Culture

Elderly women battling breast cancer who have anxiety, depression or other mental health conditions are more likely to use opioids and more likely to die, a new study led by the University of Virginia School of Medicine suggests.

The findings should encourage doctors to better manage mental health in patients with breast cancer and spur care providers to consider alternative pain management such as physical therapy, massage and acupuncture, the researchers say.

"The complex relationship among breast cancer, mental health problems, and the use of opioids is not well understood and the results of this study provide clinicians the evidence they need to make optimal patient treatment related decisions," said lead researcher Rajesh Balkrishnan, PhD, of the Department of Public Health Sciences and the UVA Cancer Center. "Our findings suggest that patients with breast cancer with mental health conditions have higher opioid use and reduced survival. These results highlight the need for health care providers to evaluate treatment goals and assess whether better concurrent management of breast cancer and mental health conditions is required."

Breast Cancer and Opioids

Breast cancer kills more than 40,000 people in the United States each year, and patients often suffer from anxiety and depression. Research suggests that about 40 percent of patients with breast cancer have some type of mental health diagnosis.

Balkrishnan and his team set out to shed light on the relationship among mental health, opioid use and breast cancer outcomes. To do that, they reviewed more than 10,000 breast cancer cases recorded in the national SEER cancer database, which contains detailed (but depersonalized) information on care provided to Medicare beneficiaries with cancer. These cases consisted of women aged 65 years and older who were diagnosed with stage I, II or III breast cancer between Jan. 1, 2006, and Dec. 31, 2012. All received adjuvant endocrine therapy as treatment.

The researchers sorted the cases into two groups: women with mental health diagnoses and those without. They found that those with mental health diagnoses had higher opioid use and lower survival rates.

"Opioid use is higher in the women with breast cancer who suffer from mental health comorbidities and remains a significant problem," the researchers write in a new paper outlining their findings. "In addition, mental health comorbidities also contribute to reduced survival in these women. A need exists for collaborative care in the management of mental health comorbidities in women with breast cancer, which could improve symptoms, adherence to treatment, and recovery from these mental conditions. Mental health treatments also are recommended to be offered in primary care, which not only would be convenient for patients but also would reduce the stigma associated with treatments for mental health comorbidities and improve the patient-provider relationship."

The researchers, including UVA palliative care expert Leslie Blackhall, MD, recommend that doctors and other care providers consider "complementary forms of treatment for pain," such as physical therapy, cognitive behavioral therapy, acupuncture, acupressure and massage.

Findings Published

The researchers have published their findings in the Journal of Oncology Practice. In addition to Balkrishnan and Blackhall, the study's authors were Raj Desai, of the University of Florida; Fabian Camacho of the UVA School of Medicine; Xi Tan of West Virginia University; and Virginia LeBaron, of the UVA School of Nursing.

The researchers noted potential limitations to their study such as a lack of information on the opioids used and a lack of details on the patients' pain assessments. They also suggest that mental health conditions such as depression may be underdiagnosed and that, as a result, the research may underestimate the percentage of patients with those conditions.

Tan disclosed potential conflicts of interest including owning stock in and receiving compensation from biopharmaceutical company Merck. Balkrishnan disclosed that he has done consulting or advising for Merck.

An international team of BHF-funded researchers may have discovered why some people experience muscle pain after taking statins. The research, published in JACC: Basic to Translational Science, could help doctors prevent a known side effect of statins and ensure people are able to reap the benefits of the life-saving drugs.

According to the research, statins cause spontaneous and irregular leaks of calcium from storage compartments within muscle cells. Under normal conditions, coordinated releases of calcium from these stores make the muscles contract. Unregulated calcium leaks may cause damage to muscle cells, potentially leading to muscle pain and weakness.

The researchers suggest that in most people, muscle cells can tolerate this calcium leak. However, in people already susceptible due to their genes or lifestyle, the leak caused by statins may overwhelm the muscle cells, giving rise to muscle pain and weakness.

The findings explain why only some people experience muscle pain after taking statins and could help doctors to identify those most likely to experience symptoms so they can be offered alternative therapies.

The researchers also showed that exercise may prevent the changes which lead to calcium leaks from occurring, and it may be an effective way for people taking statins to avoid muscle symptoms.

Statins reduce a person's risk of a heart attack or stroke by lowering the levels of so-called 'bad cholesterol' in the body. They are particularly beneficial for people who have already had a heart attack or stroke and are also effective in those who are identified as being at risk of having one in future. Although side effects are rare, muscle pain and weakness are important reasons why some people stop taking these potentially life-saving drugs.

Researchers based at the University of Leeds and the Karolinska Institute in Sweden investigated the effects of statins on muscle biopsies from patients taking statins long term and from rats treated with statins for 4 weeks.

Treatment with statins compromised gatekeeper proteins called ryanodine receptors, which control calcium release from storage compartments in muscle cells, leading to spontaneous and irregular calcium leaks that could trigger signals promoting cell death. Pro-cell death signals were elevated in muscles from both people and rats treated with statins compared to untreated controls.

Despite the cell changes, statins did not affect muscle function or strength in rats. These findings support the theory that muscle cells can tolerate the calcium leak, meaning only those who are susceptible experience symptoms.

Importantly, the study also suggests that the potentially harmful effects of statins on muscle can be countered with exercise. When rats were given free access to an exercise wheel, the statin-related changes to the gatekeeper proteins no longer occurred and pro-cell death signals were not elevated in the muscles. In fact, rats treated with statins ran twice as far as control rats. The findings challenge previous reports that exercise makes statin side effects worse.

The researchers point out that they did not directly show that the cell changes lead to muscle weakness and pain in people, but note that this is likely. The proposed mechanism may also explain why heart muscle, which has different gatekeeper proteins for calcium release, is protected from any potentially harmful effects of statins.

Dr Sarah Calaghan, Associate Professor in Cardiac Physiology from the University of Leeds said:

"The idea that exercise makes statin side effects worse might be a misconception - what really matters is the intensity of exercise. We found that moderate exercise cancelled out the changes in muscle cells caused by statins. We know around 7 in 10 professional athletes can't tolerate statins - and we know that intense endurance exercise has profound effects on the gatekeeper proteins targeted by statins. The added effect of statins could push muscles over the edge, leading to symptoms.

"The good news is, after twenty years of searching, we finally have an explanation for statin-associated muscle pain, along with a possible solution. If you weren't convinced to exercise already, here's another reason."

Professor Metin Avkiran, Associate Medical Director at the British Heart Foundation said:

"Statins are life-saving drugs and most people who take them don't experience side effects. Those who do suffer muscle pain and weakness should always ask their doctor if a different statin or dose might solve the problem.

"Identifying how statins affect muscle cell biology is the first step in preventing potential muscle side effects - and ensuring that people who are susceptible to those side effects do not miss out on the protection afforded by statins.

"Ultimately, everyone has control over the medications they choose to take. When weighing up whether to take statins, talk to your GP. After assessing your personal risk and advising on lifestyle changes, they will help you make an informed decision that is right for you."

A new species of gigantic tumbleweed once predicted to go extinct is not only here to stay -- it's likely to expand its territory.

The species, Salsola ryanii, is significantly larger than either of its parent plants, which can grow up to 6 feet tall. A new study from UC Riverside supports the theory that the new tumbleweed grows more vigorously because it is a hybrid with doubled pairs of its parents' chromosomes.

Findings from the study are detailed in a new paper published in the Oxford University-produced journal AoB Plants.

"Salsola ryanii is a nasty species replacing other nasty species of tumbleweed in the U.S.," said study co-author Norman Ellstrand, UCR Distinguished Professor of Genetics. "It's healthier than earlier versions, and now we know why."

Humans are diploid organisms, with one set of chromosomes donated by the mother and one set from the father. Sometimes a mother's egg contains two sets of chromosomes rather than just the one she is meant to pass on. If this egg is fertilized, the offspring would be triploid, with three sets of chromosomes. Most humans do not survive this.

Plants with parents closely related enough to mate can produce triploid offspring that survive but are unable to reproduce themselves. However, a hybrid plant that manages to get two copies from the mother and two from the father will be fertile. Some species can have more than four sets of chromosomes. They can even have "hexaploidy," with six sets of chromosomes.

Scientists have long assumed there must be some kind of evolutionary advantage to polyploidy, the term for hybrids that have multiple sets of chromosomes, since it poses some immediate difficulties for the new hybrids.

"Typically, when something is new, and it's the only one of its kind, that's a disadvantage. There's nobody exactly like you to mate with," said study co-author Shana Welles, the graduate student in Ellstrand's laboratory that conducted the study as part of her Ph.D. research. She is now a postdoctoral fellow at Chapman University.

The advantage to having multiple sets of chromosomes, according to the study, is that the hybrid plant grows more vigorously than either of its parents. This has been suggested as the reason polyploidy is so common in plants. However, it has not, until now, been demonstrated experimentally.

Polyploidy is associated with our favorite crops; domesticated peanuts have four sets of chromosomes, and the wheat we eat has six.

Though tumbleweeds are often seen as symbols of America's old West, they are also invasive plants that cause traffic accidents, damage agricultural operations, and cause millions in property damage every year. Last year, the desert town of Victorville, California, was buried in them, piling up to the second story of some homes.

Currently, Salsola ryanii has a relatively small but expanding geographic range. Since the new study determined it is even more vigorous than its progenitors, which are invasive in 48 states, Welles said it is likely to continue to expand its range. Additionally, Welles said climate change could increase its territory takeover.

Though this tumbleweed is an annual, it tends to grow on the later side of winter.

"It's one of the only things that's still green in late summer," Welles said. "They may be well positioned to take advantage of summer rains if climate changes make those more prevalent."

Given its potential for damage, the knowledge now available about Salsola ryanii could be important for helping to suppress it, and Ellstrand believes that is what should happen before it takes over.

"An ounce of prevention is a pound of cure," he said.

As a disposable version of the instrument used in one of the most common medical procedures in the United States inches closer to widespread availability, a team of Johns Hopkins data researchers is studying the economic and safety implications associated with the devices used to perform colonoscopies.

Gastroenterology researcher Susan Hutfless led a first-of-its-kind study published online last week in the BMJ journal Gut, reporting that while disposable devices might lead to lower rates of post-colonoscopy infection, institutions that perform the procedure thousands of times per year might better benefit from improved disinfection methods of reusable scopes.

Today, colonoscopies are performed with reusable scopes, which are flexible, fiber-optic devices that are inserted into the anus and guided through the colon. The scopes allow endoscopists to examine patients for cancerous or precancerous conditions, as well as diagnose chronic disease. The nature of the devices and the microorganisms they encounter during use mandates rigorous cleaning.

In 2016, the Food and Drug Administration approved a disposable colonoscope designed to be used only once. With the new devices on the horizon, Hutfless and her colleagues aimed to determine which centers, if any, might benefit from using them.

Only a small fraction of the more than 15 million Americans who had colonoscopies last year contracted infections from the procedure. But, as Hutfless noted in a 2018 publication, the rates of infection at facilities that perform a relatively small number of the procedures are far higher than previously believed. In that paper, Hutfless reported that rates of post-colonoscopy infection at facilities known as ambulatory surgery centers (ASCs) are more akin to 1 in 1,000, rather than the 1 in 1 million figure previously accepted in the field.

Given that the one-time-use scopes have yet to be introduced, Hutfless focused on the cleaning, capital and operating costs associated with the reusable versions currently available. Purchase, maintenance and cleaning costs per procedure range from $189 at centers that perform at least 3,000 colonoscopies per year to $501 at centers performing 1,000 or fewer. When the cost of treating post-procedural infections is included, the numbers rise even higher, ranging from an additional $20 per procedure in high-volume, low-infection centers to almost $47 for centers with greater infection rates. The average cost of a hospitalization to treat a post-colonoscopy infection is more than $12,000.

Colonoscopies are recommended for people age 50 and above for routine cancer screenings. The procedures are performed under mild sedation in hospitals or ASCs. Hutfless' research has shown direct correlations between the number of procedures performed at a particular center and the rates of infection.

"High-volume centers tend to have lower infection risks," says Hutfless, adding that she and her colleagues attribute the lower risk to more experience and a faster turnover of colonoscopes. "It may not be cost-effective for high-volume centers to switch to disposable."

The researcher says that certain low-volume centers could benefit from disposable scopes. "They may decrease device-related infection transmission and may prove cost-effective for some facilities, particularly those with low volume and patients with a high infection risk."

She also points to the environmental impact that millions of throw-away plastic scopes would have. "That's something that very much needs to be considered," she says.

SAN DIEGO, Aug. 26, 2019 -- Flame retardants are present in thousands of everyday items, from clothing to furniture to electronics. Although these substances can help prevent fire-related injuries and deaths, they could have harmful effects on human health and the environment. Of particular concern are those known as organohalogens, which are derived from petroleum. Today, scientists report potentially less toxic, biodegradable flame retardants from an unlikely source: plants.

The researchers will present their results at the American Chemical Society (ACS) Fall 2019 National Meeting & Exposition. ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features more than 9,500 presentations on a wide range of science topics.

"The best flame-retardant chemicals have been organohalogen compounds, particularly brominated aromatics," says Bob Howell, Ph.D., the project's principal investigator. "The problem is, when you throw items away, and they go into a landfill, these substances can leach into the environment."

Most organohalogen flame retardants are very stable. Microorganisms in the soil or water can't degrade them, so they persist for many years in the environment, working their way up the food chain. In addition, some of the compounds can migrate out of items to which they are added, such as electronics, and enter household dust. Although the health effects of ingesting or breathing organohalogen flame retardants are largely unknown, some studies suggest they could be harmful, prompting California to ban the substances in children's products, mattresses and upholstered furniture in 2018.

"A number of flame retardants are no longer available because of toxicity concerns, so there is a real need to find new materials that, one, are nontoxic and don't persist, and two, don't rely upon petroleum," Howell says. His solution was to identify compounds from plants that could easily be converted into flame retardants by adding phosphorous atoms, which are known to quench flames. "We're making compounds that are based on renewable biosources," he says. "Very often they are nontoxic; some are even food ingredients. And they're biodegradable -- organisms are accustomed to digesting them."

To make their plant-derived compounds, Howell and colleagues at the Center for Applications in Polymer Science at Central Michigan University began with two substances: gallic acid, commonly found in fruits, nuts and leaves; and 3,5-dihydroxybenzoic acid from buckwheat. Using a fairly simple chemical reaction, the researchers converted hydroxyl groups on these compounds to flame-retardant phosphorous esters. Then, the team added the various phosphorous esters individually to samples of an epoxy resin, a polymer often used in electronics, automobiles and aircraft, and examined the different esters' properties with several tests.

In one of these tests, the researchers showed that the new flame retardants could strongly reduce the peak heat release rate of the epoxy resin, which reflects the intensity of the flame and how quickly it is going to spread. The plant-derived substances performed as well as many organohalogen flame retardants on the market. "As a matter of fact, they may be better," Howell says. "Because gallic acid has three hydroxyl groups within the same molecule that can be converted to phosphorous esters, you don't have to use as much of the additive, which reduces cost."

The researchers also studied how the new compounds quench flames, finding that the level of oxygenation at the phosphorous atom determined the mode of action. Compounds with a high level of oxygenation (phosphates) decomposed to a substance that promoted char formation on the polymer surface, starving the flame of fuel. In contrast, compounds with a low level of oxygenation (phosphonates) decomposed to species that scavenged combustion-promoting radicals.

Howell's team hasn't yet performed toxicity tests, but he says that other groups have done such studies on similar compounds. "In general, phosphorous compounds are much less harmful than the corresponding organohalogens," he notes. In addition, the plant-derived substances are not as volatile and are less likely to migrate from items into household dust. Howell hopes that the new flame retardants will attract the attention of a company that could help bring them to market, he says.

SAN DIEGO, Aug. 26, 2019 -- Saliva from a tick's bite can transmit pathogens that cause serious illnesses, such as Lyme disease, and significant agricultural losses. Current insecticides have drawbacks, so scientists have been seeking new ways to prevent these pesky arachnids from spreading pathogens. Now, researchers report that compounds they previously identified can dry up ticks' saliva by upsetting the balance of ions in the salivary gland, reducing feeding and potentially limiting pathogen transmission.

The researchers will present their results today at the American Chemical Society (ACS) Fall 2019 National Meeting & Exposition. ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features more than 9,500 presentations on a wide range of science topics.

A brand-new video on the research is available at www.acs.org/HLS_Dry_Ticks.

"Lyme disease is exploding in the northeastern U.S.," says Daniel Swale, Ph.D., the project's principal investigator. "Most methods to kill ticks in the agricultural sector involve the use of neurotoxic insecticides, but it's difficult to effectively use these insecticides to control ticks in residential areas. So we wanted to identify a new way to control these disease-carrying ticks."

"We knew that the salivary gland is critical to the biological success of ticks, suggesting it had potential as a target for a pesticide that works through a new mechanism," Zhilin Li, a doctoral student who is presenting the work at the meeting, says. The researchers, who are at Louisiana State University, reasoned that if they could stop ticks from producing saliva, then they could prevent them from feeding -- a situation that would be incompatible with sustaining life.

Li and Swale focused on a potassium ion channel, known as a Kir channel, which has been shown to be important for the excretory systems of arthropods -- a classification of animals that includes mosquitoes, as well as ticks. These microscopic channels allow potassium to move in and out of cells in the salivary gland and elsewhere in the ticks, maintaining an ionic balance essential to saliva secretion and the ticks' health.

In their current work, they fed ticks blood laced with two compounds known to act on the Kir channels. Two of the molecules -- known as VU0071063 and pinacidil, a human hypertension drug -- were effective, reducing saliva secretion by 95% or more and reducing blood ingestion by approximately 15-fold. Importantly, ticks that fed on bovine blood infused with either of these compounds were dead within 12 hours. That timeframe is significant because transmission of pathogens via ticks' saliva into their human or animal hosts typically takes at least 12 hours and sometimes as many as 40 hours. These initial studies were conducted in artificial host feeding systems that contained a blood meal. Next, the researchers plan to test whether their treatment can in fact prevent pathogen transmission when ticks feed on rodents.

Ticks removed from the blood meal before they died were obviously sick, the researchers report. The ticks were uncoordinated and lethargic, and they couldn't walk well. The researchers attribute this behavior to an imbalance of potassium, sodium and chloride ions in the ticks. Normally, when a tick feeds, its saliva returns excess water and ions from human or animal blood back into the host. But the treated ticks were spitting out more ions despite producing much less saliva, disrupting their biological functions. "We think their nervous system wasn't working normally, and we suspect that's why we saw high mortality in the treated ticks," Li says.

Li and Swale will follow up on initial results suggesting that the ion channel is expressed in the salivary gland only during blood feeding and then disappears. And the researchers are zeroing in on the exact type of cells in which the ion channels are produced within the salivary gland. Once they have a more complete understanding of the reliance of blood feeding and pathogen transmission on Kir channel function, they hope industry can use their findings to create a commercial product such as a spray for gardens, or an injection or oral treatment for the agricultural industry for those animals at risk of getting tick bites. Swale notes that the method also seems to reduce saliva production and feeding in aphids and fruit flies, so it could potentially be used to control these agricultural pests, too.

SAN DIEGO, Aug. 26, 2019 -- Polyurethane waste is piling up in landfills, but scientists have a possible solution: They have developed a method to make polyurethane degradable. Once the original product's useful life is over, the polymer can easily be dissolved into ingredients to make new products such as superglue. These polyurethanes could also be used in microscopic capsules that break open to release cargo such as biocides.

The researchers will present their results today at the American Chemical Society (ACS) Fall 2019 National Meeting & Exposition. ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features more than 9,500 presentations on a wide range of science topics.

"Millions of tons of polyurethanes are produced every day, and they're widely used in foams, plastics, sneakers, insulation and other products," says Ephraim Morado, a doctoral student who is presenting the work at the meeting. "But when people finish using them, these materials are usually discarded." Waste polyurethane either ends up in landfills, or it's incinerated, which requires a lot of energy and generates toxic byproducts, he notes. "As an alternative, we want to develop the next generation of polyurethane that can degrade easily and be reprocessed into a new material that can then be commercialized, such as adhesives or paint," he says.

Of course, Morado isn't alone in seeking ways to reuse polymers. "A lot of people interested in recycling are trying to make polymers that will break down into their original starting materials and then remake the same polymer," says Steven Zimmerman, Ph.D., the project's principal investigator. "We're taking a very different, intermediate approach, which industry might be more interested in pursuing in the short term because it would be easier and cheaper," adds Zimmerman, whose lab is based at the University of Illinois at Urbana-Champaign. "We're trying to break our polymers down into some other starting materials that are familiar to industry."

The key difference between standard polyurethane and Morado's version is the incorporation of a hydroxy acetal as one of the monomers, alongside the traditional monomers. Zimmerman's team had first used a special iodine-containing acetal to make degradable polymers and polyacrylamide gels. In that earlier work, the polymer could be dissolved in slightly acidic water.

Morado invented a new type of acetal to incorporate in his unconventional polyurethane so he could dissolve the polymer in the absence of water. After months of investigation, he discovered that a solution of trichloroacetic acid in dichloromethane, an organic solvent, could dissolve the polyurethane at room temperature in just three hours. That's in contrast to the harsher conditions of the typical incineration method, which requires more than 1,400 F to avoid toxic gas formation. Unlike water, dichloromethane causes the material to swell. That expansion enables the acid to reach the backbone of polyurethane's molecular chains, which it can break at positions where the acetal groups are located. Degradation releases alcohol monomers that can then be used to make new products such as adhesives whose performance rivals superglue.

Morado created other acetal-containing polyurethanes that can be triggered to degrade when exposed to light. He used these materials to make microcapsules that could contain herbicides or even biocides for killing barnacles and other creatures that stick to ship hulls. He and Zimmerman are also developing adhesives that dissolve when treated with a few drops of acid in dichloromethane solvent. One potential application is on circuit boards, where a chip that had been securely glued to the board could be swapped out for a replacement if the original chip had failed.

In addition, the team is working on polyurethanes that can degrade under even milder conditions, such as exposure to vinegar. That would be particularly useful for, say, degradable sutures or household applications such as removable picture hangers.

SAN DIEGO, Aug. 26, 2019 -- Proteins are good for building muscle, but their building blocks also might be helpful for building sustainable organic batteries that could someday be a viable substitute for conventional lithium-ion batteries, without their safety and environmental concerns. By using synthetic polypeptides -- which make up proteins --- and other polymers, researchers have taken the first steps toward constructing electrodes for such power sources. The work could also provide a new understanding of electron-transfer mechanisms.

The researchers will present their results today at the American Chemical Society (ACS) Fall 2019 National Meeting & Exposition. ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features more than 9,500 presentations on a wide range of science topics.

"The trend in the battery field right now is to look at how the electrons are transported within a polymer network," says Tan Nguyen, a Ph.D. student who helped develop the project. "The beauty of polypeptides is that we can control the chemistry on their side chains in 3D without changing the geometry of the backbone, or the main part of the structure. Then we can systematically examine the effect of changing different aspects of the side chains."

Current lithium-ion batteries can harm the environment, and because the cost of recycling them is higher than manufacturing them from scratch, they often accumulate in landfills. At the moment, there is no safe way of disposing of them. Developing a protein-based, or organic, battery would change this situation.

"The amide bonds along the peptide backbone are pretty stable -- so the durability is there, and we can then trigger when they break down for recycling," says Karen Wooley, Ph.D., who leads the team at Texas A&M University. She envisions that polypeptides could eventually be used in applications such as flow batteries for storing electrical energy. "The other advantage is that by using this protein-like architecture, we're building in the kinds of conformations that are found in proteins in nature that already transport electrons efficiently," Wooley says. "We can also optimize this to control battery performance."

The researchers built the system using electrodes made of composites of carbon black, constructing polypeptides that contain either viologen or 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO). They attached viologens to the matrix used for the anode, which is the negative electrode, and used a TEMPO-containing polypeptide for the cathode, which is the positive electrode. The viologens and TEMPO are redox-active molecules. "What we've measured so far for the range, the potential window between the two materials, is about 1.5 volts, suitable for low-energy requirement applications, such as biosensors," Nguyen says.

For potential use in an organic battery, Nguyen has synthesized several polymers that adopt different conformations, such as a random coil, an alpha helix and a beta sheet, to investigate their electrochemical characteristics. With these peptides in hand, Nguyen is now collaborating with Alexandra Danielle Easley, a Ph.D. student in the laboratory of Jodie Lutkenhaus, Ph.D., also at Texas A&M University, to build the battery prototypes. Part of that work will include testing to better understand how the polymers function when they're organized on a substrate.

While this early stage research has far to go before organic-based batteries are commercially available, the flexibility and variety of structures that proteins can provide promise wide potential for sustainable energy storage that is safer for the environment.

SAN DIEGO, Aug. 26, 2019 -- You are what you eat -- right down to the microbiome living in your gut. Diet can affect which microbes are in the intestinal tract, and research has shown that harmful gut microbiome changes can lead to illnesses such as heart disease, obesity and cancer. Today, scientists will report the development of molecules that can change, or remodel, unhealthful gut microbiomes in mice into more healthful ones. The research could also someday be applied to other conditions related to diet.

The researchers will present their results at the American Chemical Society (ACS) Fall 2019 National Meeting & Exposition. ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features more than 9,500 presentations on a wide range of science topics.

"The gut microbiome contains hundreds of different species of bacteria and is where the largest concentration of bacteria living in us resides," says M. Reza Ghadiri, Ph.D., leader of the study. "If we all ate a healthy diet, exercised and didn't age, we wouldn't have problems with our gut microbiome and many diseases. But, that's not how all people live. Current methods aimed at improving the makeup of gut microbiomes have involved prebiotics, probiotics or drug therapies. Our goal was to take a totally new approach -- to remodel the microbiome."

The key to the research is a class of molecules called self-assembling cyclic D, L-α-peptides. They were created in Ghadiri's laboratory originally to kill pathogenic bacteria. Peptides are short chains of amino acids linked together; they are the building blocks of proteins. Ghadiri's peptides are not found in nature and have a highly specific mode of activity and selectivity against different bacterial species.

"Our hypothesis was that instead of killing bacteria, if we could selectively modulate the growth of certain bacteria species in the gut microbiome using our peptides, more beneficial bacteria would grow to fill the niche, and the gut would be 'remodeled' into a healthful gut," Ghadiri explains. "Our theory was that process would prevent the onset or progression of certain chronic diseases."

To test this hypothesis, Ghadiri chose cardiovascular disease and used a strain of mice known as LDL receptor knockout mice. "These mice have been bred to thrive on low-fat diets, but when they are fed a diet high in saturated fat -- a so-called Western diet -- they develop high plasma cholesterol, especially the LDL or 'bad' type," Ghadiri explains. "Within 10 to 12 weeks, they develop plaques in their arteries such as you would find in atherosclerosis patients." LDL receptor knockout mice are the "gold standard" to test the effectiveness of statins, which are widely used to reduce cholesterol levels.

To find the best peptides to test on the mouse model, the team developed a mass screening assay. The scientists grew a representative mouse microbiome in the lab and then tested various peptides with it. Ghadiri then selected two peptides that appeared to be the most effective for remodeling the mouse gut microbiome into a state resembling the gut microbiome of the mice on a low-fat diet.

The subsequent study included three groups of mice. One group was fed a low-fat diet, another group was fed a Western diet, and a third group was fed a Western diet plus oral doses of one or the other of the two peptides. From fecal samples, the researchers sequenced the gut microbiome from all three groups before and after dosing. They also measured the levels of molecules that affect the immune system, inflammation and metabolism, and examined the animals' arteries for plaques.

"Mice fed the Western diet with our peptides had a 50% reduction in total plasma cholesterol, and there was no significant plaque in the arteries, compared to the mice fed a Western diet and no peptides," Ghadiri says. "We also saw suppressed levels of molecules that increase inflammation and rebalanced levels of disease-relevant metabolites. These mice resembled those on a low-fat diet."

The mechanisms by which this takes place most likely involve genes that affect bile acids, which in turn affect the metabolism of cholesterol, as well as other genes that affect inflammatory processes such as atherosclerosis, Ghadiri says.

"This is the first time anyone has shown that there are molecules to purposefully remodel the gut microbiome and turn an unhealthful gut into a more healthful one," he says. "This opens up clear therapeutic possibilities. We can sequence the guts of individuals and eventually develop therapies."

CHAMPAIGN, Ill. -- Polyurethane is used in a wide range of materials, including paints, foam mattresses, seat cushions and insulation. These diverse applications generate large amounts of waste. A team at the University of Illinois has developed a method to break down polyurethane waste and turn it into other useful products.

The researchers will report their findings at the American Chemical Society National Meeting and Exposition.

In the U.S. alone, 1.3 million tons of polyurethane waste is generated each year. The waste usually ends up in landfills or is incinerated, a process that requires a large energy input and generates toxic byproducts.

"We want to solve the waste problem by repurposing polyurethane," said Ephraim Morado, a graduate student in the laboratory of chemistry professor Steven Zimmerman, who led the research.

Polyurethanes are made of two components that are hard to break down: isocyanates, which are composed of nitrogen, carbon and oxygen; and alcohol groups called polyols.

"The polyol is usually petroleum-based and is not degradable," Morado said. To address this difficulty, the team incorporated a more easily degraded chemical unit, an acetal, to the polyol. And because polyurethanes are water-resistant, the researchers invented an acetal unit that degrades in solvents other than water.

"When we add a combination of trichloroacetic acid and dichloromethane, the material swells and rapidly degrades at room temperature," Morado said.

The degradation products that are formed can then be repurposed to new materials. For example, the researchers were able to convert elastomers - a type of polyurethane used in rubber bands, packaging and car parts - into an adhesive glue.

"One of the challenges with our approach is that the starting material is costly," Zimmerman said. "We are trying to find a better, cheaper way to accomplish this. Our second hurdle will be to get a patent and find someone who is interested in commercializing it."

The researchers are testing the same technique on other polyurethane materials. They also hope to use milder solvents, such as vinegar, to carry out the degradation.

"The polyurethane materials have different properties based on the chemical structure of the isocyanate," Zimmerman said. "We can change the structure of the acetal accordingly."

In one of the largest studies of its kind, researchers at Orlando Health are making new progress in finding ways to detect a traumatic yet sinister brain injury -- and getting closer to preventing further damage.

Subconcussive injuries often show no symptoms or immediate effects, but can cause wear and tear on the brain over time with repeated injuries. The latest study, published in the journal BMJ Paediatrics Open, includes more than 700 emergency room patients -- children and adults. The study gets us closer to developing a standard blood test to spot these injuries as early as possible.

"A unique feature of this study is that it includes patients who hit their heads but have no symptoms," said Linda Papa, MD, lead author of the study and emergency medicine doctor at Orlando Health. "This group is rarely -- if ever -- included in biomarker studies."

The blood test looks for two proteins (GFAP and UCH-L1) found in our brains and released into blood after an injury -- higher levels of which could indicate a concussion or subconcussive injury. Dr. Papa has been studying these biomarkers for more than a decade. Some of her previous studies have focused on athletes, but now she's expanding her research on subconcussive injuries to the general population and all age groups.

Historically, people who suffer head trauma without concussion symptoms may have been classified as having "no injury." Plus, there are very few studies addressing the impact of subconcussive injuries following head trauma in the civilian population, as opposed to military members or athletes.

"It is estimated that up to 3.8 million concussions occur in the U.S. annually from organized and recreational sports -- and there are more than 2 million ER visits for traumatic brain injuries and concussions," said Papa. "It is a significant health problem in both athletes and non-athletes."

The study looked at patients with concussions, those with head trauma without overt signs of concussion and those with body trauma without head trauma or concussion. Elevated levels of both biomarkers were found in patients with nonconcussive head trauma, potentially signaling a subconcussive brain injury.

Furthermore, this blood test goes even deeper than a routine CT scan. Previous studies using the two biomarkers have focused on detecting brain lesions, but subconcussive injuries don't necessarily result in lesions -- and even the vast majority of patients with concussions tend to have a normal CT scan.

"The study includes an array of patients with different injury mechanisms, including car crashes, falls and bicycle accidents in addition to recreational and sports injuries," said Papa. "It is not limited to just one group of injury types."

A number of companies are now working on developing a bench-top device for the hospital lab -- along with a point-of-care handheld device that can be used to detect subconcussive injuries in a variety of settings -- including sporting events, in the ambulance, at the scene of car crashes, in military settings or even after a simple bump to the head.

"The technology is only a year or two away," said Papa.

Tempe, Ariz. (August 26, 2019) - Nearly one in four Arizona teens have used a highly potent form of marijuana known as marijuana concentrate, according to a new study by Arizona State University researchers.

Among nearly 50,000 eighth, 10th, and 12th graders from the 2018 Arizona Youth Survey, a biennial survey of Arizona secondary school students, one-third (33%) had tried some form of marijuana, and nearly a quarter (24%) had tried marijuana concentrate.

Marijuana concentrates have about three times more THC, the constituent of marijuana that causes the "high," than a traditional marijuana flower. This is concerning because higher doses of THC have been linked to increased risk of marijuana addiction, cognitive impairment and psychosis, said the study's lead researcher, Madeline Meier, an ASU assistant professor of psychology.

The research team also found that teens who used concentrates had more risk factors for addiction. The researchers compared teens who had used marijuana concentrates with teens who had used some form of marijuana but not marijuana concentrates and teens who had never used any form of marijuana on known risk factors for addiction, such as lower perceived risk of harm of marijuana, peer substance use, parental substance use, academic failure and greater perceived availability of drugs in the community. They found that teens who had used marijuana concentrates were worse off on every addiction risk factor.

"This is important because it shows that teens who have a diverse array of risk factors for developing marijuana addiction may be further amplifying their risk for addiction by using high-THC marijuana concentrates," explained study co-author, Dustin Pardini, an associate professor in ASU's School of Criminology & Criminal Justice.

The study "Cannabis Concentrate Use in Adolescents," is published in the early online edition (Aug. 26, 2019) of Pediatrics.

The team - which includes ASU researchers Meagan Docherty, School of Criminology & Criminal Justice; Scott Leischow, College of Health Solutions; and Kevin Grimm, Department of Psychology - also found that teens who had used concentrates had much higher rates of e-cigarette use. One explanation for this might be that teens are using e-cigarettes to vape marijuana concentrate, according to Meier. Earlier studies, including those by Meier, have shown that youth put marijuana in e-cigarettes to conceal their marijuana use.

"Vaping marijuana can be passed off as nicotine vaping," Meier explained.

This finding reinforces the recent decision by the Food and Drug Administration to impose new restrictions on e-cigarettes and their constituents as a means of reducing marijuana use, according to the researchers.

Marijuana concentrates don't look like the traditional marijuana flower. Concentrates can look like wax, oil, or a brittle substance that shatters easily.

"What concerns me most is that parents might have no idea that their child is using marijuana, especially if their child is using marijuana concentrate," said Meier. "Marijuana is not harmless, particularly for adolescents."

Meier's earlier research suggests that frequent marijuana use from adolescence through adulthood is associated with IQ decline. Pardini's prior research has linked regular marijuana use during adolescence with the emergence of persistent subclinical psychotic symptoms.

The researchers' next steps are to ascertain if concentrate users do in fact exhibit higher rates of addiction, cognitive impairment and psychosis.

Theoretical physicists from SISSA and the University of California at Davis lay brand new foundations to such a fundamental process as heat transport in materials, which finally allow crystals, polycrystalline solids, alloys, and glasses to be treated on the same solid footing. This feat opens the way to the numerical simulation of the thermal properties of a vast class of materials that, while being key in important technologies such as energy saving, conversion, scavenging, and storage, or heat dissipation or shielding, and even in the planetary sciences, have thus far dodged a proper computational treatment. The research has been published in Nature Communications.

Heat flows from the warm to the cool as time flows from the past to the future. In a sense, heat flow is the defining feature of the arrow of time. In spite of the foundational importance of heat transport, the father of its modern theory, Sir Rudolph Peierls, wrote in 1961: "It seems there is no problem in modern physics for which there are on record as many false starts, and as many theories which overlook some essential feature, as in the problem of the thermal conductivity of nonconducting crystals." Half a century has passed since and still now heat transport is one of the most elusive chapters of theoretical materials science. As a matter of fact, no unified approach existed so far to treat crystals and (partially) disordered solids on a equal footing, thus tampering with the efforts of generations of materials scientists to simulate different materials, or different states of a same material, occurring in a same physical system or device with the same accuracy.

This major gap has been finally closed by a group of researchers from SISSA and UC Davis, led by Stefano Baroni and Davide Donadio in the framework of the MAX EU Centre for Supercomputing Applications, who have developed a new methodology, based on the Green-Kubo theory of linear response and concepts from lattice dynamics, that nicely bridges different approaches applying to crystals and glasses. The new methodology naturally accounts for quantum mechanical effects, thus finally enabling the predictive modelling of heat transport in complex disordered materials also in the low-temperature quantum regime, to which none of the techniques thus available would apply.

This feat will thus empower scientists and engineers to understand and design heat transport for a broad variety of applications. Achieving extremely low thermal conductivity is essential for thermoelectric energy harvesting and solid-state cooling, thermal insulation and thermal barrier coating, while high thermal conductivity is key for heat management in high-power electronics, batteries, and photovoltaics. All the materials utilised in these applications are nanostructured, polycrystalline, highly defective or even glassy: finally they can be studied with high accuracy, within a unified and practicable framework.

Modern flamingoes employ filter feeding and their feces are, as a result, rich in remains of microscopically-small aquatic prey. Very similar contents are described from more than 150 million year old pterosaur droppings in a recent paper in PeerJ. This represents the first direct evidence of filter-feeding in Late Jurassic pterosaurs and demonstrates that their diet and feeding environment were similar to those of modern flamingoes.

Pterosaurs were a diverse group of flying reptiles that roamed the skies during the age of dinosaurs. Skeletal fossils suggest that they, just like modern birds, adapted to diverse lifestyles and feeding habits. Direct evidence on diets such as gut contents, however, are rare and only known from a few pterosaur species.

Coprolites, that is fossil droppings, are surprisingly common fossils and they potentially hold valuable information on the diet of extinct animals. Unfortunately, it is often difficult to know which animal produced which dropping.

In a recent paper, researchers from Uppsala University and the Polish Academy of Sciences describe the contents of three coprolites collected from a surface with abundant pterosaur footprints in the Wierzbica Quarry in Poland. The coprolites' size, shape and association to the tracks suggest that they were produced by pterosaurs, most probably belonging to a group called Ctenochasmatidae.

The fossil droppings were scanned using synchrotron microtomography, which works in a similar way to a CT-scanner in a hospital but with much stronger x-ray beams. This makes it possible to image the contents of fossils in three dimensions. The scans of the pterosaur coprolites revealed many microscopic food remains including foraminifera (small amoeboid protists with external shells), small shells of marine invertebrates and possible remains of polychaete worms.

"A reasonable explanation for how a pterosaur big enough to have produced the droppings ingested such small prey is through filter feeding," says Martin Qvarnström, PhD student at Uppsala University and one of the authors of the article.

Some ctenochasmid pterosaurs are thought to have been filter feeders. Pterodaustro, which comes from the Cretaceous and is thus slightly younger than the Polish coprolites, possessed a sieving basket consisting of many long, thin teeth and was certainly a filter feeder. Older ctenochasmids did not possess such an obvious sieving basket, but some had elongated snouts with many slender teeth, also interpreted as adaptations for filter feeding. These pterosaurs were around at the time the droppings were made, and as the footprints from the site have also been attributed to ctenochasmids it is likely that such pterosaurs produced both the droppings and the footprints.

The modern Chilean flamingo, which is a filter feeder, can produce droppings full of foraminifera when feeding in coastal wetlands.

"The similar contents of the droppings of these flamingos and the pterosaur coprolites could be explained by similar feeding environments and mesh sizes of the filter-feeding apparatus. It appears therefore that the pterosaurs which produced the footprints and droppings found in Poland were indeed the flamingos of the Late Jurassic," says Martin Qvarnström.

How come today's conservatives are more liberal than yesterday's liberals? Why has the public opinion in large parts of the world shifted so rapidly in favour of gay and lesbian rights, but been virtually unchanged on other contested issues such as abortion rights? A study from a Swedish team of researchers recently published in the social science journal Nature Human Behaviour answers several critical questions on how public opinion changes on moral issues. They have created a scientific model that can predict public opinion changes on moral issues.

"Our study shows that the connection between a certain moral position and the type of argument that is raised in its defence, can predict what opinions will gain ground", says Pontus Strimling, research leader at Institute for Futures Studies in Stockholm, Sweden.

The four researchers - mathematicians, psychologists and social scientists at the Institute for Futures Studies and Stockholm University - have built mathematical models based on new findings within moral psychology and used these to predict opinion changes on moral issues over time. The predictions were then compared with over 40 years of data on public opinion. Their conclusion is that the key characteristic of opinions that gain ground is that they are supported by arguments about what is fair and what does not cause harm to others.

"The connection is very clear. And the model can be used to make qualified assessments about the future", says Pontus Strimling.

Opinions based on other classical grounds used to determine right and wrong actions - loyalty, authority, purity, religion - can gain support temporarily, but over time opinions based on these arguments lose support all over the political spectrum. The stronger the connection an opinion has to arguments about fairness and harm, the greater is the probability that it will gain ground in the public opinion. Also, the stronger the connection is, the faster the change will come.

"This can explain why public opinion have changed so rapidly in favour of gay and lesbian rights. Arguments in favour of same sex marriage for instance are based on principles of fairness, while arguments against are based on authority and purity. Over time the latter arguments lose support. On other issues such as support for active euthanasia or to ban pornography, there are powerful arguments on both sides so change goes slower", says Pontus Strimling.