Tech

Worcester, Mass. - If a genetically or synthetically engineered organism is released into the environment, how will we know? How can we tell it apart from the millions of microorganisms that exist naturally in the wild? That's the challenge being taken on by a multi-institution research team, including Eric Young, assistant professor of chemical engineering at Worcester Polytechnic Institute (WPI), that is developing a biosecurity tool that can detect engineered microorganisms based on their unique DNA signatures.

Genetic engineering, in which genes are added to the genomes of organisms, and synthetic biology, which focuses on understanding and designing better DNA sequences, are both used today to make a wide array of products, such as pharmaceuticals, like insulin, and agricultural crops. Genetic engineering also is used by biotechnology companies--from start-ups to multinational corporations--to manufacture products like detergents, food ingredients, and biofuels.

For decades, the U.S. government has sponsored research on and development of engineered organisms and better ways to design DNA, while the government and the synthetic biology community have worked together to develop safety and ethical practices to ensure the organisms that are made are safe and can be contained. For example, the government has sponsored the development of "kill switches" that make it impossible for engineered organisms to survive outside the lab.

Recently, the U.S. government and research scientists have identified a need for new tools that can identify engineered organisms when they are mixed in with a myriad of naturally occurring microorganisms. These tools could eventually be deployed to detect engineered organisms in the environment. They could be used to protect a company's intellectual property should an organism it designed accidentally escape the lab or to detect intentional releases of potentially harmful organisms.

This is the task being taken on by the multi-institutional team charged with developing such a tool. The project is funded by an 18-month award from the Finding Engineering Linked Indicators (FELIX) program, which is run through Intelligence Advanced Research Projects Activity (IARPA), an organization within the Office of the Director of National Intelligence that funds research to address challenges facing the U.S. intelligence community. The award has a second phase that could be renewed for an additional 24 months. Raytheon, a Massachusetts-based defense contractor, is the primary contractor; Young, who has received a $377,746 award for his part of the project, is one of five subcontractors. The others are Johns Hopkins University, Princeton University, University of California at San Francisco, and Mission Bio, a San Francisco-based biotech company.

"We realize the power of engineering and bioengineering," said Young, whose expertise is in synthetic biology, including the genetic engineering of bacteria, yeast, and fungi. "We are excited about the promise of synthetic biology, but we also have an ethical responsibility to think about the potentially negative uses of the technologies we develop.

"My lab is developing engineered organisms to solve problems, and we use safety practices beyond what we are required to use," he added. "Hopefully, this project will lead us to a low-cost tool that we can use to make sure everyone is working to prevent the release of organisms into the environment, from universities to manufacturing plants to DIY bio enthusiasts in their garages."

Scientists create engineered microorganisms by introducing new genes into their genomes that enable them to produce valuable drugs, biofuels, or food products. A bacterium containing the human gene for producing insulin, or a yeast bearing multiple genes from several organisms to make the antimalarial drug artemisinin are examples. Because many of the genes in these engineered organisms exist in nature, telling them apart from non-engineered organisms in soil or water samples can be challenging. "It's akin to finding the proverbial needle in a haystack," Young said.

He added that the key to making that distinction will be identifying genetic signatures for each organism. By virtue of the way they are produced, the majority of genetically engineered organisms have one or more short sections of DNA that are unique to their genomes and make them different from their non-engineered cousins. These DNA signatures can be used as markers to quickly spot an engineered organism in a population of naturally occurring microorganisms. Young's role in the research project is to generate examples of bioengineered organisms that contain these specific markers.

"We are supplying the 'expert' information the detection device will look for," he said. "We are taking into account the genetic engineering of the past 50 years and reducing all of that knowledge and information down to a set of essential signatures for bioengineered organisms that we would most likely need to find. It's up to our sponsor and the team to decide which organisms are important, and we help decide what signatures we have to look at. It's very exciting work."

Initially, Young, who is working with two graduate students, will focus on brewer's yeast, which he says is increasingly becoming the organism-of-choice for bioengineering companies because it is easy to engineer and simple to grow, given the decades of large-scale fermentation experience in the brewing industry. The signatures he is identifying will be useful for detecting known engineered organisms that may have come from corporate and university labs. Detecting potentially harmful organisms that may have been intentionally released into the environment will be a greater challenge.

"It's a whole lot more complicated when you don't know what organisms you might need to look for," he said. "We have to think about what is most likely to be out there and what would somebody with limited resources create. We need to create tools that can detect a wide range of engineered organisms. And they need to be flexible enough that they could detect a specific set of signatures but then detect newly added signatures as they are found. We are helping develop a technology to do that."

The knowledge Young is generating will ultimately be incorporated into a benchtop detection device that will be developed by other members of the research team. Other team members are creating machine learning algorithms that will find new signatures that experts may not identify. Young said he expects a usable detection device for yeast will be ready at the conclusion of the program, but it could be five to 10 years before the more complex challenges are solved.

Invasive lionfish (Pterois volitans and P. miles) are now ubiquitous throughout the Caribbean and Western Atlantic on both shallow and deep reefs. While many invasive species disrupt natural ecosystems by spreading disease or competing for food and habitat, lionfish are particularly problematic owing to their voracious appetites and high reproductive capacities.

Lionfish are indiscriminate predators, feeding on over 70 species of fish, invertebrates, and mollusks, and a single lionfish can eat 30 times its stomach volume in one meal. Additionally, each female lionfish can produce more than two million eggs each year during her average 16-year lifespan, making lionfish a significant threat to native fishes and reef systems.

Recent surveys in Bermuda have revealed dense aggregations of lionfish on mesophotic reefs (located at depths between 100 and 500 feet, or 30 to 150 meters), yet these densities are not consistent across reefs at this depth. Newly published research in the journal Frontiers, led by BIOS reef ecologist Gretchen Goodbody-Gringley, examines how lionfish distribution on mesophotic reefs may be affected by ecological factors, such as the abundance of prey organisms, as well as environmental factors, such as water temperature.

The research team, which included scientists from the University of Massachusetts at Dartmouth, the Bermuda Department of Environmental and Natural Resources, and the Bermuda Natural History Museum, used diver-led visual surveys to investigate 11 sites at a depth of 196 feet (60 meters). During the surveys, divers recorded numbers of both lionfish and prey fish, as well as the size class of individual prey fish and the bottom temperature.

High densities of lionfish were recorded in areas with higher abundances of prey fish--specifically the creole fish (Paranthias furcifer), which is a preferred prey among lionfish--and higher prey fish biomass. However, the influence of seawater temperature was found to have the strongest effect on lionfish distribution, where higher lionfish densities were found at sites with lower bottom temperature.

Lower temperatures also were correlated with higher densities of prey fish, prey fish biomass, and P.furcifer biomass, implying that physical factors in the environment (such as temperature) likely influence the ecology of the same area. These results suggest that cold-water upwelling currents may be fueling the food chain in certain locations, resulting in high abundances of prey fish and, thus, lionfish.

"Understanding why high densities of lionfish occur in specific locations will aid the ability of scientists and managers to identify and target areas for lionfish control efforts, thereby increasing the efficacy of future management," Goodbody-Gringley said.

A new framework to enable retailers to better position their products to consumers has been devised by Tamer Boyaci and Frank Huettner at ESMT Berlin together with Yalcin Akcay from Melbourne Business School. According to the researchers, consumers often lack the full information when making purchasing decisions on variety of products, from day-to-day items to luxuries such as holidays, resulting in them making poor choices, and superior products losing out on sales.

"Consumer choice behaviour is a crucial factor in many practical operational problems," says Boyaci. "For example, for an online firm like airbnb.com or booking.com, when consumers search for a particular accommodation there is usually a large number of potential hits, which they do not have the time to fully assess. Options displayed on the first page typically receive the most attention, while, from the buyer's perspective, choices listed on the following pages require additional effort to evaluate."

The problem is exacerbated as consumers are required to put a great deal of time and effort into acquiring the necessary additional information to make the best choice.

Boyaci points out, "Facing an abundance of product choices, and with only limited time and attention to evaluate, consumers have to quickly come to grips with how much and what type of information to acquire and pay attention to, and what to ignore. They then make purchasing decisions based on partial information, therefore it's quite possible that consumers routinely make the wrong choices."

To tackle this, professors Boyaci and Huettner devised a model that can help retailers and companies to market their products more effectively, by enabling them to better judge how much and what types of product information to make available to customers. The Consumer Choice Model measured how decisions were made by consumers, when given a set of alternative products to consider in their purchasing activities.

The results show that, in instances where similar items were compared and the information costs were lower, consumers preferred to select the item which provided the easiest access to further information, regardless of whether the other product was superior, as they felt more confident with their decision.

In instances where hard-to-evaluate products were perceived as less attractive, the model proved that simply improving the provision of information to customers could significantly improve sales. The study revealed significant implications for online retailers also.

How adult penguins fish and the body condition of their chicks are directly linked to local fish abundance, and could potentially inform fishery management, a new study has found.

The researchers studied an endangered African penguin colony during a rare three-year closure of commercial fisheries around Robben Island, South Africa, and their findings are published today in the Journal of Applied Ecology.

Fishing is often considered to be one of the biggest drivers of biodiversity loss in the ocean. It is so widespread that we lack an understanding of the 'natural' relationships between marine predators and their prey, and thus the extent to which predators are disrupted by competition from fisheries.

This is a critical knowledge gap since many marine predators such as penguins are considered indicator species: a species whose success indicates the condition of their habitat.

Dr Kate Campbell, who led the research at the University of Cape Town as part of her PhD project, said: "Understanding how African penguins forage to feed their chicks in their variable marine environment can help us identify conservation measures for these endangered populations."

"A three-year commercial fisheries closure around Robben Island, South Africa created a unique opportunity to study how African penguins directly respond to natural changes in local abundance of their prey - anchovies and sardines", she added.

The researchers estimated fluctuations in prey fish populations over three years within the fisheries closure zone (20km radius around Robben Island) using 12 hydro-acoustic surveys, which detect the presence of anchovies and sardines by bouncing sound waves off their swim bladders (gas-filled organs).

Over the same time period researchers used GPS-temperature-depth loggers to monitor adult penguins' fishing behaviours for one trip to sea per breeding season. At the Robben Island colony, researchers also measured the diet of breeding adults and the body condition of chicks.

They found that local abundance of anchovy and sardine was directly linked to African penguin foraging behaviour and chick offspring condition; a common assumption about predator-prey relationships which has rarely been tested in the absence of fishing.

When fish abundance was lower, adults increased foraging effort: foraging for longer, swimming further and diving more often. This likely explains why chick body condition also declined, as finding fish became more challenging for breeding adults and required more energy.

Dr Richard Sherley of the University of Exeter said: "Interestingly, the variation in foraging behaviour between individuals also increased when prey fish were scarcer."

"While some 'superstar' penguins find food easily, others are less successful. Once food gets harder to find, more individuals will start to struggle and work harder, but they will do so at different rates, increasing the variation we see in foraging effort", he added.

These results indicate that penguin foraging behaviour and chick condition could be key indicators for local fish abundance, making a case for their inclusion in monitoring of local ecosystem health.

"Since these short-term changes will likely have knock-on effects for chick survival and penguin population size, they could be used as powerful early warning signs to inform fisheries' policies and marine conservation efforts", said Campbell.

"Technological advances also means there's exciting potential to better understand how these endangered penguins behave when prey resources are scarce", she added.

"Hopefully, In the future, we could aim to effectively balance fishery management with penguins' needs, to reduce the impact on local economies whilst maximising the benefits to our oceans", Sherley concluded.

New research supports the effectiveness and safety of esketamine nasal spray in treating depression in people who have not responded to previous treatment. The research will be published online today in the American Journal of Psychiatry. This study is one of the key studies that led to the recent Food and Drug Administration (FDA) approval of esketamine nasal spray, in conjunction with an oral antidepressant, for use in people with treatment-resistant depression.

Depression is common, and as many as one-third of people with depression are considered treatment resistant--not finding relief from symptoms even after trying several antidepressants. Esketamine offers a new fast-acting treatment for people that have not responded to other depression treatments.

Michael Thase, M.D., one of the study authors, described the study during a briefing held during the Annual Meeting of the American Psychiatric Association. The phase 3, double-blind, active-controlled study was conducted at 39 outpatient centers from August 2015 to June 2017 and involved nearly 200 adults with moderate to severe depression and a history of not responding to at least two antidepressants. Participants were randomly assigned to one of two groups. One group was switched from their current treatment to esketamine nasal spray (56 or 84 mg twice weekly) plus a newly initiated antidepressant (duloxetine, escitalopram, sertraline, or extended-release venlafaxine). The other group was switched from their current treatment to a placebo nasal spray in combination with a new antidepressant.

The improvement in depression among those in the esketamine group was significantly greater than the placebo group at day 28. Similar improvements were seen at earlier points in time.

Adverse events in the esketamine group generally appeared shortly after taking the medication and resolved by 1.5 hours later while patients were in the clinic. The most common side effects included dissociation, nausea, vertigo, dysgeusia (distortion of the sense of taste) and dizziness. Seven percent of patients in the esketamine group discontinued the study due to side effects.

"This trial of esketamine was one of the pivotal trials in the FDA's review of this treatment for patients with treatment resistant depression. Not only was adjunctive esketamine therapy effective, the improvement was evident within the first 24 hours," Thase said. "The novel mechanism of action of esketamine, coupled with the rapidity of benefit, underpin just how important this development is for patients with difficult to treat depression."

In an accompanying commentary in the American Journal of Psychiatry, Alan Schatzberg, M.D., at Stanford University School of Medicine, highlights several areas where information about the best use of esketamine is lacking, such as how long and how often to prescribe it, and raises concerns about the potential for abuse. While he notes that esketamine could be useful for many patients with depression, he cautions that "there are more questions than answers with intranasal esketamine, and care should be exercised in its application in clinical practice."

The commentary describes esketamine's relationship to ketamine, an anesthetic in use for decades that has also been used recreationally as a party drug. While ketamine administered intravenously at sub-anesthetic doses is an effective treatment being used for refractory depression, at present, intravenous ketamine for the treatment of depression has not been approved by the FDA, although it can be prescribed off-label. Ketamine is composed of molecules that are mirror images of each other (S-ketamine and R-ketamine). It is the intranasal formulation of the S-ketamine molecule (i.e., esketamine) that received FDA approval.

(New York, NY) - The International Pediatric MS Study Group (IPMSSG) has released updated standards for clinical trials involving children and teens with multiple sclerosis (MS). The new recommendations were published in the May 1, 2019, online issue of Neurology®, the medical journal of the American Academy of Neurology.

The updated recommendations include:

Pharmacokinetic/pharmacodynamic studies (how a therapy is absorbed and how it affects the patient) should be completed for all new agents to identify the appropriate dose in children.

If an immune-modulating agent has been proven to be effective in adult MS, it is inappropriate to test that agent in pediatric MS using a placebo (inactive) control.

Phase 3 trials in adults should consider enrolling teenagers.

Open-label extension studies should be conducted.

In some cases, when therapies have been well studied in adults, an open-label study should be considered as sufficient for approval in pediatric MS.

"Thankfully, the number of pediatric MS cases is low compared to adult cases - but these are children, facing a chronic illness and we need to do everything we can to help them," said lead author Emmanuelle Waubant, MD, Professor of Neurology at the University of California, San Francisco. "We are confident these consensus recommendations will help address the need for high-quality evidence to inform the optimal treatment of children and teens living with multiple sclerosis."

Conducting clinical trials in children can be complicated; some issues include the low numbers of children with MS at any one study site, the necessity to obtain parental approval in addition to the child agreeing to participate, and the fact that treatments can have unanticipated side effects in immature individuals. The IPMSSG is a group of 165 care providers representing 44 countries, dedicated to optimizing worldwide care, education and research in pediatric MS. In 2012, they held an international meeting to develop consensus on how to conduct clinical trials in children with MS. In 2018, they recognized the need to update recommendations, and convened a meeting in New York City in January, which was sponsored by the National MS Society (USA) and the MS Society of Canada.

Many measures have been introduced around the world with the aim of reducing outdoor air pollution and concomitantly improving public health. These efforts include, for example, the regulation of industrial emissions, the establishment of low emission zones and the subsidies for public transport, as well as restrictions on the use of wood and coal for heating in private households. The link between these actions and improved air quality and health seems obvious, but it is actually very difficult to quantify their effects. "It's quite a challenge to evaluate the introduction of a measure like the low emission zone," says Jacob Burns from the Institute for Medical Information Processing, Biometry and Epidemiology (IBE) at the LMU's Pettenkofer School of Public Health.

The negative effects of air pollution on public health linked to cardiovascular and respiratory diseases, among others, are well established. But whether measures designed to improve outdoor air quality actually reduce the concentration of pollutants present, and mitigate their effects on public health, is less clear. "It's important to remember how many factors influence both air quality and the relevant health conditions," says Burns. "Levels of energy consumption in industry, transport and domestic households all play a substantial role in air pollution levels, as does the weather," he points out. And with respect to health, the risk of developing cardiovascular disease, to cite one example, is influenced not only by particulate matter and other pollutants we breathe in, but also by numerous genetic, physiological und social risk factors. "This illustrates how difficult it can be to attribute changes in air pollutant concentrations, numbers of individuals admitted to hospitals, or mortality rates to any single measure."

These difficulties are reflected in the new review published in the Cochrane Library. Cochrane is a network of more than 13,000 researchers, whose primary aim is to improve the quality of the scientific knowledge base upon which policy decisions relevant to human health are based. The authors of the new study, led by Professor Eva Rehfuess' research group from the IBE at the Pettenkofer School of Public Health, provide the first systematic review aiming to identify and critically appraise all studies that evaluate the impact of measures aiming to improve air quality. The study considers 38 specific measures, ranging from those to reduce traffic, to the regulation of industrial emissions and opportunities for cleaner and more efficient household heating systems.

"For the most part, the studies that we reviewed show either positive or unclear effects. But these studies differ so much from one another that we could not, with confidence, draw general conclusions about what works and what does not work," Burns explains. The LMU epidemiologists emphasize, however, that this is not an argument against such interventions. Indeed, the authors explicitly note that "it is important to emphasize that lack of evidence of an association is not equivalent to evidence of no association." For them, the more important message is that "the methods of evaluation in this area must be improved, so that decision-makers have a reliable basis on which to base their policy choices," says Rehfuess.

In this study, the LMU researchers make a number of specific recommendations - in particular with respect to the design of future studies in this area, but some of which also directed at policymakers. "At the moment," says Rehfuess, "many studies are conducted retrospectively. Ideally, the evaluation could be incorporated into the planning and introduction of the measure."

ANN ARBOR, Mich. -- Despite evidence that helmets are critical to preventing head injuries, not all children wear them while biking, skateboarding and riding scooters, a new national poll finds.

Eighteen percent of parents say their child never wears a helmet on a bike ride, and even more say their kids skip helmets on a skateboard (58 percent) and scooter (61 percent), suggests the C.S. Mott Children's Hospital National Poll on Children's Health at the University of Michigan.

The risks are significant. More than 426,000 children - nearly 50 every hour - visited an emergency department in 2015 due to a wheeled sports-related injury, according to a 2017 report from the Safe Kids Worldwide and Nationwide's Make Safe Happen program.

"Helmets are vital to preventing head injuries in case a child falls or is struck by a car," says poll co-director and Mott pediatrician Gary Freed, M.D., MPH.

"It is very concerning that so many children ride bikes and other non-motorized wheeled vehicles without ever using helmets."

The nationally-representative poll was based on responses to questions about non-motorized vehicles from 1,330 parents of at least one child aged 4-13.

Results indicate a wide range in the use of safety strategies when children are playing with wheeled-toys outside. Most parents said their child gives cars the right of way (93 percent) and stops their bike at stop signs (82 percent.) However, the majority of parents also acknowledged their child does not use hand signals or walk their bike across crosswalks.

"Unfortunately, a substantial number of parents polled reported that their children do not consistently follow basic safety strategies on wheels, "Freed says. "Our report suggests that families should take more precautions to ensure children are safe, including wearing helmets and understanding safety in the streets."

Of the 4 in 5 parents polled whose child rides a bicycle, most said their child uses sidewalks (73 percent) or parks or trails (59 percent). More children also ride on streets without bike lanes (42 percent) than streets with bike lanes (11 percent).

Parents were also more likely to say that younger children always wear a helmet compared to older children but not all families enforced a strict helmet rule.

Older children (ages 11-13) are more likely to ride in a street (with or without bike lanes) compared with younger children (ages 4-10). Just wearing a helmet is not enough, Freed notes. To get the most protection, helmets should fit snugly on the head, and be used correctly.

Freed says that in areas that allow it, children should also ride non-motorized vehicles on the sidewalk. Parents should accompany younger children and teach them top safety lessons, such as slowing down, using a bell, or calling out to alert pedestrians that they are approaching. Children biking on the sidewalk should also stop at intersections and walk their bike across the crosswalk, as passing cars may not be looking for a bike to emerge from the sidewalk.

Children also need to be on the lookout for people getting in or out of parked cars, experts say. Many children are injured each year when a driver opens their car door onto the street and strikes an oncoming bicycle.

"With summer around the corner, bikes, skateboards, and scooters will be a fun way for kids to play outside and get exercise," Freed says.

"We encourage parents to talk to their children about safety rules and expectations ahead of time to make sure these outdoor activities are both fun and safe."

Johns Hopkins researchers have discovered a long-sought protein, the proton-activated chloride channel (PAC), that is activated in acidic environments and could protect against the tissue-damaging effects of stroke, heart attack, cancer and inflammation. The researchers believe the discovery of this protein could provide a new drug target for potential therapies for stroke and other health issues.

"Knowing the identity of this acid-stimulated protein opens up a broad new avenue of both basic research and drug discovery," says the study's principal investigator Zhaozhu Qiu, Ph.D., an assistant professor in the Department of Physiology at the Johns Hopkins University School of Medicine.

The study was published April 26 in Science.

Acidity builds in tissues as a result of oxygen deprivation caused by damage or disease. As the acidity of the tissues grows, it damages cells and can cause them to die. The acidic buildup, say researchers, is known to open the gate of specialized channels through the cell membrane, causing an abnormal accumulation of ions inside the cell, which eventually causes it to swell and die. However, the identity of this channel has remained a mystery until now.

To solve this long-standing puzzle, the research team set up a method to rapidly test cells for these channel proteins. The researchers engineered human cell lines to produce a fluorescent molecule -- its glow would be turned off when channels through the cell membrane open in response to acid. Using these cells, the researchers systematically tested a library of 2,725 genes one by one. In this way, they found a single gene, called TMEM206, the inactivation of which reliably eliminated channel activity in response to acid. Through further study, the researchers found that the gene corresponded to a single protein, which they named PAC.

This gene can be found from the human genome all the way to fish. "Its evolutionary conservation and wide expression suggest a broad role for this new channel family in physiology and disease -- now we are very excited to figure it all out," says Qiu.

Curiously, the PAC gene is one of the genes most frequently different between Tibetan highlanders and Han Chinese. "This leads us to believe," says Qiu, "PAC could have a conserved role in the adaptation to hypoxia," a condition that also results in increased acidity in the body.

Philadelphia, May 20, 2019--Teen drivers diagnosed with attention-deficit hyperactivity disorder (ADHD) are significantly more likely to crash, be issued traffic and moving violations, and engage in risky driving behaviors than their peers without ADHD, according to a Children's Hospital of Philadelphia (CHOP) study published today in the journal Pediatrics.

The multidisciplinary team of researchers from CHOP's Center for Injury Research and Prevention and Center for Management of ADHD analyzed detailed crash and traffic violation records for newly licensed drivers to conduct the first large-scale longitudinal study on this topic.

By highlighting the specific types of crashes and traffic violations, this study identifies risky driving behaviors that those with ADHD may be more likely to engage in, such as driving while intoxicated, not wearing a seat belt, and speeding. Because these behaviors are amenable to change, these findings suggest that clinicians and families can work with this at-risk group of teens to practice safe driving behaviors and potentially reduce their crash risk.

"What this study suggests is that we have to go beyond current recommendations of medication and delaying the age of getting licensed to decrease crash risk for teens with ADHD," said Allison E. Curry, PhD, MPH, lead author of the study and a Senior Scientist and Director of Epidemiology and Biostatistics at the Center for Injury Research and Prevention at CHOP and an Assistant Professor of Pediatrics at the University of Pennsylvania Perelman School of Medicine. "Their higher rate of citations suggest that risky driving behaviors may account for why they crash more. More research is needed to objectively measure if and how these behaviors specifically contribute to crash risk."

According to the Centers for Disease Control and Prevention (CDC), an estimated 6.1 million children ages 2 to 17 living in the United States have been diagnosed with ADHD. Many of these youth with ADHD are potential drivers, and safe transportation is a growing concern. Evidence-based guidance to clinicians and families is urgently needed to protect these drivers, as well as others on the road.

For the retrospective study, researchers reviewed the records of 14,936 adolescents who were patients at six CHOP primary care practices in New Jersey and had obtained an intermediate driver's license between January 2004 and December 2014. The study team linked the adolescents' electronic health data with New Jersey driver licensing records, traffic violations, and police-reported crash data. Within this group, the researchers identified 1,769 adolescents with childhood-diagnosed ADHD who obtained an intermediate driver's license during the study period, and compared their crash outcomes with those of the drivers without ADHD.

Although crash risk is elevated for all newly licensed drivers, the study team found it is 62 percent higher for those with ADHD the first month after getting licensed, and 37 percent higher during the first four years after licensure, regardless of their age when licensed. Drivers with ADHD also experienced higher rates of specific crash types, including driving with passengers, at-fault-, single vehicle-, injury- and alcohol-related crashes, the last risk being 109 percent higher than those without ADHD.

The rates of traffic and moving violations were also significantly higher among young drivers with ADHD as compared to those without ADHD. Among these drivers, nearly 37 percent were issued a traffic violation and nearly 27 percent a moving violation within their first year of driving, compared to 25 percent and 18 percent respectively among their peers without ADHD. Drivers with ADHD had higher rates of alcohol or drug violations and moving violations (including speeding, nonuse of seat belts, and electronic equipment use). Their rate was 3.5 times that of young drivers without ADHD in the first year of driving and 1.5 times that of young drivers without ADHD in the first four years of driving.

"We need additional research to understand the specific mechanisms by which ADHD symptoms influence crash risk so that we can develop skills training and behavioral interventions to reduce the risk for newly licensed drivers with ADHD," said Thomas J. Power, PhD, ABPP, study co-author and director of the Center for Management of ADHD at CHOP. "There's not enough research currently being conducted on older adolescents and young adults with ADHD, particularly studies focused on promoting safe driving behavior."

San Diego, Calif. (May 19, 2019) -- Coffee drinkers know that coffee helps keep the bowels moving, but researchers in Texas are trying to find out exactly why this is true, and it doesn't seem to be about the caffeine, according to a study presented at Digestive Disease Week® (DDW) 2019. Researchers, feeding rats coffee and also mixing it with gut bacteria in petri dishes, found that coffee suppressed bacteria and increased muscle motility, regardless of caffeine content.

"When rats were treated with coffee for three days, the ability of the muscles in the small intestine to contract appeared to increase," said Xuan-Zheng Shi, PhD, lead author of the study and associate professor in internal medicine at the University of Texas Medical Branch, Galveston. "Interestingly, these effects are caffeine-independent, because caffeine-free coffee had similar effects as regular coffee."

Coffee has long been known to increase bowel movement, but researchers have not pinpointed the specific reason or mechanism. Researchers examined changes to bacteria when fecal matter was exposed to coffee in a petri dish, and by studying the composition of feces after rats ingested differing concentrations of coffee over three days. The study also documented changes to smooth muscles in the intestine and colon, and the response of those muscles when exposed directly to coffee.

The study found that growth of bacteria and other microbes in fecal matter in a petri dish was suppressed with a solution of 1.5 percent coffee, and growth of microbes was even lower with a 3 percent solution of coffee. Decaffeinated coffee had a similar effect on the microbiome.

After the rats were fed coffee for three days, the overall bacteria counts in their feces were decreased, but researchers said more research is needed to determine whether these changes favor firmicutes, considered "good" bacteria, or enterobacteria, which are regarded as negative.

Muscles in the lower intestines and colons of the rats showed increased ability to contract after a period of coffee ingestion, and coffee stimulated contractions of the small intestine and colon when muscle tissues were exposed to coffee directly in the lab.

The results support the need for additional clinical research to determine whether coffee drinking might be an effective treatment for post-operative constipation, or ileus, in which the intestines quit working after abdominal surgery, the authors said.

Women who breastfed their babies are less likely to develop heart disease later in life, according to findings to be presented in Lyon, at the European Society of Endocrinology annual meeting, ECE 2019. The study also suggests that the protective effect on heart health is increased in women who breastfed for longer periods of time. These findings provide further evidence for the long-term health benefits of breastfeeding and that women should be encouraged to do so when possible.

Breastfeeding has previously been shown to reduce the risk of postpartum depression and the risk of certain cancers in women. It has also been established that breastfeeding can help mothers to maintain a healthy body weight and regulate their blood sugar. These benefits are likely to be related to the higher levels of the hormone, prolactin, in breastfeeding mothers. More recently, studies have indicated that prolactin reduces the risk of diabetes, which is a major risk factor for cardiovascular disease. Cardiovascular disease is a leading cause of death among women worldwide but the long-term protective effects of breastfeeding on heart disease risk have not been adequately investigated.

In this study, Professor Irene Lambrinoudaki from the University of Athens and colleagues, measured markers of heart and blood vessel health in postmenopausal women, in relation to their history of breastfeeding. After adjusting for other cardiovascular health risk factors, including body weight, age, cholesterol levels and smoking habits, the data indicated that women who had breastfed had significantly lower levels of heart disease and heart disease risk indicators. This effect was even more significant in women that had breastfed for longer periods of time.

Prof Lambrinoudaki says, "These findings indicate that breastfeeding lowers the risk of heart disease in women. However, this is an association study only, we are now interested in looking at establishing the underlying causes of this protective effect."

Prof Lambrinoudaki comments, "If we can show causality for the protective effect, women will have one more reason to nurse their infants, beyond the already documented benefits of breastfeeding for short- and long term health of both them and their children."

Prof Lambrinoudaki's team are now investigating the molecular mechanisms of how prolactin affects blood sugar, which is a major risk factor for heart disease. This research could uncover new mechanisms to target in the prevention of heart disease for everyone, not just breastfeeding women.

Measuring the blood plasma levels of an enzyme called PDIA1 could one day become a method of diagnosing a person's predisposition to cardiovascular disease even if they are healthy, i.e., not obese, diabetic or a smoker, and with normal cholesterol.

This is suggested by a study published in the journal Redox Biology by Brazilian researchers affiliated with the University of São Paulo (USP), the University of Campinas (UNICAMP) and Butantan Institute.

The investigation was conducted under the aegis of the Center for Research on Redox Processes in Biomedicine (Redoxome), one of the Research, Innovation and Dissemination Centers (RIDCs) funded by the São Paulo Research Foundation (FAPESP). Redoxome is hosted by USP's Chemistry Institute.

"This molecule belongs to the protein disulfide isomerase [PDI] family. Our study showed that people with low plasma levels of PDIA1 have a more inflammatory protein profile and hence run a higher risk of thrombosis. On the other hand, people with high levels of PDIA1 have more 'housekeeping' proteins associated with cell adhesion, homeostasis and the organism's normal functioning," said Francisco Rafael Martins Laurindo, a professor at the University of São Paulo's Medical School (FM-USP) and principal investigator for the study.

The study was conducted during the PhD research of Percíllia Victória Santos de Oliveira with a scholarship from FAPESP.

The group analyzed blood plasma samples from 35 healthy volunteers with no history of chronic or acute disease. None was a smoker or a user of recreational drugs or chronic medication.

Plasma was collected 10-15 times at intervals of days or weeks during a period of 10-15 months. Circulating PDI levels were within a small range for most individuals. Moreover, in a cohort of five individuals, PDIA1 levels were measured three times in a nine-hour period. The variability of the results was again negligible.

"However, the measurements showed that some patients had high levels of PDIA1, while the levels were very low, almost undetectable, in others. When the tests were repeated for the same person over time, these values hardly varied at all," said Laurindo, who heads the Translational Cardiovascular Biology Laboratory at the Heart Institute (InCor) attached to FM-USP's teaching and general hospital (Hospital das Clínicas).

The researchers also measured the levels of PDIA1 in 90 plasma bank samples from patients with chronic cardiovascular disease. The analysis consistently showed low levels of the enzyme.

They then conducted several additional proteomic studies to investigate how the plasma levels of PDIA1 correlated with an individual's protein signature. The adhesion and migration of cultured vein endothelial cells treated with PDIA1-poor plasma were impaired in comparison with those of cells treated with PDIA1-rich plasma.

These results led to the hypothesis that the plasma level of PDIA1 could be a window onto individual plasma protein signatures associated with endothelial function, which could indicate a possible predisposition to cardiovascular disease.

The study also showed no correlation between PDIA1 levels and well-known risk factors for cardiovascular disease, such as triglycerides and cholesterol.

The next steps for the research group include studying PDIA1 levels in conditions such as acute coronary disease, as well as other members of the protein disulfide isomerase family (there are more than 20 PDIs all told), to compare results and confirm whether all these enzymes are potential markers of vulnerability to cardiovascular disease.

Inhibitors

Clinical trials of inhibitors of other PDIs are being conducted by different groups of researchers in several parts of the world. Because these enzymes play various essential roles in cell survival, Laurindo explained, it is important to understand their specific interactions in the cancer context to design inhibitors capable of eliminating tumors with a minimum of toxicity to normal cells.

In another study, published in the American Journal of Physiology-Heart and Circulatory Physiology, the researchers used an antibody to inhibit PDIA1 on the surface of vascular cells and observed the effects of stimulation with several different mechanical forces, such as stretching and alterations to the rigidity of the extracellular matrix.

Resulting from research conducted during Leonardo Yuji Tanaka's postdoctoral internship (https://bv.fapesp.br/en/pesquisador/77430/leonardo-yuji-tanaka) with support from FAPESP (https://bv.fapesp.br/en/bolsas/151090), the study concluded that surface PDIA1 inhibition affected the cytoskeleton, an intracellular framework of filaments, thereby hindering cell migration.

"PDIA1 is fundamental for the ability of cells to migrate within the organism, and so it mustn't be completely inhibited. When the surface portion, which corresponds to less than 2% of total PDIA1, is silenced, the cell survives but loses fine regulation of cell direction during migration. This can be leveraged in the search for new disease mechanisms and drugs," Laurindo explained.

Researchers at Indiana University School of Medicine have found a way to charge up the fight against bacterial infections using electricity.

Work conducted in the laboratories of the Indiana Center for Regenerative Medicine and Engineering, Chandan Sen, PhD and Sashwati Roy, PhD has led to the development of a dressing that uses an electric field to disrupt biofilm infection. Their findings were recently published in the high-impact journal "Annals of Surgery."

Bacterial biofilms are thin, slimy films of bacteria that form on some wounds, including burns or post-surgical infections, as well as after a medical device, such as a catheter, is placed in the body. These bacteria generate their own electricity, using their own electric fields to communicate and form the biofilm, which makes them more hostile and difficult to treat. The Centers for Disease Control and Prevention estimates 65 percent of all infections are caused by bacteria with this biofilm phenotype, while the National Institutes of Health estimates that number is closer to 80 percent.

Researchers at IU School of Medicine are the first to study the practice of using an electric field-based dressing to treat biofilms rather than antibiotics. They discovered the dressing is not only successful in fighting the bacteria on its own, but when combined with other medications can make them even more effective. This discovery has the potential to create significant changes in the way physicians treat patients with bacterial infections which are resistant to antibiotics. The dressing can also help prevent new biofilm infections from forming in the future. The dressing electrochemically self-generates 1 volt of electricity upon contact with body fluids such as wound fluid or blood, which is not enough to hurt or electrocute the patient.

"This shows for the first time that bacterial biofilm can be disrupted by using an electroceutical dressing," said Chandan Sen, PhD, director of the Indiana Center for Regenerative Medicine and Engineering and associate vice president of research for the IU School of Medicine Department of Surgery. "This has implications across surgery as biofilm presence can lead to many complications in successful surgical outcomes. Such textile may be considered for serving as hospital fabric - a major source of hospital acquired infections"

Marketing of the dressing for burn care was recently approved by the Food and Drug Administration. The team is now studying the device's effectiveness in patients recovering from burns.

E-commerce is sizzling. Last year, consumers spent more than $517 billion online with US merchants, up 15 percent from the year before, according to Internet Retailer.

However, independent musicians, self-published authors and others have sometimes found it difficult to participate in the e-commerce revolution. That's because they typically must set up an account with a third party, say a credit card company, to protect against fraud while simultaneously increasing the comfort level of potential buyers. Those credit card accounts, though, cost money. That can result in lower profits for artists and other online sellers and higher prices for buyers.

Bhaskar Krishnamachari, a professor at the USC Viterbi School of Engineering, and Aditya Asgaonkar - a recent undergraduate computer science alum at BITS Pilani, India who visited and worked with Krishnamachari at USC Viterbi over several months in 2018 - believe they have found a way to make the buying and selling of digital goods less costly, more efficient, and less vulnerable to fraud. Their proposed solution involves blockchain, "smart contracts," and game theory.

"Our scheme offers potentially a big improvement over the state-of-the-art in electronic commerce because it allows buyers and sellers to interact directly with each other without the need for third-party mediators of any kind," said Krishnamachari, a Ming Hsieh Faculty Fellow in Electrical and Computer Engineering and director of the Viterbi Center for Cyber-Physical Systems and the Internet of Things.

"It uses a dual-deposit method, escrowing a safety deposit from both buyer and seller that is returned to them only when they behave honestly. And the verification of who is at fault and who is honest is done automatically by the smart contract," added Krishnamachari.

On May 15, 2019, Asgaonkar presented the researchers' joint paper titled, "Solving the Buyer and Seller's Dilemma: A Dual-Dual-Deposit Escrow Smart Contract for Provably Cheat-Proof Delivery and Payment for a Digital Good without a Trusted Mediator," at the IEEE International Conference on Blockchain and Cryptocurrency in Seoul, South Korea.

Asgaonkar and Krishnamachari have created an algorithm that runs on a programmable blockchain as a "smart contract." Blockchains allow multiple stakeholders to transact money or data virtually over linked peer-to-peer computer networks.

Here's how it might work.

An author wants to sell her digital masterwork, "The Great American Novel." However, she hopes to avoid going through Amazon or some other company that takes a commission.

Instead, she uses Asgaonkar's and Krishnamachari's blockchain-based solution and lists the book's price at $20. An interested buyer contacts her. To ensure an honest deal, both the buyer and seller agree to pony up a $10 deposit through Ethereum or some other programmable blockchain platform.

The author then sends the digital book to the buyer, who could only access it by making a verifiable payment for the correct amount. If the transaction satisfies everybody, then both parties receive their deposits back.

But what if someone tries to cheat? What happens, for instance, if the seller intentionally sends the wrong e-book? What recourse does the aggrieved party have?

This is where the so-called smart contract kicks in.

The contract stores a good's digital hash code, or "digital fingerprint," in Krishnamachari's words. The buyer has access to that code before making a purchase. If they receive an item with a different hash code, however, they can dispute the transaction. In this instance, the seller would forfeit their deposit after the algorithm determined that they had attempted to cheat the buyer.

Now, consider a different scenario in which the buyer tries to cheat by falsely claiming they received the wrong item. If the digital fingerprint, shows otherwise, the unscrupulous buyer would lose their deposit.

Asgaonkar and Krishnamachari call their system "cheat proof." Their paper uses game theory to prove mathematically that, in their proposed protocol, the best option for buyers and sellers is to behave honestly, lest they lose their deposits or access to desired goods.

"Our solution, a crypto-economic system, disincentivizes malicious behavior from either party," said Asgaonkar, now a researcher at the Ethereum Foundation.

Added Clifford Neuman, a computer scientist at USC Viterbi's Information Sciences Institute: "The significance of this work is that it changes the structure of incentives for correct behavior in online transactions so that the optimal benefit to both parties occurs when they transact fairly."

At present, Asgaonkar's and Krishnamachari's system works only with digital goods because physical products can't have a cryptographic hash associated with them. However, physical goods stored in a safe-box that can be opened with a digital password could be potentially transacted using their system.

The researchers' blockchain-based system, under-girded by algorithms and smart contracts, solves what's known as the "Buyer and Seller's Dilemma," all without the need for credit-card companies or legal adjudications, Krishnamachari said.

"The dilemma is that with a traditional online transaction, either the buyer or seller will have to go first, either trusting that the buyer will pay honestly after delivery or that the seller will deliver honestly after payment. But either party has the incentive and ability to cheat the other if no other dispute resolution mechanism or trust third party is involved," Krishnamachari said.

"By providing for the dual-deposit escrow and an automated verification process as a piece of software running on a blockchain," he added, "we are able to guarantee that neither party will cheat the other."

A Future of Microtransactions

What most excites Krishnamachari about this new protocol is its ability to facilitate microtransactions, "which I see as the future of digital commerce among individuals and between organizations," he said.

Made popular in games and mobile apps, microtransactions allow users to pay small amounts of money for virtual goods like a new sword in "World of Warcraft" or unlocking hidden levels in a game.

However, with the advent of the Internet of Things, the potential for these tiny microtransactions is far, far greater.

Such automated arrangements, for instance, could include micropayments to the owner of a sensor-laden car digitally providing another driver with traffic data or air quality information. These and other microtransactions, Krishnamachari said, will multiply with the increased interconnection, via the Internet, of data-exchanging computing devices embedded in everyday objects.

"Creating these data economies is going to require us to lower the friction for transactions down to zero. And that's what we're trying to do," Krishnamachari said. "Millions of transactions could become frictionless, digitized and monetized, and the Internet of Things would be more robust."