Culture

Scientists discovered a set of enzymes to create glowing organisms

image: Artificially glowing yeast cells in a test tube.

Image: 
Sergei Shakhov

In daylight, Neonothopanus nambi is a rather unremarkable brown fungus. But a surprise hides behind the drab façade: at night, the fungus glows ghostly green. Neonothopanus nambi is one of over 100 species of mushrooms that emit light. Aristotle already documented this phenomenon, called bioluminescence, when he described glowing, rotting treebark. Now, scientists have for the first time identified the biochemical pathway that allows bioluminescent fungi to light up. But they went even further: by putting the three genes necessary to generate luminescence into a non-glowing yeast, they created an artificially luminescent eukaryote. Fyodor Kondrashov, professor at the Institute of Science and Technology Austria (IST Austria) was co-author of the study published today in PNAS, which was led by Ilia Yampolsky at the Institute of Bioorganic Chemistry of the Russian Academy of Sciences in Moscow.

Flitting fireflies and glowing mushrooms on the forest floor are among the few things to be seen in a dark night deep in the Brazilian forest. Both behave like living night-lights thanks to the process of bioluminescence, a natural phenomenon by which a substance called luciferin is oxidized with the help of the enzyme luciferase to emit a light. Bioluminescence is found in many species, from glowing worms to deep-sea fish. So far, however, the biochemical pathway that makes luciferin was not understood in any organism except bacteria. This lack of knowledge hampered attempts to make higher organisms, like animals and plants, glow. Now, an international collaboration between twelve different institutions and led by Ilia Yampolsky, with the participation of Fyodor Kondrashov, Louisa Gonzalez Somermeyer and his previous group member Karen Sarkisyan, identified how the eukaryote Neonothopanus nambi glows.

The scientists found the key genes responsible for the bioluminescence of Neonothopanus nambi. Using library screening and genome analysis, the team identified the enzymes that contribute to the synthesis of luciferin. They showed that fungal luciferin, the substrate for the bioluminescence reaction, is only two enzymatic steps away from a well-known metabolite, called caffeic acid, which the fungus generates. Comparing mushrooms that glow with those that don't, Kondrashov's team also uncovered how gene duplication allowed bioluminescence to evolve more than a hundred millions of years ago. Why it evolved is, as yet, unclear, says Kondrashov: "Is bioluminescence beneficial or just a side product? We don't know yet. There are evidences that the glow attracts insects which distribute the spores. But I don't think that's convincing."

Knowing how bioluminescent fungi glow, the researchers then lit up non-bioluminescent eukaryotes. Inserting the gene encoding luciferase in Neonothopanus nambi along with three other genes whose products form the chain that converts the metabolite caffeic acid into the substrate for the reaction, luciferin, into the yeast Pichia pastoris resulted in glowing colonies of yeasts. "We don't supply a chemical that makes the yeast glow. Instead, we supply the enzymes it needs to convert a metabolic product that is already present in the yeast into light", explains Kondrashov.

This discovery could find widespread applications, from tissues that report changes in their physiology by lighting up to creating glowing animals and plants. "If we think of sci-fi scenarios in which glowing plants replace street lights - this is it. This is the breakthrough that can lead to this", Kondrashov concludes, "However, it may take several years until such a plant street light is engineered."

Credit: 
Institute of Science and Technology Austria

Extract from soursop leaves can prevent the symptoms of fibromyalgia

image: Soursop leaves.

Image: 
University of Seville

Researchers from the Department of Pharmacology at the University of Seville have recently published a study in which they state that diets supplemented with aqueous extract of Annona muricata L. leaves can prevent the symptoms associated with fibromyalgia, so improving the lives of these patients.

Leaves of the species Annona muricata L. come from a tree of between 4 and 6 metres in height, from the botanical family Annonaceae. They are simple leaves, oblong and egg-like or oblong and elliptical in shape and between 5 and 15 cm in length. This species is native to the tropical areas of the Americas and is especially abundant in the Amazon region. It is usually cultivated for its medicinal use. The leaves have different ethnomedical uses according to their country of origin. The most important uses in traditional medicine, scientifically validated in pre-clinical tests, are for inflammation, pain, infections, diabetes and cancer.

"The consumption of extract of Annona muricata L. leaves in pharmaceutical form and in the correct dosage can reduce the chronic pain, anxiety and depression that accompany this disease. This extract comes from the traditional preparation using decoction", informs the expert Ana María Quilez from the Medicinal Plants research group at the University of Seville.

This study was carried out over one month using 60 five-week old female rats in the laboratories of the Faculty of Pharmacy. The animals were divided into six groups that were fed a standard diet supplement with different quantities of this plant.

After the results obtained by the researchers, the next step will be to carry out clinical tests with patients, to corroborate the extract's activity and establish the safe and effective dose in humans.

This study was made available online in June 2018 ahead of final publication in print in October 2018.

Credit: 
University of Seville

How changing labs revealed a chemical reaction key to cataract formation

image: When damaged by oxidative stress or UV light, an eye lens protein called gamma-crystallin, can begin to aggregate, forming the cloudy clumps that we call cataracts. Researchers have recently uncovered a chemical function for gamma-crystalline that helps reduce clumping unless the protein is already damaged. Their work may lead to new treatments that can delay cataract surgery.

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Қазақша: Кәрілік катаракта

Researchers working to understand the biochemistry of cataract formation have made a surprising finding: A protein that was long believed to be inert actually has an important chemical function that protects the lens of the eye from cataract formation.

The lens is made up of cells packed with structural proteins called crystallins. Crystallins within each lens cell form a protein-dense gel, and the gel's optical properties -- like its transparency and the way it refracts light -- help focus light onto the retina.

But when crystallin proteins clump together, they are no longer so transparent. If enough of the proteins go from their usual water-soluble, densely packed organization to clumpy aggregates, they begin to scatter incoming light, forming cloudy deposits known as cataracts.

According to Harvard postdoctoral fellow Eugene Serebryany, lead author on a recent study in the Journal of Biological Chemistry, for a long time researchers believed that crystallin proteins were chemically inert. That is, except for aggregating as an individual ages, the proteins were not believed to interact much with fellow proteins. Serebryany said, "This was the model: (crystallin's) real function is to remain monomeric and transparent and avoid aggregating for as long as possible."

Back when he was a graduate student at MIT, Serebryany used a mutant form of the lens protein gamma-crystallin to mimic UV damage to the protein. While studying how that mutation leads crystallin to aggregate into clumps, Serebryany found something surprising: The mutant was more likely to aggregate if wild-type, or undamaged, protein was also present.

Harvard professor Eugene Shakhnovich, who collaborated with Serebryany and his graduate adviser, Jonathan King, on the earlier studies, described the finding as "a fairly striking phenomenon" and explained: "If you had these damaged proteins in a test tube, they would not aggregate for a while. If you had the wild-type protein, it would not aggregate forever. But then, when you mix the two, you see rapid and precipitous aggregation."

In other words, the healthy version of a protein everyone had thought was inert was somehow causing a slightly damaged version to get much worse -- and fast.

When Serebryany graduated, Shakhnovich hired him to continue working to understand how a supposedly inactive protein could cause this effect. Serebryany said, "The first thing I had to do was basically try to get the experiments from my Ph.D. lab to work in this (new) lab."

"They're just two stops apart on the subway!" Shakhnovich joked.

But, for some reason, Serebryany had trouble replicating the results. "It's a different place, it's a different set of instruments, a slightly different set of procedures. You see where this is going," he said. "All of a sudden, experiments that were highly reproducible before were giving a lot of variability."

Indeed, in the Harvard lab sometimes the wild-type crystallin caused mutant crystallin to aggregate, and sometimes it didn't. The scientists were mystified.

Serebryany said, "Obviously, if there is suddenly variability, there is a hidden variable that we didn't see before." He set up a series of experiments trying to pinpoint that variable.

A close comparison of the molecular weights of the wild-type protein that caused the mutant to clump and the protein that didn't revealed a difference equivalent to the weight of two hydrogen atoms. This gave the researchers a hint that the redox state - whether two sulfur atoms within a protein molecule were bound to one another instead of to hydrogen atoms -- might make a difference.

"By carrying out isotopically resolved mass spectrometry experiments, we got more than we bargained for," Serebryany explained. "Not only did the aggregation-prone mutant acquire one internal disulfide bond per molecule during the aggregation reaction, but the aggregation-promoting wild-type protein lost its disulfide at the same time."

By mutating the sulfur-containing cysteine amino acid residues one by one to non-sulfur-containing residues, Serebryany found that two cysteine amino acids close together on the surface of gamma-d-crystallin acted as a kind of switch. When the two bound, making a structure called a disulfide bond, crystallin seemed to be able to push damaged fellow molecules toward aggregation. When the two cysteines were not bound, each instead took on a hydrogen atom, explaining the protein's tiny change in mass. Under that condition, wild-type crystallin was inert.

But how could one bond between amino acids on the surface of this protein make it drive other proteins to aggregate?

Using biophysical and biochemical techniques, the team found that although the disulfide bond forms easily, it also introduces strain into the protein's structure. This made each protein molecule likely to pass along the disulfide bond to a nearby molecule of the protein, receiving two protons in return. In this way the disulfide bond could be constantly passed around among crystallin protein molecules. The authors compared the process to passing a hot potato.

Given a whole population of healthy, undamaged crystallin proteins, this process could go on indefinitely. But if one protein was already a little damaged, the authors showed, it caught the hot potato with a different set of cysteines, which were less able to pass it on. This drove the damaged protein to clump up. The authors' previous work revealed that mutations mimicking damage caused by UV changed the stability of the protein, making it more floppy, and therefore more likely to acquire the conformation that exposes new cysteines that could catch the hot potato.

This helps us understand cataract formation. According to Shakhnovich, the team is working on peptide treatments that might keep the "hot potato" from reaching damaged proteins. Serebryany hopes such peptides "could actually soak up some of those disulfides and delay the time that it takes to form the more aggregation-prone species." That could lead to slower cataract formation for patients.

Credit: 
American Society for Biochemistry and Molecular Biology

Exposure to e-cigarette adverts linked to teenagers using e-cigarettes and smoking

The more often adolescents say they have seen adverts for e-cigarettes, the more often they use both e-cigarettes and smoke tobacco cigarettes, according to a study published in ERJ Open Research [1].

The study took place in Germany, where regulations around tobacco and e-cigarettes advertising are more permissive than in other parts of Europe. Elsewhere there are firm bans on advertising tobacco but certain types of adverts and promotions for e-cigarettes are permitted.

Researchers say their work provides evidence that children and teenagers should be protected from the potential harms of smoking and using e-cigarettes by a comprehensive ban on adverts and promotions.

Dr Julia Hansen, a Senior Researcher at the Institute for Therapy and Health Research (IFT-Nord), Kiel, Germany was a co-researcher on the study. She said: "The World Health Organization recommends a comprehensive ban on tobacco advertising, promotion and sponsorship in its Framework Convention on Tobacco Control. Despite this, in Germany, tobacco and e-cigarettes can still be advertised in shops, on billboards and in cinemas after 6pm. Elsewhere, although tobacco advertising may be banned, the regulations on advertising e-cigarettes are more variable. We wanted to investigate the impact that advertising might be having on young people."

The researchers asked 6,902 pupils from schools in six German states to fill in anonymous questionnaires. They were aged between 10 and 18 years, with an average age of 13. They were asked about their lifestyle, including diet, exercise, smoking and use of e-cigarettes. They were also asked about their socioeconomic status and school performance.

The pupils were presented with pictures of real e-cigarette adverts with brand names removed and asked how often they had seen each one.

Overall 39% of the pupils said they had seen the adverts. Those who said they had seen the adverts were 2.3 times more likely to say that they use e-cigarettes and 40% more likely to say that they smoke tobacco cigarettes. The results also suggest a correlation between seeing more adverts and using e-cigarettes and smoking tobacco cigarettes more often. Other factors such as age, sensation-seeking tendency, the type of school the teenagers attended and having a friend who smokes were also all linked to the likelihood of using e-cigarettes and smoking.

Dr Hansen said: "In this large study of adolescents we clearly see a pattern: those who say they have seen e-cigarette adverts are more likely to say they have used e-cigarettes and conventional cigarettes.

"This type of research cannot prove cause and effect, but it does suggest that e-cigarette advertising is reaching these vulnerable young people. At the same time, we know that the makers of e-cigarettes are offering kid-friendly flavours such as gummi bear, bubblegum and cherry.

"There is evidence that e-cigarettes are not harmless, and this study adds to existing evidence that seeing e-cigarette advertising and using e-cigarettes might also be leading adolescents on to smoking. There are concerns that e-cigarette use might act as a 'gateway' to cigarette smoking and may contribute to the development of a new generation of cigarette smokers. So youth should be protected from any kind of marketing actions."

Dr Hansen hopes to continue to study this large group of school pupils to see if there are any changes over time. She says this may help clarify the cause and effect between exposure to adverts, using e-cigarettes and smoking.

Professor Charlotta Pisinger is Chair of the European Respiratory Society's Tobacco Control Committee and was not involved in the research. She said: "Producers of e-cigarettes may argue that advertising is a legitimate way to inform adult users about their products. However, this study suggests that children and young people may be suffering 'collateral damage' as a result of lax regulation of e-cigarette advertising. Policy makers need to realise that advertising is reaching adolescents and that this may not only be promoting the use of e-cigarettes, but also the likelihood of smoking and the health problems that brings."

Credit: 
European Respiratory Society

Parental alienation: An understudied form of child abuse

image: This is Jennifer Harman, associate professor of psychology at Colorado State University.

Image: 
John Eisele/Colorado State University

The scene: a bitter divorce, and a custody battle over the couple's 7-year-old son. Awarded full custody, the mother - perhaps seeking revenge? - sets out to destroy the son's relationship with his father. The mother tells the son lies about the father's behavior, plants seeds of doubt about his fitness as a parent, and sabotages the father's efforts to see his son. The son begins to believe the lies; as he grows up, his relationship with his father becomes strained.

According to Colorado State University social psychologist Jennifer Harman, about 22 million American parents, like that fictional father, have been the victims of behaviors that lead to something called parental alienation. Having researched the phenomenon for several years, Harman is urging psychological, legal and child custodial disciplines to recognize parental alienation as a form of both child abuse and intimate partner violence.

An associate professor in CSU's Department of Psychology, Harman has authored a review article in Psychological Bulletin defining the behaviors associated with parental alienation and advocating for more research into its prevalence and outcomes. She and her co-authors explain how these behaviors are the source of long-term negative consequences for the psychological health and well-being of children and adults all over the world.

"We have to stop denying this exists," said Harman, who previously co-authored a book about parental alienation with Zeynep Biringen, a professor in the Department of Human Development and Family Studies. "You have to treat an alienated parent like an abused person. You have to treat the child like an abused child. You take the child out of that abusive environment. You get treatment for the abusive parent, and you put the child in a safe environment - the healthier parent."

In their new paper, Harman and co-authors Edward Kruk of University of British Columbia and Denise Hines of Clark University categorize parental alienation as an outcome of aggressive behaviors directed toward another individual, with the intent to cause harm. They draw direct lines between widely recognized patterns of abuse, like emotional or psychological aggression, and the behavior of alienating parents.

For example, psychological aggression is a common form of child maltreatment that involves "attacking a child's emotional and social well-being." In a similar manner, alienating parents terrorize their children by targeting the other parent, purposely creating fear that the other parent might be dangerous or unstable - when no evidence of such danger exists. Alienating parents will further reject, shame or guilt-trip their children for showing loyalty or warmth to the other parent.

The authors also argue that such alienating behaviors are abusive to the targeted parent, and they liken these behaviors to more familiar forms of intimate partner violence between spouses or dating partners.

Harman is an expert in power dynamics in human relationships. Her research has found that parental alienation is similar to what's known as "intimate terrorism." Intimate terrorism is chiefly characterized by a lopsided power dynamic, in which one partner subjugates the other through intimidation, coercion, or threats of (or actual) physical violence. Such a scenario is distinct from situational couple violence, in which both partners have relatively equal power in the relationship but cannot get along and resort to physical or emotional violence.

Analogously, children are used as weapons in the form of intimate terrorism known as parental alienation, Harman argues. The power imbalance in such intimate terrorism can be seen in custody disputes, in which one parent is awarded full custody of a child. This parent wields that court-ordained power to subjugate the other parent by withholding contact or actively seeking to destroy the other parent's relationship with the child.

The family court systems see these situations every day, Harman says, but judges, lawyers and social workers aren't attuned to the prevalence of parental alienation as child abuse or intimate partner abuse. Instead, such situations are regarded as simple custody disputes, or the inability of the parents to get along.

Harman says she's hopeful her reframing of parental alienation will spur other social scientists to continue studying the problem. More research into this particular form of family violence will bring greater awareness, and may marshal resources to better identify and stop such behaviors.

Credit: 
Colorado State University

Is your office messy? If so, you may be seen as uncaring, neurotic

ANN ARBOR--An extremely messy personal space seems to lead people to believe the owner of that space is more neurotic and less agreeable, say University of Michigan researchers.

Psychologists from U-M's Flint and Ann Arbor campuses explored the degree of messiness in one's workspace and how it affects perceptions of the owner's personality.

In three experiments, about 160 participants were randomly assigned to sit in a researcher's office that was clean and uncluttered, or in another office that was either "somewhat" or "very" messy.

All offices were identically decorated to suggest that it belonged to a male researcher. They included various personal items, such as a baseball cap hanging on a door hook, a cup containing candy, a baby photo, and science books and academic journals in a bookcase.

In the neat office (office A), papers were neatly stacked on the desk, books and journals were upright on the bookshelves, file drawers had typewritten labels, and all garbage was in the wastebasket.

The "somewhat" messy office (office B in experiment 1) had books tilted over on the shelves, a textbook and papers lying on the floor, and a wall clock an hour off. The "very" messy office (office B in experiments 2 and 3) appeared even dirtier, more disorganized and had increased clutter.

Participants tried to guess the researcher's personality based on the office's appearance--rating the person's extraversion (social), agreeableness, conscientiousness, neuroticism and openness to experience. In each experiment, participants thought that the office B researcher (messy office) was less conscientious than the office A researcher (organized office).

"When there are cues related to less cleanliness, order, organization and more clutter in an owner's primary territory, perceivers' ascribe lower conscientiousness to the owner, whether that owner is a worker in the real world (office), a job-seeker (apartment), a student (bedroom) or a researcher at a university (lab office)," said lead author Terrence Horgan, professor of psychology at UM-Flint.

In everyday life, if people think that a person might be careless, cranky and uncaring because his/her office is very messy, then these impressions could subsequently impact how--or even whether--they decide to deal with him/her in the future, either on a personal or professional basis, the researchers say.

In experiments 2 and 3, participants also thought that the office B researcher was less agreeable and more neurotic than the office A researcher. The messier offices led to some participants thinking the owner possessed one or more negative personality traits.

The researchers said from the perspective of perceivers, high neuroticism, low conscientiousness and low agreeableness could signal potentially undesirable qualities in an employee. The bottom line: Perceivers' impressions of targets matter in terms of how they subsequently treat them.

"Once trait information about a target becomes activated in perceivers' minds, either consciously or unconsciously, that information can subsequently affect how they process information about, the types of questions they ask of, and how they behave toward the target, possibly bringing out the very trait information that they expected to see from the target in the first place," said study co-author Sarah Dyszlewski, a research technician in the Department of Psychology.

The findings appear in the journal Personality and Individual Differences.

Credit: 
University of Michigan

First ancient DNA from mainland Finland reveals origins of Siberian ancestry in region

image: This is an artistic impression of an ancient fisherman from Bolshoy Oleni Ostrov.

Image: 
Kerttu Majander

Researchers from the Max-Planck-Institute for the Science of Human History and the University of Helsinki have analyzed the first ancient DNA from mainland Finland. As described in Nature Communications, ancient DNA was extracted from bones and teeth from a 3,500 year-old burial on the Kola Peninsula, Russia, and a 1,500 year-old water burial in Finland. The results reveal the possible path along which ancient people from Siberia spread to Finland and Northwestern Russia.

Researchers found the earliest evidence of Siberian ancestry in Fennoscandia in a population inhabiting the Kola Peninsula, in Northwestern Russia, dating to around 4,000 years ago. This genetic ancestry then later spread to populations living in Finland. The study also found that people genetically similar to present-day Saami people inhabited areas in much more southern parts of Finland than the Saami today.

For the present study, genome-wide genetic data from 11 individuals were retrieved. Eight individuals came from the Kola Peninsula, six from a burial dated to 3,500 years ago, and two from an 18th to 19th century Saami cemetery. "We were surprised to find that the oldest samples studied here had the highest proportion of Siberian ancestry," says Stephan Schiffels, co-senior author of the study, of the Max Planck Institute for the Science of Human History.

The other three individuals analyzed for the study came from a water burial in Levänluhta, Finland. Levänluhta is one of the oldest known burials in Finland in which human bones have been preserved. The bodies were buried in what used to be a small lake or a pond, and this seems to have contributed to exceptionally good preservation of the remains.

Siberian ancestry persists today

The study compared the ancient individuals not only to each other, but also to modern populations, including Saami, Finnish and other Uralic language speakers. Among modern European populations, the Saami have the largest proportion of this ancient Siberian ancestry. Worldwide, the Nganasan people, from north Siberia, have the largest proportion of ancient Siberian ancestry.

"Our results show that there was a strong genetic connection between ancient Finnish and ancient Siberian populations," says Thiseas Lamnidis, co-first author of the study, "suggesting that ancient populations from Siberia may have also shared a subsistence strategy, languages and/or cultural behaviours with Bronze Age and Iron Age Finns, despite the large geographical distance." Ancient Finnish populations possibly lived a mobile, nomadic life, trading and moving over a large range, with far-reaching contacts to other populations.

People found in Levänluhta, Finland, most resemble modern-day Saami

The researchers found that the population in Levänluhta was more closely related to modern-day Saami people than to the non-Saami Finnish population today.

"People closely related to the Saami inhabited much more southern regions of Finland than the Saami do today," explains Kerttu Majander, co-first author, of the University of Helsinki and the Max Planck Institute for the Science of Human History. Interestingly, a recent linguistic study suggested that the place names around Levänluhta trace back to Saami languages.

"This is the first exploration of ancient DNA from Finland and the results are very interesting," states Schiffels. "However more ancient DNA studies from the area will be necessary to better understand whether the patterns we've seen are representative of Finland as a whole."

The study was conducted as a collaboration between the SUGRIGE-project (Universities of Helsinki and Turku), and the Max Planck Institute for the Science of Human History. The archaeological materials and expertise were provided by the Peter the Great Museum of Anthropology and Ethnography (Kunstkamera) and the Levänluhta-project with the Finnish Heritage Agency.

Credit: 
Max Planck Institute of Geoanthropology

Pulsed radiofrequency relieves acute back pain and sciatica

image: Illustration of muscles contracting in response to pain

Image: 
Radiological Society of North America

CHICAGO - A minimally invasive procedure in which pulses of energy from a probe are applied directly to nerve roots near the spine is safe and effective in people with acute lower back pain that has not responded to conservative treatment, according to a study being presented today at the annual meeting of the Radiological Society of North America (RSNA).

Lumbar disk herniation is a common, often debilitating, condition that affects the disks that act as cushions between the vertebrae of the lower spine. Herniation occurs where the jelly-like material in the center of the disk bulges through a tear in the disk's tough exterior layer and puts pressure on the roots of the nerves. Herniated disks are often the source of sciatica, or pain that radiates downward from the lower back into the leg.

Conservative treatment options for herniated disks range from over-the-counter pain medications to injections of corticosteroids directly into the affected area of the spine. Those who don't respond may require surgery. In some cases, the entire disk must be removed and the vertebra fused together for stability.

An alternative technique, CT-guided pulsed radiofrequency (pRF), applies energy through an electrode under CT guidance to the portion of the nerve responsible for sending pain signals.

"Pulsed radiofrequency creates a nerve modulation, significantly reducing inflammation and its associated symptoms," said study senior author Alessandro Napoli, M.D., Ph.D., professor of interventional radiology at Sapienza University of Rome in Italy.

Dr. Napoli and colleagues studied the approach in patients with back pain from lumbar disk herniation that had not responded to prolonged conservative treatment. In 128 patients, the pRF treatment was delivered directly under CT guidance to the root of the nerve. The treatment was applied for 10 minutes.

For comparison, a group of 120 patients received one to three sessions of CT-guided steroid injection on the same anatomical target with no pRF.

The one-year outcomes demonstrated that CT-guided pRF was superior to the injection-only strategy. Patients who received pRF saw greater overall improvement in pain and disability scores during the first year. Relief of leg pain was faster in patients assigned to pRF, and they also reported a faster rate of perceived recovery. The probability of perceived recovery after one year of follow-up was 95 percent in the pRF group, compared with 61 percent in the injection only group.

"Given our study results, we offer pulsed radiofrequency to patients with herniated disk and sciatic nerve compression whose symptoms do not benefit from conservative therapy," Dr. Napoli said.

The results of the study are superior to those typically reported for usual care strategies and injections and may help a substantial number of patients with sciatic disk compression to avoid surgery, Dr. Napoli added.

The use of pRF also could improve outcomes for patients set to receive corticosteroid injections.

"We learned that when pulsed radiofrequency is followed by steroid injection, the result is longer lasting and more efficacious than injection only," Dr. Napoli said. "The effect of pulsed radiofrequency is fast and without adverse events."

Today, therapy for spine disorders allows for definitive treatment of symptoms and conditions using different techniques and technologies.

"Of the different therapies available, pulsed radiofrequency is among the least invasive," Dr. Napoli said. "Treatment lasts 10 minutes, and one session was enough in a large number of treated patients."

Co-authors are Roberto Scipione, M.D., Fabrizio Andrani, M.D., Susan Dababou, Cristina Marrocchio, Michele Anzidei, M.D., and Carlo Catalano, M.D.

Credit: 
Radiological Society of North America

Touch can produce detailed, lasting memories

Exploring objects through touch can generate detailed, durable memories for those objects, even when we don't intend to memorize the object's details, according to findings published in Psychological Science, a journal of the Association for Psychological Science.

"An especially interesting finding was that participants were able to visually identify an object they had never seen but only touched one week before without the intention of memorization," says researcher Fabian Hutmacher of the University of Regensburg. "This is even more remarkable as the competing objects in the recognition test belonged to the same basic-level category - that is, the previously presented object was only identifiable based on subtle touch-based details but not on much more salient visual details."

"The study challenges existing cognitive and neural models of memory storage and retrieval, as these models seem to be unable to account for the large amount of stored information," Hutmacher adds.

Compared with visual information, relatively little is known about long-term memory for information sensed through other modalities. Hutmacher and coauthor Christof Kuhbandner decided to focus specifically on haptic, or touch-based, experiences.

In one experiment, participants wore a blindfold as they explored 168 everyday objects, such as a pen, for 10 seconds each. The researchers told the participants they would be tested on the objects later, so they should pay close attention to the texture, shape, and weight of each object. The participants, still blindfolded, completed a haptic memory test for half of the objects immediately after exploring them. They held each object they had explored and a similar novel object that was distinguishable only by subtle details - their task was to indicate which object they had explored before. They completed the same test with the other half of the objects 1 week later.

Participants showed almost perfect recall on the test that followed the exploration period, correctly identifying the object they had explored 94% of the time. Remarkably, participants still showed robust memory for the original objects 1 week later, with 84% accuracy.

But would they still remember objects so well if they weren't intentionally memorizing them? And could objects that were explored by touch be recognized via a different sensory modality?

In a second experiment, a new group of participants explored the same 168 objects without knowing they would be tested on them. Instead, the experimenters said that they were investigating aesthetic judgments, and they asked the participants to rate the pleasantness of each object based on texture, shape, and weight.

Participants returned 1 week later for a surprise memory test, completing a blindfolded touch-based recognition task for half of the objects. For the rest of the objects, they completed a visual recognition task, in which they saw the original object and a similar object placed on a table, and indicated which one they previously explored. After each trial, the participants also reported if they answered based on recalling details of their touch-based exploration, feeling a vague familiarity, or simply guessing.

Again, the results showed that participants remembered the objects with high accuracy. In the blindfolded test, participants answered correctly on 79% of the trials. In the cross-modal visual test, participants identified the correct object 73% of the time.

For both tests, participants were most accurate for objects they said they recalled details for, moderately accurate for objects that seemed vaguely familiar, and least accurate for those they guessed on. Notably, participants showed better-than-chance recognition even when they reported that they had guessed.

The fact that participants could recognize objects across sensory modalities is intriguing given that the familiar and novel objects only differed on subtle details that would have to be distinguished on the basis of haptic experiences.

"These results suggest that the human mind effortlessly and automatically stores detailed and durable representations of a vast amount of perceptual experiences, including haptic ones," says Hutmacher. "We want to explore the idea that storing such a vast amount of information may in fact be functional as it may guide our behavior and contribute to its fine-tuning without being accompanied by conscious experience."

Credit: 
Association for Psychological Science

Electrical stimulation in the nose induces sense of smell in human subjects

Boston, Mass - Physicians at Massachusetts Eye and Ear have, for the first time, induced a sense of smell in humans by using electrodes in the nose to stimulate nerves in the olfactory bulb, a structure in the brain where smell information from the nose is processed and sent to deeper regions of brain. Reporting online today in International Forum of Allergy & Rhinology, the research team describes their results, which provide a proof of concept for efforts to develop implant technology to return the sense of smell to those who have lost it.

"Our work shows that smell restoration technology is an idea worth studying further," said corresponding author Eric Holbrook, MD, Chief of Rhinology at Mass. Eye and Ear and associate professor of otolaryngology at Harvard Medical School. "The development of cochlear implants, for example, didn't really accelerate until someone placed an electrode in the cochlea of a patient and found that the patient heard a frequency of some type."

Smell loss, or anosmia, has an estimated prevalence of 5 percent of the general population. While some cases of anosmia may be treated by caring for an underlying cause (often nasal obstruction, in which odors can't reach the nerves of the olfactory system due to swelling, polyps or sinus disease), other cases involving damage to the sensory nerves of the nose (i.e. head injury, viruses and aging) are much more complex. There are currently no proven therapies for these cases.

Our sense of smell not only contributes to our enjoyment of life, but also to our daily safety and well being. We rely on our sense of smell to make us aware of smoke in detecting a fire, natural gas leaks and to avoid eating rotten food. In the elderly, of whom there are estimates that greater than 50 percent of the population over the age of 65 has experienced smell loss, it can be difficult to get proper nutrition, as the sensation of flavor is closely tied to the sense of smell, and as flavor diminishes, appetite decreases in this population.

A Cochlear Implant for the Nose

Motivated by work conducted by research colleagues at Virginia Commonwealth University's School of Medicine, Mass. Eye and Ear physicians wanted to address the question of whether electrical stimulation of the olfactory bulb could induce the sense of smell in human subjects.

The findings described in the International Forum of Allergy & Rhinology report demonstrate this feasibility. In the report, the researchers describe endoscopic procedures to position electrodes in the sinus cavities of five patients with an intact ability to smell. Three patients described sensations of smell (including reports of onions, antiseptic, sour and fruity aromas) as a result of the stimulation.

This breakthrough in human patients opens the door for a "cochlear implant for the nose" to be developed -- though the study authors caution that the concept of an olfactory stimulator is more challenging than existing technologies. The most successful neuroprosthesic device in the world, cochlear implants have been on the market for more than three decades to electrically stimulate the auditory nerve to restore hearing in people with profound hearing loss.

"There's currently so little that we can do for these patients, and we hope to eventually be able to reestablish smell in people who don't have a sense of smell," Dr. Holbrook said. "Now we know that electrical impulses to the olfactory bulb can provide a sense of smell -- and that's encouraging."

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Mass Eye and Ear

No clear evidence that diverting patients from emergency departments curbs overcrowding

Given the considerable costs of providing alternative sources of care, there is remarkably little good quality evidence to back this approach, conclude the researchers.

Redirecting low need patients from emergency care departments to alternative sources of care, has been proposed as a potential solution to tackling the overcrowding that often occurs in these facilities.

But it isn't clear whether this strategy actually works or is safe. The researchers therefore systematically reviewed and pooled the data from 15 relevant studies, evaluating the impact of redirecting patients to alternative sources of care before reaching, or once in, an emergency care department.

No strong evidence emerged to either back or refute the safety and effectiveness of this strategy, the data analysis showed.

What's more, the proportion of patients suitable for diversion was relatively low and a considerable proportion of those who were suitable didn't want to use alternative sources of care either.

Redirecting patients to alternative sources of care was twice as common among those who had already reached an emergency care department.

But compared with those who weren't redirected, doing this before the patient reached hospital didn't cut the proportion transferred to emergency care.

Nor did it stop them subsequently using emergency care services: their patterns of use didn't differ from those of patients who weren't redirected.

While only three studies looked at the costs involved, none found any difference in total healthcare spend between patients who were diverted away from emergency care departments and those who weren't.

The overall quality of the published evidence was not particularly good. This included varying definitions of low need; limited information on the outcomes of patients given standard care; the numbers of patients willing and able to accept alternative sources of care; or the costs involved.

"Despite the clear resource implications for implementing [emergency department] diversion strategies, including training and hiring additional staff, costs of implementing the diversion strategies were infrequently reported," they write.

All this makes it difficult to draw definitive conclusions, they caution, concluding: "At this time there is insufficient evidence to recommend the implementation of diversion protocols as effective and safe strategies to address emergency department overcrowding."

And in a linked podcast in discussion with the journal's editor, Professor Ellen Weber, lead author, Dr Brian Rowe, University of Alberta, isn't convinced 'the juice is worth the squeeze.'

"I am not sure the efforts involved in doing diversion are really worth all the costs, time, and surveillance," he says. And not all emergency department patients are the same, although the diversionary strategies to date tend to assume that they are, he says.

Surveys in Canada indicate that patients have often tried many other options before coming to an emergency department, or that they are there because the health system has failed them, he suggests.

What's more, he adds, patients like the 'one-stop shop' service provided by hospitals, and younger patients often don't register with a family doctor, leaving them with few other options.

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BMJ Group

Weight loss procedure shrinks both fat and muscle

image: Body composition segmentation at the L3 lumbar vertebral body level. Boundaries for subcutaneous fat (SF), visceral fat (VF) and skeletal muscle (SM) are delineated by the white lines.

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Radiological Society of North America

CHICAGO - Left gastric artery embolization, a novel interventional procedure used to treat obesity, leads to the loss of both fat and muscle, according to a new study presented today at the annual meeting of the Radiological Society of North America (RSNA). Researchers said the loss of muscle mass is concerning and underscores the importance of proper nutritional counseling after the procedure.

Obesity is a major health issue worldwide, linked with serious conditions like heart disease, cancer and diabetes. First-line treatments such as diet and exercise often don't work, leading many patients to opt for gastric bypass surgery. The surgery, which reduces the size of the stomach, has been effective in treating obesity, but carries with it significant costs and potential complications.

Currently under investigation in clinical trials, left gastric artery embolization is a less invasive option to surgery. In the procedure, microscopic beads are injected under imaging guidance into the artery that supplies blood to the stomach. The beads block blood flow to the stomach and reduce the production of ghrelin, a hormone that stimulates hunger. Early studies have shown that embolization is effective in helping people lose weight, but information is lacking on how it might change a patient's composition of muscle and fat.

"There has been lots of research focused on the efficacy of gastric artery embolization for weight loss," said the study's lead author, Edwin A. Takahashi, M.D., vascular and interventional radiology fellow at the Mayo Clinic in Rochester, Minn. "However, there has been no data on what is contributing to the weight loss, whether the patients are losing fat, as desired, or muscle mass, or some combination of the two."

To learn more, Dr. Takahashi and colleagues studied CT scans of 16 overweight or obese patients who had undergone left gastric artery embolization to treat gastrointestinal bleeding. CT scans, when used in conjunction with special software, allow for measurements of body composition based on the different densities of tissues like fat and muscle.

The scans were done before and approximately 1.5 months after the procedure. The results were compared to those of a control group of 16 outpatients who did not undergo left gastric artery embolization but had CT scans at two different time periods for nonspecific abdominal pain.

All 16 individuals experienced significant weight loss after the embolization procedure, losing an average of 6.4 percent of their body weight over 1.5 months. Body mass index, a measure of body weight relative to a person's height, dropped by 6.3 percent.

While the weight loss was not surprising to the researchers, the changes in body composition were. The skeletal muscle index, a measure of the amount of muscle that connects to the skeleton and helps move the limbs, fell by 6.8 percent. Skeletal muscle is important to health, and loss of it can impair physical function and metabolism and put a person at higher risk of injury.

"The significant decrease in the amount of skeletal muscle highlights the fact that patients who undergo this procedure are at risk for losing muscle mass and need to be managed accordingly after procedure," Dr. Takahashi said. "We must make sure they receive adequate nutrition to minimize the amount of muscle tissue they lose."

The patients also lost a significant amount of body fat. Their overall body fat index dropped by an average of 3.7 percent. However, much of the fat loss was subcutaneous, or the fat that lies directly under the skin. Visceral fat, the more dangerous fat surrounding the organs and associated with serious health problems like heart disease and diabetes, did not decrease significantly over the course of follow-up.

The researchers plan to expand their studies in the future to include people who are specifically undergoing embolization as a treatment for obesity.

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Radiological Society of North America

Urgent need to reduce meat and dairy consumption to meet climate targets, says expert

The livestock sector could use almost half of the 1.5 degree C greenhouse gas emission budget allowed by 2030, so addressing this should be a key part of the strategy to hit climate targets, according to a new study published in Climate Policy.

Dr Helen Harwatt, farmed animal law and policy fellow at Harvard Law School, advises that getting protein from plant sources instead of animal sources would drastically help in meeting climate targets and reduce the risk of overshooting temperature goals.

For the first time, Dr Harwatt proposes a three-step strategy to gradually replace animal proteins with plant-sourced proteins, as part of the commitment to mitigate climate change. These are:

1) Acknowledging that current numbers of livestock are at their peak and will need to decline ('peak livestock').

2) Set targets to transition away from livestock products starting with foods linked with the highest greenhouse gas emissions such as beef, then cow's milk and pig meat ('worst-first' approach).

3) Assessing suitable replacement products against a range of criteria including greenhouse gas emission targets, land usage, and public health benefits ('best available food' approach).

Harwatt further elaborates that recent evidence shows, in comparison with the current food system, switching from animals to plants proteins, could potentially feed an additional 350 million people in the US alone.

Previous studies suggested reducing meat and dairy consumption also provides a range of added benefits such as preserving biodiversity and improving human health.

The article reports that the current livestock population in the world is around 28 billion animals and constitutes the highest source of two major greenhouse gases - methane and nitrous oxide. The production of methane in particular is troublesome, as it has an 85 times greater global warming potential than carbon dioxide over a 20-year time frame. Methane emissions from the livestock sector are projected to rise by 60 percent by 2030 - the same time period over which strong and rapid reductions are needed.

"Given the livestock sector's significant contribution to global greenhouse gas emissions and methane dominance, animal to plant protein shifts make a much-needed contribution to meeting the Paris temperature goals and reducing warming in the short term, while providing a suite of co-benefits," Harwatt says.

She adds, "Failure to implement animal to plant protein shifts increases the risk of exceeding temperature goals and requires additional, and unrealistic, greenhouse gas reductions from other sectors. The current revision of national contributions to meeting the Paris Agreement from 2020 onwards should ideally integrate animal to plant-protein shifts. As a next step, the COP24 in December this year provides an excellent opportunity for policy makers to start this important conversation."

The article acknowledges establishments, such as businesses, can spearhead these efforts. As an example, Dr Harwatt is already putting her three-step animal to plant protein shift approach into practice in the food service sector in her role as Sustainable Food Policy Advisor to charity Humane Society International UK (HSI).

HSI run the Forward Food programme providing free plant-based culinary training for public and private sector chefs. Here, Dr Harwatt can, and other experts could too, assess food-related greenhouse gas emissions at the institutional level and apply the three-step strategy to identify opportunities for emissions reductions through peaking purchase of animal products, tackling the 'worst first' and replacing them with best available foods.

She comments, "The food sector is already making progress on these issues and demonstrating that it's commercially viable to incorporate animal to plant protein shifts. We need policy makers to enable the creation of Paris-compliant food systems on a much larger and faster scale - and animal to plant-protein shifts play a key role".

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Taylor & Francis Group

New service in south London reduces hospital readmissions for people with bipolar disorder

A new specialist programme at South London and Maudsley NHS Foundation Trust (SLaM) has been shown to significantly reduce the rate of hospital readmissions for people with bipolar disorder, in an early-stage audit funded by the NIHR Maudsley Biomedical Research Centre. The findings have been published in BJPsych Bulletin today.

Bipolar disorder is a condition in which an individual experiences recurrent episodes of mania, hypomania and depression. Bipolar disorder is fairly common: one in 50 adults will be diagnosed with the condition. An initial three-year audit of admissions at South London and Maudsley NHS Foundation Trust showed that there were approximately 500 hospital admissions of people with bipolar disorder each year. Two-thirds of these were re-admissions in that three year period, and approximately 150 people were admitted more than once a year. This audit strongly evidenced the need for a strong focus on effective preventative strategies in service users' recovery programmes.

The OPTIMA Mood Disorders Service was established in 2015 to address this need. The Core Programme is an intensive, specialist programme for people who have recently had frequent hospital admissions for manic or depressive episodes. At the time of the audit, 30 people had been through the OPTIMA programme. The average rates of hospital admission and home treatment for these 30 patients, over the three years prior to them beginning the programme, were calculated using their electronic health records. These were compared to the average rates of admission for the patients over their post-programme period (an average of 9.5 months).

The average rate of hospital readmission post-OPTIMA was substantially lower than the average rate over the three years pre-OPTIMA. The finding provides initial evidence that the treatments provided by the OPTIMA programme are successful in reducing hospital readmissions for frequently admitted patients.

The core programme is designed to consolidate recovery. It involves a range of treatments tailored to the individual, including frequent psychiatric review, expert pharmacotherapy (therapy using pharmaceutical drugs), specialist nursing interventions, occupational therapy and individual and group psychoeducation.

Psychoeducation helps people with bipolar disorder gain more control over their illness. It sensitively looks at the past course of illness to identify episode triggers and early warning signs of mania or depression. By recognising that an episode is just beginning and accessing help early, the development of full episodes can be prevented. Pragmatic planning on when and how to access help in a developing crisis is essential. The programme also offers occupational therapy, which helps service users find a balance between rest, work and leisure activity when building their functional recovery following a bipolar episode.

Senior author, Professor Allan Young, Director of the Centre for Affective Disorders, Institute of Psychiatry, Psychology & Neuroscience, King's College London, said: "It is extremely encouraging to see that our specialist OPTIMA programme is successfully helping people with bipolar disorder, resulting in fewer readmissions to hospital. However, this early-stage audit does have some limitations. It examines a relatively small number of patients and a relatively short period of time post-programme, a more extensive study is required to confirm these benefits."

First author, Dr Karine Macritchie, Lead Consultant Psychiatrist at OPTIMA said: "The period immediately following hospital admission for bipolar depression or mania is often a very vulnerable time for people struggling with this illness. Our early results show that this period offers a valuable opportunity to optimise on-going treatment and to prevent loss of recovery, episode recurrence and re-admission.

"People with bipolar disorder can be given appropriate treatment, frequent support and a greater sense of agency over their condition at the time when they need these things the most. OPTIMA shows the very positive results that can be achieved when a flexible, responsive service is offered in a timely and targeted way."

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King's College London

How to pay for national pharmacare in Canada - more taxes and hope America keeps giving you discounts

A new analysis in CMAJ (Canadian Medical Association Journal) http://www.cmaj.ca/lookup/doi/10.1503/cmaj.180897 outlines the potential government cost of a national Canadian pharmacare program and sets out approaches to shifting the funding for drugs in Canada to realize billions in savings.

"We believe there is a compelling argument for the federal government to raise the incremental revenues needed to implement this long-recommended expansion of Canadian medicare," write Drs. Michael Wolfson, Faculties of Medicine and Law, University of Ottawa, and Steven Morgan, School of Population and Public Health, University of British Columbia.

Implementing a national pharmacare program in 2020 would require $9.7 billion in public funding and result in $13.5 billion in savings to the private sector because of lower costs of private insurance, according to estimates from the Parliamentary Budget Officer.

The authors suggest using a mix of federal revenue sources, including relatively small increases in personal income taxes (0.5 percentage points), corporate tax rates (1 percentage point) and GST (0.25 percentage points).

For policy-makers, advanced modelling tools can help inform the different approaches to funding a national pharmacare program.

"Without national pharmacare by 2020, Canadians could be paying $4.2 billion more for medicines than they would need to under a universal, comprehensive public pharmacare plan," the authors write. "The question, therefore, isn't whether Canada can afford national pharmacare; rather, it is how government should raise the needed public revenues and, correspondingly, who should benefit from the billions of dollars in net savings as a result."

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Canadian Medical Association Journal