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Neuroinflammation seen in spinal cord, nerve roots of patients with chronic sciatica

A study by Massachusetts General Hospital (MGH) investigators has found, for the first time in humans, that patients with chronic sciatica - back pain that shoots down the leg - have evidence of inflammation in key areas of the nervous system. In their paper published in the May issue of the journal Pain, the research team reports finding that average levels of a marker of neuroinflammation were elevated in both the spinal cord and the nerve roots of patients with chronic sciatica. Additionally, the study showed an association between neuroinflammation and response to anti-inflammatory steroid injections, with levels of neuroinflammation differing between those whose pain was and those whose pain was not relieved by steroid injection treatment.

"Sciatica is an extremely common pain condition and is estimated to affect around 5 percent of men and 4 percent of women in their lifetimes," says Yi Zhang, MD, PhD, of the Center for Pain Management in the MGH Department of Anesthesia, Critical Care and Pain Management, a co-senior author of the report. "More than 5 million cases of sciatica are seen annually in the U.S., which represent a major cause of lost work days."

Several animal studies have documented activation of the immune system - including glial cells, which function as the immune cells of the nervous system - in chronic pain, raising the possibility that blocking neuroinflammation could be a viable treatment. Recent evidence from the laboratory of co-senior author Marco Loggia, PhD, of the MGH-based Martinos Center for Biomedical Imaging, found glial cell activation in the brains of patients with chronic pain, but no prior studies have demonstrated neuroinflammation beyond the brain in humans with chronic pain. Even though a contribution of inflammation to acute pain in sciatica provides the rationale for anti-inflammatory steroid injections, evidence linking neuroinflammation with chronic sciatic pain in humans has been limited.

The current study combined both MR and PET imaging to test the hypothesis that chronic radiculopathy, a condition combining sciatica with additional lower-back-pain symptoms, would be associated with inflammatory activation in both the neuroforamina - the spaces around the spine through which nerve roots pass into the spinal cord - and within the spinal cord itself. Study participants - including 16 patients with chronic radiculopathy and 10 control volunteers - had combined MR/PET imaging with a radiopharmaceutical that binds to TSPO, a marker for neuroinflammation. MR/PET imaging focused on neuroforamina in the lumbar spine for all participants, and in a subset of 18 - 9 patients and 9 controls - images were also taken of the sections of the lower spinal cord that are connected to the nerve roots affected in sciatica.

Overall the study results indicated that, compared with those of control participants, TSPO levels in sciatica patients were higher in both the neuroforamina and the spinal cord. The sciatica-associated elevations were seen in nerve roots on the side of affected legs and in spinal cord segments known to process sensory signals from the legs. Among 9 patient participants who received steroid injections as part of their clinical care - 2 before the scanning and 7 after - only 5 experienced significant relief from the procedure, and those 5 all had results indicating higher neuroforaminal TSPO levels.

"The fact that patients with stronger TSPO elevations in the nerve roots benefited most from a local anti-inflammatory treatment makes sense," says Loggia. "For patients who didn't benefit from steroid injections, the source of pain and inflammation may be the spinal cord or, as shown in our previous paper, the brain itself."

Zhang adds, "If larger studies confirm that the efficacy of steroid injections correlates with nerve root inflammation, physicians will have a way to identify which patients are most likely to benefit from the procedure. Our results also suggest that directly treating neuroinflammation in the spinal cord may help patients who don't respond to steroid injections. Finding a way to treat spinal neuroinflammation for those patients is a goal that we are actively pursuing."

Credit: 
Massachusetts General Hospital

Basing everyday decisions on risk of pain or loss linked to increased anxiety

Scientists have shone new light on how the human brain uses past experiences and generalizes them to future events, helping us safely navigate the world around us, a study in eLife reveals.

Our ability to 'generalize' is an important survival technique, but over-generalizing from bad events could explain why some people fear and then avoid scenarios that are not actually dangerous. This over-avoidance has been identified as a significant factor in anxiety, obsessive-compulsive disorder, chronic pain and depression.

"If eating a particular food in the past has made you ill, it is likely you will want to avoid eating similar-looking or smelling foods in the future," says lead author Agnes Norbury, Research Associate at the University of Cambridge, UK. "We wanted to look at how people decide whether or not to avoid particular situations, how this information is represented in the brain, and whether people who generalize more from negative events tend to be more anxious."

Norbury and her team took two groups of people - 26 did a test in the lab while having an MRI scan of their brain, and 482 did the test online. Both groups were presented with different flower-like shapes on a screen, some of which were 'safe' and some of which were 'dangerous'.

To avoid a dangerous shape, the participants could hit an 'escape' button. If they didn't do this, those in the lab group would receive an electric shock, and those doing the test online would lose some of their online cash stake. However, hitting the escape button also came at a cost - of receiving additional shocks at the end, or losing more money.

This test allowed the researchers to see when people were over-generalizing and hitting the escape button too much. They then used mathematical models to reconstruct how people decided to avoid the situation when faced with images similar to those they associated with pain or loss, and combined this with the brain scans and questionnaires about psychological symptoms.

They found that people were more likely to generalize from negative events, compared to safe or neutral outcomes. In addition, different parts of the decision-making process were linked to activity in different brain regions, including areas involved in vision, fear response and safety learning. They also found that those people who generalized more from the negative events (pain or loss) reported a greater experience of anxious feelings and intrusive thoughts (negative thoughts that enter your mind against your will and are hard to get rid of).

"We hope that these findings will contribute to a greater understanding of the thought processes that underlie anxiety in some people," said senior author Dr Ben Seymour, Clinical Research Associate at the University of Cambridge. "Our results show the benefits of analysing complex behavioral processes such as generalization into separate components that can be examined and linked back to brain activity and symptoms. By better understanding what causes these symptoms in different cases, we might be able to tailor treatments more effectively to people with anxiety in future."

Credit: 
eLife

Blocking the molecular source of idiopathic pulmonary fibrosis

ANN ARBOR, Mich. - Idiopathic pulmonary fibrosis (IPF) is one of the most challenging and frustrating diseases that pulmonologists face.

And despite affecting 1 out of 200 adults over the age of 65 in the United States, general awareness of IPF is low.

"There's a tremendous disconnect between the human impact of this disease and its recognition by the public. Few people have ever heard of it," says Marc Peters-Golden, M.D., a professor of internal medicine in the Division of Pulmonary and Critical Care Medicine at Michigan Medicine. "By the time most patients with IPF finally see a pulmonologist, their disease is already fairly advanced."

Fibrosis, or scarring, can occur in every organ of the body. But the lungs are delicate and must inflate with every breath. If scarred, they become stiff and make breathing extremely difficult, Peters-Golden says.

The disease, which for many has a life expectancy of three to five years, often leads to respiratory failure.

Even worse, the cause of scarring in IPF remains a mystery.

It's why Peters-Golden, research investigator L. Raghu Penke, Ph.D., and team sought to find out whether blocking a problematic gene known as FOXM1 could stop or slow the development of fibroblasts -- highly activated cells that contribute to scar tissue production in fibrotic lung disease.

Published in the Journal of Clinical Investigation, the Michigan Medicine study breaks new ground: "The role of FOXM1 within lung fibroblasts in pulmonary fibrosis had never before been investigated," Peters-Golden says. "We proved that, in principle, if we block FOXM1, we can reduce the activation of fibroblasts as well as the process of fibrosis itself."

In normal lung tissue, few fibroblasts are present. However, in IPF patients, those fibroblasts proliferate and expand, similar to the way cancer cells do in a tumor.

This analogy led Peters-Golden and his team to look for potential clues in the arena of cancer research to explain these rogue fibroblasts. Prior research has shown that FOXM1 promotes cancer cell growth; drugs to block it have been under development.

Mice subjects show promise

The study, which examined lung fibroblasts from patients with IPF and mice (the rodents' lung fibrosis was triggered by a toxic drug), found that both groups had increased levels of FOXM1.

"After we engineered the mice to eliminate the FOXM1 gene from the fibrotic fibroblasts, we administered the toxic drug that causes fibrosis," Peters-Golden says.

The result: "The mice were substantially protected," he says. "This showed us that FOXM1 in fibroblasts was important for the process of fibrosis."

Next, the team used a drug treatment approach. They took unaffected mice and gave them siomycin, an experimental compound designed to block FOXM1, and they saw that the drug prevented fibrosis in vivo.

"When we blocked FOXM1 with either the drug or the genetic approach, we reduced the accumulation of fibroblasts and decreased production of scar proteins, indicating to us that the excessive FOXM1 seemed to contribute to the bad behavior of the fibroblasts," Peters-Golden says.

Moving forward with research, treatment

Three years ago, the FDA approved the first drugs for IPF. While these medications slow progression of the disease, they don't reverse the fibrosis that has already developed.

"Although having some treatment options for IPF is no doubt an advance, in my view, these drugs are like a bunt single, rather than the home run we all want," Peters-Golden says.

Peters-Golden points out that siomycin isn't approved for use in humans, but scientists are working on better drugs to block the overactivity of FOXM1 in cancer cells. When those drugs have been demonstrated to be safe in humans, they could one day be tested in clinical trials for IPF and perhaps other scarring diseases of the lung and different organs.

There is still much to learn about how FOXM1 affects fibroblasts and how pulmonary fibrosis can be reversed, Peters-Golden says. In upcoming research, his team will see how inhibiting or deleting FOXM1 affects mice with a more advanced degree of fibrosis.

Credit: 
Michigan Medicine - University of Michigan

Texas A&M study links breast cancer to the body's internal clock

image: Altered expression of luminal and basal markers in Per2-/- mammary glands. Immunflorescent staining showing localization of myoepthelial (K14 -green) and luminal (E-cadherin-red) markers in virgin Per2-/- mammary glands.

Image: 
Dr. Cole McQueen, Texas A&M University

For years, doctors have associated the BRCA1 and BRCA2 gene mutations with an increased risk of breast cancer.

But researchers at Texas A&M University have now identified another gene that may have an impact on breast cancer--associated with the body's circadian rhythm.

Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVM) professor Weston Porter and his team have found that Period 2 (Per2), a regulatory mechanism within each cell's peripheral clock, plays a crucial function in mammalian mammary gland development and that when suppressed, Per2 leads to severely disrupted gland development in mice.

The findings, published in the scientific journal Development, add to a growing list that ties disruptions to our circadian rhythm--that is, the "central clock" mechanism in our brains--to a higher risk of cancer progression, obesity, some neuromuscular diseases, and other impairments, including jetlag.

Circadian rhythm is controlled by the suprachiasmatic nucleus (SCN) in the brain's anterior hypothalamus. In addition to coordinating our sleep patterns, the SCN coordinates the other peripheral clocks in our body, which run on a 24-hour cycle that corresponds with each day.

"Not only do we have a central clock, but every one of our cells has one of these peripheral clocks and they're in coordination with the central clock," Porter said. "When you wake up in the morning and see light, the light goes right into the brain and it triggers this molecular mechanism that regulates the (circadian rhythm) process."

In their study, Porter's team evaluated Per2, which provides the "negative feedback," or counterbalance, to the circadian rhythm process.

"The negative and positive feedback mechanisms are constantly in balance, going up and down. One's up during the day, the other one's up at night--they oscillate right at 24 hours--but when you see light, that resets it in the morning," Porter said. "When Per2 comes back, it suppresses another gene called BMAL or CLOCK."

Their finding--that Per2 has a crucial function outside of timekeeping in mammalian mammary gland development where Per2 plays a role in cell differentiation and identity--describes a potentially important role for Per2 in breast cancer. Per2 expression is lost in a large percentage of mammary tumors, which suggests it may have protective effects.

"We discovered that these glands have what we call a kind of a bipotent phenotype; they're actually halfway to cancer," Porter said. "They've already have many of the characteristics you would see in a premalignant cell.

"We started to look at the mechanism associated with that and found that the stem cell markers associated with a loss of Per2 are more basal, which is characteristic of more invasive cancer," he said. "This reinforces the idea that Per2 is functioning as a tumor suppressor gene associated with cell identity."

In addition to disruption of the developing mammary gland, Porter also saw the same defect in transplant studies, showing that it is Per2, and not just the central clock itself, that is responsible for the lack of mammary ductal growth in the developing gland.

Their next step is to revisit studies that correlate working a night shift with an increased risk of breast cancer.

"Right now, we are investigating how our findings relate to humans," Porter said. "There are studies out there showing a relationship between decreased levels of Per2 and certain types of breast cancer, which are more invasive. So, we believe that there is a direct relationship."

Understanding circadian rhythm and its effects on the body have become increasingly important to the science community. The 2017 Nobel Prize for Physiology or Medicine was awarded to researchers for discoveries of the molecular mechanisms controlling the circadian rhythm, and the National Cancer Institute recently named the role of circadian rhythms in cancer as one of their 12 provocative questions for the year.

Credit: 
Texas A&M University

Leopard meals: Females go for diversity

image: This is a leopard in the study area.

Image: 
Leibniz-IZW/Miha Krofel

Leopards, top predators of the African savannah, are known to feed on a variety of prey species. These include smaller and medium-sized mammals such as impala, gemsbok, kudus and warthogs but they can also target relatively small "appetizers" such as hares.

It has been largely unknown, however, whether they specialise in certain prey animals and which factors might influence prey preferences. Christian Voigt and his colleagues from the Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW) in Berlin investigated these questions by studying the diet of leopards on commercial farmland in central Namibia.

Leopards avoid humans and it is difficult to observe them when they catch their prey. The team of scientists, therefore, chose an indirect method: they measured the composition of stable isotopes of carbon and nitrogen in leopard whiskers. The tissue of prey animals consists of specific isotopes of an element which is characteristic for that prey species. Once leopards consumed their prey, the isotope composition of the prey is assimilated into the leopard's body, including their whiskers, according to the relative abundance in the overall diet. This allows conclusions about the main diet of each leopard and the variety of items it might have consumed.

While the leopards were sedated to facilitate GPS collaring and examination of their health, the researchers cut off one whisker from each of the 18 adult female and 18 male animals. Back in the laboratory the hair was then cut into 5 mm segments and analyzed on stable isotope ratios. As the whiskers of leopards grow at a rate of approximately 0.65 mm per day, each segment therefore corresponds to a period of approximately eight days. The 8 to 10 cm long whiskers allowed the scientists to look back on approximately 150 days of the "feeding history" of each animal.

Voigt, the lead author of the study, and his colleagues identified prey groups with similar isotopic composition based on the ratio of the rare and common stable isotopes of the elements carbon and nitrogen (δ13C and δ15N). "The females used a significantly wider isotope food niche than males", explains Voigt, head of the stable isotope laboratory at Leibniz-IZW. The scientists suggest that one of the reasons for this result lies in the size differences between the sexes: female leopards, at 34 kg on average, are substantially smaller and weigh less than their male counterparts at up to 58 kg. Females need less energy owing to their lower body weight, but are also restricted in their movements when rearing young cubs, which they do on their own. "The females cannot specialize on certain prey species because the abundance of these prey species would decrease over time and access to them would become more difficult in their restricted home range when rearing cubs. They therefore need to feed on a wider range of, by necessity then smaller, prey species", says Jörg Melzheimer, ecologist at the Leibniz-IZW and initiator of the study. The males, on the contrary, have large home ranges, thus more options and specialize on a relatively small number of prey species.

In central Namibia leopards are currently spreading and increase in numbers on commercial farmland. At the same time the local population of cheetahs is apparently declining. "Whether there is a correlation between these two trends is currently unknown. However, it is known that lions, spotted hyenas and also leopards sometimes chase cheetahs away when encountered or even kill them", explains Bettina Wachter, lead scientist of the cheetah research project of the Leibniz-IZW.

The current study is based on a previous study of the cheetah research project. "In cheetahs, we also documented a high specialization in certain prey groups, but no difference in the diet between the sexes", Voigt explains. Unlike leopards, cheetah females are quite similar in body size to males.

The expansion of leopards in central Namibia might lead to new conflicts with local farmers. They are likely to persecute these charismatic big cats if they lose an increasing number of their livestock. Therefore, it is important to be aware of the diet of leopards and to develop solutions for potential conflicts in close cooperation with farmers.

Credit: 
Forschungsverbund Berlin

ONC201 kills breast cancer cells in vitro by targeting mitochondria

image: Figure 8 shows the proposed mechanism of action of ONC201 (see detail in Discussion).

Image: 
Stanley Lipkowitz

TRAIL, a member of the TNF family of ligands, causes caspase-dependent apoptosis through activation of its receptors, death receptor 4 and DR5.

ONC201 was originally identified as a small molecule that inhibits both Akt and ERK, resulting in dephosphorylation of Foxo3a and thereby induces TRAIL transcription.

Recently, two independent groups, Wafik El Deiry at Fox Chase and Michael Andreeff at MD Anderson,reported that ONC201 induces cell death via cell stress mechanisms, independent of TRAIL transcription. Gene expression profiling analysis revealed that ONC201 induces endoplasmic reticulum (ER) stress or integrated stress response -related genes, such as Activating Transcription Factor 4 (ATF4) and C/EBP-homologous protein (CHOP).

The researchers in Dr. Lipkowitz's group at the Center for Cancer Research in the National Cancer Institute observed that ONC201 kills breast cancer cells via a TRAIL-independent mechanism. Time-lapse live cell imaging revealed that ONC201 induces cell membrane ballooning followed by rupture, distinct from the morphology of cells undergoing apoptosis. They found that ONC201 inhibits mitochondrial respiration and induces mitochondrial structural damage. Moreover, they found ONC201 reduces mitochondrial DNA copy number. Importantly, cells dependent on glycolysis, such as fumarate hydratase deficient cancer cells and multiple cancer cell lines with reduced amounts of mitochondrial DNA were resistant to ONC201. ONC201 induced ATF4 and CHOP in breast cancer cells, and the stress response it was partially dependent on the mitochondrial effects of ONC201.

"Our work identifies a novel mechanism of ONC201 cytotoxicity that is based on the disruption of mitochondrial function, leading to ATP depletion and cell death in cancer cells that are dependent on mitochondrial respiration. Our study also suggests that cancer cells that are dependent on glycolysis will be resistant to ONC201" Dr. Stanley Lipkowitz, Chief, Women's Malignancies Branch, NCI.

Credit: 
Impact Journals LLC

Researchers find genetic 'dial' can control body size in pigs

Researchers from North Carolina State University have demonstrated a connection between the expression of the HMGA2 gene and body size in pigs. The work further demonstrates the gene's importance in body size regulation across mammalian species, and provides a target for gene modification.

"Essentially, HMGA2 is a gene that controls the total number of cells that an animal has," says Jorge Piedrahita, the Randall B. Terry Distinguished Professor of Translational Medicine and Director of the Comparative Medicine Institute at NC State. "The gene is only active during fetal development, and 'programs' in the number of cells that the animal will be able to generate. When the animal is born, it will only be able to grow to the size dictated by the number of cells that it can produce."

Researchers had previously studied the HMGA2 analogue in mice, which have two different genes (HMGA2 and HMGA1) involved in body size and body mass index determination. Pigs and humans share the HMGA2 gene responsible for growth regulation in their species. The NC State study looked at body size in pigs that expressed both copies of the gene, one copy, or neither copy.

"We found that the amount of the gene expressed is proportional to the size of the animal," Piedrahita says. "If both copies were expressed the pig was 'normal' sized. If one copy was expressed the pig was roughly 25 percent smaller than normal, and if neither copy was expressed the pig was 75 percent smaller.

"The animals grow and develop normally, although the boars with both copies of the gene deleted were sterile. Overall, it seems that controlling the expression of HMGA2 is like using a dial to control body size."

The researchers also found that the deletion of HMGA2 affected the resources that the pig fetuses received in utero. In litters containing fetuses with both copies of the gene deleted and fetuses with one or more copy of the gene expressed, the fetuses with both copies deleted did not survive the pregnancy. However, if the litter only contained fetuses with both copies deleted, the fetuses survived and developed normally.

Credit: 
North Carolina State University

Greenhouse gas 'feedback loop' discovered in freshwater lakes

image: This is a lake in Canada's Boreal Shield, near Sudbury, Ontario, with aquatic plants in the foreground providing fuel for methane production.

Image: 
Andrew Tanentzap

A new study of chemical reactions that occur when organic matter decomposes in freshwater lakes has revealed that the debris from trees suppresses production of methane - while debris from plants found in reed beds actually promotes this harmful greenhouse gas.

As vegetation in and around bodies of water continues to change, with forest cover being lost while global warming causes wetland plants to thrive, the many lakes of the northern hemisphere - already a major source of methane - could almost double their emissions in the next fifty years.

The researchers say that the findings suggest the discovery of yet another "feedback loop" in which environmental disruption and climate change trigger the release of ever more greenhouse gas that further warms the planet, similar to the concerns over the methane released by fast-melting arctic permafrost.

"Methane is a greenhouse gas at least twenty-five times more potent than carbon dioxide. Freshwater ecosystems already contribute as much as 16% of the Earth's natural methane emissions, compared to just 1% from all the world's oceans," said study senior author Dr Andrew Tanentzap from the University of Cambridge's Department of Plant Sciences.

"We believe we have discovered a new mechanism that has the potential to cause increasingly more greenhouse gases to be produced by freshwater lakes. The warming climates that promote the growth of aquatic plants have the potential to trigger a damaging feedback loop in natural ecosystems."

The researchers point out that the current methane emissions of freshwater ecosystems alone offsets around a quarter of all the carbon soaked up by land plants and soil: the natural 'carbon sink' that drains and stores CO2 from the atmosphere.

Up to 77% of the methane emissions from an individual lake are the result of the organic matter shed primarily by plants that grow in or near the water. This matter gets buried in the sediment found toward the edge of lakes, where it is consumed by communities of microbes. Methane gets generated as a byproduct, which then bubbles up to the surface.

Working with colleagues from Canada and Germany, Tanentzap's group found that the levels of methane produced in lakes varies enormously depending on the type of plants contributing their organic matter to the lake sediment. The study, funded by the UK's Natural Environment Research Council, is published today in the journal Nature Communications.

To test how organic matter affects methane emissions, the scientists took lake sediment and added three common types of plant debris: deciduous trees that shed leaves annually, evergreen pine-shedding coniferous trees, and cattails (often known in the UK as 'bulrushes') - a common aquatic plant that grows in the shallows of freshwater lakes.

These sediments were incubated in the lab for 150 days, during which time the scientists siphoned off and measured the methane produced. They found that the bulrush sediment produced over 400 times the amount of methane as the coniferous sediment, and almost 2,800 times the methane than that of the deciduous.

Unlike the cattail debris, the chemical makeup of the organic matter from trees appears to trap large quantities of carbon within the lake sediment - carbon that would otherwise combine with hydrogen and get released as methane into the atmosphere.

To confirm their findings, the researchers also "spiked" the three samples with the microbes that produce methane to gauge the chemical reaction. While the forest-derived sediment remained unchanged, the sample containing the bulrush organic matter doubled its methane production.

"The organic matter that runs into lakes from the forest trees acts as a latch that suppresses the production of methane within lake sediment. These forests have long surrounded the millions of lakes in the northern hemisphere, but are now under threat," said Dr Erik Emilson, first author of the study, who has since left Cambridge to work at Natural Resources Canada.

"At the same time, changing climates are providing favourable conditions for the growth and spread of aquatic plants such as cattails, and the organic matter from these plants promotes the release of even more methane from the freshwater ecosystems of the global north."

Using species distribution models for the Boreal Shield, an area that covers central and eastern Canada and "houses more forests and lakes than just about anywhere on Earth", the researchers calculated that the number of lakes colonised by just the common cattail (Typha latifolia) could double in the next fifty years - causing current levels of lake-produced methane to increase by at least 73% in this part of the world alone.

Added Tanentzap: "Accurately predicting methane emissions is vital to the scientific calculations used to try and understand the pace of climate change and the effects of a warmer world. We still have limited understanding of the fluctuations in methane production from plants and freshwater lakes."

Credit: 
University of Cambridge

First robotic system plays tic tac toe to improve task performance

image: Researchers from Ben-Gurion University of the Negev (BGU) in Beer-Sheva, Israel have demonstrated for the first time the feasibility of a robotic system that plays Tic Tac Toe with rehabilitation patients to improve real-life task performance.

Image: 
Ben-Gurion University

NEW YORK...May 3, 2018 - Researchers from Ben-Gurion University of the Negev (BGU) in Beer-Sheva, Israel have demonstrated for the first time the feasibility of a robotic system that plays Tic Tac Toe with rehabilitation patients to improve real-life task performance.

The interdisciplinary research team designed a game with a robotic arm to simulate "3D Functional Activities of Daily Living"--actions people undertake daily, like drinking from a cup, that are often a focus of rehabilitation. Click here to watch the video.

Designing a social robot to help rehabilitate a patient is a new field which requires much research and experimentation in order to determine the optimal conditions. The research was published in Restorative Neurology and Neuroscience.

"Playing Tic Tac Toe with a set of cups (instead of X's and O's) is one example of a game that can help rehabilitate an upper limb," says Dr. Shelly Levy-Tzedek of BGU's Department of Physical Therapy, and Zlotowski Center for Neuroscience. "A person can pick up and place many cups while enjoying a game and improving their performance of a daily task."

Researchers compared study participants' motivation to play with a robot vs. a set of computer-controlled LED lights to determine the importance of interacting with an actual physical robot.

They tested the system on 62 healthy right-handed people from two age groups: 40 young adults around 25 years old (23 women and 17 men) and 22 older adults around 75 years old (10 women and 12 men). Both groups preferred the robotic system over the LED lights system. The older adults said it was more human-like, while the young adults reported the robot "was more interesting, fun and appealing."

When asked which partner they would prefer to play two additional games with, both groups selected the robotic system over the lights. However, when asked to play an additional 10 games, the older adults still preferred the robot, but the young group preferred to play against the LED lights system.

"Some of the young adults complained that the robot moved too slowly; therefore, they preferred the quicker system when asked to play many more games," says Dr. Levy-Tzedek. "That indicates a need to personalize the speed of the robot to each participant."

An unexpected finding was that the robot's movement influenced human movement. Both young and older adults moved significantly slower when they played with the slower robot compared to the faster lighting system.

These results indicate that people are willing to continue to interact with a robotic device in a social-like setting, and that embodiment plays an important role, which is a positive sign for the future of such systems. Now that they have established feasibility, the researchers recommend testing their system on rehabilitating stroke victims.

Credit: 
American Associates, Ben-Gurion University of the Negev

Scientists call for 'open-skies' imagery policy over Israel and Palestine

image: A 2013 CNES/Airbus satellite image of a new site that could be identified because looting pits over the site are visible on high-resolution satellite imagery.

Image: 
Map data ©2018 Google.

New Oxford University research has called for an 'open-skies policy' around the availability of high resolution satellite imagery of Israel and Palestine.

Since 1997, the Kyl-Bingaman Amendment (KBA) to the 1997 U.S. National Defense Authorization Act, has limited the availability of high-resolution satellite imagery of these countries. Although this law only applies to the United States of America, as a global super power, with dominance over the commercial satellite imagery market, its international impact has been significant. However, new Oxford University research has called for these restrictions to be lifted immediately and set in line with the international standard.

Satellite imagery has transformed the way that scientists can investigate, map and monitor the changing human and physical landscape of the earth. The current KBA Amendment limits the resolution of U.S - produced imagery for Israel to c.2m, which is relatively blurry and means that features smaller than this are not detectable from aerial footage. As a result, the satellite images available on platforms such as Google Earth, of both Israel and Palestine, are of poor quality, significantly restricting the scientific research opportunities in these areas.

In an attempt to overcome these limitations, researchers from the Endangered Archaeology Project at the Oxford School of Archaeology, which relies on satellite imagery to identify and monitor heritage sites across the Middle East and North Africa, investigated the justification for the Kyl-Bingaman Amendment, and reviewed how the regulations works in practice.

Published in Space Policy, the research conducted by Dr Andrea Zerbini and Dr Michael Fradley of Oxford's School of Archaeology, finds that while this regulation was broadly assumed to be a static censorship, the limitations were intended to mirror the standard of satellite imagery available outside the United States. However, much stronger high-resolution images have in fact been available from companies such as Airbus in France from as long ago as 2012.

The paper also reveals that there has been some quiet resistance to the US regulation, particularly from Google Earth, where high-resolution images covering areas of the West Bank, Golan Heights and the border areas of Israel, provided by Airbus, are already available on the platform.

The findings demonstrate that these regulations need urgent review, and recommends that US imagery should meet what has become the international standard of 0.5m.

Dr Michael Fradley said: 'Our research demonstrates not only how the current restrictions have hampered scientific research in this area, but also importantly highlights a clear rationale for moving on from the Kyl-Bingaman Amendment. The reduction or removal of these restrictions would open up access to modern satellite imagery, as well as historical images captured by spy satellite that remain classified due to the legal reach of the Kyl-Bingaman Amendment, which could allow researchers to record longer-term landscape change.'

The minutes of the latest meetings of the U.S. regulatory body for commercial satellite imagery suggest that restrictions may indeed be lifted, potentially ushering in a new phase of remote-sensing research by archaeologists, geographers and earth scientists across this area of the Levant.

Staff at the National Oceanic and Atmospheric Administration (NOAA), who regulate the implementation of the Kyl-Bingaman Amendment, have acknowledged the important role of this new research by the EAMENA team in their ongoing evaluation of regulations. The Endangered Archaeology project has already begun to identify new archaeological sites using higher-resolution satellite in the region, and its work has set a precedent for future scientific research in this area.

Commenting on the potential impact of lifting these sanctions, Dr. Brian Boyd, Program Director, Center for Archaeology, Columbia University, said: 'Zerbini and Fradley's call for an "open-skies policy" with regard to the availability of high resolution satellite imagery of archaeological sites and landscapes in Israel/Palestine has the potential to revolutionize our understanding of the human occupation of this region from the earliest prehistoric times to the present day. Their research will also be invaluable in highlighting contemporary endeavors to record and hopefully preserve sites, monuments and landscapes that are under threat from political and military actions not only in Israel/Palestine but in the wider Middle East'.

Credit: 
University of Oxford

Highly elastic biodegradable hydrogel for bioprinting of new tissues

image: Yi Hong, UTA professor of bioengineering and leader of the project.

Image: 
UTA

Researchers at The University of Texas at Arlington have developed a highly elastic biodegradable hydrogel for bio-printing of materials that mimic natural human soft tissues. Bio-printing uses live cells within the scaffolding of the new tissues and could potentially transform cell printing.

A provisional patent application has been filed on this new material, which will be able to generate multiple types of human soft tissues, including skin, skeletal muscles, blood vessels and heart muscles.

"Soft tissue bio-printing suffers from significant challenges as the hydrogels were often brittle and un-stretchable and could not mimic the mechanical behavior of human soft tissues," said Yi Hong, UTA professor of bioengineering and leader of the project.

"To overcome these challenges, we developed a simple system using a single cross-linking mechanism activated by visible light to achieve a highly elastic and robust, biodegradable and biocompatible hydrogel for cell printing," Hong added.

The researchers have described their findings in a new journal paper published recently in the American Chemical Society's ACS Applied Materials and Interfaces as "Highly Elastic Biodegradable Single-Network Hydrogel for Cell Printing." The paper was also selected as an American Chemical Society Editors' Choice.

A tri-block biodegradable polymer of polycaprolactone - poly (ethylene glycol) - polycaprolactone (PCL-PEG-PCL) with two end groups of acrylates and a visible-light water-soluble initiator forms this hydrogel for cell printing.

"Polycaprolactone and poly (ethylene glycol) are already widely used in Food and Drug Administration - approved devices and implants, which should facilitate quick translation of the material into pre-clinical and clinical trials in the future," Hong said.

"The tunability of the mechanical properties of this hydrogel to match different soft tissues is a real advantage," he added.

Michael Cho, UTA chair of bioengineering, congratulated Hong and his colleagues on this research.

"These colleagues may have created a new way of thinking about hydrogel bio-printing research," Cho said. "This work is also critical in advancing UTA's strategic theme of health and the human condition through cross-disciplinary work."

Credit: 
University of Texas at Arlington

CWD prions discovered in Wisconsin soils for the first time

image: Locations of sampled mineral licks and prevalence of chronic wasting disease (CWD) in hunter-harvested white-tailed deer from 2010-2013 in south-central Wisconsin, USA. Squares are townships of 9.66 km per side. Inset shows state of Wisconsin, USA. Site 6 denotes the mineral lick with CWD-positive fecal samples.

Image: 
<i>PLOS ONE</i>

MADISON - New research out of the University of Wisconsin-Madison has, for the first time, detected prions responsible for chronic wasting disease (CWD) in samples taken from sites where deer congregate.

Scientists searched for prions at mineral licks -- areas where deer seek out essential nutrients and minerals -- in the CWD endemic area across south-central Wisconsin. Out of 11 sites, nine had detectable levels of the disease-causing misfolded proteins. Prions were found both in soil and in water from the sites, as well as in nearby fecal samples from one site.

This research helps confirm longstanding suspicions that prions can accumulate in the environment in areas such as mineral licks or feeding and baiting sites where deer congregate. Scientists believe that environmental reservoirs of prions could serve as an additional transmission route of CWD, which also passes between deer through direct contact. Environmental reservoirs of prions are not expected to pose a health hazard to humans but could be a potential source of transmission to other animals.

In Wisconsin, CWD is concentrated in southwestern and southeastern counties. More than 30 percent of adult male deer are infected in portions of Iowa County, according to the Department of Natural Resources. The disease is fatal and is transmitted through infectious prion proteins. It is unknown if humans can contract CWD from eating infected meat, but the World Health Organization has recommended that people avoid doing so. No cases of human transmission have been reported.

The study, which was funded by the U.S. Geological Survey with support from the National Science Foundation, was published May 2 in the journal PLOS ONE. Michael Samuel, an emeritus professor of wildlife ecology, and Joel Pedersen, a professor of soil science, led the work, with colleagues in forest and wildlife ecology and the Molecular and Environmental Toxicology Center at the UW School of Medicine and Public Health.

"This is the first time that anyone has demonstrated the existence of prions in naturally contaminated soil," says Pedersen.
Environmental prions have previously been shown to infect deer in heavily contaminated experimental enclosures of deer. In 2009, researchers in Colorado also identified prions in untreated water entering a water treatment plant.

The prions were detected using a technique that amplifies the small amount of misfolded, diseased version of prion proteins isolated from soil or water samples. The misfolded varieties are added to a pool of properly folded proteins from mice engineered to produce them. The diseased folding state is transmitted to properly folded proteins, increasing the number of diseased prions and facilitating measurement.

It is not clear if the quantity of soil-dwelling prions detected in the current study are sufficient to infect deer. "Although we are able to detect prions, quantifying the amount present is still difficult using this technique," says Pedersen. Previous research by the Pedersen lab has demonstrated that soil-bound prions are more effective than free prions at infecting hamsters.

"It's a great advance for trying to understand how this disease transmits in the environment," says Rodrigo Morales, a professor of neurology and prion researcher at the University of Texas Health Science Center at Houston who was not affiliated with the study. "It explains what could be the main source of (transmission)."

Samuel says the significance of prion-contaminated environments in the spread and persistence of CWD among free-ranging deer remains unknown.

"We know it can occur, but we just don't know how it occurs in the wild, or how important it is relative to deer contacting each other," says Samuel.

Ten of the mineral lick sites tested in the study were artificial, while one was natural. Nine of the 11 sites were on private land and were tested with permission of the landowner.

"We manage most diseases by trying to interrupt their spread. Having CWD concentrated at animal licks means that's going to be difficult," says Don Waller, a professor of botany and environmental studies at UW-Madison who researches Wisconsin's deer herds and was not involved in the study.

"It's not easy to test for CWD, but this result suggests we should be looking for hot-spots of CWD prions in the environment and doing all we can to cover them up so animals can't get to them. We may also want to do more testing in other animal species to see which may be vulnerable to CWD infection," says Waller.

Credit: 
University of Wisconsin-Madison

Environmental quality research questions identified for Latin American region

image: This is Bryan W. Brooks, Ph.D., Distinguished Professor of Environmental Science and Biomedical Studies and director of the environmental health science program at Baylor University.

Image: 
Baylor University

WACO, Texas (May 3, 2018) - Using an innovative initiative, Latin American researchers from academia, government agencies and businesses leaders identified priority research questions for the region to tackle pressing environmental quality issues.

In an article published recently in the journal of Integrated Environmental Assessment and Management, Bryan W. Brooks, Ph.D., Distinguished Professor of Environmental Science and Biomedical Studies and director of the environmental health science program at Baylor University, led the Global Horizon Scanning Project (GHSP), which focuses on identifying environment and health issues internationally. Brooks also facilitated GHSP workshops in Africa, Australia, Central and Southeastern Asia, Europe and North America.

"The GHSP was initiated to identify multidisciplinary scientific research needs that, if answered, would achieve more sustainable environmental quality around the world," Brooks said.

Tatiana Heid Furley, the study's first author and director of Aplysia Environmental Consulting in Brazil, said the GHSP was "an extremely important project because it offers the opportunity to prioritize environmental issues that need to be investigated and addressed in the short and medium-term future."

As part of the study, members of the Society of Environmental Toxicology and Chemistry's (SETAC) Latin America geographic unit, environmental scientists and engineers completed Internet-based surveys to identify the most pressing issues facing Latin America.

"The process was intentionally inclusive, bottom-up, multidisciplinary, multisector and transparent," Brooks said. "It is not one academic coming up with an idea. It is not one arm of government. It is not one business. It really is groupthink, which is needed across disciplines and sectors. It facilitates a healthy environment that allows people to think together."

At a workshop on Buenos Aires, Argentina, Brooks and his Latin American colleagues analyzed the survey responses, identified 20 priority research questions and organized them into six themes:

Risk assessment

Environmental chemistry

Ecotoxicology

Health, contaminants of emerging concern, and environment

Spotlight on Latin America

Environmental management and policy

The Latin American region "holds 40 percent of the world's biological diversity, 30 percent of the Earth's available freshwater and almost 50 percent of the world's tropical forests" making the GHSP execution and timing important, according to the article.

"This project is part of a larger effort to identify important international research needs. It is essentially, for the first time, a research roadmap towards achieving more sustainable environmental quality," Brooks said.

The GHSP project already has led to forward movement in South America, culminating with the announcement of significant grant funding for environmental research.

"In Brazil, the results of this project arrived at an excellent time," Heid Furley said. "The eighth World Water Forum was held March 22 in Brazil. Nineteen of the 20 priority issues raised by Latin American participants relate to water. A call for proposals was prepared based on the GHSP Latin America results and announced at the forum," Heid Furley said.

"We face palpable global environment and health challenges, which require innovative understanding, tools, products and systems to prevent, diagnose and manage adverse outcomes to public health and the environment. The GHSP is identifying timely research questions that are important to all of us," Brooks said.

Credit: 
Baylor University

Understanding fear of guilt key in better treating OCD

Advances in our understanding of the development and persistence of Obsessive-Compulsive Disorder (OCD) have the potential to improve treatment according to a new study by the University of Waterloo.

The study found that fear of guilt evokes feelings of doubt in decision-making, with greater fear of guilt being associated with greater self-reported difficulty making decisions, less satisfaction with the decisions made, and less confidence in those decisions. A person's fear of being guilty for something that they have done or haven't done also results in them wanting more information before making a decision.

"People with OCD have generally been shown in research to have this inflated feeling of responsibility," said Waterloo graduate student and lead researcher on the study, Brenda Chiang. "They often feel that they are going to be responsible for something bad that will happen or that if they fail to do something, they will be responsible for that harm too. So, they naturally have slightly higher levels of fear of guilt making them more susceptible to indecisiveness.

"This indecisiveness leads to difficulty terminating an action as well as evokes doubt as to whether an action was done properly, which leads to repetition of that action."

The study assessed 63 undergraduate students from the University of Waterloo, who were previously identified as having a wide range of trait levels of fear of guilt; from low to high.

"The next step would be to examine this in people who have OCD," said Professor Christine Purdon, co-author of the study. "The current gold standard for treating OCD is Cognitive Behavioral Therapy, which has about a 50 to 60 per cent success rate if you include people who drop out because they can't tolerate it or people who decline the treatment because they anticipate that they can't do it.

"We're only getting about half of the people with OCD treated properly, so once we have a better understanding of factors that cause repetition and doubt, we can develop treatment that addresses a greater number of persons."

The study was recently published in the Journal of Obsessive-Compulsive and Related Disorders.

Credit: 
University of Waterloo

Blood type O patients may have higher risk of death from severe trauma

Blood type O is associated with high death rates in severe trauma patients, according to a study published in the open access journal Critical Care that involved 901 Japanese emergency care patients.

Researchers at Tokyo Medical and Dental University Hospital, Japan found that severe trauma patients (those with an injury that has the potential to cause long-term disability or death) with blood type O had a death rate of 28%, compared to a rate of 11% in patients with other blood types.

Dr. Wataru Takayama, the corresponding author said: "Recent studies suggest that blood type O could be a potential risk factor for hemorrhage (bleeding in large quantities). Loss of blood is the leading cause of death in patients with severe trauma but studies on the association between different blood types and the risk of trauma death have been scarce. We wanted to test the hypothesis that trauma survival is affected by differences in blood types."

Patients with blood type O have been shown to have lower levels of von Willebrand factor, a blood clotting agent, than those with other blood types. Lower levels of von Willebrand factor may be linked to higher levels of haemorrhage. The authors suggest that a lower level of the factor is a possible explanation for the higher death rate in trauma patients with blood type O. Wataru Takayama said: "Our results also raise questions about how emergency transfusion of O type red blood cells to a severe trauma patient could affect homeostasis, the process which causes bleeding to stop, and if this is different from other blood types. Further research is necessary to investigate the results of our study and develop the best treatment strategy for severe trauma patients."

The authors used data from medical records of 901 patients with severe trauma who had been transported to either of two tertiary emergency critical care medical centers in Japan during 2013 to 2016.

The authors caution that all the patients whose data was analyzed in this study were Japanese and therefore there is a need for further research to understand if the findings apply to other ethnic groups. Additionally, there was no evaluation of the impact of the individual blood types A, AB or B on severe trauma death rates. Instead, the authors compared type O to non-O blood type which may have diluted the effect of individual blood types on patient survival.

Credit: 
BMC (BioMed Central)