Culture

Orlando, Fla. (April 6, 2019) - Acetaminophen -- a commonly used pain reliever and fever reducer -- is the leading cause of quickly developing, or acute, liver failure in the U.S. Findings from a new mouse study suggest that treatments that increase levels of the protein thrombospondin-1 could help the liver recover from an overdose of acetaminophen.

"The only treatment available now for acetaminophen overdose must be administered early, before significant liver injury occurs," said Matthew McMillin, PhD, who performed the research. "We are working to identify new drug targets to improve treatment options and reduce the need for liver transplantation, which is often the only option for patients with acute liver failure due to drug toxicity."

McMillin, an assistant professor at the University of Texas at Austin and research biologist at Central Texas Veterans Health Care System, will present the research at the American Society for Investigative Pathology annual meeting during the 2019 Experimental Biology meeting to be held April 6-9 in Orlando, Fla.

McMillin and his colleagues found that mice with acute liver failure from acetaminophen toxicity had higher levels of thrombospondin-1 than mice with normal liver function. When they administered acetaminophen to genetically modified mice that lack thrombospondin-1, the liver injury and loss of liver function was more severe compared to unmodified mice. The researchers also observed impaired liver regeneration and increased cell death in the mice without thrombospondin-1.

"Our study is the first to investigate thrombospondin-1 during acetaminophen toxicity," said McMillin. "We were able to identify cell communication pathways that do not work properly during acetaminophen-induced liver injury and thus lead to worse outcomes."

Next, the researchers plan to give mice different drug treatments that manipulate thrombospondin-1 to find out which treatment might be suited for potential clinical studies. They also plan to examine patients with acetaminophen-induced acute liver failure to determine if their thrombospondin-1 findings from mice hold true in people.

Matthew McMillin will present this research on Saturday, April 6 at 7 p.m. during the Experimental Biology Welcome Reception in Valencia Ballroom ABCD, Orange County Convention Center and on Monday, April 8, from 11:45 a.m.-12:45 p.m. in room Exhibit Hall-West Hall B (poster A62 662.62 ) (abstract). Contact the media team for more information or to obtain a free press pass to attend the meeting.

ARLINGTON, Virginia, April 6, 2019 -- Heart attack victims over age 65 are less likely than younger patients to receive timely percutaneous coronary intervention to open their blocked heart arteries, according to preliminary research presented at the American Heart Association's Quailty of Care and Outcomes Research Scientific Sessions 2019, a premier global exchange of the latest advances in quality of care and outcomes research in cardiovascular disease and stroke for researchers, healthcare professionals and policymakers.

In the study, older heart attack patients suffered more complications, such as shock and heart failure, had longer hospital stays and an increased chance of death. Despite staying in the hospital on average a half-day longer, older patients had lower total charges, something the researchers said could be attributed to the lack of undergoing more costly interventions such as percutaneous coronary intervention (PCI).

PCI, often referred to as angioplasty, is a non-surgical procedure used to treat narrow or blocked coronary arteries. During the procedure, special tubing with an attached deflated balloon is inserted into the blockage and the balloon is inflated to push open the blockage. Sometimes a stent may be placed during the procedure to keep the blood vessel open.

"Our study found that seniors were less likely to undergo PCI for a heart attack and if they do receive the procedure it's not within the optimal time for the best possible outcome," said Wojciech Rzechorzek, M.D., lead study author and a resident at Mount Sinai St. Luke's and Mount Sinai West Hospital in New York. "Their prognosis is worse than for younger patients with the same conditions, and this lack of treatment or delay in treatment could be a factor."

Researchers used the 2014 Nationwide Inpatient Sample to review records of 115,042 heart attack patients, 54 percent of whom were over 65.

The average age of the older group was 78. They were more likely than their younger counterparts to have high blood pressure, heart failure, chronic kidney disease and diabetes.

Researchers found, compared to younger patients, older patients were:

34 percent less likely to receive PCI to open blocked arteries;

36 percent less likely to have a stent inserted to keep the artery open after the blockage is removed;

34 percent less likely to have stents placed within 48 hours.

There appeared to be no difference between the two groups in the use of drugs or surgery to open blocked arteries.

Older patients were more likely to fare worse. Compared to younger counterparts they were:

62 percent more likely to develop heart failure;

28 percent more likely to go into shock;

21 percent more likely to experience cardiac arrest; and

10 percent more likely to need assistance from a breathing machine.

Despite older patients having to stay in the hospital longer, their adjusted total hospital charges were lower by approximately $3,231 per stay compared to younger patients.

"I am surprised that the costs of stay are lower despite the increased length of stay, but this could be primarily driven by decreased use of PCI, which is an expensive procedure," Rzechorzek said.

The researchers said because this was a retrospective analysis based on a very limited data set, further research is needed.

"Elderly patients are underrepresented in clinical trials, and we need more prospective studies evaluating the impact of PCI on outcomes," Rzechorzek said.

Researchers have known for decades that inflammation accompanies Alzheimer's disease (AD) brain lesions. Several early studies suggested that "super-aspirins" or Nonsteroidal anti-inflammatory drugs (NSAID) could help avoid the disease. However, after clinical trials showed that NSAIDs don't help patients who already have AD symptoms, doctors wondered whether these drugs could still be helpful to people who were at risk of developing the disease, but weren't yet showing symptoms.

To test this hypothesis, researchers at McGill University's Faculty of Medicine developed a new approach to AD prevention trials, and used it to test whether the common NSAID naproxen could indeed stop the disease in its tracks, before people developed AD symptoms. Sadly, the results were not encouraging, according to research published in the April 5, 2019, online issue of Neurology®, the medical journal of the American Academy of Neurology.

"To give the NSAID story one more chance to end well, we enrolled trial participants at the earliest stages of disease development, before they exhibited cognitive impairment," explains Dr. John Breitner, Professor of Psychiatry at McGill and the study's senior author. "The resulting trial, known as INTREPAD, examined the effects of naproxen in people who had a strong family history of AD but 'squeaky-clean' memory and other cognitive abilities."

Developing a new method to assess effectiveness

Many researchers have noted the special challenge of measuring disease development at a time when they could not rely on symptoms to assess effects of a treatment. To deal with this challenge the McGill team collaborated in developing a new Alzheimer Progression Score (APS) that was shown elsewhere to predict the onset of clinical disease over the coming decade or more. The APS measures the early development of disease by combining many little changes into a composite score.

Applying the APS to a trial sample of 200 people (100 assigned to naproxen and 100 to placebo), the INTREPAD results showed real changes over the two-year trial period. However, there was no evidence that the APS change was reduced in those taking naproxen. "The usual side effects were there," notes Pierre- François Meyer, a PhD candidate in Dr. Breitner's lab and the study's first author, "but there was not the slightest suggestion of any benefit."

"We think this is the end of the road for the use of NSAIDs for treatment or prevention of Alzheimer's disease, and it suggests a need for caution about using other anti-inflammatory drugs for this purpose," adds Dr. Breitner, who is Founding Director of the Centre for Studies on Prevention of Alzheimer's Disease at the Research Centre of the Douglas Mental Health University Institute. "The world desperately needs a way to prevent this horrible disease," he says, "and many other avenues are being investigated." In this process, researchers argue ever more strongly for the importance of publishing negative or "null" trial results like this one.

Although the majority of patients who have blood cancers are older adults, they make up only a small percentage of participants in the clinical trials that lead to new therapies. That's because the standard research methods used in oncology (cancer medicine) are not ideal for identifying certain vulnerabilities linked to aging, such as having multiple chronic diseases and being frail.

To help remedy that situation, the American Society of Clinical Oncology (ASCO) issued a guideline recommending that older adults who have cancer receive a geriatric assessment to see if they are at increased risk for experiencing side effects from medication and other complications from cancer and its treatment. Recently, a team of researchers examined older adults who have cancer to see whether their ability to manage daily activities as measured by these assessments was linked to staying alive longer. The team published their study in the Journal of the American Geriatrics Society.

A key part of the geriatric assessment is to determine how well an older adult performs the basic activities of daily living (ADLs). These include bathing, dressing, getting themselves from a chair to the bed (and vice versa), eating, grooming, and using the toilet. The geriatric assessment also takes into account an older adult's ability to perform instrumental activities of daily living (IADLS), or activities necessary for them to live on their own in the community. These activities include shopping, preparing meals, housework, taking medication, and handling their finances.

The researchers studied how performing daily activities was linked to survival and also to the use of medical care for adults living with cancer and aged 75 years and older. The researchers suspected that being unable to perform their daily activities would mean higher rates of death and unexpected visits to the Emergency Department (ED) and admissions to the hospital.

Participants included 464 people who on average were nearly 80 years old; 65 percent were male. All the participants were treated for blood cancers, including leukemia, multiple myeloma, and lymphoma, at the Dana-Farber Cancer Institute in Boston. About 38 percent of the participants had an aggressive form of blood cancer.

Of the participants, 11 percent reported they had trouble with at least one ADL and almost 27 percent had trouble performing at least one IADL.

The researchers also looked at a group of 318 participants who had visited the ED or had unplanned hospitalizations. Of them, 17 percent had at least one ED visit and 19 percent had at least one unplanned hospitalization. The five most common causes of hospitalization were pneumonia, fever, sepsis (the medical term for a blood infection), pain, and congestive heart failure.

For their main findings, the researchers reported that participants who had trouble performing at least one IADL had a higher risk for death, ED visits, and unplanned hospitalizations. This risk was not affected by how old they were, whether they had other chronic illnesses, how aggressive their cancers were, or the intensity of their cancer treatment.

What's more, the researchers found that many of the patients who were dependent in performing their IADLS (meaning they relied on help from others) also had higher rates of age-related conditions, such as memory issues, problems with mobility, and feelings of loneliness or depression. The researchers concluded from their study that it is not only important to ask about function for older adults with blood cancer but to also screen for age-related conditions that could limit functioning. Treating these other conditions to improve function might help older adults better tolerate the stress of blood cancers and their treatment, the researchers suggested.

PHILADELPHIA (April 5, 2019) -Breastfeeding is an accepted practice for millions of women worldwide and strongly endorse by the World Health Organization. To provide appropriate counseling about human milk and breastfeeding, it is important to understand cultural beliefs and customs related to the practice.

Understanding Orthodox Jewish customs regarding breastfeeding is especially important for health care providers because the Orthodox population in the United States is growing. Orthodox women get married younger and have twice as many children as non-Orthodox Jews. Some of these families are at higher risk for conceiving infants with genetic disorders, who may require special care and continued hospitalization after the mother has been discharged.

In a new article published in The American Journal of Maternal/Child Nursing, nurse researchers examine Orthodox Jewish practices related to the provision of human milk and breastfeeding for a sick newborn. The article guides nurses in providing culturally competent lactation education, and evidence based guidance to meet the individual needs of each Orthodox Jewish infant and family. It is critical for the family to have conversations with their Rabbi ideally before delivery or at time of birth to determine needs for saving colostrum and milk, as well as, milk expression during Shabbat or religious holidays.

"Personalized, culturally and religiously tailored care, education, and counseling can ensure that Orthodox mothers are able to meet their personal breastfeeding goals even if their infant requires hospitalization at birth," says Diane L. Spatz, PhD, RN-BC, FAAN, the Helen M. Shearer Term Professor of Nutrition at University of Pennsylvania School of Nursing (Penn Nursing), one of the article's co-authors.

April 5, 2019 -- Even tiny amounts of gluten in foods are troublesome for people with celiac disease, and restaurants may be the hardest places to avoid the protein, finds a study by Benjamin Lebwohl, MD, MS, Celiac Disease Center at NY-Presbyterian Hospital and assistant professor of medicine and epidemiology at Columbia Mailman School. More than half of gluten-free pizza and pasta dishes in restaurants tested positive for the presence of gluten; about one-third of supposedly gluten-free foods had detectable gluten. Results are published in the American Journal of Gastroenterology.

"Patients have long suspected that gluten contamination in restaurant foods is a frequent occurrence, and these results support that," said Lebwohl. "Our findings suggest that pizza, pasta and foods served at dinner were more likely to have a problem."

Lebwohl used data uploaded by users of the portable device Nima Gluten Sensor which restaurant patrons use to test foods. The manufacturer supplied 5,624 food tests by 804 users over 18 months. The research showed 32 percent of tests revealed detectable gluten in dishes that were supposed to be gluten-free.

Gluten-free pasta samples were positive in 51 percent of tests; gluten-free pizza contained gluten for 53 percent. Gluten was detected in 27 percent of breakfasts, 29 percent of lunches and 34 percent of dinners.

There are limitations to the data, notes Lebwohl. "Users may have uploaded results that surprised them the most." Also, the device is very sensitive. To be labeled gluten-free in the U.S., a product must contain less than 20 parts per million. "The device can detect levels as low as 5 to 10 ppm, which most do not consider clinically significant, so a 'gluten found' result does not necessarily mean 'unsafe for celiac disease.' The device also does not detect certain forms of gluten, such as fermented gluten. So both false positives and false negatives will affect this estimate."

Lebwohl suspects that gluten-free foods are inadvertently contaminated, and "the solution may be better education for food preparers."

With new genome analysis tools, scientists have made significant advances in our understanding of modern humans' origins and ancient migrations.

But trying to find ancient DNA, let alone prove that the ancient DNA is ancestral to a population living today is extremely challenging.

A new study in Molecular Biology and Evolution (MBE) adds to this understanding by reconstructing artificial genomes with the analyses of the genome of 565 contemporary South Asian individuals to extract ancient signals that recapitulate the long history of human migration and admixture in the region.

"All in all, our results provide a proof-of-principle for the feasibility of retrieving ancient genetic signals from contemporary human subjects, as if they were genomes from the past embedded in amber," said Luca Pagani, the research coordinator of the study.

The study was led by Burak Yelmen and Mayukh Mondal from the Institute of Genomics of the University of Tartu, Estonia and coordinated by Luca Pagani from the same institution and from the University of Padova, Italy.

"The genetic components we managed to extract from modern genomes are invaluable, given the shortage of ancient DNA available from South Asian human remains, and allow us to elucidate the genetic composition of the ancient populations that inhabited the area," said Burak Yelmen, co-first author of the study.

While studying the mixing events that brought ancient human populations to form contemporary South Asians, the researchers also noted that some portion of the genomes had not mixed as expected, as if the genetic variants that evolved in South Asia or the ones that arrived from West Eurasia were important for adapting to the local lifestyle through admixture.

"Among these variants, we found genes important for immunity and for dietary changes, as one may expect for human populations adapting to new sets of pathogens or food," said Mayukh Mondal, joint first author of this work.

The human evolution of skin pigmentation also revealed many genetic variants for the population studied.

"Intriguingly we also noted that some genetic variants implicated in the skin pigmentation of West Eurasians were under opposite selective forces, some becoming highly frequent and others being almost lost after the admixture events. Skin pigmentation is surely a fascinating and complex subject and we are still trying to understand what, if any, would be the adaptive implications of the signal we detected."

The study will add to the growing picture of the diversity of South Asians, and future studies of modern human population origins.

"These signals can complement the picture emerging from the booming field of ancient DNA by providing high quality genomic sequences especially for areas of the world where archaeological human remains are scarce or poorly preserved."

Chestnut Hill, Mass. (4/5/2019) - Like old photographs, memories fade in quality over time - a surprising finding for a team of Boston College researchers who expected recollections would become less accurate, but found people also report declines in the vibrancy and visual qualities of their memories.

When people remember the past, they remember it with varying degrees of clarity, said Boston College Assistant Professor of Psychology Maureen Ritchey, a cognitive neuroscientist and co-author of the study, published in an online edition of the journal Psychological Science.

Sometimes people remember lots of details about an event, as if they are reliving the moment as it happened, said Ritchey. Other times, it seems like the memory has faded, and the details are fuzzy. Prior memory research has shown that emotionally significant events-- like a car accident-- are remembered more vividly than everyday events.

"We wanted to know whether this feeling of memory vividness is related to not just what is remembered, but how it is remembered - the visual quality of the memory," said Ritchey, who conducted the study with Boston College Professor of Psychology Elizabeth Kensinger and post-doctoral researcher Rose Cooper.

As events are stored in memory or forgotten, the team asked, how do their visual features change? Ritchey said people reported changes to their memories akin to using a filter to edit a picture.

"A simple analogy is what happens when you post a photo on Instagram," Ritchey said. "You're cued to apply a filter that changes the brightness or color saturation of the image. In our study, we asked if forgetting is like applying a filter to past experience, and whether or not the emotional significance of the event would change which filter you apply."

In three experiments, participants studied emotionally negative and neutral images that varied in visual quality -- luminance and color saturation. They then reconstructed the visual qualities of each image in a subsequent test.

The findings revealed that memories were recollected as less visually vibrant than they were encoded, demonstrating a novel memory-fading effect, the researchers reported.

Negative emotions subjects experienced when viewing the images increased the likelihood that images would be accurately remembered but did not influence memory fading. In addition, subjective ratings of memory vividness were lower for less accurate memories and for memories that had visually faded, the team found.

These findings provide evidence that the vibrancy of low-level details - such as colors and shapes associated with an event -- fade in memory while the gist of the experience is retained.

People may remember going to a music festival and watching their favorite band, but the intensity of that sensory experience, including the bright stage lights and strength of the bass, will slowly fade.

"We found that memories seem to literally fade: people consistently remembered visual scenes as being less vibrant than they were originally experienced," said Cooper. "We had expected that memories would get less accurate after a delay, but we did not expect that there would be this qualitative shift in the way that they were remembered."

The fading effect happened less for memories that were rated as subjectively stronger. "We were also surprised to find that emotional memories did not influence the amount of fading, only the likelihood with which people remembered the images at all," she added.

Cooper and Ritchey said the team's next steps are to figure out what exactly drives the memory fading effect - does it stem from forgetting over time or interference from new information? How is it influenced by individual differences in memory for other kinds of event details?

ITHACA, N.Y. - Dr. Sunita Sah practiced general medicine for several years in the United Kingdom's National Health Service. When she came to the United States, she noticed something strange.

The U.K. guidelines for tests such as mammograms and colon cancer screenings drastically differed from those in the U.S. - even though they were based on the same medical evidence.

"Having colonoscopy at the age of 50 - that struck me as rather odd when I moved to the U.S., because you don't really hear about people having colonoscopies as a screening procedure in the U.K.," said Sah. "It's much less invasive to test for blood in the stool. It's also less costly and doesn't have the risks of undertaking a colonoscopy."

Now an assistant professor of management and organizations at Cornell, Sah and Ismail Jatoi of the University of Texas Health, San Antonio, say the treatment guidelines recommended by medical specialist organizations are more likely to call for greater use of health care services and exacerbate overdiagnosis, overtreatment and spiraling health care costs. Their commentary, "Clinical Practice Guidelines and the Overuse of Health Care Services: Need for Reform," appeared March 18 in the Canadian Medical Association Journal.

The implications are significant, she said, because guidelines are supposed to provide standard evidence-based treatment practices for all doctors.

"The recommendations put out by specialty organizations - like the American College of Cardiology or the American College of Radiology - show specialty bias in recommending more aggressive and/or more frequent screening procedures," said Sah, an expert on conflict of interest. "In the U.S. in particular, where the fee-for-service compensation model dominates medicine, which is different from countries like the U.K., you see even more recommendations for greater use of health care services."

Specialty bias refers to the tendency of physicians to recommend the treatments in which they are trained to deliver. For example, localized prostate cancer can be treated with either surgery or radiation.

"If you go to a surgeon, chances are that they are more likely to recommend that you have surgery; if you go to a radiation oncologist, they are more likely to recommend that you have radiation," she said. "They each often believe that the treatment that they're trained in is the better one."

In the case of screening for colorectal cancer, the American College of Gastroenterology's panel - all of whom were gastroenterologists - recommended colonoscopy as the best strategy.

But the United States Preventive Task Force, with no gastroenterologists or gastrointestinal surgeons, recommended testing the stool, sigmoidoscopy (an exam of only the lower part of the colon) or colonoscopy as a last resort. Stool testing was also recommended by the European Society of Medical Oncology panel, which consisted of six medical oncologists, no gastroenterologists and one gastrointestinal surgeon. The panel said there was limited evidence that screening colonoscopy is effective.

"Colonoscopies are more invasive than stool testing and come with potentially greater risks and costs for patients - but increased clinical volume and profits for gastroenterologists," Sah said.

Specialty guidelines are also subject to fee-for-service bias, according to the commentary. Doctors who receive a payment for each treatment may tend to recommend that treatment more often, because they have a financial interest in it.

"The bias is not necessarily malicious or intentional," Sah said. "In a fee-for-service environment, they may be biased to do more rather than less, so it becomes a habit."

But more is not necessarily better, she said. "Sometimes the risks of those procedures are just not worth the benefits."

The authors call for a reduction in conflicts of interest in the fee-for-service model, and more professional diversity in the makeup of the guideline committees. "You need a variety of different voices on those committees," Sah said.

And patients could ask their doctors which guidelines they follow and why. "Ask them questions," she said. "Ask your doctor to explain their thought process in recommending the particular guideline and the advantages or disadvantages of one guideline versus another."

Tucked away in the noncoding regions of bird DNA, researchers have discovered molecular roots of the loss of flight seen in so many disparate paleognathous birds. In contrast with previous work, which emphasized changes to protein-coding DNA as driving flightlessness, this study associates loss of flight more strongly with regulatory evolution in noncoding DNA. The results provide an example for future genome studies of so-called convergent phenotypes throughout the animal kingdom. Over time, species of divergent lines of the tree of life can develop similar evolutionary traits. Various species of birds, for example, have experienced the loss of flight many times independently in the course of bird evolution. However, what drives convergent evolution is not well understood; in particular, the underlying genetic changes responsible are a question, with many previous studies implicating changes in protein-coding regions of bird DNA, as opposed to those in regulatory regions. To better understand genetic drivers of the convergent evolution of flightlessness, Timothy Sackton and colleagues investigated the genomes of various ratites, a group of flightless birds that includes the ostrich, kiwi, emu and extinct moa, among others. Sackton et al. combined phylogenetic, developmental and epigenomic analyses of the genomes of ratites, including eleven new genomes, with similar analyses of closely related, flight-capable tinamous. The researchers' analyses suggest that the loss of flight is more strongly associated with changes in noncoding regulatory regions of the DNA, and less so with changes in protein-coding genes, contradicting the results of previous studies. Furthermore, the results indicate that changes in regulatory regions could result in rapid, convergent changes across taxa.

Inside the body, disease and injury can leave behind quite the mess -- a scattering of cellular debris, like bits of broken glass, rubber and steel left behind in a car accident.

Inside the central nervous system (CNS), a region that includes the brain and spinal cord, it is the job of certain cells, called microglia, to clean up that cellular debris. Microglia have counterparts called macrophages that serve similar function outside the CNS in the peripheral nervous system (PNS), the region that contains most of the sensory and motor nerves.

Scientists have long believed that microglia are restricted to the CNS, and in cases of injury the two cells clean up their own sides of the highway, so to speak.

In a new study published in PLOS Biology, scientists at the University of Notre Dame discovered microglia actually squeeze through the spinal boundary, crossing into the peripheral nervous system in response to injury. The surprising result could have broad implications in the area of nervous system diseases, while opening the door to a completely new set of questions in the study of both systems.

"Microglia are defined as central nervous system cells. So if they're seen outside in the peripheral nervous system -- that was surprising to us -- that opens up a ton of new questions," said Cody J. Smith, the Elizabeth and Michael Gallagher Assistant Professor of Biological Sciences at Notre Dame and at the University's Center for Stem Cells and Regenerative Medicine. "It has been shown during different disease states that the macrophages in the peripheral can get into the CNS, but we certainly didn't know or really expect for the central nervous system cells to cross over, because there was little literature that suggested that was likely." Smith co-authored the study with Lauren Green, who is currently studying biology at Notre Dame and led the study.

In the study, Smith and his team modeled a brachial plexus injury in zebrafish and observed how microglia and macrophages responded. Brachial plexus injuries take place at the intersection of the central and peripheral nervous systems, affecting nerves that connect the brain and spinal cord to the shoulders, arms and hands. According to the National Institutes of Health, brachial plexus injuries occur in one to three out of every 1,000 births.

Once inside the peripheral nervous system, Smith said, microglia do their job of clearing cellular debris at the point of injury, but they return to the CNS with that debris, and could potentially carry it straight to the brain.

The study also showed the microglia return to the CNS in an altered state, which makes the results of this research of particular concern to the study of post-injury development and function.

Altered microglia have been seen widespread in countless neurodegenerative diseases, Smith said, and have been implicated in autism spectrum disorder.

In disease, altered microglial cells can clear too much cellular material -- including material they normally do not clear -- in the brain. If microglia are altered, the suggestion is that it could cause neuropathic pain, disorder or disease-type states, because the cells are clearing or removing cellular material that's necessary for proper nervous system function.

"There was little thought these cells could leave the central nervous system, so there are few studies of microglia in the context of diseases and function within both central and peripheral nervous system diseases," Smith said. "What happens when they do go into the brain after being in the PNS? What else are they capable of doing? Our study shows the full function, the full capability of these cells is not limited to the central nervous system. It opens up so many more exciting questions than it answers."

Although separated by more than one billion years of evolution, plants and animals have hit upon similar immune strategies to protect themselves against pathogens. One important mechanism is defined by cytoplasmic receptors called NLRs that, in plants, recognize so-called effectors, molecules that invading microorganisms secrete into the plant's cells. These recognition events can either involve direct recognition of effectors by NLRs or indirect recognition, in which the NLRs act as 'guards' that monitor additional host proteins or 'guardees' that are modified by effectors. Host recognition of effectors, whether direct or indirect, results in cell death to confine microbes to the site of infection. However, until now, a detailed understanding of the mechanisms of action of plant NLRs has been lacking, and much of our understanding of how these molecules function in plants has been based on comparison with animal counterparts.

In two new studies published in the journal Science, Jijie Chai who is affiliated with Tsinghua University in Beijing as well as the University of Cologne and the Max Planck Institute for Plant Breeding Research together with the groups of Hong-Wei Zhang and Jian-Min Zhou at Tsinghua University and the Chinese Academy of Sciences in Beijing have now pieced together the sequence of molecular events that convert inactive NLR molecules into active complexes that provide disease resistance.

The authors focused their attentions on a protein called ZAR1, an ancient plant molecule that is likely to be of broad importance since it interacts with multiple 'guardees' to recognize unrelated bacterial effectors.

Using cryo-electron microscopy, Chai and co-authors observed that in the absence of bacterial effectors, ZAR1, together with the plant protein RKS1, is maintained in a latent state through interactions involving multiple domains of the ZAR1 protein. Upon infection, a bacterial effector modifies the plant 'guardee' PBL2, which then activates RKS1 resulting in huge conformational changes that first allow plants to swap ADP for ATP and then result in the assembly of a pentameric, wheel-like structure that the authors term the 'ZAR1 resistosome'.

One striking feature of this structure is its similarity with animal NLR proteins, which, once activated, also assemble into wheel-like structures that act as signaling platforms for cell death execution and immune signaling. However, one important difference between the structures offers a tantalizing clue as to how ZAR1 induces cell death. The authors could identify a highly ordered funnel-like structure in ZAR1 that tethers the resistosome to the plasma membrane and is required for cell death and disease resistance. The authors speculate that ZAR1 may form a pore in the plasma membrane and in this way perturb cellular function leading to immune signaling and cell death.

Other plant NLRs also assemble into complexes that associate with the plasma membrane and it is thus highly likely that Chai's findings have important general implications for understanding plant immunity. MPIPZ director Paul Schulze-Lefert, who was not involved in the studies, is in no doubt about the importance of the new studies: "This will become textbook knowledge."

The health claims made on the product packaging for a large proportion of foods marketed to children in the UK are 'confusing', and could be contributing to rising rates of childhood obesity, suggests research published online in the Archives of Disease in Childhood.

Stricter regulations are needed for food labelling and product content to lessen this risk, urge the researchers

Child-focused marketing techniques, using cartoon characters, toys, games and promotions (cards and vouchers), have long been an advertising staple. But the use of health and nutrition claims for particular foodstuffs is a more recent trend, note the researchers.

And the evidence suggests that when such claims are made, they create a positive impression, a phenomenon known as the 'health halo effect'.

While steps have been taken to control the advertising to children of products high in fat and sugar, such as sweets, chocolates and sugar sweetened drinks, rather less attention has been paid to other foods carrying product packaging claims suggesting that they contribute to good health/nutrition, say the researchers.

To try and address this, they scrutinised the energy, fat, sugar, and salt content of foods marketed to children above the age of 1, and widely available in various large food retail outlets in the UK.

The researchers focused on products with child-focused imagery and health and nutrition claims on the product packaging, including terms such as "one of 5 a day," in reference to the UK government's push to get everyone to eat five portions of fruit/vegetables every day.

In all, 332 different products, including breakfast cereals, fruit snacks, fruit-based drinks, dairy products, such as yogurts, and ready meals were assessed, using the broadcast regulator's tool (Ofcom NPM) to identify so-called 'healthy' food .

This uses a scoring system, made up of seven elements--energy; total sugars; saturated fat; salt; fruit/vegetables/nuts; fibre; protein--from the product labelling information, to classify the nutritional quality of foods.

The calculations showed that a large proportion of the products, including those commonly perceived as 'healthy' (41%), were classified as 'less healthy,' by the tool scoring system.

Cereal bars had the highest energy and saturated fat content, while cereals had the highest salt content.

Fruit snacks had the highest sugar content, averaging 48 g/100 g, but still made the 5-a day claim, in many cases--something which is likely to be confusing for parents, suggest the researchers.

One in three products contained concentrated fruit juice as an added ingredient while one in four used pureed fruit.

Nearly a quarter of the products, most of which were fruit based drinks and snacks, made 'no added sugars' claims. But half had concentrated juice or fruit puree as the added ingredients.

"Processed fruits are perceived by the public as a healthy natural alternative to added sugars, but because of the breakdown of the cellular structure they potentially have the same negative effect on weight gain as other forms of sugar, which is why they have recently been classified as free sugars in the UK," write the researchers.

Many products (over 41%) made 5-a day claims, most of which were fruit drinks, ready meals, and fruit snacks. Processed fruit, concentrated fruit juice, or puree appeared as ingredients in nearly half (just over 44%) of these products.

But despite most (82%) of them claiming to contain one portion of fruit or vegetables, three out of four didn't contain the recommended 80 g portion size. And half of the products making 5-a day claims didn't specify whether these were adult or child size portions.

The serving size for most (nearly 95%) fruit-based drinks exceeded the recommended 150 ml limit for fruit juice, yet the fruit and vegetable portions for most products were below the recommended portion size.

The researchers caution that while they tried to include as representative a sample of products as possible, some may have been missed, and they were obliged to estimate the content of some products in the absence of adequate ingredient information on the packaging.

But the findings indicate that "health and nutrition claims used on product packaging are currently confusing," they say.

"Prepacked foods targeted to children can be consumed as part of a 'balanced and healthy' diet, yet their health and nutrition claims remain questionable. Given the current rising rates of childhood obesity, the consumption of less healthy foods may have long term negative implications on child health." write the researchers.

"Stricter regulations on product composition, food labelling, and marketing techniques are required to discourage the promotion of foods which might be considered obesogenic," they conclude.

A small peptide produced in the skin of predatory nematodes prevents them from cannibalizing their immediate family members, while they feed upon their close relatives, a new study finds. The ability to recognize self is an important trait and regulates many crucial biological processes. While it's observed in a wide variety of organisms, the molecular mechanisms that underlie self-recognition systems are not well understood. This is particularly true for nematodes - one of the most well-studied organisms on the planet - in which the ability to discriminate self from other organisms has not yet been described. Previous research has shown that the predatory Pristionchus nematodes will feed on the larvae of other species of nematodes; however, it is unknown if this cannibalistic nature is due to their ability to discriminate amongst their own kin versus other species. James Lightfoot and colleagues investigated the prey interactions between Pristionchus, their kin and other nematode species and revealed a self-recognition system that enables Pristionchus nematodes to recognize their offspring. Over a series of experiments, predatory Pristionchus nematodes were observed killing and eating the larvae of other species, including closely related Pristionchus pacificus strains. However, the authors found that in each case, the killing and eating of self-progeny was avoided (see video). By mapping and comparing the genomes of two P. pacificus strains including after amino acid manipulations done with CRISPR/Cas9 to explore specific molecular drivers of self-recognition, Lightfoot et al. identified a peptide responsible - hypervariable small peptide SELF-1. Alterations to the self-1 gene resulted in elimination of self-recognition and individuals who lost the related peptide were promptly cannibalized by their own strains. According to the authors, the results demonstrate a likely molecular system P. pacificus use to prevent cannibalism.

Mass drug administration (MDA) of two antibiotics can be highly effective at reducing cases of scabies and the bacterial infection impetigo, according to new research published in Lancet Infectious Diseases.

The study was conducted by the London School of Hygiene & Tropical Medicine (LSHTM), Murdoch Children's Research Institute (MCRI), the Kirby Institute at UNSW Sydney and the Solomon Islands Ministry of Health and Medical Services.

It saw the entire population of Choiseul Province of the Solomon Islands (26,000 people), in the Pacific, given one round of the antibiotics ivermectin and azithromycin together. The prevalence of scabies and impetigo in residents of 10 randomly selected villages before and after Mass Drug Administration (MDA) by the Solomon Islands Ministry of Health and Medical Services was then compared.

The strategy reduced scabies cases from 19% to 2% (90% reduction), and impetigo cases from about 25% to about 6% (75% reduction), in one year.

The study is the largest evaluation of ivermectin-based mass drug administration for the control of scabies, and supports large-scale implementation of this strategy for control of scabies in locations where the condition is identified as a public health priority.

Dr Michael Marks from LSHTM and co-author of the study, said: "We know that treating individual cases of scabies is not effective, however treatment of entire communities has been shown in small community-based trials to substantially reduce cases. Our study demonstrates this can be an effective approach when delivered at a larger scale."

Scabies is a parasitic skin disease that affects an estimated 200 million people worldwide. The disease causes skin inflammation with itch that is frequently severe, and often associated with bacterial skin infection caused by Staphylococcus aureus and Streptococcus pyogenes (impetigo). This can in turn lead to severe complications including septicaemia and post-streptococcal glomerulonephritis. In 2017, growing awareness of the burden of disease due to scabies led the World Health Organization to recognise it as a neglected tropical disease.

Dr Lucia Romani from the Kirby Institute and lead author on the paper, said: "Scabies is too common in many tropical developing countries, especially in rural and remote communities where people share small living and sleeping spaces access to treatment is limited."

This new study was conducted in Choiseul Province of the Solomon Islands where a very high number of scabies cases have been reported. 1,399 people had their skin examined at the start of the MDA in 2015, with 261 (one in five) having scabies and 347 having impetigo. Twelve months on, 1,261 people were examined with only 29 people with scabies and 81 with impetigo. Additionally, there was also almost 6,000 less people presenting to outpatient clinics, a drop of 36.1% cent, in the three-months after MDA. Presentations for skin sores, boils and abscesses also fell by 50.9%.

MCRI Professor and study PI Andrew Steer said: "Treatment is highly effective at reducing both scabies and impetigo and we saw significant reductions in outpatient presentations, especially those needing treatment for skin sores, boils and skin abscesses."

Oliver Sokana, from the Solomon Islands Ministry of Health, said: "Both diseases were most common in children aged between five and nine years old."

The safety and feasibility of large-scale mass co-administration of ivermectin and azithromycin in Choiseul Province was reported in a recent study.

Dr Marks said: "Scabies is extremely common, and is a major risk factor for dangerous bacterial skin infection. Our study provides crucial evidence for the global strategy of scabies control being developed."

The authors acknowledge limitations of their study including that is was non-randomised so they are unable to say with certainty that factors other than the intervention did not influence the outcome. Further research is needed to assess durability and scalability of mass drug administration in larger, non-island populations, and to assess its effect on the severe bacterial complications of scabies.