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LOS ANGELES (STRICTLY EMBARGOED UNTIL JAN. 27, 2020 @ 11AM EST) -- People who develop Parkinson's disease before age 50 may have been born with disordered brain cells that went undetected for decades, according to new Cedars-Sinai research. The research points to a drug that potentially might help correct these disease processes.

Parkinson's occurs when brain neurons that make dopamine, a substance that helps coordinate muscle movement, become impaired or die. Symptoms, which get worse over time, include slowness of movement, rigid muscles, tremors and loss of balance. In most cases, the exact cause of neuron failure is unclear, and there is no known cure.

At least 500,000 people in the U.S. are diagnosed with Parkinson's each year, and the incidence is rising. Although most patients are 60 or older when they are diagnosed, about 10% are between 21 and 50 years old. The new study, published in the journal Nature Medicine, focuses on these young-onset patients.

"Young-onset Parkinson's is especially heartbreaking because it strikes people at the prime of life," said Michele Tagliati, MD, director of the Movement Disorders Program, vice chair and professor in the Department of Neurology at Cedars-Sinai. "This exciting new research provides hope that one day we may be able to detect and take early action to prevent this disease in at-risk individuals." Tagliati was a co-author of the study.

To perform the study, the research team generated special stem cells, known as induced pluripotent stem cells (iPSCs), from cells of patients with young-onset Parkinson's disease. This process involves taking adult blood cells "back in time" to a primitive embryonic state. These iPSCs can then produce any cell type of the human body, all genetically identical to the patient's own cells. The team used the iPSCs to produce dopamine neurons from each patient and then cultured them in a dish and analyzed the neurons' functions.

"Our technique gave us a window back in time to see how well the dopamine neurons might have functioned from the very start of a patient's life," said Clive Svendsen, PhD, director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute and professor of Biomedical Sciences and Medicine at Cedars-Sinai. He was the study's senior author.

The researchers detected two key abnormalities in the dopamine neurons in the dish:

Accumulation of a protein called alpha-synuclein, which occurs in most forms of Parkinson's disease.

Malfunctioning lysosomes, cell structures that act as "trash cans" for the cell to break down and dispose of proteins. This malfunction could cause alpha-synuclein to build up.

"What we are seeing using this new model are the very first signs of young-onset Parkinson's," said Svendsen. "It appears that dopamine neurons in these individuals may continue to mishandle alpha-synuclein over a period of 20 or 30 years, causing Parkinson's symptoms to emerge."

The investigators also used their iPSC model to test a number of drugs that might reverse the abnormalities they had observed. They found that that one drug, PEP005, which is already approved by the Food and Drug Administration for treating precancers of the skin, reduced the elevated levels of alpha-synuclein in both the dopamine neurons in the dish and in laboratory mice.

The drug also countered another abnormality they found in the patients' dopamine neurons - elevated levels of an active version of an enzyme called protein kinase C - although the role of this enzyme version in Parkinson's is not clear.

For the next steps, Tagliati said the team plans to investigate how PEP005, currently available in gel form, might be delivered to the brain to potentially treat or prevent young-onset Parkinson's. The team also plans more research to determine whether the abnormalities the study found in neurons of young-onset Parkinson's patients also exist in other forms of Parkinson's.

"This research is an outstanding example of how physicians and investigators from different disciplines join forces to produce translational science with the potential to help patients," said Shlomo Melmed, MB, ChB, executive vice president of Academic Affairs and dean of the Medical Faculty at Cedars-Sinai. "This important work is made possible by the dual leadership of Cedars-Sinai as both a distinguished academic institution and an outstanding hospital."

At a time when scams seem all around us and fake news appears to be on the rise, you might be relieved to know that even young children show some impressive skills when it comes to identifying poor sources of information, suggests new research from the University of British Columbia.

In a new study published today in the Public Library of Science ONE (PLOS ONE), researchers found that young children between the age of four and five not only prefer to learn from people who appear confident, they also keep track of how well the person's confidence has matched with their knowledge and accuracy in the past (a concept called 'calibration') and avoid learning new information from people who have a history of being overconfident. This is the first research of its kind to demonstrate that children track a person's calibration.

"We now know that children are even more savvy at social learning, learning from others, than we previously thought," said Susan Birch, the study's lead author and a UBC psychology associate professor. "They don't just prefer to learn from anyone who is confident; they avoid learning from people who have confidently given wrong information in the past."

Birch says this ability makes children less likely to fall prey to misinformation and ultimately ensures they are learning the most accurate information.

Interestingly, despite these sophisticated reasoning abilities in young children, they still don't have an adult-like understanding of confidence, and its opposite hesitancy, even by eight years old.

"Children appear to treat hesitancy as separate from, rather than the opposite of, confidence," said Birch. "They don't fully understand what it means to be hesitant and the inferences they apply to whether a person's confidence is justified don't get applied to hesitancy."

For example, adults recognize responding hesitantly is justified when you don't know the answer to something, but the children in their experiments did not recognize this.

Across three experiments, the researchers tested 662 children between the ages of three and 12. The researchers showed them pre-recorded videos of actors displaying justified and unjustified confidence as well as justified and unjustified hesitancy and then documented who the children preferred to learn new words from and who they found smarter.

The researchers say that the children may be quicker to learn that a person's confidence can be justified (match with their level of knowledge) than to learn that a person's hesitancy can also be justified, because their brains are wired to attend more to clues than misinformation. In other words, learning to trust people when they are justifiably hesitant may be harder than learning to mistrust people when they are unjustifiably confident. More research will need to be conducted to find out when children start having a better understanding of hesitancy.

As a result of this study, researchers recommend that parents and educators should not only pay attention to what they're communicating to children but also how they're doing it, as it may undermine their credibility in the long term.

In the same way that a single piece of a puzzle fits into the whole, the molecule hypoxanthine binds to a ribonucleic acid (RNA) chain, which then changes its three-dimensional shape within a second and in so doing triggers new processes in the cell. Thanks to an improved method, researchers are now able to follow almost inconceivably tiny structural changes in cells as they progress - both in terms of time as well as space. The research group led by Professor Harald Schwalbe from the Center for Biomolecular Magnetic Resonance (BMRZ) at Goethe University has succeeded, together with researchers from Israel, in accelerating a hundred thousand-fold the nuclear magnetic resonance (NMR) method for investigating RNA.

"This allows us for the first time to follow the dynamics of structural changes in RNA at the same speed as they occur in the cell," says Schwalbe, describing this scientific breakthrough, and stresses: "The team headed by Lucio Frydman from the Weizmann Institute in Israel made an important contribution here."

The new types of NMR experiments use water molecules whose atoms can be followed in a magnetic field. Schwalbe and his team produce hyperpolarized water. To do so, they add a compound to the water which has permanently unpaired electron radicals. The electrons can be aligned in the magnetic field through excitation with a microwave at -271°C. This unnatural alignment produces a polarization which is transferred at +36°C to the polarization of the hydrogen atoms used in the NMR. Water molecules polarized in this way are heated in a few milliseconds and transfered, together with hypoxanthine, to the RNA chain. The new approach can in general be applied to observe fast chemical reactions and refolding changes in biomolecules at atomic level.

In particular the imino groups in RNA can be closely analyzed using this method. In this way, the researchers were able to measure structural changes in RNA very accurately. They followed a small piece of RNA from Bacillus subtilis, which changes its structure during hypoxanthine binding. This structural change is part of the regulation of the transcription process, in which RNA is being made from DNA. Such small changes at molecular level steer a large number of processes not only in bacteria but also in multicellular organisms and even humans.

This improved method will in future make it possible to follow RNA refolding in real time - even if it needs less than a second. This is possible under physiological conditions, that is, in a liquid environment and with a natural molecule concentration at temperatures around 36 °C. "The next step will now be not only to study single RNAs but hundreds of them, in order to identify the biologically important differences in their refolding rates," says Boris Fürtig from Schwalbe's research group.

«First prize is a Cadillac Eldorado, second prize a set of steak knives, third prize you're fired». What Alec Baldwin introduces in a famous Glengarry Glen Ross scene is a particularly crude form of performance ranking and what follows in the movie is a story of cheating, betrayal, and infighting as actors attempt to get ahead in the raking. In the real life, the risks with performance rankings are not too far off. Rankings can help attract and retain top talent who thrive in competitive environments, improve the speed of group decision-making, and have been known to reduce biases in performance evaluations. But, rankings have a dark side--they often enhance competitive pressures, making them potentially problematic for the maintenance of continued cooperation. Despite these potential drawbacks, rankings are still widely used to incentivize employees and successful companies are able to rank employees while managing to achieve high levels of cooperation.

Making use of an experiment, Cassandra Chambers, an Assistant Professor at Bocconi University's Department of Management and Technology, highlights on the one hand that performance rankings do in fact dramatically reduce levels of cooperation in groups and, on the other, that sharing reputational information (individuals' histories of pro-social contributions) almost completely offsets the disruptive effect of performance ranks.

In her experimental setting, the introduction of performance rank information reduced the odds that a participant would cooperate to 0.36 times those in the control condition who did not receive any information. However, the odds of cooperating for participants who received reputation information (i.e., how much others gave in the past) alongside rank information were 1.87 times that of participants who just received information about their rank.

In the lab experiment, 592 people (students, lecturers and staff of an American university), divided into 74 groups, were asked to decide whether or not to give points with other participants in an extended period of decision-making. After some rounds, when an organic routine of cooperation was established, a ranking system was introduced and participants were provided with information about their own rank.

The propensity to give to others plummeted, due to concerns about losing one's rank position or perceptions of unfairness. Furthermore, the drop was larger in the groups that had proved to be more generous in the first stage of the game, suggesting that performance rankings can be particularly disruptive in the most cooperative cultures.

However, it turns out that this disruptive effect of rank can be largely offset by the introduction of information about others' rates of giving. After a brief disruption in cooperation levels, groups that received both types of information restored cooperation to almost pre-disruption levels.

«Our key finding is that displaying prosocial reputations - giving recognition to helpers - is a mechanism that allows systems of cooperation to withstand disruptive forces created by performance rankings. In a way, managers may be able to have the best of both worlds--a thriving system of cooperation without sacrificing a ranking system that motivates high levels of effort», Prof. Chambers says.

«Put differently», she continues, «our research suggests that managers should be very careful utilizing performance rankings, if they don't want to disrupt a cooperative culture, but that minor efforts to provide recognition for prosocial activities may greatly shore up cooperative cultures. For example, managers can make a special effort to offer public recognition for employees' prosocial contributions, use peer-to-peer bonus systems that enable employees to recognize and reward helpers, and create formal performance reviews that explicitly focus on rewarding helpful behaviors.»

Compared with routine care, weight loss surgery was linked with a reduced risk of hypertension, heart failure, and early death in a study based on information from a primary care database in the UK. The findings are published in BJS (British Journal of Surgery).

Although clinical studies have shown that weight loss surgery may reduce the risk of developing and dying from cardiovascular disease, studies using real-world data are limited. In the BJS study, investigators analysed data on 5,170 patients with obesity who underwent weight loss surgery and 9,995 patients with obesity who received only routine care.

Patients who underwent surgery had a 30% lower risk of dying from any cause, a 59% lower risk of developing hypertension, and a 43% lower risk of developing heart failure, compared with patients who did not undergo surgery.

Also, patients who underwent gastric bypass surgery--a specific kind of weight loss surgery--had a lower risk of cardiovascular diseases in general compared with patients who did not have surgery.

"Obesity is a chronic disease that is associated with many comorbidities and complications. Our results show the benefits of weight loss surgery in reducing the health burdens of obesity in real-world data," said senior author Abd A. Tahrani, MD, of Queen Elizabeth Hospital, in the UK. "This is important considering the lower provision and availability of weight loss surgery in the UK compared with other European countries that have a lower prevalence of obesity. Weight loss surgery is an important treatment option in people with obesity, and improved access can help reduce the burden of this disease."

Weight loss surgery may reduce the risk of developing colorectal cancer by one-third, according to an analysis of all relevant published studies. The findings are published in BJS (British Journal of Surgery).

Obesity increases the risk of many conditions, including type 2 diabetes, cardiovascular diseases, and most cancers, including colorectal cancer. The BJS analysis, which included seven studies with a total of 1,213,727 patients and an average follow-up of seven years, was conducted because individual studies have presented conflicting results.

The overall risk of developing colorectal cancer was 3 in 1,000 in patients with obesity who underwent weight loss surgery, compared with 4 in 1,000 in those who did not.

"Day by day, the scientific community is continuing to uncover the benefits of weight loss surgery, and this paper affirms this," said lead author Sulaiman Almazeedi, MD, of Jaber Al-Ahmed Hospital, in Kuwait. "Obesity today remains one of the most preventable causes of morbid disease and early death, and despite the controversy, we believe weight loss surgery can be an important tool in tackling this epidemic."

HOUSTON - (Jan. 27, 2020) - That banana peel, turned into graphene, can help facilitate a massive reduction of the environmental impact of concrete and other building materials. While you're at it, toss in those plastic empties.

A new process introduced by the Rice University lab of chemist James Tour can turn bulk quantities of just about any carbon source into valuable graphene flakes. The process is quick and cheap; Tour said the "flash graphene" technique can convert a ton of coal, food waste or plastic into graphene for a fraction of the cost used by other bulk graphene-producing methods.

"This is a big deal," Tour said. "The world throws out 30% to 40% of all food, because it goes bad, and plastic waste is of worldwide concern. We've already proven that any solid carbon-based matter, including mixed plastic waste and rubber tires, can be turned into graphene."

As reported in Nature, flash graphene is made in 10 milliseconds by heating carbon-containing materials to 3,000 Kelvin (about 5,000 degrees Fahrenheit). The source material can be nearly anything with carbon content. Food waste, plastic waste, petroleum coke, coal, wood clippings and biochar are prime candidates, Tour said. "With the present commercial price of graphene being $67,000 to $200,000 per ton, the prospects for this process look superb," he said.

Tour said a concentration of as little as 0.1% of flash graphene in the cement used to bind concrete could lessen its massive environmental impact by a third. Production of cement reportedly emits as much as 8% of human-made carbon dioxide every year.

"By strengthening concrete with graphene, we could use less concrete for building, and it would cost less to manufacture and less to transport," he said. "Essentially, we're trapping greenhouse gases like carbon dioxide and methane that waste food would have emitted in landfills. We are converting those carbons into graphene and adding that graphene to concrete, thereby lowering the amount of carbon dioxide generated in concrete manufacture. It's a win-win environmental scenario using graphene."

"Turning trash to treasure is key to the circular economy," said co-corresponding author Rouzbeh Shahsavari, an adjunct assistant professor of civil and environmental engineering and of materials science and nanoengineering at Rice and president of C-Crete Technologies. "Here, graphene acts both as a 2D template and a reinforcing agent that controls cement hydration and subsequent strength development."

In the past, Tour said, "graphene has been too expensive to use in these applications. The flash process will greatly lessen the price while it helps us better manage waste."

"With our method, that carbon becomes fixed," he said. "It will not enter the air again."

The process aligns nicely with Rice's recently announced Carbon Hub initiative to create a zero-emissions future that repurposes hydrocarbons from oil and gas to generate hydrogen gas and solid carbon with zero emission of carbon dioxide. The flash graphene process can convert that solid carbon into graphene for concrete, asphalt, buildings, cars, clothing and more, Tour said.

Flash Joule heating for bulk graphene, developed in the Tour lab by Rice graduate student and lead author Duy Luong, improves upon techniques like exfoliation from graphite and chemical vapor deposition on a metal foil that require much more effort and cost to produce just a little graphene.

Even better, the process produces "turbostratic" graphene, with misaligned layers that are easy to separate. "A-B stacked graphene from other processes, like exfoliation of graphite, is very hard to pull apart," Tour said. "The layers adhere strongly together.

But turbostratic graphene is much easier to work with because the adhesion between layers is much lower. They just come apart in solution or upon blending in composites.

"That's important, because now we can get each of these single-atomic layers to interact with a host composite," he said.

The lab noted that used coffee grounds transformed into pristine single-layer sheets of graphene.

Bulk composites of graphene with plastic, metals, plywood, concrete and other building materials would be a major market for flash graphene, according to the researchers, who are already testing graphene-enhanced concrete and plastic.

The flash process happens in a custom-designed reactor that heats material quickly and emits all noncarbon elements as gas. "When this process is industrialized, elements like oxygen and nitrogen that exit the flash reactor can all be trapped as small molecules because they have value," Tour said.

He said the flash process produces very little excess heat, channeling almost all of its energy into the target. "You can put your finger right on the container a few seconds afterwards," Tour said. "And keep in mind this is almost three times hotter than the chemical vapor deposition furnaces we formerly used to make graphene, but in the flash process the heat is concentrated in the carbon material and none in a surrounding reactor.

"All the excess energy comes out as light, in a very bright flash, and because there aren't any solvents, it's a super clean process," he said.

Luong did not expect to find graphene when he fired up the first small-scale device to find new phases of material, beginning with a sample of carbon black. "This started when I took a look at a Science paper talking about flash Joule heating to make phase-changing nanoparticles of metals," he said. But Luong quickly realized the process produced nothing but high-quality graphene.

Atom-level simulations by Rice researcher and co-author Ksenia Bets confirmed that temperature is key to the material's rapid formation. "We essentially speed up the slow geological process by which carbon evolves into its ground state, graphite," she said. "Greatly accelerated by a heat spike, it is also stopped at the right instant, at the graphene stage.

"It is amazing how state-of-the-art computer simulations, notoriously slow for observing such kinetics, reveal the details of high temperature-modulated atomic movements and transformation," Bets said.

Tour hopes to produce a kilogram (2.2 pounds) a day of flash graphene within two years, starting with a project recently funded by the Department of Energy to convert U.S.-sourced coal. "This could provide an outlet for coal in large scale by converting it inexpensively into a much-higher-value building material," he said.

What can be reused and what can be disposed of? Cells also face this tricky task. Researchers from the Biozentrum of the University of Basel have now discovered a cellular machine, called FERARI, that sorts out usable proteins for recycling. In Nature Cell Biology, they explain how FERARI works and why it is so special.

Recycling, the reuse of material, saves energy and resources. No wonder that nature also recycles. In the cells, tiny organelles, so-called endosomes, separate the delivered cellular material into reusable material and waste.

However, how exactly the endosomes sort the material remains an enigma. A research team led by Professor Anne Spang at the Biozentrum, University of Basel, has now discovered that FERARI is a key player in this process. FERARI distributes the recyclable molecules, mainly transport proteins and receptors, and reintroduces them into the cellular cycle. In this way, valuable cell components do not have to be constantly produced anew, which not only saves energy but also time.

Recycling and disposal by endosomes

Endosomes are small membrane-bound vesicles inside animal and plant cells. During their maturation, endosomes pass through various stages in which they carry out different tasks. The early endosomes mainly absorb material, the more mature ones sort out the recyclable material and the late endosomes dispose of the non-reusable residual waste.

FERARI is a central distribution station

In the sorting endosomes, the researchers have now demonstrated that FERARI acts as a kind of distribution platform. "FERARI consists of different proteins and is responsible for ensuring that vesicles, used for recycling, dock onto the sorting endosomes and can be loaded with reusable material," explains Spang.

The special feature of FERARI is that it coordinates both the fusion of the endosome with the recycling vesicle (kiss) as well as the pinching off of the recycling vesicle after it has been loaded with the cargo (run). The loaded vesicles then transport their cargo to the site of action, the cell membrane. "Our work contradicts the current thinking which assumes that all recycling vesicles are pinched off directly from the endosome," says Spang. "We are the first to show this kind of 'kiss-and-run' mechanism."

Disturbed recycling is associated with diseases

If FERARI does not work properly, recycling in the cell is impaired. Disorders in cellular transport and recycling processes can lead to a variety of diseases, including cancer, metabolic and neurodegenerative diseases.

Roughly one-third of young males and 1 in 10 females in rural communities have carried a handgun, reports a new University of Washington study. And, the study found, many of those rural kids started carrying as early as the sixth grade.

"This is one of the first longitudinal studies of rural adolescent handgun carrying across multiple states in the U.S. It provides evidence that youth handgun carrying in these settings is not uncommon," said lead author Dr. Ali Rowhani-Rahbar, a UW associate professor of epidemiology and Co-Director of Firearm Injury & Policy Research Program at Harborview Injury Prevention & Research Center.

The study of rural communities across the country, published Jan. 24 in the Journal of Adolescent Health, also found the practice was associated with pro-handgun attitudes and with having friends who carry handguns.

Knowing that some kids as young as 12 report carrying a handgun indicates that firearm violence and injury-related prevention programs may need to be introduced early in a child's life, researchers say.

"Youth handgun carrying and firearm violence are often presented as an exclusively inner-city problem," said Dr. Rowhani-Rahbar, who is the Bartley Dobb Professor for the Study and Prevention of Violence in the UW School of Public Health. "However, that focus should not come at the cost of ignoring non-urban settings. Indeed, youth in some rural areas experience similar or even higher rates of handgun carrying and certain forms of interpersonal violence -- for example, being attacked or threatened with a weapon -- than their counterparts in urban areas."

Specifically, the researchers found:

In sixth grade, 11.5% of males and 2.8% of females had carried a handgun within the past year.

From the sixth grade to age 19, 33.7% of males and 9.6% of females reported carrying at least once during that time.

Of those who carried, 34% of males and 29.3% of females had carried a handgun for the first time in the sixth grade. However, of those who carried, a majority of both sexes carried a handgun only once over the seven years.

More kids who carried had friends who did the same. For instance, in the 10th grade, 63% of males who carried had a friend who carried. And of those young males who had not carried a handgun, only 6% had a friend who did. The same pattern was apparent for females.

A far higher percentage of kids who carried also endorsed pro-handgun norms. For instance, they were much more likely to view taking a handgun to school or work as "not very wrong" than their non-carrying peers.

The study of handgun carrying among rural youth is based on 2,002 kids who started answering survey questionnaires in the sixth grade when they lived in 12 rural communities in seven states. Participants took annual surveys over a seven-year period, 2005 to 2012, as part of the UW's Community Youth Development Study. That larger study is designed to evaluate the university's Communities That Care program, which helps communities take a broad approach to preventing youth problem behaviors.

The 12 communities included in the new study had been randomly selected to not implement the Communities That Care prevention program, which has been found to reduce a variety of risky behaviors among youth, including carrying a handgun.

"We looked at handgun questions only in the control communities, those that did not receive the risk prevention program," Dr. Rowhani-Rahbar explained. "This is because we did not want to measure the effect of the Communities That Care intervention in this study. We wanted to characterize the age at initiation, prevalence and patterns of handgun carrying in the absence of the intervention."

The dangers of young people's exposure to guns are well-documented -- firearm injury is second only to vehicle crashes as a leading cause of death among U.S. kids, with 65% of those deaths resulting from a conflict with another young person. Carrying firearms is associated with adolescent bullying, physical fighting and assault. The researchers also point out that federal law prohibits people under age 18 from possessing a handgun.

This is just the first step toward studying health effects, Dr. Rowhani-Rahbar said. A lack of foundational information about youth handgun carrying in rural settings means studies of the causes and consequences of this behavior have also been missing. The team now plans to study these factors -- risk of violence or injury among rural youth who carry a handgun compared to those who do not, for instance -- in the near future.

Could artificial intelligence improve educational and clinical decisions made by your child's teacher, or your mental-health professional or even your medical doctor? Yes, indeed, says a study by an UdeM psychoeducator and behaviour analyst published in Perspectives on Behavior Science.

When working with persons who experience daily challenges such as autism, ADHD, learning difficulties or mental health issues, practitioners often rely on their professional judgment to determine whether behavior is improving following intervention. But that's not enough, according to the study.

"Unfortunately, experts often disagree when drawing conclusions based on behavioral data, which may lead to the premature interruption of an effective intervention or to the continuation of an ineffective treatment," said lead author Marc Lanovaz, a researcher at the Institut universitaire en santé mentale de Montréal.

To find a better way, Lanovaz and colleagues at UdeM-affiliated Polytechnique Montréal and Manhattanville College in Purchase, N.Y. independently labeled more than 1,000 graphs and trained new decision models using machine learning.

The conclusions drawn by these models were then compared to those produced by the visual-aid tool most studied by today's researchers.

"Although we always assumed that our models would perform well, we did not expect them to be as accurate," said Lanovaz, an associate professor who heads the Applied Behavioral Research Lab at UdeM's School of Psychoeducation.

"Not only did the conclusions drawn by our models match the interpretation of experts more frequently than the most popular tool, they also produced more accurate conclusions on novel data," he said.

According the authors, these models could eventually support practitioners in making better decisions about the effectiveness of their interventions.

"By improving decision-making, practitioners should more rapidly and accurately identify effective and ineffective behavioral interventions," said Lanovaz. "Ultimately, we hope this change would translate to better tailored interventions for people with developmental disabilities, mental health issues or learning difficulties."

A research team from the Fraunhofer Society and the Technical University of Munich (TUM) led by chemist Volker Sieber has developed a new polyamide family which can be produced from a byproduct of cellulose production - a successful example for a more sustainable economy with bio-based materials.

Polyamides are important plastics. They can be found in ski bindings and in cars or items of clothing. Commercially, they have been made predominantly from crude oil up until now; there are just a few "green" alternatives, such as polyamides based on castor oil.

Bio-based compounds are often significantly more expensive to produce and have therefore only been able to penetrate the market before now if they have had particular properties.

A team led by Volker Sieber, Professor of the Chemistry of Biogenic Raw Materials at TU Munich, has now developed a completely new polyamide family which can be produced from a byproduct of cellulose production.

New polyamide family

The biogenic starting material, (+)-3-carene, is made up of two rings which are fused to one another. The chemists at the TUM and the Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB) in Straubing have now modified one of the rings in such a way that it can be opened up, yielding a long chain of molecules, a polymer.

The second ring remains intact here. In this way, instead of a linear polymer chain like in traditional polyamides, a chain which bears many small rings and other side groups emerges. This gives the polymer completely new functions.

Special properties

The new polyamides impress thanks to their special properties which make them attractive for many applications. For example, they melt at higher temperatures than the competing crude oil derived products. In addition, the new compounds can be produced transparently as well as in a partially crystalline manner, which increases its later application possibilities using the same starting substance.

"By way of reaction conditions and catalysts during synthesis, we can easily control whether we will obtain a transparent or partially crystalline polyamide in the end," explains Sieber. "However, the basis for this is offered above all by the specific structure of the bio-based starting material which would be very expensive to obtain from fossil raw materials."

Increasing sustainability

From an industrial point of view, it is important that the synthesis basically takes place in one reaction container. This "one-pot" process would not just allow a significant reduction in costs, but would also mean a clear increase in sustainability, according to Sieber.

The biogenic starting material (+)-3-carene can actually be distilled at a high purity and comparatively low cost from the turpentine oil produced as a secondary product in the cellulose industry.

Up until now, the turpentine oil was only heated in the cellulose factories. "We use it as a vital starting material for plastics," says Sieber. "This is an enormous increase in value."

No competition with food production

Sieber points out that with turpentine oil being a side product of the forest industry, in contrary to the use of castor oil, we are not competing against food production. The researchers are not yet completely satisfied with the achieved overall yield of the process, this is at 25 percent by mass.

"Thanks to the simple scalability, the potential for an efficient process is very high," says Paul Stockmann, whose doctoral thesis at the TUM is based on the findings. At the Fraunhofer IGB, the chemist is now working on establishing (+)-3-carene-based polyamides on the market as alternatives to crude-oil-based high-performance polyamides.

According to a new Dartmouth study published in JAMA Internal Medicine, pharmaceutical companies' promotional access to outpatient practices that deliver primary care in the U.S. is substantial, especially in smaller practices, those outside of healthcare systems, and those without academic affiliation, possibly impacting prescribing quality and cost.

While direct-to-consumer advertising has been the fastest growing segment of pharmaceutical marketing in the U.S. in recent years, drug companies actually spend more (a total of $18.5 billion in 2016) on promoting their products directly to physicians--through clinician office visits known as "detailing" and free drug samples known as "sample closets."

Detailing and free samples have been shown to affect prescribing quality and costs, often by promoting new and expensive brand name drugs over equally effective, older, and less expensive options.

To help determine the widespread prevalence of detailing and sample closets, the researchers surveyed a national sample of U.S. outpatient practices delivering primary care services and with at least three physicians between June 2017 and August 2108. They compared visit frequency and the presence of sample closets overall (across 2,190 practices), and by ownership, practice size, geographic location, and academic affiliation.

Ownership characteristics were organized into the following categories: independent multi-physician practices (with at least three primary care physicians), medical groups (with at least one multi-physician practice), simple systems (those with at least one multi-physician practice and at least one hospital), and complex systems (those with multiple simple systems).

The researchers found that weekly detailing was more common in independent multi-physician practices than in those who were part of complex systems (60 percent versus 39 percent), smaller practices with less than 10 doctors vs. those with more than 20 physicians (55 vs. 27 percent), non-academic-affiliated practices vs. those with academic affiliations (56 percent vs. 32 percent), and in those practices located in the Southern region of the country. A very similar pattern was seen for the presence of free sample closets.

"These findings are consistent with a study of broader physician populations from 2007 and likely reflect limited infrastructure in these practices to impose access restrictions or to provide independent drug information," explains lead author Steven Woloshin, MD, MS, a general internist and a professor of medicine and community and family medicine at Dartmouth's Geisel School of Medicine, and of The Dartmouth Institute for Health Policy and Clinical Practice.

"Although our findings are insufficient to fully explain the higher level of promotional access in the South, it's noteworthy that healthcare spending is also higher in the South than in other regions of the U.S.," he says.

While factors such as industry consolidation and stricter policies among hospitals and medical centers have limited some of the promotional access previously afforded to pharmaceutical companies, these activities still have a substantial effect on prescribing quality and expenditures.

"If reducing industry influence on prescribing is a priority, our findings indicate that further measures are needed, at least in practices delivering primary care, and particularly in smaller practices and those outside of health systems or academic settings," says Woloshin.

The cover for issue 3 of Oncotarget features Figure 3, "Hierarchical clustering of tonsil squamous cell carcinoma cohorts based on viral signature detection pattern with associated pathological features (perineural invasion (PNI), lymphovascular invasion (LVI), and tumor stage (T stage))," by Carey, et al.

In this prospective study, a pan-pathogen microarray was used to determine the virome of early stage, p16-positive OPSCC and neck metastasis treated with transoral robotic surgery and neck dissection.

The virome findings of primary tumors and neck lymph nodes were correlated with clinical data to determine if specific organisms were associated with clinical outcomes.

This will serve as a foundation for future research investigating the role of the virome in OPSCC.

Dr. Erle S. Robertson Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA said, "Head and neck squamous cell carcinomas (HNSCCs), including oropharyngeal squamous cell carcinoma (OPSCC), are classically associated with risk factors such as tobacco and alcohol use."

Head and neck squamous cell carcinomas, including oropharyngeal squamous cell carcinoma, are classically associated with risk factors such as tobacco and alcohol use.

HPV-positive OPSCCs have a higher incidence amongst younger patients with higher performance status, lower tobacco consumption, and higher socioeconomic status.

Compared to HPV-negative OPSCCs, HPV-positive OPSCCs have an improved overall survival and disease-free survival, which is at least partially related to the increased sensitivity to chemotherapy and radiation therapy.

The survival advantage of HPV-positivity persists even after adjusting for confounders, suggesting a difference in the tumor biology between HPV-positive and -negative OPSCCs.

The Robertson Research Team concluded, "In summary, specific viruses, including HPV16, are known to impact the tumor biology and clinical behavior of OPSCCs. The virome of HPV-positive OPSCC primary tumors and neck lymph nodes include the virus families Papillomaviridae, Herpesviridae, Baculoviridae, Reoviridae, Siphoviridae, Myoviridae, and Polydnaviridae. Additional studies are necessary to determine if the identified viral signatures correlate with tumor behavior."

Using a single-needle biopsy and new technology for tumor diagnosis developed by Baylor College of Medicine and the Broad Institute of MIT and Harvard, researchers have been able to provide a more detailed and wider window into cancer biology, tumor type and the mechanisms of response and resistance to therapy than with conventional approaches.

This new-method analyzes the combination of tumor genetic material (genomics) with deep protein and phosphoprotein characterization (proteomics) using a single-needle core biopsy from a patient's tumor. This type of proteogenomic analysis had only been possible before with much larger tissue samples taken at surgery and shows promise for future use in clinical application.

The study outlining this new micro-scale technology appears in the journal Nature Communications.

The need for new technology

"Patients die from cancer because, at a sufficiently fundamental level, we have not been able to work out what kind of cancer we are treating," said co-corresponding author Dr. Matthew Ellis, professor and director of the Lester and Sue Smith Breast Center, McNair scholar, and associate director of Precision Medicine at the Dan L Duncan Comprehensive Cancer Center at Baylor. "The analysis of proteogenomics data, which combines information on tens of thousands of proteins and genes together using a system developed by the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (NCI-CPTAC) investigators, provides much more complete details about what is going on in each tumor. However, the application of proteogenomics to both scientific research and cancer diagnosis has been limited by the size of the tissue sample required."

"Typically, patient tumor biopsies are about one-fifth the size of what is needed for proteogenomics analyses, so we invested considerable effort to identify methods to successfully 'microscale' the process to match the smaller amount of material obtained in the routine diagnostic setting and, importantly, not sacrifice depth of coverage of the proteome and phosphoproteome," said Dr. Steven Carr, co-corresponding author and senior director of proteomics and institute scientist at the Broad Institute.

The published study describes the methods developed that enable detailed analyses of high-quality DNA, RNA and proteins from a single core needle biopsy.

"Importantly, our new methodology includes the analysis of phosphoproteins, which refers to proteins that are activated by the addition of phosphate chemical groups," said Ellis, who also is an investigator in the NCI-CPTAC. "For some cancers, such as ERBB2+ (HER2+) breast cancer, the ability to measure these modifications is critical because they are what drives disease."

Testing the new technology

To test the new technology, Carr, Ellis and their colleagues applied the methods to a pilot study designed to evaluate the feasibility of proteogenomic profiling before and 48 to 72 hours after initiating ErbB2 targeting chemotherapy. They expected to gain insights into the variability of outcomes after treatment by assessing the ability of ErbB2 antibodies to inhibit the drug target.

"For the first time, we were able to detect statistically significant reduction of ERBB2 protein phosphorylation after treatment in patients that responded to treatment. We did not see a reduction in this protein for those who did not respond to treatment," Ellis said. "In patients that did not respond to treatment, our deep-scale data analyses suggested diverse resistance mechanisms to ERBB2-directed therapeutics that could be addressed with alternative approaches to the ones the patient actually received."

The test of the micro-scaled technology provided large amounts of data from the tumors, revealing fundamental insights into the diverse elements that drive tumor responses, including those from the tumor immune microenvironment. The test served as proof of principle that these technologies have promise for precision medicine, meaning it can be used to examine individual tumors and find precise treatment plans for each one.

"However, before we bring the new technologies to the clinic, it is necessary to apply them to a larger number of tumor samples to confirm their diagnostic value," Ellis said.

"Under the auspices of the NCI-CPTAC, we will expand studies into larger groups of patients undergoing treatment for breast cancer in the context of clinical trials," said Carr, a co-principal investigator with Ellis in the NCI-CPTAC.

A key challenge will be access to a large number of high-quality, preserved clinical samples. The feasibility of learning insightful biology as demonstrated in this paper should provide an incentive to clinicians and clinical trial teams to collect and store biopsy material for large-scale prospective studies and for understanding the biology of drugs in patient samples.

"The ability to study signaling pathways in patients is unparalleled," said first and co-corresponding author Dr. Shankha Satpathy, a research scientist in the Carr lab at the Broad.

"Moving forward, our plan is to develop a laboratory at Baylor to conduct these types of diagnosis using micro-scaled proteogenomic technologies in order to provide a better diagnostic platform for our patients," Ellis said.

"I am particularly excited by the potential to move from the current discovery paradigm that requires considerable time to generate the results to a targeted approach that will enable rapid profiling of large lists of proteins we illustrate in our proof of principle paper," said Carr. "But the first step is to define what should be measured that is of biological significance and clinically actionable, as opposed to just what can be measured. That is the most important contribution that our technology is making."

Hamilton, ON (January 27, 2020) - The controversy about whether eggs are good or bad for your heart health may be solved, and about one a day is fine.

A team of researchers from the Population Health Research Institute (PHRI) of McMaster University and Hamilton Health Sciences found the answer by analyzing data from three large, long-term multinational studies.

The results suggest there is no harm from consuming eggs. Given that the majority of individuals in the study consumed one or fewer eggs per day, it would be safe to consume this level, says Mahshid Dehghan, first author and a PHRI investigator.

"Moderate egg intake, which is about one egg per day in most people, does not increase the risk of cardiovascular disease or mortality even if people have a history of cardiovascular disease or diabetes," she said.

"Also, no association was found between egg intake and blood cholesterol, its components or other risk factors. These results are robust and widely applicable to both healthy individuals and those with vascular disease."

The details are published in The American Journal of Clinical Nutrition.

Although eggs are an inexpensive source of essential nutrients, some guidelines have recommended limiting consumption to fewer than three eggs a week due to concerns they increase the risk of cardiovascular disease.

Previous studies on egg consumption and diseases have been contradictory, said Salim Yusuf, principal investigator of the study and director of PHRI.

"This is because most of these studies were relatively small or moderate in size and did not include individuals from a large number of countries," he said.

The researchers analyzed three international studies conducted by the PHRI. Egg consumption of 146,011 individuals from 21 countries was recorded in the PURE study and in 31,544 patients with vascular disease from the ONTARGET and the TRANSEND studies.

The data from these three studies involved populations from 50 countries spanning six continents at different income levels, so the results are widely applicable, said Yusuf.