Culture

In a records review of 290 people at risk for Alzheimer's disease, scientists at Johns Hopkins say they have identified an average level of biological and anatomical brain changes linked to Alzheimer's disease that occur three to 10 years -- some even more than 30 years -- before the disease's first recognizable symptoms appear.

"Our study suggests it may be possible to use brain imaging and spinal fluid analysis to assess risk of Alzheimer's disease at least 10 years or more before the most common symptoms, such as mild cognitive impairment, occur," says Laurent Younes, Ph.D., professor and chair of the Department of Applied Mathematics and Statistics at The Johns Hopkins University. A report of their findings was published online April 2 in Frontiers in Aging Neuroscience.

Younes cautions that brain changes vary widely in people, and that their research findings reflect an average level of such changes in a small group of research subjects. As a result, he says, the scientists cannot yet use them to draw any precise conclusions about brain changes in individual people. Nor, they say, are there any drug or other interventions yet known to slow or stop the disease process even if risk is identified early. But the work, he adds, could lead eventually to a test to determine an individual's relative risk for Alzheimer's disease and to guide the use of treatments when and if they are developed.

For the study, the scientists reviewed medical records collected from 290 people age 40 and older by the National Institutes of Health and the Johns Hopkins University School of Medicine as part of the BIOCARD project, an effort to develop predictors of cognitive decline. It is currently directed by Johns Hopkins neurologist Marilyn Albert, Ph.D.

Most of the 290 people had at least one first degree relative with dementia of the Alzheimer's disease type, putting them at higher than usual risk.

As part of the BIOCARD studies, scientists collected cerebrospinal fluid and performed MRI brain scans of study participants every two years between 1995 and 2005. They also conducted five standard tests of memory, learning, reading and attention annually from 1995 to 2013.

Because all 290 participants were cognitively normal when the study began, the scientists were able to track various biological and clinical features associated with Alzheimer's disease in the years leading up to the appearance of symptoms. By the time of their last appointment with the BIOCARD project, 209 study participants remained cognitively normal, and 81 were diagnosed with mild cognitive impairment or dementia due to Alzheimer's disease.

In the 81 people who developed cognitive problems or dementia, the Johns Hopkins team found subtle changes in cognitive test scores 11 to 15 years before the onset of clear cognitive impairment. They also found increases in the rate of change of a protein called Tau, which has long been considered a marker of Alzheimer's disease, in cerebrospinal fluid an average of 34.4 years (for t-tau, or total Tau) and 13 years (for a modified version called p-tau) before the beginning of cognitive impairment.

The online complaint system used by web giants like Google and Twitter is a 'Wild West' with evidence of abuse by complainants, according to a new study from Queen Mary University of London.

Despite this, the UK government is considering promoting similar systems to underpin parts of future web regulation, and the researchers believe this raises questions for its effectiveness.

Over one year, they observed more than 1 billion URLs being complained about, primarily with the intent of removing content.

They investigated the nature of various types of complaints that are issued to many web companies, also including Vimeo and Bing, which now allow any third party to file complaints. To date, there is little evidence regarding how these complaint procedures are handled, how successful they are, or who they are targeted against and by whom.

The study, which will be presented at The Web Conference 2019, shows that the top ten complainants dominate the entire system and generate hundreds of millions of complaints, or 41 per cent of all notices, mostly about copyright.

The majority of these are generated by a tiny set of hypergiants including Fox, NBC and copyright pursuit specialists Rivendell that issue complaints widely.

However, that leaves a large number of organisations sending a small number of complaints (fewer than 100) as the majority of senders just send a few notices, leaving a small minority to send a very large number.

Some complainants do not seem to take much care when sending complaints as they often send repeat complaints again and again, send complaints for URLs that do not exist, or send complaints for content already taken down.

For those receiving the complaints, this creates a huge overhead of sifting through these non-existent URLs and potentially crowds out smaller senders of complaints because of the sheer volume to deal with.

Dr Gareth Tyson, co-author of the study from Queen Mary University of London, said: "As the web grows, it is unclear how sustainable this complaint model is and at the moment it resembles something like the Wild West. It is unclear how effectively small organisations could handle this approach. Should the UK government, and other governments around the world, be adopting a similar system to underpin web regulation, or thinking of new approaches and tools to support the web? The answer is not yet clear."

It is also often the same websites that are repeatedly targeted as the top 1 per cent of sites accumulate 63 per cent of complaints. However, the researchers found this is very unstable because some complainants suddenly send aggressive bursts of complaints which then cease soon after.

Most of these include well know pirate video portals such as gorillavid, daclips, movpod, googlevideo.com (part of YouTube) and the website piratebay which is a BitTorrent portal.

The efficacy of these complaints vary a lot with many websites just ignoring them, while some tend to remove content and almost 20 per cent of all websites do not even have live domains anymore.

Although previous studies have looked at copyright notices, the researchers generalise across a number of different complaint types including defamation and court orders.

For the first time, they also show the dynamics between complainants and websites who generate negative attention from those people sending complaints.

Damilola Ibosiola, lead author of the study and a PhD candidate from Queen Mary University of London, said: "People often assume that the only reason content gets blocked is because an intermediate party like a government censors it. In reality, however, there is a huge ecosystem of organisations constantly exchanging complaints about the activities of others. This has far reaching implications for how the world wide web is structured, yet it is rarely seen."

Dr Gareth Tyson added: "Our study also sheds light on the efficacy of these various regulatory practices, and highlights both the use and misuse of web complaint mechanisms. We hope that the findings can lead to a better regulatory structure surrounding the takedown of illegal material from the web, and a better idea of what works. Importantly, we also hope that this can be used by those people generating complaints to better streamline their activities to avoid overwhelming recipients with many erroneous complaints."

Surface engineering of nanocarriers devotes considerable contribution to the field of biomedicine ranging from drug delivery to theranostic. Conventional chemical/physical approaches trend to use PEG functionalization, morphological control, and lipid modification, which allow nanocarriers participate various tasks in complex biological conditions. Although the in-vivo performance of nanocarries was improved by using these aforementioned methods, nanocarriers still suffer from drug delivery barrier caused by immune clearance, resulting in a low therapy efficacy. Furthermore, synthetic components of nanocarriers with undesired biocompatibility and biotoxicity also limits their biomedical applications. It is highly needed to develop biomimetic nanocarriers for the current drug delivery systems.

Recently, increase interest inspires that coating cell membranes on the surface of nanocarriers as a promising strategy can help address these issues. Cell membranes isolated from red blood cells are considered as the coating materials on the surface of nanocarriers. This novel bioimimetic hybrid system combines synthetic materials and naturally biological components, which breaks through the traditional concept of nanocarrier. By directly inheriting biological components of cell membrane (proteins, lipids, antigens), nanocarriers successfully achieve the immune-evasion and prolong the circulation time in the blood stream. To pursue functional diversity, some other cells, such as platelets, immune cells, cancer cells, and bacterium, contribute their membranes to cover nanocarriers for versatile properties (Image), including bioadhesion, target recognition, or deep tissue penetration. Compared with synthetic carriers, cell membrane-covered nanocarriers obviously improve their biocompatibility and get great efficiency to perform drug delivery, bioimaging, phototherapy, and detoxification. These above advantages indicate that cell membranes-inspired delivery systems will play an important role in the next-generation nanomedicine with extensive medical applications.

Prof. Junbai Li at Beijing National Laboratory for Molecular Sciences, CAS Key Lab of Colloid, Interface and Chemical Thermodynamics, Institute of Chemistry?Chinese Academy of Sciences, heads an expertise biomaterial team that develop a series of cell membrane-camouflaged nanocarriers for cancer therapy ranging from drug delivery to photothermal therapy as well as photodynamic therapy. A recent review article published in National Science Review, Prof. Junbai Li's group reviews recent progress of cell membranes-covered nanoparticles from biomaterials perspective, and demonstrate their unique advantages and highlight relevant biomedical applications. The appearance of this review will help researchers of interdisciplinary science to understand cell membrane coating materials, and further promote the development in this field.

Evidence of crawling in an Italian cave system sheds new light on how late Stone Age humans behaved as a group, especially when exploring new grounds, says a study published today in eLife.

The cave of Bàsura at Toirano and its human and animal fossil traces have been known since the 1950s, with the first studies conducted by Italian archaeologist Virginia Chiappella. In the current study, promoted by the Archaeological Heritage Office of Liguria, researchers from Italy, Argentina and South Africa used multiple approaches to analyse the human traces and identified for the first time crawling behaviours from around 14,000 years ago.

"In our study, we wanted to see how ancient humans explored this fascinating cave system," says first author Marco Romano, Postdoctoral Fellow at the University of the Witwatersrand, South Africa. "Specifically, we set out to discover how many people entered the cave, whether they explored as individuals or as a group, their age, gender and what kind of route they took once inside the cave."

To answer these questions, the multidisciplinary team studied 180 tracks from within the cave, including foot and handprints on the clay-rich floor. They applied various modern dating methods, software that analyses the structure of the tracks, and different types of 3D modelling. "Together, these approaches allowed us to construct a narrative of how the humans entered and exited the cave, and their activities once they were inside," Romano explains.

The team determined that five individuals, including two adults, an adolescent of about 11 years old, and two children of three and six years old, entered the cave barefoot and illuminated the way using wooden sticks. This suggests that young children were active group members during the late Stone Age, even when carrying out apparently dangerous activities.

The researchers reported the first evidence of crawling in footprints from a low tunnel - a route that was taken to access the inner part of the cave. Anatomical details in the footprints suggest that the explorers went bare-legged as they navigated this pathway.

When analysing the various handprints, the team found that some of them appear 'unintentional' and relate to exploring the cave only, while others are more 'intentional' and suggest that social or symbolic activities took place within the inner chambers. "Hunter-gatherers may therefore have been driven by fun activities during exploration, as well as simply the need to find food," Romano adds.

"Together, our results show how a varied approach to studying our ancestors' tracks can provide detailed insights on their behaviour," concludes senior author Marco Avanzini, head of the geology department at MUSE - Trento Museum of Science, Italy. "We hope our approach will be useful for painting similar pictures of how humans behaved in other parts of the world and during different periods of time."

TALLAHASSEE, Fla. -- When it comes to choosing a mate, female guppies often go for the mates with the flashiest, most interesting color patterns.

But why is that? Turns out, it's all about psychology.

In a new study, Florida State University researchers found that these tiny, tropical fish often choose a mate that physically stands out from the rest of the pack because of a common type of learning called habituation. Through habituation, animals -- in this case guppies -- stop responding to a stimulus after prolonged exposure.

In other words, the female guppy is often immune to the charms of a male guppy that looks like all the other male guppies. Ones with unusual color patterns stand a better chance at successfully wooing a mate.

"If they've seen certain patterns in the past, they've gotten used to them," said Mitchel Daniel, a postdoctoral researcher working with Professor of Biological Science Kimberly Hughes. "But when a male guppy comes along with a novel pattern, they're not used to it, so they find that male more attractive. We've shown that this attraction to the unusual happens because of habituation, which means that females tune out repetitive information, and pay more attention to things that look different."

Their study is published in the Proceedings of the Royal Society B.

The team's research builds on a study Hughes conducted several years ago that found that guppies' color patterns did seem to influence mate choice. When Daniel came to work in Hughes' lab, he wanted to explore the psychological theory of habituation and whether that explained how female guppies choose mates.

"It's been hard to figure out," Hughes said. "Why do females have that preference? That's been a tough nut to crack."

Researchers exposed female guppies to a large number of males with the same color patterns and tracked their responses to male courtship displays. In guppy courtship, the male guppy performs a type of dance around the female to express his interest. If the female wants to participate in this courtship ritual, she will respond to the approach and move toward the male.

Then, researchers exposed the same female guppies to male guppies with widely different color patterns to investigate the response. In some cases, they held the group of female guppies in isolation for a short period of time.

The researchers found that females typically preferred the novel male guppies. But, they also found that male guppies with familiar patterns became interesting again to the guppies held in isolation.

Through these experiments, researchers showed that this choice met four criteria that indicate habituation.

First, the female guppies' responsiveness to a stimulus -- male guppies with a familiar pattern -- decreased with added exposure.

Second, the females' interest in males with novel patterns was not affected by exposure to the familiar pattern, showing something called stimulus specificity.

Third, they demonstrated what is called spontaneous recovery, meaning these same females became interested in the familiar pattern again after it had been removed from them for a period of time.

And fourth, they became interested in the initial group of guppies again after exposure to novel-patterned guppies, a phenomenon called dishabituation.

"Nobody had linked this idea of habituation to mate choice for novelty," Hughes said. "It's a good example of how ideas from different fields can be helpful in explaining biology."

In another major clinical breakthrough of the Walk Again Project, a non-profit international consortium aimed at developing new neuro-rehabilitation protocols, technologies and therapies for spinal cord injury, two patients with paraplegia regained the ability to walk with minimal assistance, through the employment of a fully non-invasive brain-machine interface that does not require the use of any invasive spinal cord surgical procedure. The results of this study appeared on the May 1 issue of the journal Scientific Reports.

The two patients with paraplegia (AIS C) used their own brain activity to control the non-invasive delivery of electrical pulses to a total of 16 muscles (eight in each leg), allowing them to produce a more physiological walk than previously reported, requiring only a conventional walker and a body weight support system as assistive devices. Overall, the two patients were able to produce more than 4,500 steps using this new technology, which combines a non-invasive brain-machine interface, based on a 16-channel EEG, to control a multi-channel functional electrical stimulation system (FES), tailored to produce a much smoother gait pattern than the state of the art of this technique.

"What surprised us was that, in addition to allowing these patients to walk with little help, one of them displayed a clear motor improvement by practicing with this new approach. Patients required approximatively 25 sessions to master the training before they were able to walk using this apparatus," said Solaiman Shokur one of the authors of the study.

The two patients that used this new rehabilitation approach had previously participated in the long-term neurorehabilitation study carried out using the Walk Again Project Neurorehabilitation (WANR) protocol. As reported in a recent publication from the same team (Shokur et al., PLoS One, Nov. 2018), all seven patients who participated in that protocol for a period of 28 months improved their clinical status, from complete paraplegia (AIS A or B, meaning no motor functions below the level of the injury, according to the ASIA classification) to partial paraplegia (AIS C, meaning partial recovery of sensory and motor function below the injury level). This significant neurological recovery included major clinical improvements in sensory discrimination (tactile, nociception, vibration, and pressure), voluntary motor control of abdomen and leg muscles, and important gains in autonomic control, such as bladder, bowel, and sexual functions.

"The last two studies published by the Walk Again Project clearly indicate that partial neurological and functional recovery can be induced in chronic spinal cord injury patients by combining multiple non-invasive technologies that are based around the concept of using a brain-machine interface to control different types of actuators, like virtual avatars, robotic walkers, or muscle stimulating devices, to allow the total involvement of patients in their own rehabilitation routine," said Miguel Nicolelis, scientific director of the Walk Again Project and one of the authors of the study.

In a recent report by another group, one AIS C and two AIS D patients were able to walk thanks to the employment of an invasive method for spinal cord electrical stimulation, which required a spinal surgical procedure. In contrast, in the present study two AIS C patients - which originally were AIS A (see Supplemental Material below)- and a third AIS B subject, who recently achieved similar results, were able to regain a significant degree of autonomous walking without the need for such invasive treatments. Instead, these patients only received electrical stimulation patterns delivered to the skin surface of their legs, so that a total of eight muscles in each limb could be electrically stimulated in a physiologically accurate sequence. This was done in order to produce a smoother and more natural pattern of locomotion.

"Crucial for this implementation was the development of a closed-loop controller that allowed real-time correction of the patients' walking pattern, taking into account muscle fatigue and external perturbations, in order to produce a predefined gait trajectory. Another major component of our approach was the use of a wearable haptic display to deliver tactile feedback to the patients´ forearms in order to provide them with a continuous source of proprioceptive feedback related to their walking," said Solaiman Shokur.

To control the pattern of electrical muscle stimulation in each leg, these patients utilized an EEG-based brain-machine interface. In this setup, patients learned to alternate the generation of "stepping motor imagery" activity in their right and left motor cortices, in order to create alternated movements of their left and right legs.

According to the authors, the patients exhibited not only "less dependency on walking assistance, but also partial neurological recovery, with substantial rates of motor improvement in one of them." The improvement in motor control in this last AIS C patient was 9 points in the lower extremity motor score (LEMS), which was comparable with that observed using invasive spinal cord stimulation.

Based on the results obtained over the past 5 years, the WAP now intends to combine all its neurorehabilitation tools into a single integrated, non-invasive platform to treat spinal cord injury patients. This platform will allow patients to begin training soon after the injury occurs. It will also allow the employment of a multi-dimensional integrated brain-machine interface capable of simultaneously controlling virtual and robotic actuators (like a lowerlimb exoskeleton), a multi-channel non-invasive electrical muscle stimulation system (like the FES used in the present study), and a novel non-invasive spinal cord stimulation approach. In this final configuration, this WAP platform will incorporate all these technologies together in order to maximize neurological and functional recovery in the shortest possible time, without the need of any invasive procedure.

According to Dr. Nicolelis, "there is no silver bullet to treat spinal cord injuries. More and more, it looks like we need to implement multiple techniques simultaneously to achieve the best neurorehabilitation results. In this context, it is also imperative to consider the occurrence of cortical plasticity as a major component in the planning of our rehabilitation approach."

Researchers from McLean Hospital and Yale University have published findings of their study of large-scale systems in the brain, findings that could improve understanding of the symptoms and causes of bipolar disorder, schizophrenia, depression, and other mental illnesses. Their paper, "Functional Connectomics of Affective and Psychotic Pathology," published in the Proceedings of the National Academy of Sciences of the United States of America, details their investigation into brain network connectivity in patients with psychotic disorders.

According to lead researcher Justin T. Baker, MD, PhD, scientific director of the McLean Institute for Technology in Psychiatry, the study "took a birds-eye view to look into the ways large-scale systems in the brain interact with one another." Baker and his colleagues used functional magnetic resonance imaging data from more than 1,000 individuals, including patients who had been diagnosed with conditions such as bipolar disorder, schizophrenia, and depression. Information was collected through rest scans, in which subjects were asked to simply lie in a scanner with their eyes open, allowing researchers to capture data about spontaneous fluctuations in the brain.

Baker explained that the work is based on connectomics, the concept of "measuring all connections in the brain at the same time." He said that this type of "whole-system perspective" differs from most research into the biological foundations of psychiatric conditions. "For most studies, illnesses are studied in isolation, but evidence strongly suggests that distinct psychiatric diagnoses are not separated by clear neurobiological boundaries," said Baker. "The approach we've taken is to look at the whole brain so you can see not only how individual systems--like the visual system and motor system--are functioning, but how higher order systems--like cognitive systems--are functioning in the brain to see if there are correlations."

He said that the study is significant because "we don't have any objective measures of psychiatric illnesses that allow us to verify a patient's reports about their symptoms--there are no vital signs in psychiatry." This work, however, allows for "brain 'fingerprinting' to try to address what changes in the brain are shared across illnesses and what aspects might be specific to different illnesses," said Baker. "This work points to evidence at a high level that there are very pronounced changes in the brain that could start to serve as an objective biomarker."

Moreover, Baker stated that "the study begins to give us a better way of seeing how schizophrenia, bipolar disorder, and depression are similar or have shared underlying causes." He explained that prior research has indicated "that there is significant genetic risk for schizophrenia and bipolar disorder, and we also know that these conditions affect certain parts of the brain, but this study highlights that one system is affected or disrupted as a function of how severe the illness is, irrespective of whether it was psychosis or an affected illness like depression."

Baker said that he and his colleagues plan to build on this research through studies into the functioning of large-scale brain systems related to OCD and trauma and longer-term investigations. "We want to see if there is a fingerprint for different conditions and then use that information and apply it to the individual," he said. "We are conducting studies that follow individuals over time to look at the brain to see how symptoms are changing. We're trying to go from the snapshot view of these biomarkers to something that is much more dynamic and captures changes and nuances."

Scientists might have found an early detection method for some forms of dementia, according to new research by the University of Arizona and the University of Toronto's Baycrest Health Sciences Centre.

According to the study published in the journal Neuropsychologia last month, patients with a rare neurodegenerative brain disorder called Primary Progressive Aphasia, or PPA, show abnormalities in brain function in areas that look structurally normal on an MRI scan.

"We wanted to study how degeneration affects function of the brain," said Aneta Kielar, the study's lead author and assistant professor in the UA Department of Speech, Language and Hearing Sciences.

But what she and her team discovered was that the brain showed functional defects in regions that were not yet showing structural damage on MRI.

Structural MRI provides 3D visualization of brain structure, which is useful when studying patients with diseases that literally cause brain cells to wither away, like PPA.

Magnetoencephalography, or MEG, on the other hand, "gives you really good spatial precision as to where the brain response originates. We want to know if the decreased brain function is coming from the areas that are already atrophied or areas in an earlier stage of decline," said Jed Meltzer, the study's senior author and an assistant professor of psychology at the University of Toronto.

Kielar and her colleagues compared brain scans of patients with PPA to healthy controls while both groups performed language tasks. The researchers also imaged participants' brains while at rest. The functional defects were related to worse performance in the tasks, as individuals with PPA lose their ability to speak or understand language while other aspects of cognition are typically preserved.

Identifying the discrepancy between a PPA brain's structural and functional integrity could be used as an early-detection method.

This is promising because "many drugs designed to treat dementia are proving to be not really affective and that might be because we're detecting the brain damage too late," Kielar said. "Often, people don't come in for help until their neurons are already dead. We can do compensation therapies to delay disease progress, but once brain cells are dead, we can't get them back." This technique could allow patients to get ahead of the damage.

Kielar acknowledged that this was a small study, which is partially because PPA is such a rare form of dementia, and that further investigation is needed.

Next, she hopes to uncover why this structural and functional mismatch is happening in PPA brains.

"It's interesting that the affected areas are so far from the neurodegeneration," Kielar said. "One reason this might be happening is that those areas could be connected with white matter tracts," which facilitate communication between different brain regions. "When one area is dead, the area connected to it doesn't get normal input. It doesn't know what to do, so it starts to lose its function and atrophy because it doesn't get stimulation."

1. T2Bacteria panel rapidly and accurately diagnoses common bloodstream infections

More research suggested to determine effect on clinical practice

Editorial: http://annals.org/aim/article/doi/10.7326/M19-0971

Abstract: http://annals.org/aim/article/doi/10.7326/M18-2772

URLs go live when the embargo lifts

In a clinical trial, the T2Bacteria Panel showed promise for rapidly and accurately diagnosing bloodstream infections or sepsis caused by five common bacteria. The test could be used in a clinical setting in place of blood cultures, which are insensitive and can take a long time to show results. How these findings will affect clinical practice is not yet determined. Findings from a diagnostic accuracy study are published in Annals of Internal Medicine.

In 2018, the T2Bacteria Panel was cleared by the FDA to identify sepsis-causing bacteria directly from whole blood without the wait for blood culture, which currently takes 1 to 5 or more days and is the current standard of care for diagnosing bloodstream infections. The T2Bacteria Panel can deliver results in 3 to 5 hours for the most common ESKAPE bacteria, or Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli.

Researchers from the University of Pittsburgh School of Medicine studied 1,427 patients at 11 U.S. hospitals for whom blood cultures were ordered to assess performance of the T2Bacteria Panel in diagnosing suspected bloodstream infections. The researchers compared blood culture results to those obtained using the T2Bacteria Panel. The T2Bacteria Panel accurately identified or excluded bloodstream infections caused by five common ESKAPE pathogens in about 4 to 8 hours versus about 24 to 72 hours and 5 days, respectively, for blood cultures. According to the researchers, these findings suggest that using the T2Bacteria Panel could shorten the time to appropriate antibiotic treatment in patients, which has the potential to improve clinical outcomes.

The authors of an accompanying editorial from Atrium Health - Carolinas Medical Center caution that the clinical benefit of the T2Bacteria Panel is still uncertain. Outcomes studies are needed to determine if use of the T2Bacteria Panel can lead to better outcomes, such as significantly shorter time to appropriate therapy. Other factors, such potential overuse of antibiotics, cost, and laboratory time must also be considered.

Notes and media contacts: For an embargoed PDF, please contact Lauren Evans at laevans@acponline.org. To speak with the lead author, M. Hong Nguyen, MD, please contact mhn5@pitt.edu.

2. Low back pain is prevalent among workers and may be underreported

Abstract: http://annals.org/aim/article/doi/10.7326/M18-3602

URLs go live when the embargo lifts

Low back pain affects more than a quarter of working adults, often affecting their ability to work. However, these estimates may be underreported. Survey findings are published in Annals of Internal Medicine.

There are few estimates available in the U.S. of the proportion of back pain that is related to work. In 2015, the NHIS (National Health Interview Survey) collected supplemental data about the work-relatedness and the effects on work of back pain--specifically, low back pain -- among U.S. workers for the first time in nearly 3 decades.

Researchers randomly surveyed more than 19,000 adults to estimate the burden of low back pain among U.S. workers and whether the pain was related to work and/or had an effect on work. They found that the 3-month prevalence of any low back pain among U.S. workers was approximately 26.4 percent, representing almost 40 million workers. Many of these cases were attributed to work by a health care professional, but most workers affected did not discuss work-relatedness with their providers. They also found that low back pain had affected many current workers' ability to work. According to the researchers, these findings may greatly underestimate the total occupational effect of low back pain in the population because of the short recall period and exclusion of former workers, some of whom may have left the workforce because of work-related low back pain.

Notes and media contacts: For an embargoed PDF, please contact Lauren Evans at laevans@acponline.org. The lead author, Sara Luckhaupt, please contact Marie Sweeney at mhs2@cdc.gov.

New research in The Journal of Physiology has found, using a mouse model, that microbes in the maternal intestine may contribute to impairment of the gut barrier during pregnancy.

Scientists previously thought the changes in maternal metabolism that happen during pregnancy were due entirely to pregnancy hormones. We now believe that changes in the microbes that live in the maternal gut may contribute to these metabolic changes. If they do, then this provides us with a therapeutic opportunity to modify this microbial community during pregnancy to improve maternal and offspring health.

The gut acts as a barrier preventing microbes and other intestinal contents from entering the bloodstream, but in pregnant mice more molecules were able to cross this barrier. This loss of barrier was even greater when pregnant mice were fed a high-fat diet, resulting in increased inflammatory markers in maternal circulation.

These changes in the mother may be impacting the development of the placenta, as placental oxygen levels were decreased by maternal high-fat diet. Changes in the placenta could contribute to altered fetal development which was what the authors found in the fetal intestines. Impaired fetal intestinal development could lead to altered intestinal function after birth and ultimately impact the baby's metabolism.

Researchers discovered these changes by feeding their female mice a diet high in fat for 6 weeks before and throughout pregnancy. They then studied how the intestinal community of microbes changed. They tested the maternal intestinal barrier by measuring how much of a large molecule was able to cross the from the maternal intestine into the bloodstream and then looked at how the placenta and fetus developed.

Deborah Sloboda, senior author on the study, said:

"We are currently investigating when these changes in maternal barrier function occur and how they interact with the microbes in the intestines to influence the metabolism of the mom and development of the baby."

GPs must be better-equipped to support patients to manage the psychological challenge of reducing their opioid use - according to new research from the University of East Anglia.

The recommendation is part of a toolkit being launched today to help GPs reduce the amount of opioids they prescribe.

The toolkit outlines seven areas of best practice to tackle chronic opioid use - based on international research evidence, the experiences of health organisations and individual practitioners.

It comes after figures for England and Wales revealed an increase in opioid prescriptions of more than 60 per cent over the last decade - from 14 million in 2008 to 23 million last year.

Lead researcher Dr Debi Bhattacharya, from UEA's School of Pharmacy, said: "Opioids, like morphine, tramadol and fentanyl, can be effective for the short-term management of severe pain. However, they are highly addictive which makes stopping difficult yet long-term use can impair quality of life and overuse can be deadly."

"GPs and other health professionals need to urgently, proactively work with patients prescribed long-term opioids for non-cancer pain to gradually reduce or 'taper' their doses.

"But if GPs are expected to initiate discussions about tapering or stopping opioids, they must be equipped with training to manage the psychological challenges experienced by patients when trying to reduce their opioid use."

"Without this training, prescribers are reticent to open 'a can of worms' that they know they don't have the skills to manage."

"For opioid tapering interventions to be effective, GPs need training in giving their patients the skills to manage any withdrawal effects."

Dr Bhattacharya said: "There needs to be a clear expectation that opioid de-prescribing is the responsibility of the prescriber.

"Incentives may help GPs and other health professionals to prioritise reducing the amount of opioids being prescribed to patients, particularly among those who have been taking them long-term.

"Prescribers need to better understand the consequences of excess opioid use, and they need better guidelines about how to gradually reduce or 'taper' doses."

RIVERSIDE, Calif. -- A team of psychologists has found strong associations between working memory -- a fundamental building block of a functioning mind -- and three health-related factors: sleep, age, and depressed mood. The team also reports that each of these factors is associated with different aspects of working memory.

Working memory is the part of short-term memory that temporarily stores and manages information required for cognitive tasks such as learning, reasoning, and comprehension. Working memory is critically involved in many higher cognitive functions, including intelligence, creative problem-solving, language, and action-planning. It plays a major role in how we process, use, and remember information.

The researchers, led by Weiwei Zhang, an assistant professor of psychology at the University of California, Riverside, found that age is negatively related to the "qualitative" aspect of working memory--that is, how strong or how accurate the memory is. In other words, the older the person, the weaker and less precise the person's memory.  In contrast, poor sleep quality and depressed mood are linked to a reduced likelihood of remembering a previously experienced event -- the "quantitative" aspect of working memory.

"Other researchers have already linked each of these factors separately to overall working memory function, but our work looked at how these factors are associated with memory quality and quantity - the first time this has been done," Zhang said. "All three factors are interrelated. For example, seniors are more likely to experience negative mood than younger adults. Poor sleep quality is also often associated with depressed mood. The piecemeal approach used in previous investigations on these relationships -- examining the relationship between one of these health-related factors and working memory -- could open up the possibility that an observed effect may be influenced by other factors."

The researchers are the first to statistically isolate the effects of the three factors on working memory quantity and quality. Although all three factors contribute to a common complaint about foggy memory, they seem to behave in different ways and may result from potentially independent mechanisms in the brain. These findings could lead to future interventions and treatments to counteract the negative impacts of these factors on working memory.

Research results appear in the Journal of the International Neuropsychological Society.

The researchers performed two studies. In the first study, they sampled 110 college students for self-reported measures of sleep quality and depressed mood and their independent relationship to experimental measures of working memory. In the second study, the researchers sampled 31 members of a community ranging in age from 21 to 77 years. In this study, the researchers investigated age and its relationship to working memory.

"We are more confident now about how each one of these factors impacts working memory," Zhang said. "This could give us a better understanding of the underlying mechanism in age-related dementia. For the mind to work at its best, it is important that senior citizens ensure they have good sleep quality and be in a good mood."

Wildfires can have dramatic impacts on Western landscapes and communities, but human values determine whether the changes caused by fire are desired or dreaded. This is the simple - but often overlooked - message from a collaborative team of 23 researchers led by University of Montana faculty in a study published in the May issue of the journal BioScience.

The interdisciplinary team developed a framework that helps integrate scientific understanding of fire and its effects on ecosystems and human communities with an understanding of the human values that ultimately determine what people care about in and want from landscapes.

The paper, "Integrating Subjective and Objective Dimensions of Resilience in Fire-Prone Landscapes," was selected as "Editor's Choice" for the issue and is available online at https://doi.org/10.1093/biosci/biz030.

Part of the unique story behind this research is how it was undertaken: It was born from an interdisciplinary effort from a group of leading ecologists and social scientists from across the U.S. As part of a grant from the Joint Fire Science Program, this group gathered at UM to help tackle the question: "What does it mean for ecosystems and communities to be resilient to wildfires?"

Workshop participants and coauthors at UM in May 2017. Workshop participants and coauthors at UM in May 2017. The discussions that ensued were lively, challenging and invigorating. The paper published this week is a key outcome from that effort. "One of the most satisfying parts of this work is that it represents a genuine team effort, integrating perspectives from varying disciplines and backgrounds. This is the type of interdisciplinary perspective needed to help us figure out how to better live in an increasingly fire-prone West," said Philip Higuera, lead author of the study and UM associate professor of fire ecology in the Department of Ecosystem and Conservation Sciences.

"Communities and fire managers across the West are told they need to be more 'resilient' to wildfire, but it's actually pretty unclear what that means and what that resilience would look like on the ground," said Alex Metcalf, UM assistant professor of human dimensions and paper coauthor. "We developed this framework to help people work through this process to ultimately 'live well with wildfire.'"

"While fire ecology helps society understand the role of fire in ecosystems and the important impacts fires have on forests, decisions on how people live in an increasingly fire-prone West are complex and tug on deeply-held human values. Conversations about fire management - and land management in general - have to start by identifying what aspects of a landscape or community humans value and thus want to protect or promote," said Higuera.

So what does resilience to wildfire look like? The answer, the paper emphasizes, needs to come from community members, policy makers and land managers working together, calling upon the best scientific understanding of how fire operates and how it affects the things we value. This past April, the research team held a workshop at UM with 21 land managers and community leaders, as a next step in the larger research project. The group worked through the process of identifying what resilience means to them and how they can promote social-ecological resilience in their own communities.

Researchers at Aalto University have discovered a surprising phenomenon that changes how we think about how sound can move particles. Their experiment is based on a famous experiment recognisable from high school science classrooms worldwide - the Chlandni Plate experiment, where particles move on a vibrating surface. The experiment was first performed in from 1787 by Ernst Chladni, who is now known as the father of acoustics. Chladni's experiment showed that when a plate is vibrating at a frequency, heavy particles move towards the regions with less vibration, called nodal lines. This experiment has been extensively repeated during the centuries since, and shaped the common understanding of how heavy particles move on a vibrating plate. But researchers at Aalto University have now shown a case where heavy particles move towards the regions with more vibrations, or antinodes. "This is a surprising result, almost a contradiction to common beliefs," says Professor Quan Zhou.

The researchers installed a silicon plate on a piezoelectric transducer and submerged it into water. They spread sub-mm glass spheres on the plate, and vibrated the plate with signals of different frequencies, creating waves on the plate. The researchers were then surprised to observe that the particles move towards the antinodes, forming what they have dubbed "inverse Chladni patterns".

An interesting aspect is that the system can create predictable motion at a wide range of frequencies. "We can move particles at almost any frequency, and we do not rely on the resonance of the plate", says Zhou. "This gives us a lot of freedom in motion control".

Using the newly discovered phenomenon, the researchers were able to precisely control the motion of single particles and a swarm of particles on the submerged plate. In one example, they moved a particle in a maze on the plate, wrote words consisting of separate letters, and merged, transported and separated a swarm of particles by playing different musical notes.

"Many procedures in pharmaceutical research and microsystem assembly require the ability to move and manipulate small particles easily. Using just a single actuator to do all these different things, we are opening a path to new particle handling techniques", says Zhou. "Additionally, the method can inspire the future factory-on-a-chip systems."

As states crack down on doctor and pharmacy "shopping" by people who misuse opioids, a new study reveals how often those individuals may still be able to find opioids to misuse in their family medicine cabinets.

For every 200 patients prescribed opioids in 2016, one had a family member whose opioid-misuse problem led them to seek the drugs from multiple prescribers and fill prescriptions at multiple pharmacies to avoid detection. If these family members have access to the patient's opioids, this could increase their risk of misuse and possibly overdose.

The University of Michigan team that published the findings in JAMA Network Open notes the new research highlights the need to decrease the amount of opioid medication available for this kind of diversion, by avoiding unnecessary opioid prescribing in the first place.

The findings also highlight the importance of helping patients understand safe storage and disposal practices for their opioid medications to prevent misuse by family members.

"Our study demonstrates yet another reason why clinicians should not overprescribe opioids," says Kao-Ping Chua, M.D., Ph.D., the U-M pediatrician and healthcare researcher who led the study.

Small percentages, but large implications

The study is the first to look at doctor and pharmacy shopping within families. The team focused on opioid prescription-filling patterns by 554,000 privately insured people and relatives covered under the same family insurance plan.

They used a conservative definition of "shopping" behavior, counting only people who had received opioid prescriptions from four or more prescribers, and filled them at four or more pharmacies, in the past year.

Of the 1.4 million opioid prescriptions for the 554,000 patients in 2016, 0.6 percent, or 1 out of 167, were filled when a family member met criteria for doctor and pharmacy shopping. And the researchers argue that this likely underestimates the size of the problem due in part to their conservative definition.

Because so many Americans receive opioid prescriptions each year, even a modest percentage like 0.6 percent implies that 1.2 million of the 210 million opioid prescriptions in 2016 may have been dispensed to people who have family members with doctor and pharmacy shopping behavior.

For opioid prescriptions to children, 0.2 percent were filled when the child met doctor and pharmacy shopping criteria.

However, according to Chua, "This apparent doctor and pharmacy shopping behavior in children is likely driven by an adult family member, since children can't obtain opioid prescriptions from multiple prescribers and fill them at multiple pharmacies on their own."

In contrast, 0.7 percent of opioid prescriptions to children went to those who had a family member that met doctor and pharmacy shopping criteria. Most of those family members were in their early 40s, and although Chua and his colleagues can't be sure from the data source, they believe these are mostly the children's parents.

When the researchers changed their definition of "doctor and pharmacy shopping" to receiving opioid prescriptions from three or more prescribers and filling them at three or more pharmacies in the past year, 1.9 percent of opioid prescriptions were filled by patients who had family members meeting shopping criteria.

Chua also notes that the study does not track opioid prescriptions that were paid for out-of-pocket, rather than using insurance.

Message for clinicians

Chua notes that 39 states now specify situations in which physicians, physician assistants and nurse practitioners must check their state prescribing databases before prescribing opioids and other controlled substances. Many states also have requirements for pharmacists to check before dispensing an opioid.

These systems, called prescription drug monitoring programs, allow providers to see if the patient has already received opioid prescriptions from multiple prescribers and filled them at multiple pharmacies.

Chua and his colleagues note that it's not likely that privacy laws such as HIPAA will change to allow providers to check these databases to look for "shopping" behavior among their patients' relatives, even for children. Also, it may be difficult for clinicians to predict which patients have family members engaged in doctor and pharmacy shopping.

Chua argues that to prevent opioids from being misused by family members engaged in doctor and pharmacy shopping, the most effective step clinicians can take is to avoid opioids when over-the-counter alternatives are equally effective at controlling pain, and to avoid prescribing more doses of opioids than patients need.

Chua notes that counseling on safe storage and disposal should always be done when prescribing opioids and may also help prevent opioid misuse within families. However, he believes this counseling may be less effective at preventing misuse of opioids for children.

"With children, the person receiving counseling on opioid storage and disposal is usually an adult family member like a parent. The problem is that this adult family member could be the person with doctor and pharmacy shopping behavior," Chua said.