Culture

Preliminary research shows noninvasive therapy may reverse atherosclerosis

SAN FRANCISCO - An injection may one day be able to reverse atherosclerosis, according to emerging research presented at the American Heart Association's Vascular Discovery: From Genes to Medicine Scientific Sessions 2018, a premier global exchange of the latest advances in vascular biology for researchers and clinicians.

Atherosclerosis is characterized by a narrowing of arteries and blood vessels caused by a build-up of a hard, waxy substance called plaque, which is rich in cholesterol.

Drugs such as statins are used to control low density lipoprotein (LDL) the so-called bad cholesterol and thus decrease "plaque burden", explained Neel A. Mansukhani, M.D. lead author of the study and an integrated vascular surgery fellow at Northwestern University Feinberg School of Medicine in Chicago. "But statins have not been proven to reverse the disease." Mansukhani said.

Other treatment approaches for atherosclerosis, which can narrow blood vessels and arteries throughout the body, include bypass surgery and stenting, but neither reverses the disease and each can cause damage to the vessel wall, he said.

"Our aim was to develop a non-invasive, non-surgical, novel therapy to halt and reverse the disease by actually targeting the vessel wall with peptide-based nanofibers developed in the laboratory," Mansukhani said. The tiny fibers contained particles that helped remove cholesterol deposits from the plaque in the artery walls.

Researchers synthesized self-assembling peptide amphile nanofibers that targeted areas of plaque and could be delivered by intravenous injection. Importantly these synthetically engineered nanofibers contained an amino acid sequence that promotes the cholesterol to dissolve.

To test the concept, mice were genetically modified to rapidly develop atherosclerosis, then fed high fat diets for 14 weeks and after which the mice received biweekly injections of either the peptide amphile nanofiber or saline for 8 weeks.

"It was important that we were able to achieve reproducible results in this model in the lab, so first we wanted to confirm that the therapy actually targeted areas of atherosclerosis," Mansukhani said.

They used imaging techniques -- fluorescent microscopy and pixel quantification -- to determine optimum dose, concentration, binding duration and biodistribution and found they could observe the targeting effect after 24 hours, and after 48 to 72 hours the nanofiber would dissipate and it was cleared in 7 to 10 days.

After 8 weeks of treatment, plaque area in the arteries of the male mice was reduced by 11 percent and in the female mice by 9 percent.

The results "demonstrate that a novel targeted nanofiber binds specifically to atherosclerotic lesions and reduces plaque burden after a short treatment duration," Mansukhani said.

He noted, however, that this is preliminary research, and more is needed before this approach can be tested in humans.

Credit: 
American Heart Association

Should patients in remission stop taking expensive Rheumatoid Arthritis drugs?

Stopping expensive biological drugs used to treat rheumatoid arthritis in patients who are in remission or who have low disease activity can save considerable costs, but it results in a small loss of quality-adjusted life years, according to a recent Arthritis & Rheumatology study.

In the study, stopping tumor necrosis factor inhibitors in patients with stable low disease activity, on average, was associated with a cost saving of €7,133, a loss of 0.022 quality-adjusted life years, and an increase of 0.41 arthritis flares per patient per year.

"The subpopulation of patients receiving biological disease modifying anti-rheumatic drugs including tumor necrosis factor inhibitors... has increased over time and accounted for up to 20% of the population of rheumatoid arthritis patients in various Western healthcare systems," the authors wrote.

Credit: 
Wiley

Alignment of mother and offspring body clock could prevent diseases such as heart disease and obesity

The care provided by a mother can impact the body clock and health of offspring after birth, according to new research published in The Journal of Physiology. By reducing abnormalities in the body clock of offspring, it may be possible to develop therapies for serious lifestyle-related diseases, such as heart disease and obesity.

The body has an internal clock that regulates sleepiness over a 24 hour period, called your circadian rhythm. The circadian system is important so that processes in our body are synchronised with day and night, i.e. when it is light or dark outside. Disturbances in these mechanisms can lead to poor health, such as heart disease.

The mother-offspring interaction is very important for health later in adulthood. This is the first study to provide compelling evidence that the circadian characteristics of a mother may positively affect the likelihood of disease developing in offspring. Providing better maternal care significantly reduced abnormalities in the circadian system and resulted in a lower likelihood of development of heart disease.

The study conducted by the Institute of Physiology of the Czech Academy of Sciences was performed in two strains of laboratory rats, in which the maternal care and synchrony of their circadian clocks with external day/night cycle differed. The effect of maternal care provided by the genetic mother of these pups was compared with maternal care of the foster mother. The pups either had an aberrant circadian system and were genetically determined to develop disease in adulthood or they were healthy controls. The researchers tested the effect of maternal care on the body clock before and just after weaning, and on their activity rhythms, heart rate and blood pressure in adulthood. Proper maternal care provided to pups genetically predisposed to develop disease led to improvement of their clock function and abolished the rise in their heart rate in adulthood.

The data obtained in pups before weaning were based on population samples because the researchers could not assess circadian rhythms of the clocks in each individual pup within the body without disturbing the maternal behaviour. Additionally, in the rat strain spontaneously developing disease, the molecular mechanisms connecting the circadian clock and the pathology has not been understood.

Alena Sumova, corresponding author for the study said: "These results point to a real possibility to reduce abnormalities in the offspring's body clock and therefore limit the progression of disease in order to improve health. Our future research will be directed at understanding in more detail how an aberrant circadian system contributes to the progression of disease. We believe that this research is worth future explorations as it may provide novel therapies for serious life-style related diseases in humans.'

Credit: 
The Physiological Society

UCI-Harvard research may help combat the deadly gastrointestinal infection C. diff

image: Clostridium difficile (C. diff) causes severe gastrointestinal tract infections. The 3-D structure shows how a key C. diff toxin, TcdB (in orange), recognizes the human Frizzled protein (in green) as its receptor to invade cells, leading to damage in the intestinal barrier. Shown in the background is immunofluorescent staining of the healthy mouse cecum tissue (left) and the one damaged by TcdB (right).

Image: 
Rongsheng Jin, University of California, Irvine

Researchers from the University of California, Irvine and Harvard University have discovered how the Clostridium difficile toxin B (TcdB) recognizes the human Frizzled protein, the receptor it uses to invade intestinal cells and lead to deadly gastrointestinal infections. The findings, published today in Science, could pave the way for new C. diff antitoxins and also show potential for the development of novel anti-cancer drugs.

In a C. diff infection (CDI), TcdB targets colonic epithelia and binds to what are called Frizzled (FZD) receptors. Researchers in the labs of Rongsheng Jin, PhD, professor of physiology & biophysics from the UCI School of Medicine, and Min Dong, PhD, from Boston Children's Hospital - Harvard Medical School, found that during this binding process, the toxin locks certain lipid molecules in FZD, which block critical Wnt signaling that regulates renewal of colonic stem cells and differentiation of the colonic epithelium.

"This toxin is indeed very smart. It takes advantage of an important lipid that FZD uses for its own function, to improve its binding affinity and specificity to FZD," said Jin, "However, the need for this lipid also exposes a vulnerability of TcdB that could be exploited to develop antitoxins that block toxin-receptor recognition."

Jin and Dong believe that the novel FZD-antagonizing mechanism exploited by toxin B could be used to turn this deadly toxin into a potential pharmacological tool for research and therapeutic applications, including anti-cancer drugs.

The team's preliminary data show that a non-toxic fragment of TcdB that they identified could significantly inhibit the growth of some cancer cells with dysregulation in Wnt signaling. A patent application has been filed.

Clostridium difficile, also called "C. diff," causes severe gastrointestinal tract infections and tops the Center for Disease Control and Prevention's list of urgent drug-resistant threats. Clostridium difficile infection has become the most common cause of antibiotic-associated diarrhea and gastroenteritis-associated death in developed countries, accounting for half-million cases and 29,000 deaths annually in the United States. It is classified as one of the top three "urgent threats" by the CDC.

Credit: 
University of California - Irvine

Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

image: This is a visualization of the gravitational wave emission from a pair of orbiting compact objects. The upcoming space-based gravitational wave observatory LISA will be able to observe hundreds of such binary star systems in the Milky Way galaxy, including approximately 50 binaries found in globular clusters, reports a new Northwestern University study.These binary sources would contain all combinations of black hole, neutron star and white dwarf components.

Image: 
NASA

EVANSTON, Ill. --- The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A string of detections -- four more binary black holes and a pair of neutron stars -- soon followed the Sept. 14, 2015, observation.

Now, another detector is being built to crack this window wider open. This next-generation observatory, called LISA, is expected to be in space in 2034, and it will be sensitive to gravitational waves of a lower frequency than those detected by the Earth-bound Laser Interferometer Gravitational-Wave Observatory (LIGO).

A new Northwestern University study predicts dozens of binaries (pairs of orbiting compact objects) in the globular clusters of the Milky Way will be detectable by LISA (Laser Interferometer Space Antenna). These binary sources would contain all combinations of black hole, neutron star and white dwarf components. Binaries formed from these star-dense clusters will have many different features from those binaries that formed in isolation, far from other stars.

The study is the first to use realistic globular cluster models to make detailed predictions of LISA sources. "LISA Sources in Milky-Way Globular Clusters" was published today, May 11, by the journal Physical Review Letters.

"LISA is sensitive to Milky Way systems and will expand the breadth of the gravitational wave spectrum, allowing us to explore different types of objects that aren't observable with LIGO," said Kyle Kremer, the paper's first author, a Ph.D. student in physics and astronomy in Northwestern's Weinberg College of Arts and Sciences and a member of a computational astrophysics research collaboration based in Northwestern's Center for Interdisciplinary Exploration and Research in Astrophysics (CIERA).

In the Milky Way, 150 globular clusters have been observed so far. The Northwestern research team predicts one out of every three clusters will produce a LISA source. The study also predicts that approximately eight black hole binaries will be detectable by LISA in our neighboring galaxy of Andromeda and another 80 in nearby Virgo.

Before the first detection of gravitational waves by LIGO, as the twin detectors were being built in the United States, astrophysicists around the world worked for decades on theoretical predictions of what astrophysical phenomena LIGO would observe. That is what the Northwestern theoretical astrophysicists are doing in this new study, but this time for LISA, which is being built by the European Space Agency with contributions from NASA.

"We do our computer simulations and analysis at the same time our colleagues are bending metal and building spaceships, so that when LISA finally flies, we're all ready at the same time," said Shane L. Larson, associate director of CIERA and an author of the study. "This study is helping us understand what science is going to be contained in the LISA data."

A globular cluster is a spherical structure of hundreds of thousands to millions of stars, gravitationally bound together. The clusters are some of the oldest populations of stars in the galaxy and are efficient factories of compact object binaries.

The Northwestern research team had numerous advantages in conducting this study. Over the past two decades, Frederic A. Rasio and his group have developed a powerful computational tool -- one of the best in the world -- to realistically model globular clusters. Rasio, the Joseph Cummings Professor in Northwestern's department of physics and astronomy, is the senior author of the study.

The researchers used more than a hundred fully evolved globular cluster models with properties similar to those of the observed globular clusters in the Milky Way. The models, which were all created at CIERA, were run on Quest, Northwestern's supercomputer cluster. This powerful resource can evolve the full 12 billion years of a globular cluster's life in a matter of days.

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Northwestern University

Multi-drug resistant infections rising in children

Antibiotic-resistant Acinetobacter baumannii infections, one of the most common hospital-acquired infections in children across the United States, are on the rise, according to results of a recent study published in the Journal of the Pediatric Infectious Diseases Society on March 22.

"Acinetobacter are bacteria known to cause serious infections and notoriously difficult to treat because of growing antibiotic resistance. The bacteria survive for long periods in the environment," said study primary author Dr. Latania Logan, chief of pediatric infectious diseases and associate professor of pediatrics at Rush University Medical Center.

The research examined national and regional trends of antibiotic resistance in clinical specimens over a 13-year period. The data was taken from The Surveillance Network Database, a network of 300 laboratories distributed throughout the U.S. and is compiled by the Centers for Disease Dynamics Economics and Policy in Washington, D.C.

Children with chronic conditions are at higher risk of infection

Because A. baumannii is an infection caused by bacteria that takes advantage of patients with compromised immune systems, children with a chronic condition are at a higher risk of infections of the lung, urinary tract, or other sites after surgery, intubation, trauma, or catheterization.

The amount of A. baumannii samples in infected children that were resistant to the antibiotics cephalosporin and carbapenem increased between 1999 and 2012 overall. However, the authors of the study noted a slight decline after a peak in 2008. Antibiotic stewardship guidelines released in 2007 or infection control guidance specifically designed to combat multi-drug resistant A. baumannii in health care settings may have been related to the decrease.

"While we are encouraged by the slight downtrend in resistance after 2008, there is still an overall increase in these infections. Further studies are needed to assess the most effective prevention strategies in children," Logan said.

'A perfect storm' of drug resistant infections

A. baumannii has numerous ways that protect it from antibiotics. The bacteria are able to protect themselves by using genetic adaptations that support survival in dry, harsh environments, and additionally have in place several mechanisms to render antibiotics ineffective. In this situation, "a perfect storm" results, Logan said. As a result, highly resistant A. baumannii infections are increasingly being reported worldwide.

The study results show that the number of cephalosporin resistant A baumannii increased from 13.2 percent of infections in 1999 to 23.4 percent in 2012, whereas the number of carbapenem resistant A baumannii increased from 0.6 percent in 1999 to 6.1 percent in 2012. From 1999 to 2012, the proportion of cephalosporin resistant and carbapenem resistant bacteria among all A baumannii increased each year by 3 percent and 8 percent, respectively After 2008, a downward trend was observed, but resistance remained higher than the 1999 baseline.

"It is encouraging to see the downtrend after 2008, but we need to continue to monitor," said the study co-author Dr. Sumanth Gandra, a resident scholar in the Center For Disease Dynamics, Economics & Policy, an independent research initiative based in Washington, DC and New Delhi, India.

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Rush University Medical Center

Reducing tapeworm infection could improve academic performance, reduce poverty

video: Tapeworm infection from eating contaminated pork can damage the brain, causing learning impairments and possibly enforcing cycles of poverty. A new study is the first to look at infection rates within schools and propose solutions targeting children.

Image: 
Rob Jordan and Ian Fitzgerald

A Stanford-led study in China has revealed for the first time high levels of a potentially fatal tapeworm infection among school-age children. The researchers suggest solutions that could reduce infections in this sensitive age range and possibly improve education outcomes and reduce poverty.

"This disease invades the brain," said John Openshaw, the study's lead author and an infectious disease instructor at Stanford School of Medicine. "Children who are affected during formative school years risk cognitive deficits which could enforce a cycle of poverty."

The study, published in PLoS Neglected Tropical Diseases, focuses on Taenia solium, a tapeworm that infects millions of impoverished people worldwide and can cause a disorder of the central nervous system called neurocysticercosis. The World Health Organization estimates that the infection is one of the leading causes of epilepsy in the developing world and results in 29 percent of epilepsy cases in endemic areas. It is thought to affect about 7 million people in China alone.

"While historically researchers have studied adults with this disease, the burden on kids and what that burden means for affected countries in terms of lost productivity and lost income is unknown," Openshaw said. "We hope our work will fuel interest in figuring that out."

A global scourge

Found commonly in the muscle of pigs allowed to roam and consume human feces in regions without indoor toilets, the tapeworm can infest the intestines of people who consume under-cooked pork. Thousands of tapeworm eggs are then shed in the infected person's feces, contaminating the environment, including drinking water sources and food crops fertilized with human feces.

The disease can take a tragic turn when people directly consume the tapeworm eggs, either through contact with a person who has the eggs on their hands and clothing or by eating food contaminated with the eggs. In those cases, the tapeworm migrates out of the human digestive tract and can invade the brain. Symptoms of this infection can range from chronic headaches to seizures to psychiatric disturbances such as hallucinations.

Schools as infection points

To explore whether children are particularly at risk of tapeworm infection, the researchers tested fifth and sixth grade students, mostly 11- to 13-year-olds, in a remote Himalayan region of western Sichuan province. The majority of the children boarded at their schools during the week. The researchers found antibodies for neurocysticercosis in as many as 22 percent of the children they tested in some schools - a rate that's higher than what the group saw in adults in surrounding villages.

Openshaw said that the brain form of this disease spreads human to human, with no pigs required. "All you need is a couple people with gastrointestinal tapeworms and poor hygiene," he said, conditions that exist in rural schools studied.

Many of the children only have one or two pairs of clothes at school, so they wear and sleep - sometimes in shared beds - the same set of clothes for days at a time. Attempts to have the children wash their clothes are infrequent and of mixed success, according to Openshaw. School bathrooms are generally unhygienic pit latrines, soap is rarely available, and taps for handwashing don't work in many cases.

Unlocking a solution

"Schools appear to be hotbeds of transmission, as well as places for potentially effective intervention," Openshaw said.

Community education will be key to pushing down infections - a third of parents who responded to a survey believed intestinal worms have no adverse effects, and 19 percent thought less activity and drinking hot water or eating spicy food would help.

The researchers also plan to distribute medication in schools to counter the tapeworms, and administer vaccines and anti-parasitic medications to pigs in the region. One such drug is particularly promising, according to co-author Stephen Felt, an associate professor of comparative medicine. The drug, oxfendazole, not only kills muscle-encysted larvae in pigs, but protects them from reinfection for up to three months. Felt cautioned that oxfendazole may lead to unsightly scarring of the meat, which might turn off consumers. A vaccine called Cysvax also appears to be highly effective, but it requires booster doses - a significant drawback. Combining Cysvax and oxfendazole might be the most effective approach, according to Felt.

In schools, Openshaw and his colleagues are working to install working hand-washing stations near bathrooms, develop cost effective ways of supplying soap, provide curriculum materials about the disease and hand washing, and integrate good hand hygiene into school-based reward systems.

The researchers have forthcoming work that measures cognitive deficiencies in the children, and better defines social links - likely transmission pathways - among them.

"The tools to eradicate this disease are available," Openshaw said. "We hope that as the true burden of this disease on children becomes clearer, governments and nongovernmental actors will commit more resources."

Credit: 
Stanford University

Does melatonin actually do anything?

image: Melatonin is a widely used supplement. Many people turn to the hormone hoping it will improve their sleep, but do claims of its efficacy have any merit? Clinical evidence suggests that the benefits of melatonin are modest, and it may not help everyone. And there's little to stop supplement makers from selling you snake oil. Reactions explains the chemistry of this popular sleep aid: https://youtu.be/qjUKsW93qRU.

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The American Chemical Society

WASHINGTON, May 10, 2018 -- Melatonin is a widely used supplement. Many people turn to the hormone hoping it will improve their sleep, but do claims of its efficacy have any merit? Clinical evidence suggests that the benefits of melatonin are modest, and it may not help everyone. And there's little to stop supplement makers from selling you snake oil. Reactions explains the chemistry of this popular sleep aid: https://youtu.be/qjUKsW93qRU.

Credit: 
American Chemical Society

Eurovision Song Contest associated with increase in life satisfaction

Participating in the Eurovision Song Contest may be linked to an increase in a nation's life satisfaction, according to new research.

The study, by scientists at Imperial College London, found that people were four per cent more likely to be satisfied with their life for every increase of ten places on the final score board - e.g. their country finishing 2nd rather than 12th.

The research, published in the journal BMC Public Health, also found doing badly in the contest was associated with a greater increase in life satisfaction compared to not taking part at all.

The team, who were surprised to find the result, say the research chimes with previous studies that show success in big events, such as sporting fixtures, can boost a nation's health and wellbeing.

Dr Filippos Filippidis, lead author of the research from the School of Public Health at Imperial, said: "This finding emerged from a jokey conversation in our department. Our 'day job' involves investigating the effect of public policies, environmental factors and economic conditions on people's lifestyle and health. Our department employs people from lots of different countries and around the time of the Eurovision Song Contest we were chatting about whether the competition could also affect a country's national wellbeing. We looked into it and were surprised to see there may be a link."

The researchers analysed data from over 160,000 people from 33 European countries. All the people completed a questionnaire as a part of a survey called the Eurobarometer, which is conducted several times each year by the European Commission. Among other things, the survey asks people how satisfied they feel with their life.

The team, who analysed data collected around the time of the Eurovision Song Contest (May and June) between 2009-2015, found that people reported being more satisfied with their life if their country had done well in the Eurovision Song Contest that year.

The researchers then calculated an increase of 10 places on the final scoreboard - e.g. if a country finished 2nd instead of 12th - was associated with a four per cent higher chance of being satisfied with life. However, winning the competition was not associated with an additional increase in life satisfaction.

The scientists then compared data from countries who participated but did badly, to countries who didn't take part at all. They found that taking part but finishing near the bottom of the table was associated with a 13 per cent higher chance of life satisfaction compared to not taking part in the competition.

The team stress the research only shows there is an association - rather than directly showing the contest is responsible for raising life satisfaction. However, Dr Filippidis says the work highlights the possible impact of big events on a nation's psyche.

"Previous work, by other teams around the world, has shown that national events may affect mood and even productivity - for instance research suggests an increase in productivity in the winning city of the US Super Bowl."

He added that doing well in Eurovision or even just being part of it gives people something positive to discuss - rather than more negative events in the news.

"It increases the amount of good feeling around, even among people who are not particularly interested in the competition. I remember when Greece won in 2005 - in the weeks that followed people seemed to be in a better mood."

He added: "Our research shows that science can be used to test unexpected questions, but more importantly we hope it will encourage people to consider how our wellbeing, and consequently our health, can be influenced by a range of factors in the public sphere."

But he admits he wouldn't call himself a fan of the competition.

"I've been known to occasionally watch it in previous years. It's certainly entertaining, but I don't take it too seriously."

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Imperial College London

New link between gut microbiome and artery hardening discovered

The level of diversity of the 'good bacteria' in our digestive systems has been found to be linked to a feature of cardiovascular disease - hardening of the arteries - in new research by experts at the University of Nottingham and King's College London.

The gut microbiome is under increasing scrutiny in medical research as it is known to affect many different aspects of our health, including our metabolism and auto-immune system. A lack of diversity or range of healthy bacteria in the gut has previously been linked to various health problems, including diabetes, obesity and inflammatory stomach and bowel diseases.

Now for the first time, researchers have found a link between gut bacteria and arterial stiffening which suggests that targeting the microbiome through diet, medication and probiotics may be a way to reduce the risk of cardiovascular disease. The British Heart Foundation and MRC-funded research has been published in the European Heart Journal1.

The gut microbiome has been implicated in a variety of potential disease mechanisms including inflammation which can predispose people to heart disease. The hardening of the arteries that happens at different rates in different people as we age, is known to be a factor in cardiovascular risk.

The researchers examined medical data from a group of 617 middle-aged female twins from the TwinsUK registry - a national registry of adult twins recruited as volunteers for data-based research. Measurements of arterial stiffening using a gold-standard measure called carotid-femoral pulse-wave velocity (PWV) were analysed alongside data on the composition of the gut microbiomes of the women.

The results of the analysis revealed that there was a significant correlation in all the women between the diversity of the microbes in the gut and the health of the arteries. After adjusting for metabolic variations and blood pressure, the measure of arterial stiffness was higher in women with lower diversity of healthy bacteria in the gut. The research also identified specific microbes which were linked to a lower risk of arterial stiffening. These microbes have also previously been associated with a lower risk of obesity.

Dr Ana Valdes, from the University of Nottingham's School of Medicine and NIHR Nottingham Biomedical Research Centre, said: "We know that a substantial proportion of serious cardiovascular events like heart attacks are not explained by traditional risk factors such as obesity and smoking, particularly in younger people and in women and that arterial stiffness is related to risk in those groups. So our results reveal the first observation in humans linking the gut microbes and their products to lower arterial stiffness. It is possible that the gut bacteria can be used to detect risk of heart disease and may be altered by diet or drugs to reduce the risk."

Dr Cristina Menni, from the Department of Twin Research and Genetic Epidemiology at King's College London, said: "There is considerable interest in finding ways to increase the diversity of gut microbes for other conditions such as obesity and diabetes. Our findings now suggest that finding dietary interventions to improve the healthy bacteria in the gut could also be used to reduce the risk of heart disease."

The research concludes that cardiovascular risk that is not explained by the usual risk factors could in the future be enhanced by analysing the health of the gut microbiome. This could be particularly useful in stratifying cardiovascular risk in younger people and in women. The gut microbiome could also be the target for nutrition-based health interventions - for example, a high-fibre diet is known to improve the quantity and diversity of useful microbes in the gut. In fact, the composition of the gut microbiome may contribute to the mechanism whereby dietary fibre intake influences cardiovascular risk, but more research into this mechanism is needed.

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University of Nottingham

Family doctors could better detect child neglect with increased dental health training

Higher levels of tooth decay are seen in abused or neglected children. Although dental care is free to all children in the UK, many children are not registered with a dentist. This means in the absence of a dentist the family doctor or GP is often the first point of medical contact for a child. New research now suggests that GPs lack the awareness and training to identify dental neglect in children, and therefore could miss the opportunity to share potential cases of wider abuse or neglect to other health and welfare professionals. The study in The British Dental Journal was led by Sascha Colgan, consultant GP and visiting researcher at the University of Southampton in the UK, and was published by Springer Nature.

Researchers estimate that around one in ten children have been or are being abused or neglected, and that one to two children in the UK die each week as a result of neglect or abuse. Although there is no single standard for identifying neglect, much research shows that dental neglect is an important marker for wider neglect.

In this study, Colgan and colleagues sent a structured survey to all National Health Service (NHS) GPs on the Isle of Wight in the UK (106). Fifty-two per cent of those GPs responded to the survey, which examined how aware GPs are of the role dental health plays in child neglect. The survey also assessed the level of training GPs received in dental pathology.

The results showed that the majority of GPs had never liaised with a dental colleague about a pediatric patient. Ninety-six per cent had never received any formal dental training and some did not perceive dental health to be important. None of the respondents worked in a clinic where the dental registration of a child was noted in medical records, and only five GPs mentioned a link between a child not being registered with a dentist and child neglect.

"This study highlights that GPs lack training in formerly identifying dental pathology and are unaware that dental neglect could be a marker for potential wider child neglect," said Colgan.

Colgan and her colleagues stress that there is a need for further collaboration between dentists and GPs, as well as improved training in dentistry for GPs.

"We know that GPs are not dentists and already have many responsibilities. Ultimately public health policy must be implemented to address the need for greater awareness and investment in improving the prioritization of universal free access to dentistry," said Colgan, who hopes that the study will be scaled up in the future.

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Springer

Aggression at work can lead to 'vicious circle' of misconduct

New research led by the University of East Anglia (UEA) reveals that frequently being the target of workplace aggression not only affects the victim's health but can also cause them to behave badly towards others.

Workplace aggression is a significant issue particularly in the healthcare sector, where nurses can be targeted by both their colleagues and co-workers through bullying, and by patients and their relatives through 'third-party' aggression.

While workplace aggression has been examined in relation to the health-related consequences for victims, less is known about the possible negative impact it may have on their own behaviour at work.

The findings of this study suggest that the experience of anger and fear associated with being the target of aggression at work could lead some nurses to translate the emotions that are triggered into misconduct, possibly disregarding professional and ethical codes.

Published in the journal Frontiers in Psychology, the study was led by Dr Roberta Fida from UEA, working with colleagues from Coventry University, and universities in Italy and the US.

It involved 855 nurses, who were asked about their experiences of aggression, negative emotions and health symptoms. They were also asked how often they engaged in a range of counterproductive work behaviours, from insulting a colleague and stealing something belonging to an employer, to clinical misbehaviour related to restraining patients and modifying prescriptions without consulting doctors.

The results have implications for designing programmes aimed at increasing employees' well-being, the quality of the interactions with patients and staff, and the quality of care.

Dr Fida, a lecturer in organisational behaviour at UEA's Norwich Business School, said: "Our findings provide further evidence that being a target of aggression represents a frustrating situation in which victims experience anger that may prompt a 'hot' and impulsive aggressive response, with likely impact on the quality of care provided to patients.

"Little research has been conducted in the healthcare sector on this type of behaviour, despite the potential importance of the issue in this setting. There are consequences, not only for the direct victim, but also for the entire organizational system, in which it is possible to envision the trigger of vicious circles leading to broader and more diffuse forms of workplace aggression."

This is the first study to examine the specific role of frequent mistreatments at work in triggering misconduct and the emotions of anger, fear, and sadness separately. These emotions were studied because they are those most regularly experienced by targets of aggression, but are different in terms of mechanisms, consequences and strategies for managing them.

The authors also investigated the role of moral disengagement, namely a set of cognitive mechanisms that temporarily silence people's moral standards, allowing them to freely engage in conduct they would generally consider wrong.

Dr Fida said: "This research provides the first evidence of fear being an important discrete emotion associated with misconduct through moral disengagement. Since individuals experiencing fear are more alert and attentive to picking up potential external threats, and tend to perceive the environment as highly dangerous and threatening, they are more likely to engage in any form of behaviour, including aggression, which may potentially help them to defend themselves and comply with their need for protection."

The findings confirm that sadness is not associated with engaging in misconduct but is exclusively associated with health symptoms. Fear and anger are also associated with health symptoms, with the authors concluding that the emotional experience associated with being target of aggression, be it bullying or third party aggression, is associated with a range of health symptoms affecting nurses' well-being and their behaviour at work.

The authors suggest that training should focus on emotions and in particular on the specificity of the emotional experience. For example, it should help employees to gain awareness about the different possible emotional responses associated with the experience of aggression at work that may potentially lead to different dysfunctional paths for themselves and others.

In relation to the relevance of moral disengagement, it is also important to design and implement interventions aimed at promoting an ethical culture and providing examples of strategies to deal with threatening and hostile interactions.

Credit: 
University of East Anglia

Stone Age hepatitis B virus decoded

image: Skeletal remains of HBV positive individual from the Stone Age site of Karsdorf, Germany. The individual was a male with an age at death of around 25-30 years.

Image: 
Nicole Nicklisch

An international team of scientists led by researchers at the Max Planck Institute for the Science of Human History and the University of Kiel has successfully reconstructed genomes from Stone Age and Medieval European strains of the hepatitis B virus. This unprecedented recovery of ancient virus DNA indicates that hepatitis B was circulating in Europe at least 7000 years ago. While the ancient virus is similar to its modern counterparts, the strains represent a distinct lineage that has likely gone extinct and is most closely related to chimpanzee and gorilla viruses.

The hepatitis B virus (HBV) is one of the most widespread human pathogens known today, affecting over 250 million people worldwide. However, its origin and evolutionary history remain unclear. Studying the evolution and history of the virus has to date been especially difficult, because until now viral DNA had not been successfully recovered from prehistoric samples. In the present study, which has been accepted for publication in the journal eLife and is due to be published on May 10, 2018, an international team of researchers led by the Max Planck Institute for the Science of Human History and the Institute of Clinical Molecular Biology at Kiel University, not only recovered ancient viral DNA from skeletons but also reconstructed the genomes of three strains of HBV.

The ancient history of hepatitis B

For this study, the researchers analyzed samples from the teeth of 53 skeletons excavated from Neolithic and medieval sites in Germany. The remains dated from around 5000 BC to 1200 AD. The researchers screened all samples for viral pathogens and detected ancient HBV in three of the individuals. Full HBV genomes were recovered from these samples, two of which were from the Neolithic period, dating to about 7000 and 5000 years ago, and one from the medieval period. The Neolithic genomes represent the by far oldest virus genomes reconstructed to date.

Interestingly, the ancient virus genomes appear to represent distinct lineages that have no close relatives today and possibly went extinct. The two Neolithic genomes, although recovered from individuals that lived 2000 years apart, were relatively similar to each other in comparison with modern strains, and were in fact more closely related to modern strains of HBV found in Chimpanzees and Gorillas. In contrast, the medieval HBV genome is more similar to modern strains, but still represents a separate lineage. This is the case even when it is compared to two previously published HBV genomes recovered from mummies dating to the 16th century. The HBV strains found in these mummies are closely related to modern strains, suggesting a surprising lack of change in the virus over the last 500 years. These findings point to a complicated history for the virus, which may have involved multiple cross-species transmission events.

Long and complicated evolution of one of today's most common viruses

"Taken together, our results demonstrate that HBV already existed in Europeans 7000 years ago and that its genomic structure closely resembled that of modern hepatitis B viruses, despite the differences observed," explains first author Ben Krause-Kyora, of the Max Planck Institute for the Science of Human History and Kiel University. "More ancient precursors, intermediates and modern strains of both human and non-human primate HBV strains need to be sequenced to disentangle the complex evolution of this virus," he adds.

New tool for studying the evolution of blood-borne viruses

Johannes Krause, senior author and director of the Department of Archaeogenetics at the Max Planck Institute for the Science of Human History, emphasizes the most important implication of the study. "Our results reveal the great potential of ancient DNA from human skeletons to allow us to study the evolution of blood-borne viruses. Previously, there was doubt as to whether we would ever be able to study these diseases directly in the past," he explains. "We now have a powerful tool to explore the deep evolutionary history of viral diseases."

Credit: 
Max Planck Institute of Geoanthropology

New study finds ginger proven to treat vomiting in children with acute gastroenteritis

image: AcuResearchers presenting at the 51st ESPGHAN Annual Meeting have today revealed the results of a new study which proves the efficacy and effectiveness of using ginger to treat vomiting in children with acute gastroenteritis [1] -- one of the most common conditions resulting in admission to paediatric emergency departments.

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ESPGHAN

(Geneva, 11 May, 2018) Researchers presenting at the 51st ESPGHAN Annual Meeting have today revealed the results of a new study which proves the efficacy and effectiveness of using ginger to treat vomiting in children with acute gastroenteritis [1] - one of the most common conditions resulting in admission to paediatric emergency departments.

All children are expected to suffer from acute gastroenteritis within the first three years of life [2] and globally there are between 3-5 billion cases each year [3]. Vomiting is reported in three quarters of children suffering the condition [4] contributing to fluid loss and oral rehydration failure - which can be life threatening. While mortality rates in Europe are low, gastroenteritis is a major cause of hospital visits and has a substantial economic impact; it accounts for over 87,000 hospital visits a year and almost 700,000 outpatient visits [5]. Globally, acute gastroenteritis is one of the leading causes of childhood mortality, accounting for 1.34m childhood deaths a year - approximately 15% of all childhood deaths [6].

Dr Roberto Berni Canani and his team of researchers have proven that ginger is effective at reducing both the duration and the severity of vomiting, leading to fewer lost school days and suggest that the findings have the potential to reduce hospitalisations and missed work days by parents.

The double-blind, randomized, placebo-controlled trial looked at 141 children between the ages of 1 and 10 with acute gastroenteritis and compared the effectiveness of ginger with a placebo in treating the condition. The results showed that the number of vomiting episodes was 20% less in the group treated with ginger and the number of children missing school for at least one day was 28% less in the group treated with ginger.

Whilst previous studies have found ginger to be effective in treating vomiting in pregnant women and adult patients undergoing chemotherapy, this study is the first time the effectiveness of ginger has been tested in children.

Commenting, Dr Berni Canani, said: "Acute gastroenteritis is not just an unpleasant condition for children. It has a significant burden on parents, schools and healthcare systems. We anticipate that the results will have a great impact on future clinical practice and the advice given to parents in the treatment of acute gastroenteritis and could potentially save lives across Europe and the globe. Research should now focus on whether ginger could also be effective in treating vomiting children who are not affected by acute gastroenteritis."

Credit: 
Spink Health

Elucidation of vibration energy of a single molecule in an external force field

image: Figure 1A: Schematic image of a single CO molecule in solitude adsorbed on a single copper crystal. 1B: Schematic images of vibrations of a CO molecule adsorbed on a copper surface. A CO molecule on a surface exhibits two types of horizontal vibrational modes. The low energy mode of vibration is called the Frustrated Translational (FT) mode, where the oxygen and carbon atoms deflect in the same direction. The high energy mode of vibration is called the Frustrated Rotational (FR) mode, where the oxygen and carbon atoms deflect in the opposite directions.

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Kanazawa University

[Background]

A molecule adsorbed on a surface (Figure 1A) vibrates on the surface (Figure 1B). The vibration energy is determined by the mass of the molecule and by the restoring forces exerted on the molecule. The restoring force originates from the interaction within the molecule and with the surface. By measuring the vibration energy, therefore, we are able to learn details of the interaction of a molecule and a surface. This knowledge is useful in understanding important processes in applied sciences like catalytic reactions*1) that take place on a surface.

Since the vibration energy of a molecule depends to a large extent on the environment of the molecule, it is necessary to measure the vibration energy of an individual molecule to obtain a deep understanding of the interaction of a molecule and a surface, taking into account the environment. For example, a single molecule in isolation on a single crystal surface as shown in Figure 1A is an ideal target of this type of research.

The vibration energy of a single molecule can be investigated, with a scanning tunneling microscope (STM)*2), by placing the metal probe of STM right above the molecule and by precisely measuring the current by changing the voltage applied between the probe of STM and the surface. As shown in Figure 2A, the current (I) and the voltage (V) show an approximately linear relationship, the second derivative of which (V derivative of dI/dV) shows a peak and trough pair as shown in Figure 2B. The peak and trough pair corresponds to the vibration energy of a molecule. Thus, using this method, the vibration energy of a single molecule can be determined.

It was previously reported, however, that when a metal probe was placed very close to a molecule in order to measure the current, the probe tip itself exerted a force on the molecule, affecting its vibration energy. In this study, we have measured the force between the probe and the molecule by atomic force microscope (AFM)*4) and the vibration energy by STM to elucidate their relationship.

[Results]

The present study was conducted by a collaboration of researchers from Kanazawa University, Japan, University of Regensburg, Germany, and Linnaeus University, Sweden. The experiments were done at University of Regensburg.

The force between a probe and a molecule was measured by using the force sensor developed by Prof. Giessibl, University of Regensburg, Germany, a coauthor of the study. The support that was attached with the force sensor was oscillated at a resonance frequency (about 50 kHz) of the cantilever of the sensor to oscillate the cantilever effectively. A metal probe was attached at the tip of the cantilever, where the probe tip consisted of just one atom. By placing the probe tip in close proximity of a molecule adsorbed on the surface, a force arises between the molecule and the probe tip, which changes the resonance frequency of the cantilever. From such changes, the force between the probe tip and the molecule can be determined. Figure 3A shows the experimental data concerning the force arising between the probe tip and CO molecule adsorbed on a copper surface upon changing the distance between the probe tip and CO molecule; one set of data is compared with another set with a different probe tip. This comparison indicates the difference in the forces exerted on the molecule by the two different probe tips. Each probe tip consists of just one atom, but the difference in the structure behind the single atom affects the forces exerted.

After the force measurements, the vibration energy was investigated by precisely measuring the current that was generated by applying a voltage between the probe tip and the surface. Figure 3B shows the change of the vibration energy upon changing the distance between the probe tip and the molecule. The probe tip that exerts the larger attracting force affects the vibration energy of the molecule to a greater extent.

Next, the experimental results were analyzed using a classical model that considers the vibration of a molecule as a double pendulum. With an ordinary pendulum, gravity provides a restoring force, while in this study, the bonds within the molecule and between the molecule and the surface provided a restoring force. The vibration energy was calculated using this pendulum model with forces arising between the probe tip and the molecule taken into consideration. In addition, it was also taken into consideration that the forces exerted by the probe tip weakened the bonds within the molecule and between the molecule and the surface. This model successfully and precisely reproduced the experimental results.

[Future prospects]

The present study significantly deepens our understanding of the interaction of a molecule and a surface and of the interaction of a probe tip and a molecule. In this study, a simple molecule, CO, having a very simple molecular structure has been employed as a target of research. It is expected that this study will stimulate further investigation of molecules of more complicated structure and technological importance. It is also expected that the bond between a molecule and a surface would be severed by a metal probe tip, which may be applied to processes inducing chemical reactions.

Credit: 
Kanazawa University