent or treat certain diseases in both animal models and humans. These reports have led to an extensive demand for probiotic supplements over the last decade, thereby prompting a massive increase in the development of new probiotic products for the consumer market. However, these studies have primarily been conducted in animal models or human subjects with underlying diseases or conditions, Yadav said. Scientific reports on the effects of probiotics in healthy, disease-free subjects have remained relatively limited and inconsistent. The School of Medicine team designed the study to examine the effects of probiotic strains derived from healthy human fecal samples and to determine how they worked."Babies are usually pretty healthy and clearly do not suffer from age-related diseases, such as diabetes and cancer," Yadav said. "And, of course, their poop is readily available." In the study, Yadav's team collected fecal samples from the diapers of 34 healthy infants. After following a robust protocol of isolation, characterization and safety validation of infant gut-origin Lactobacillus and Enterococcus strains with probiotic attributes, the researchers selected the 10 best out of the 321 analyzed.

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To test the ability of these human-origin probiotics to change the gut microbiome - bacteria that live inside the digestive track - and their capacity to produce SCFAs, mice were given a single dose, as well as five consecutive doses of this 10-strain probiotic cocktail. Then the researchers injected the same probiotic mixture in the same doses into a human feces medium. The scientists found that the single- and five-dose feeding of these selected probiotics modulated the gut microbiome and enhanced the production of SCFAs in mouse gut and human feces. "This work provides evidence that these human-origin probiotics could be exploited as biotherapeutic regimens for human diseases associated with gut microbiome imbalance and decreased SCFA production in the gut," Yadav said. "Our data should be useful for future studies aimed at investigating the influence of probiotics on human microbiome, metabolism and associated diseases."The study was limited in that it didn't test the probiotic mixture in any disease models.Funding for the study was provided by the Center for Diabetes, Obesity and Metabolism; the Kermit Glenn Phillips II Chair in Cardiovascular Medicine; the National Institutes of Health funded Claude D. Pepper Older Americans Center P30AG12232, R01AG18915, R01DK114224, the Clinical and Translational Science Center UL1TR001420 at Wake Forest School of Medicine; and the Department of Defense PR170446.Co-authors are Ravinder Nagpal, Ph.D., Shaohua Wang, Ph.D., Shokouh Ahmadi, Ph.D. candidate, Joshua Hayes, Ph.D. candidate, Sarhurunathan Subashchandrabose, Ph.D., Dalane W. Kitzman, M.D., and Thomas Becton, B.A., of Wake Forest School of Medicine; and Jason Gagliano, Ph.D. candidate, and Russel Read, Ph.D., of the National Center for Biotechnology Workforce at Forsyth Technical Community College.

http://bit.ly/2wlSZj9Earth's Magnetic Field Can Reverse Poles Ridiculously

Quickly, Study SuggestsPartial shifts in magnetic poles can occur much, much faster

than thought possible — perhaps within a single human lifetimeBy Brandon Specktor, Senior Writer | August 23, 2018 01:41pm ET

Like the invisible force shield around the Death Star, Earth's magnetic field surrounds and protects our planet from the hottest, most statically charged particles the sun can throw our way. This shield — the natural product of molten iron swirling around the planet's core — has had our backs for billions of years, and prevented Earth from becoming an irradiated, electrified wasteland. Every now and then, though, that shield lets down its guard.A few times every million years or so, Earth's magnetic field reverses polarity. Imagine a giant bar magnet inside our planet got flipped upside down; iron molecules in Earth's outer core would switch direction, the magnetic North Pole would become the magnetic South Pole, and the invisible currents of energy that make up our planet's magnetic armor would tangle and break, potentially reducing the shield's protective strength by up to 90 percent, previous studied have suggested.

Solar radiation constantly bombards Earth, and Earth’s magnetic field repels it. According to a new study, our planet’s protective shield might

weaken far more quickly and unpredictably than scientists previously thought. NASA / Marshall Space Flight Center

Luckily, full reversals are uncommon and unfold slowly over thousands of years. (The last full reversal occurred about 780,000 years ago.) But according to a new study published Monday (Aug. 20) in the journal Proceedings of the National Academy of Sciences, partial or temporary shifts in Earth's magnetic poles can occur much, much faster than was previously thought possible — potentially, within a single human lifetime.In the new study, an international team of scientists analyzed 16,000 years of geomagnetic history coded into the atoms of an

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ancient stalagmite in China. This story written in stone told them that once, about 98,000 years ago, the planet's magnetic field suddenly flipped polarity in as little as 100 years — roughly 30 times faster than the generally expected rate, and 10 times faster than what was thought to be the fastest rate possible."The record provides important insights into ancient magnetic field behavior, which has turned out to vary much more rapidly than previously thought," study co-author Andrew Roberts, a professor of Earth sciences at Australian National University, said in a statement. A chaotic historyIn their new study, Roberts and a large team of colleagues from China and Taiwan examined about 16,000 previously undocumented years of Earth's magnetic history. For their history teacher, they chose an ancient, yellow stalagmite that grew out of a cave in southwestern China between roughly 91,000 and 107,000 years ago. By dating and analyzing the iron-bearing minerals inside the stalagmite,the team was able to detect periodic variations in the direction in which Earth's magnetic field was flowing at the time those minerals formed.(Magnetic minerals orient themselves in different directions depending on where the Earth's magnetic poles are at the time.)The team found that Earth's magnetic polarity shifted several times during that 16,000-year period, which was no surprise to them. The shock emerged about 98,000 years ago, when a huge shift in polarity occurred in a period of less than 200 years — possibly within 100 years. "Such an extremely rapid polarity drift has not been shown before," the researchers wrote in their new study.Knowing that our planet is capable of such spontaneous magnetic tantrums is important, mainly because our magnetic shield can diminish to about 10-percent effectiveness when it's in the middle of a reversal. Fortunately, that weakening isn't enough to threaten

life on Earth; after all, Roberts pointed out, the planet's magnetic field has been reversing periodically for billions of years, and life still persists. Human technology, on the other hand, might have a rougher time coping.Trillions of dollars in damageSolar weather events, such as solar flares and solar wind storms, occur when blazing-hot, supercharged particles of energy blast out of the sun's surface and whiz across space on a collision course toward Earth. Even when our planet's magnetic field is at its strongest, a powerful enough solar storm can rip right past those defenses and wreak havoc on anything electrical.That surge of charged particles can garble radio signals, fry satellite and spacecraft instruments, and overload circuit breakers to take down entire power grids. That's exactly what happened on March 13, 1989, when a massive solar storm crackled through the atmosphere and knocked the power out in Quebec, Canada, for 9 hours. An earlier, even larger solar storm in 1859, known as the Carrington event, reportedly caused telegraph wires to short-circuit all around the United States, throwing off sparks that started fires and electrocuted office workers.Storms far less powerful than these could cause much more damage if they happened to hit while Earth's magnetic field was in the midst of a reversal, Roberts said. The result would likely be trillions of dollars in damage to our electrical infrastructure, and right now, there's no plan for dealing with an event of that magnitude."Hopefully, such an event is a long way in the future and we can develop future technologies to avoid huge damage," Roberts concluded. Keep your fingers (but not your magnetic-field lines) crossed.

http://bit.ly/2wgPZplTime to rewrite the textbooks

How science corrects is an important lesson in the classroom

27 5/13/23 Name Student number By Mark Peplow23 August 2018

‘Scientists are looking to rewrite the textbook’, ‘these results are going to require rewriting the textbooks’, ‘this is textbook-changing stuff’. These paeans to scientific revolution all appeared in press releases over the past few months. With the revisions arriving at such a pace, it’s a wonder that textbooks aren’t recalled the moment they are printed.‘Rewriting the textbooks’ is one of those clichés that is liberally misapplied in science writing. But it might be appropriate for two recent examples. The first is about slime, the mixture of borax and poly(vinyl alcohol) beloved of science festivals and feared by parents with deep-pile carpets. The second example – rather more highbrow – concerns the mechanism of nucleophilic aromatic substitution reactions. That’s unlikely to fire up the science fair enthusiasts, I admit, but it’s certainly useful in pharmaceutical synthesis.In both cases, the widely accepted explanations of the chemistry involved have turned out to be wrong – perhaps not radically so, but nevertheless demonstrably incorrect. Although there’s no urgent need to pulp thousands of books, it does seem entirely reasonable to update our guides at the next opportunity.But should the revision go further than simply replacing an old fact with a new one? Cases like these provide an opportunity to show how the transition happened – and understanding that process should itself be a core part of science education.Slime and prejudiceThere are many different recipes for slime, but one of the classics includes PVA glue, containing poly(vinyl acetate) poly(vinyl alcohol), and a solution made from borax, found in some washing powders.In July, Chemical & Engineering News ran a story about the booming popularity of slime demonstrations, accompanied by a

graphic showing how the chemistry worked. Some readers then pointed out mistakes in the structure of borax and the bonding that holds slime together. Yet this was no slip of the ChemDraw pen – C&EN was simply reproducing structures that are widely depicted in teaching resources. So, rather than just make a correction, the magazine investigated further.Borax is often called sodium tetraborate decahydrate (Na2B4O7·10H2O), its tetraborate anion drawn so that each boron atom bonds to three oxygens. But the actual formula is apparently Na2[B4O5(OH)4]·8H2O, which gives the boron atoms two different coordination environments – one trigonal, the other tetrahedral.When borax mixes with poly(vinyl alcohol), it forms cross-links between the polymer strands to produce a slimy material. These cross-links are typically shown as tetrahydroxyborate ions that form hydrogen bonds with the polymer’s alcohol groups. Except that’s not what happens. Instead, the slime is held together by borate esters, according to 11B NMR analysis.Aromatic persuasionOn to the second example. Nucleophilic aromatic substitution is usually described as a two-step process in undergraduate textbooks. First, a nucleophile attacks a benzene ring with a leaving group, forming a negatively-charged Meisenheimer complex; then, in the second step, the leaving group departs. Crucially, the complex exists as a discrete entity, with both nucleophile and leaving group fully bound to a carbon atom.Eric Jacobsen at Harvard University, US, wondered if this stepwise mechanism was generally true. His team studied three different benzene compounds with groups that would stabilise or destabilise the intermediate complex. Using some fancy NMR experiments that tracked kinetic isotope effects, they discovered that only one compound (dinitrofluorobenzene) formed the complex, due to its electron-withdrawing nitro groups and poor leaving group.

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Most examples of the reaction do not feature such extremes, though, and a computational study of 120 more cases showed that fewer than 20% would form the complex. The rest involved a concerted mechanism via an ephemeral transition state, with the leaving group departing as the nucleophile arrives.Sense and credibilityPerhaps obsessing over the difference between a Meisenheimer complex and a Meisenheimer transition state merely looks like hair-splitting. Maybe we shouldn’t care how slime works, as long as it helps to enthuse young minds. And how far should we retrace the origins of each fact – do kids really need to learn about phlogiston the moment they encounter oxygen?Unpacking these nuances may risk obscuring the nuts and bolts of the chemistry being taught. But some story-telling about how science actually evolves, alongside the bald facts, could offer wider benefits.One of the reasons that ‘rewriting the textbooks’ has become such a popular trope is that it feels a bit transgressive, like violating some holy canon. This feeling arises because most people still think of science as a collection of immutable facts, rather than a mechanism for discovery. That misunderstanding can sometimes make science seem inherently fickle and even untrustworthy: a view that increasingly crops up in arguments about climate change, vaccines and other contentious topics.Yet altering one’s worldview in the face of new evidence is a strength rather than a weakness. If we can tell stories about science that illustrate why being prepared to rewrite the textbooks is a good thing, it may help to foster a wider understanding of the process of science.I like the two cases outlined above because they illustrate how science works – through missteps, corrections, clever experiments and communication. Stories like that give students an opportunity

to learn more about the journey, and not just the destination, of research. That’s something worth rewriting the textbooks for.

http://bit.ly/2MzljcXViral outbreaks could be predicted two years in

advance by mathematical modelScientists have identified the cause of outbreaks of enterovirus,

one of the most prevalent types of virus in the worldScientists have identified the cause of outbreaks of enterovirus, one of the most prevalent types of virus in the world.The findings, from researchers at Imperial College London and published in the journal Science, may help the public and healthcare workers prepare for an outbreak up to two years before it occurs.The work, funded by the Wellcome Trust, has shown for the first time that the frequency of enterovirus outbreaks over time are linked to birth rates.Enteroviruses infect mostly children under 10 years old, and strike millions of youngsters every year - 50 million in the U.S. alone.There are over 100 different types of enterovirus that infect people, causing a range of illnesses, from mild cold-like symptoms such as coughs, sore throat and fever, to more serious conditions such as hand-foot-and-mouth disease, viral meningitis, and encephalitis.Infections tend to peak during summer and autumn months. Although there are no specific treatments, there is one vaccine available, and others in development.There have been a number of serious enterovirus outbreaks in recent years.In 2014 a particular strain in the U.S. was linked to severe respiratory illness in young children, and there are thought to be over one million cases of hand-foot-and-mouth disease in China each year. But despite the viruses causing so many infections, scientists still don't fully understand what causes outbreaks.

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Dr Margarita Pons-Salort, co-author of the research from the School of Public Health at Imperial said: "There are many different types of enteroviruses that infect humans. Some cause epidemics every year, while others cause epidemics every two or three years. However, until now we didn't know what determined the frequency of these outbreaks, or why some viruses seemed to cause large outbreaks in certain years."In the study, the team found that outbreaks of a given type of enterovirus were largely determined by the number of children born each year and the development of long-lasting immunity against that type following infection.Once a child is infected with a specific type of enterovirus, they usually develop immunity to further infections with that virus.The team found that after each outbreak there is a time lag - from the end of the initial outbreak to a new pool of children being born who have not encountered the virus. This second group of children then become infected, and a subsequent outbreak occurs. The team used a mathematical model to simulate these epidemic patterns for each of the 20 most common types of enterovirus. To build the model, they used Japanese enterovirus surveillance data. Japan keeps incredibly detailed information on enterovirus outbreaks, and the team used 14 years' worth of information to build the model (from 2000-2014). They then tested the model, and found that it was able to predict subsequent outbreaks in 2015 and 2016 for most types of enterovirus."The accuracy of our model to explain the data means we now understand why these outbreaks occur, and that they are actually highly predictable" said Dr Pons-Salort.She continued: "This information could allow medical staff to prepare ahead of the outbreak. Our model will also help design vaccination strategies (i.e. who should be vaccinated and when),

and anticipate the impact of the vaccine. For instance, it will allow us to calculate the proportion of children that should be vaccinated to avoid a new outbreak."The team are now testing their model on data from other countries, to ensure it can be applied to other regions around the world. Their work also suggested that certain types of enteroviruses can fundamentally change their 'appearance' and become more virulent, or more transmissible between people. The team are now working on methods to understand these changes.

http://bit.ly/2BNzQgdScientists Are Starting to Test Claims About

“Microdosing”Could psychedelics lead to improved antidepressant or anti-

anxiety therapies? By Sharon Begley, STAT on August 24, 2018

Dennis van der Meijden isn’t aiming to see the face of God, feel one with the cosmos, grasp the hidden reality of time and space, or embark on a sacred journey. What the Dutch graphic designer, producer, and rapper (under the professional name Terilekst) wants—and gets—from his twice-weekly “microdoses” of psilocybin is more modest.

Credit: James Worrell Getty Images “It sharpens all the senses, as if the frequencies of all of your atoms and energy field are raised a little bit and are being slightly more conscious,” said van der Meijden, 39, who told STAT he first microdosed psilocybin—the active ingredient in “magic mushrooms”—three years ago. It makes him energetic enough to skip coffee, “as if I’m kicked in some sort of orbit for that day.” If he becomes distracted, “I’m very much aware of that, as if seeing

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myself from a bird’s eye view, so I can correct myself very fast.” But van der Meijden says he’s careful not to exceed about 0.4 grams, because 0.5 made him “a bit too joyful and a bit too philosophical,” which wasn’t always appropriate.Microdosing involves taking roughly one-tenth the “trip” dose of a psychedelic drug, an amount too little to trigger hallucinations but enough, its proponents say, to sharpen the mind. Psilocybin microdosers (including hundreds on Reddit) report that the mushrooms can increase creativity, calm anxiety, decrease the need for caffeine, and reduce depression. There is enough evidence that trip doses might have the latter effect that, on Wednesday, London-based Compass Pathways received Food and Drug Administration approval for a Phase 2B clinical trial of psilocybin (in larger-than-microdoses) for treatment-resistant depression. But research into microdosing is minimal.In the nearly 10 years since psychologist and psychedelics researcher James Fadiman introduced the notion of microdosing and devised a widely followed protocol for it, and three years after microdosing psychedelics became the latest Silicon Valley “productivity hack,” all the evidence about its effects has been anecdotal. Psilocybin is illegal almost everywhere, so it’s been nearly impossible to study scientifically. That is changing, however, as the Netherlands and other countries effectively decriminalize it and scientists in places where it remains illegal obtain government permission to study it.The scientific interest is driven, in part, by numerous reports over the years that psilocybin might have antidepressant or anti-anxiety effects that might guide the development of better psychiatric drugs. But it also reflects an itch to see whether there is any basis for the anecdotal accounts. Now, in the first study of its kind, scientists in the Netherlands found that psilocybin microdoses have no noticeable effect on the problem-solving, rational-thinking, and

abstract-reasoning ability called fluid intelligence. But they do seem to improve two forms of thinking that underlie creativity.“Performance was significantly higher” on tests of convergent and divergent thinking, said psychologist Bernhard Hommel of Leiden University in the Netherlands, who led the study. Convergent thinking is the ability to focus on abstract concepts to identify a single solution to a well-defined problem. Divergent thinking requires meandering mental forays and mental flexibility. Psychologists consider both to be ingredients of creativity.Whatever the dose, psilocybin (O-phosphoryl-4-hydroxy-N, N-dimethyltryptamine) binds to receptors for the neurotransmitter serotonin. The cortex is packed with these 5-HT2A receptors, especially in areas that control reflection, imagination, and introspection, but “whether there is a minimum dose [of psilocybin that’s required to activate them] is an empirical question that we try to tackle,” Hommel said.To do so, he and his colleagues zeroed in on the effects that many users report: creativity, problem-solving, and the “cognitive flexibility” deemed crucial to both. Leiden’s Luisa Prochazkova took the lead in inviting members of the Psychedelic Society of the Netherlands to participate in the study; she got 38 takers.Before their microdose, the volunteers took three standard psychological tests, two related to creative problem-solving and one an assessment of fluid intelligence. The scientists ran chemical analyses of the mushroom samples to determine how much psilocybin they contained. Since a trip dose is about 3 grams of dried ’shrooms, a microdose is around 0.33 grams. Participants averaged 0.37 grams of the dried preparation, which can be taken with food or packed into gelcaps for easy swallowing.About 90 minutes after the microdose, the participants took the three tests again.

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In the Picture Concept Task, they saw three rows of three pictures, and had to choose three—one from each row—that were related. That requires converging on the correct solution, like noticing that a bathtub, a sink, and a hose all have something to do with water. The brain must focus, weigh alternatives, and reject wrong ones.In the Alternate Uses Task, the microdosers had five minutes to think of ways to use a pen (tracheotomy? finger splint?) or towel. That measures divergent thinking, to move thoughts away from writing, for example, in the case of the pen.The microdosers also took a “progressive matrices” test: In blocks of two-by-two or three-by-three patterns, with the bottom right one missing, they had to choose which of six possibilities belonged in the blank square—a task that requires fluid intelligence.The scientists found no post-microdose difference on the fluid intelligence test. But after microdosing, performance on the picture concept test was significantly higher (an average score of 7.6) than before (6.6). That suggested an improvement in the convergent thinking element of creativity.The microdosers also came up with significantly more uses for pens and towels, 16.7 vs. 14.7. That suggests a microdose of psilocybin “allowed participants to create more out-of-the-box alternative solutions for a problem,” the scientists wrote. Taken together, the three findings suggest a specific effect of psilocybin microdoses on creativity but not on fluid intelligence.For van der Meijden, a microdose of psilocybin makes his musical brainstorm sessions yield “more concepts, ideas, and solutions,” he said, partly because it lets him “better understand and visualize other people’s concepts.” In his design and illustration work, it produces a “more natural flow of line drawing” and lets him “see more possibilities in how things can be or look.” In his music, it lets him “analyze all the different instruments better” and know, for instance, whether to turn up or down the reverberation effect.

The Dutch study, which was published on a preprint site and has not undergone peer review at a journal, has several caveats. For one thing, having seen a test before might make people better at it. More problematic, the study didn’t have a control group of people who took something other than psilocybin. That leaves open the possibility that it wasn’t the compound that improved some forms of thinking, but the expectation that it would do so. Maybe people who microdose believe in its benefits enough to make those expectations reality.On the other hand, the results fit with another new study of psilocybin. In this one, scientists led by computational neuroscientist Joana Cabral of the University of Oxford used fMRI scans to study the brain activity of nine people who volunteered to be injected with 2 milligram (trip-inducing) doses. The chemical changed the functional connectivity of various brain regions, so that activity in one became synced with that in another. In particular, the rational, logical, well-behaved frontoparietal regions became “strongly destabilized,” the scientists reported, melding with activity in emotional and other regions to produce “unconstrained consciousness,” “mind wandering,” and a sense that everything is connected to everything else. Seeing connections that elude other people is almost the definition of creativity.The findings in the microdosing study also fit with many anecdotal reports. One college student who is a member of the Portland, Ore., microdosing community said that although he doesn’t microdose psilocybin with the express purpose of boosting creativity or focus, he has found that “things seem to have quieted down, in terms of racing thoughts.” He can still be distracted, said Alex, 38, who asked not to be further identified because the drug is illegal in the U.S. But “if I want to go about doing something, then I have an easier time with it because I’m not being bogged down by my thoughts,” he added.

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Jakobien van der Weijden takes one psilocybin microdose every three days, with bimonthly breaks, “to work more focused, more efficiently and be more creative” at his marketing job in the Netherlands, he said. “On the downside, I would often feel that the inspiration was still there at night and I would keep working on projects until late. So it was somewhat more difficult to maintain a healthy biorhythm.”As legal strictures loosen, there will likely be more rigorous studies of microdosing psilocybin. “Scientific studies could legitimize the claimed benefits,” said Will Burns, CEO of Wenham, Mass.-based Ideasicle, which develops branding and marketing ideas. He does not microdose, Burns said, but has called for research into its purported effects, including improving productivity and creativity. “Right now, we’re swimming in a world of anecdotes and almost no one has taken this seriously,” he said. “We need scientific studies.”Republished with permission from STAT. This article originally appeared on August 23, 2018

https://wb.md/2MOESNIWarnings About Benzodiazepine Use in the Elderly Go

UnheededDespite years of warnings, benzodiazepines continue to be used

by the elderly at a higher rate than considered appropriateAlicia Ault August 24, 2018

Despite years of warnings about the hazards of prescribing benzodiazepines for the elderly, these drugs continue to be used at a higher rate than what is considered appropriate in older Americans — particularly older women, new data show.A recent report released by Athena Health shows that individuals older than 65 years are prescribed benzodiazepines — including alprazolam (multiple brands), lorazepam (multiple brands),

diazepam (multiple brands), and clonazepam (Klonapin, Roche) — more than other age groups are.In 2017, 8.4% of individuals aged 65 and older were prescribed one of the drugs, a drop from 8.7% the previous year. Just over 8% of 50- to 64-year-olds were prescribed a benzodiazepine in 2017, compared to 7.5% of those aged 40 to 49 and 6.6% of those aged 30 to 39.Ten percent of women older than 65 were prescribed a benzodiazepine, compared to just under 6% of men.The data come from a sample of 3 million patients treated by primary care providers who are part of the Athena Health data network.The data "are consistent with earlier research that suggests significant benzodiazepine overuse, especially among older adults," Mark Olfson, MD, MPH, professor of psychiatry and epidemiology, Columbia University, New York City, told Medscape Medical News.Since 2012, the American Geriatrics Society (AGS) has urged clinicians to avoid use of benzodiazepines in older adults. That recommendation is being reiterated in the AGS 2018 prescribing guidelines (called the Beers Criteria), which are under final review.Physicians Not Getting the Message The AGS notes that benzodiazepines increase the risk for cognitive impairment, delirium, falls, fractures, and motor vehicle crashes. The drugs can be appropriate for seizure disorders, rapid eye movement sleep behavior disorder, benzodiazepine withdrawal, ethanol withdrawal, severe generalized anxiety disorder, and periprocedural anesthesia, the AGS says.Since benzodiazepines were first introduced in the 1960s, prescribing authorities and public health agencies have periodically issued warnings about the potential for addiction and other side effects.

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In May, the deprescribing guidelines for the elderly project, based at the Bruyère Research Institute in Ottawa, Ontario, Canada, launched an effort to help clinicians wean long-term users off benzodiazepines and the benzodiazepine receptor agonists zolpidem (multiple brands), zopiclone (Zunesta, Suovion), and zaleplon (Sonata, Pfizer)."We need to be a little bit more judicious with these," Nicole Brandt, PharmD, MBA, BCGP, BCPP, FASCP, executive director of the Peter Lamy Center on Drug Therapy and Aging, University of Maryland, Baltimore, told Medscape Medical News. Brandt said she continues to be concerned about the persistence of benzodiazepine use in the face of so many warnings and guidelines.Robert Roca, MD, chair of the American Psychiatric Association's Council on Geriatric Psychiatry, said he was surprised — but not entirely — at the Athena data indicating that women received benzodiazepines at twice the rate of men."Women are more willing to express distress, and they're more likely to receive psychotropics of all kinds," Roca, vice president and chief medical officer, Sheppard Pratt Health System, Baltimore, told Medscape Medical News.Women also have a higher risk for dementia, and, given the pressure to reduce the use of antipsychotics in patients with dementia, it's possible that benzodiazepines are being substituted, said Roca. But, he added, benzodiazepines "are not a particularly good alternative."Olfson said that women "have higher rates of insomnia, anxiety disorders, and mood disorders, all of which are related to benzodiazepine use." He also noted, however, that "because women assume more caregiver roles than men, they are under greater stress, which contributes to anxiety and sleep problems."

Dementia Risk Brandt agrees that caregiving is a major stressor for women. He noted that "it's easier to get a medication paid for than to get counseling paid for or respite care paid for." Benzodiazepines are prescribed for many medical problems, but "there are also lots of psychosocial issues where they may be the go-to agent," she said.She added that she's seen benzodiazepines prescribed to help older people cope with losses, including the loss of mobility and the loss of friends or family members."I think benzodiazepines are a surrogate for a much bigger issue," she said.Many factors account for the continuing popularity and persistent use of benzodiazepines. Olfson said there is limited access to alternative evidence-based treatments for insomnia and noted that there's "an unwillingness of some older people to consider reducing or discontinuing" the drugs.In addition, said Olfson, "for some primary care physicians who have competing clinical demands on their time, given common comorbid medical problems in older adults, pharmacological options for managing insomnia and anxiety may be attractive."Roca noted that they are generally safe and effective in reducing anxiety and generally are not abused, although "there is no question they are potentially addictive."Benzodiazepines can also be a bridge therapy for patients who need an antidepressant, which can take weeks to start working, said Roca. He favors short-acting benzodiazepines, which, unlike long-acting ones like diazepam, are not taken up by adipose tissue.But that type of analysis may not be familiar to physicians who more often prescribe the medications to younger people. "They are not so tuned in to the risks of prescribing to older people," said Roca.

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Besides the risks outlined by the AGS, some data now suggest that long-term exposure may increase the risk for dementia, he said. "There are all kinds of reasons to be careful," said Roca.Medicare has kept an eye on benzodiazepine use among older people who participate in the federal health plan. The Affordable Care Act initially banned coverage of benzodiazepines through Medicare Part D drug plans. That prohibition was lifted in January 2014; the drug class is now covered under Part D for any medically accepted indication.A Hidden Epidemic? The agency has taken an even closer look since it became clear that the drugs were often being prescribed in tandem with opioids. In 2015, the Centers for Medicare & Medicaid Services reported that 17% of Medicare beneficiaries were using benzodiazepines and that about a quarter were using them in conjunction with opioids.A study published in JAMA Psychiatry in June found that rates of new opioid prescriptions written for adults using a benzodiazepine skyrocketed from 189 to 351 per 1000 persons from 2005 to 2010.Although it decreased to 172 per 1,000 by 2015, "the likelihood of receiving a new opioid prescription during an ambulatory visit remained higher for patients concurrently using benzodiazepines compared with the general population after adjusting for demographic characteristics, comorbidities, and diagnoses associated with pain," the authors note.The dual use — and continued high use of benzodiazepines — has alarmed many clinicians and public health officials."Despite the many parallels to the opioid epidemic, there has been little discussion in the media or among clinicians, policymakers, and educators about the problem of overprescribing and overuse of benzodiazepines and z-drugs, or about the harm attributable to these drugs and their illicit analogues," Anna Lembke, MD, Jennifer

Papac, MD, and Keith Humphreys, PhD, wrote in an editorial published in the New England Journal of Medicine in February.Overdose deaths related to benzodiazepine use continue to rise. Lembke noted that data from the National Institute on Drug Abuse (NIDA) show that overdose deaths involving benzodiazepines increased from 1135 in 1999 to 8791 in 2015. In 2016, NIDA reported 10,684 overdoses in which benzodiazepines were involved. Most of the deaths occurred in people who were also taking opioids, said NIDA.Brandt said the opioid crisis provides lessons for how benzodiazepines should be monitored and prescribed. Benzodiazepines are not villains, however, she said. Like opioids, they are "a tool to address a problem," said Brandt. She noted that she would not want to see them blacklisted.Both Roca and Olfson said they supported adding benzodiazepines to state prescription drug monitoring programs. Including them would help flag those people who are using benzodiazepines and opioids, said Olfson. He also said that because a lot of the risk with the drug class is associated with long-term use, "policies should be considered and evaluated that restrict the days' supply of benzodiazepines in a single prescription."Roca expressed concern about overly restrictive policies. "If you put a target on the back of these medications, you may make it difficult for patients who need them," he said.Dr Brandt, Roca and Dr Olfson have disclosed no relevant financial relationships.

http://bit.ly/2P2IJ7cPregnant women with heart disease should give birth at

no later than 40 weeks gestationBeyond 40 weeks, pregnancy has no added benefit for the baby

and may even have negative effects

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Munich, Germany - Pregnant women with heart disease should give birth at no later than 40 weeks gestation. That is one of the recommendations in the 2018 European Society of Cardiology (ESC) Guidelines for the management of cardiovascular diseases during pregnancy published online today in European Heart Journal,1 and on the ESC website.2"Beyond 40 weeks, pregnancy has no added benefit for the baby and may even have negative effects," said Professor Jolien Roos-Hesselink, Co-Chairperson of the Guidelines Task Force and Cardiologist, Erasmus Medical Centre Rotterdam, the Netherlands. "Pregnancy is a risky period for women with heart disease because it puts additional stress on the heart, so the guidelines advise inducing labour or a caesarean section at 40 weeks."Heart disease is the main reason women die during pregnancy in western countries. Compared to healthy pregnant women, those with heart disease have a 100-fold greater risk of death or heart failure. Most women with heart disease have a healthy pregnancy. However, they should be aware that they have a higher risk of obstetric complications including premature labour, pre-eclampsia, and post-partum bleeding. An estimated 18-30% of offspring have complications and up to 4% of neonates die.Heart disease in pregnancy is increasing as more women with congenital heart disease reach adulthood due to improved treatment and as the age at first pregnancy rises, accompanied by the higher rates of ischaemic heart disease in older, compared to younger, women. Cardiovascular risk factors including hypertension, diabetes and overweight are also on the rise in pregnancy as older women become pregnant and women now acquire risk factors at a younger age.The guidelines provide recommendations on in vitro fertilisation (IVF), contraception, and termination of pregnancy in women with heart disease. IVF often uses high doses of hormones, which

increase the risk of thrombosis and heart failure, so women with heart disease need a cardiologist's confirmation that the chosen method is safe. Since carrying more than one baby puts more stress on the heart, women with heart disease undergoing IVF are strongly advised to transfer a single embryo. Girls with congenital heart disease need contraception advice to avoid unplanned pregnancy. Some contraception methods are contraindicated in patients with certain types of heart disease.For drugs used to treat heart disease, the guidelines list information on adverse events obtained from human and animal studies. In addition, the guidelines state: "In the case of an emergency, drugs that are not recommended by the pharmaceutical industry during pregnancy and breastfeeding should not be withheld from the mother. The potential risk of a drug and the possible benefit of the therapy must be weighed against each other."Professor Vera Regitz-Zagrosek, Chairperson of the Guidelines Task Force and Director of the Institute for Gender Medicine, Charité University Medical Centre Berlin, Germany, said: "When drug companies have no data on whether a drug is safe during pregnancy and breastfeeding they tend to say it is not recommended. It may be appropriate to give a drug to a severely ill woman if there are no harmful side effects noted in the databases listed in the guidelines."Pregnancy is not recommended in patients with certain types of heart disease - for example, pulmonary arterial hypertension, severely dilated aorta, or severely reduced ability of the heart to pump blood.Women with heart disease who want to have a baby need pre-pregnancy risk assessment and counselling. Those at moderate to high risk of complications should be reviewed by a pregnancy heart team with a cardiologist, obstetrician, gynaecologist, and anaesthesiologist. A delivery plan should be devised at 20-30 weeks

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specifying vaginal or caesarean delivery, whether an epidural or forceps will be used, and the duration of hospital stay after delivery.Professor Roos-Hesselink said: "The delivery plan should be available 24 hours a day so that when a pregnant woman with heart disease arrives at hospital in labour hospital staff know exactly what to do."Professor Regitz-Zagrosek: "We hope the guidelines will improve doctors' awareness of the risks of heart disease in pregnancy but also the therapeutic options that are available to guide pregnancy in these women."

http://bit.ly/2NjfbSsDeep forehead wrinkles may signal a higher risk for

cardiovascular mortalityAre wrinkles just an inevitable consequence of ageing, or could

they signal something more sinister?Munich, Germany - According to research presented in Munich today at the ESC Congress 2018, the annual conference of the European Society of Cardiology (1), people who have lots of deep forehead wrinkles, more than is typical for their age, may have a higher risk of dying of cardiovascular disease (CVD).Assessing brow wrinkles could be an easy, low-cost way to identify people in a high-risk category for CVD. "You can't see or feel risk factors like high cholesterol or hypertension," says study author Yolande Esquirol, associate professor of occupational health at the Centre Hospitalier Universitaire de Toulouse in France. "We explored forehead wrinkles as a marker because it's so simple and visual. Just looking at a person's face could sound an alarm, then we could give advice to lower risk."That advice could include straightforward lifestyle changes like getting more exercise or eating healthier food. "Of course, if you have a person with a potential cardiovascular risk, you have to

check classical risk factors like blood pressure as well as lipid and blood glucose levels, but you could already share some recommendations on lifestyle factors," Dr Esquirol points out.Risk of heart disease increases as people age, but lifestyle and medical interventions can mitigate the danger. The challenge is in identifying high-risk patients early enough to make a difference.According to the study authors, previous research has analysed different visible signs of ageing to see if they can presage cardiovascular disease. In prior studies, crow's feet showed no relationship with cardiovascular risk but these tiny wrinkles near the eyes are a consequence not just of age but also of facial movement. A link has been detected between male-pattern baldness, earlobe creases, xanthelasma (pockets of cholesterol under the skin) and a higher risk of heart disease, but not with an increased risk of actually dying (2). The authors of the current prospective study investigated a different visible marker of age - horizontal forehead wrinkles - to see if they had any value in assessing cardiovascular risk in a group of 3,200 working adults. Participants, who were all healthy and were aged 32, 42, 52 and 62 at the beginning of the study, were examined by physicians who assigned scores depending on the number and depth of wrinkles on their foreheads. A score of zero meant no wrinkles while a score of three meant "numerous deep wrinkles." The study participants were followed for 20 years, during which time 233 died of various causes. Of these, 15.2% had score two and three wrinkles. 6.6% had score one wrinkles and 2.1% had no wrinkles. The authors found that people with wrinkle score of one had a slightly higher risk of dying of cardiovascular disease than people with no wrinkles. Those who had wrinkle scores of two and three had almost 10 times the risk of dying compared with people who had wrinkle scores of zero, after adjustments for age, gender,

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education, smoking status, blood pressure, heart rate, diabetes and lipid levels,"The higher your wrinkle score, the more your cardiovascular mortality risk increases," explains Dr Esquirol. Furrows in your brow are not a better method of evaluating cardiovascular risk than existing methods, such as blood pressure and lipid profiles, but they could raise a red flag earlier, at a simple glance.The researchers don't yet know the reason for the relationship, which persisted even when factors like job strain were taken into account, but theorise that it could have to do with atherosclerosis, or hardening of the arteries due to plaque build-up. Atherosclerosis is a major contributor to heart attacks and other cardiovascular events.Changes in collagen protein and oxidative stress seem to play a part both in atherosclerosis and wrinkles. Also, blood vessels in the forehead are so small they may be more sensitive to plaque build-up meaning wrinkles could one of the early signs of vessel ageing."Forehead wrinkles may be a marker of atherosclerosis," says Dr Esquirol. "This is the first time a link has been established between cardiovascular risk and forehead wrinkles so the findings do need to be confirmed in future studies," cautions Dr Esquirol, "but the practice could be used now in physicians' offices and clinics." "It doesn't cost anything and there is no risk," concluded Dr Esquirol.