Drinking alcohol while pregnant could have transgenerational effects

Soon-to-be mothers have heard the warning — don’t drink while pregnant. The Centers for Disease Control and Prevention (CDC) has issued numerous statements about the dangers of alcohol consumption during pregnancy, as it can lead to Fetal Alcohol Spectrum Disorders (FASD) in newborns.

Despite this, many women drink during pregnancy, a choice that scientists have known for years could hurt these mothers’ children. Today, there is a new reason why an expectant mother should put down that glass of wine — drinking alcohol during pregnancy will not only affect her unborn child, but may also impact brain development and lead to adverse outcomes in her future grand- and even great-grandchildren.

The new study by Kelly Huffman, psychology professor at the University of California, Riverside, titled “Prenatal Ethanol Exposure and Neocortical Development: A Transgenerational Model of FASD,” was published in the journal Cerebral Cortex.

“Traditionally, prenatal ethanol exposure (PrEE) from maternal consumption of alcohol, was thought to solely impact directly exposed offspring, the embryo or fetus in the womb. However, we now have evidence that the effects of prenatal alcohol exposure could persist transgenerationally and negatively impact the next-generations of offspring who were never exposed to alcohol,” Huffman said.

Previous work from the Huffman Laboratory at UCR has shown that PrEE impacts the anatomy of the neocortex, the part of the brain responsible for complex behavior and cognition in humans, and that PrEE can lead to abnormal motor behavior and increased anxiety in the exposed offspring. Huffman and a group of UCR students have extended this research by providing strong evidence that in utero ethanol exposure generates neurobiological and behavioral effects in subsequent generations of mice that had no ethanol exposure.

To determine whether the abnormalities in brain and behavior from prenatal ethanol exposure would pass transgenerationally, Huffman generated a mouse model of FASD and tested many aspects of brain and behavioral development across three generations. As expected, the first generation, the directly exposed offspring, showed atypical gene expression, abnormal development of the neural network within the neocortex and behavioral deficits. However, the main discovery of the research lies in the subsequent, non-exposed generations of mice. These animals had neurodevelopmental and behavioral problems similar to the those of the first, directly exposed generation.

“We found that body weight and brain size were significantly reduced in all generations of PrEE animals when compared to controls; all generations of PrEE mice showed increased anxiety-like, depressive-like behaviors and sensory-motor deficits. By demonstrating the strong transgenerational effects of prenatal ethanol exposure in a mouse model of FASD, we suggest that FASD may be a heritable condition in humans,” Huffman said.

The multi-level analyses in this study suggest that alcohol consumption while pregnant leads to a cascade of nervous system changes that ultimately impact behavior, via mechanisms that can produce transgenerational effects. By gaining an understanding of the neurodevelopmental and behavioral effects of prenatal ethanol exposure that persist across generations, scientists and researchers can begin to create novel therapies and methods of prevention.

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Materials provided by University of California – Riverside. Original written by Mojgan Sherkat. Note: Content may be edited for style and length.

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Some patients with dementia may experience delayed-onset PTSD

Delayed-onset post-traumatic symptoms in the elderly may be misdiagnosed as falling under the umbrella of behavioural and psychological symptoms of dementia (BPSD), according to a recent review.

The review describes three cases where post-traumatic stress disorder (PTSD) symptoms are experienced by patients suffering with dementia long after the original traumatic event.

Considering PTSD in individuals with dementia is important because PTSD is usually associated with working-age adults and is infrequently diagnosed in the elderly. In the early stages of dementia, recognising early life trauma may enable patients to access psychological therapy prior to significant cognitive decline. In patients with more advanced dementias, an awareness of earlier trauma exposure can help clinicians differentiate between delayed PTSD and BPSD in patients suffering with emotional and behavioural disturbances.

“Every patient with dementia has a unique narrative, which if captured in the earlier stages of the disease, enables clinicians and their families to understand the origin of their distress. Therefore, it is important to look for a history of previous trauma in patients with BPSD as this could be due to delayed onset PTSD,” said Dr. Tarun Kuruvilla, senior author of the Progress in Neurology & Psychiatry review.

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Computer that reads body language

Researchers at Carnegie Mellon University’s Robotics Institute have enabled a computer to understand the body poses and movements of multiple people from video in real time — including, for the first time, the pose of each individual’s fingers.

This new method was developed with the help of the Panoptic Studio, a two-story dome embedded with 500 video cameras. The insights gained from experiments in that facility now make it possible to detect the pose of a group of people using a single camera and a laptop computer.

Yaser Sheikh, associate professor of robotics, said these methods for tracking 2-D human form and motion open up new ways for people and machines to interact with each other, and for people to use machines to better understand the world around them. The ability to recognize hand poses, for instance, will make it possible for people to interact with computers in new and more natural ways, such as communicating with computers simply by pointing at things.

Detecting the nuances of nonverbal communication between individuals will allow robots to serve in social spaces, allowing robots to perceive what people around them are doing, what moods they are in and whether they can be interrupted. A self-driving car could get an early warning that a pedestrian is about to step into the street by monitoring body language. Enabling machines to understand human behavior also could enable new approaches to behavioral diagnosis and rehabilitation for conditions such as autism, dyslexia and depression.

“We communicate almost as much with the movement of our bodies as we do with our voice,” Sheikh said. “But computers are more or less blind to it.”

In sports analytics, real-time pose detection will make it possible for computers not only to track the position of each player on the field of play, as is now the case, but to also know what players are doing with their arms, legs and heads at each point in time. The methods can be used for live events or applied to existing videos.

To encourage more research and applications, the researchers have released their computer code for both multiperson and hand-pose estimation. It already is being widely used by research groups, and more than 20 commercial groups, including automotive companies, have expressed interest in licensing the technology, Sheikh said.

Sheikh and his colleagues will present reports on their multiperson and hand-pose detection methods at CVPR 2017, the Computer Vision and Pattern Recognition Conference, July 21-26 in Honolulu.

Tracking multiple people in real time, particularly in social situations where they may be in contact with each other, presents a number of challenges. Simply using programs that track the pose of an individual does not work well when applied to each individual in a group, particularly when that group gets large. Sheikh and his colleagues took a bottom-up approach, which first localizes all the body parts in a scene — arms, legs, faces, etc. — and then associates those parts with particular individuals.

The challenges for hand detection are even greater. As people use their hands to hold objects and make gestures, a camera is unlikely to see all parts of the hand at the same time. Unlike the face and body, large datasets do not exist of hand images that have been laboriously annotated with labels of parts and positions.

But for every image that shows only part of the hand, there often exists another image from a different angle with a full or complementary view of the hand, said Hanbyul Joo, a Ph.D. student in robotics. That’s where the researchers made use of CMU’s multicamera Panoptic Studio.

“A single shot gives you 500 views of a person’s hand, plus it automatically annotates the hand position,” Joo explained. “Hands are too small to be annotated by most of our cameras, however, so for this study we used just 31 high-definition cameras, but still were able to build a massive data set.”

Joo and Tomas Simon, another Ph.D. student, used their hands to generate thousands of views.

“The Panoptic Studio supercharges our research,” Sheikh said. It now is being used to improve body, face and hand detectors by jointly training them. Also, as work progresses to move from the 2-D models of humans to 3-D models, the facility’s ability to automatically generate annotated images will be crucial.

When the Panoptic Studio was built a decade ago with support from the National Science Foundation, it was not clear what impact it would have, Sheikh said.

“Now, we’re able to break through a number of technical barriers primarily as a result of that NSF grant 10 years ago,” he added. “We’re sharing the code, but we’re also sharing all the data captured in the Panoptic Studio.”

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Exposing newborn mice to general anesthetic disrupts brain development

The U.S. Food and Drug administration (FDA) has recently issued a safety advisory warning that exposure to anesthetic and sedative drugs during the period of time between the third trimester of prenatal development and the first three years of life may have lasting adverse effects on cognitive function. New research publishing July 6 in the open access journal PLOS Biology by Eunchai Kang, David Mintz and colleagues now shows that early postnatal mice exposed to isoflurane — a standard and widely used inhaled general anesthetic agent — leads to chronic, abnormal activation of the mTOR pathway, a signaling system critical for normal brain development.

The researchers, based in The Johns Hopkins University School of Medicine, Baltimore, focused on the hippocampus, a brain region that is critical for learning and memory. The hippocampus contains a large number of neurons that develop in the early postnatal period, and which might thus vulnerable be to perturbation by anesthetic exposure.

15 day-old mice were exposed to clinically relevant doses of isoflurane and the effects on the subsequent development of the hippocampus were recorded. The structures of one class of neurons (the dentate gyrus granule cells) were found to be substantially altered. Specifically, the branches or dendrites of the neurons were almost twice the length of those in untreated animals, suggesting that the anesthetic caused an abnormal acceleration in their growth. In addition they saw a significant reduction in the number of mature dendritic spines — structures on the dendrites where synapses are found.

To see whether these changes were associated with an effect on learning, the treated and untreated mice were subjected to two standard behavioral tests (an object-place recognition test and a Y-maze test). The isoflurane-treated mice performed significantly worse in both tests.

The authors went on to show that pharmacologic inhibition of the mTOR pathway with the drug rapamycin protects mice from both the abnormal structural changes in the brain and the learning deficits associated with isoflurane exposure. This study thereby links the adverse effects of early developmental anesthetic exposure with mTOR, which in turn has been previously implicated in numerous neurodevelopmental cognitive disorders including autism and Fragile-X mental retardation, thus suggesting a molecular mechanism by which anesthetics might have adverse effects on brain development.

The FDA advisory warning is based on the findings of both human and animal studies. Some epidemiological research conducted in human populations reveals a correlation between exposure to anesthesia and worsened performance on school assessments, an increase in billing codes relevant to learning disorders, and deficits in neuropsychological testing. These findings are difficult to interpret by themselves, given that exposure to general anesthesia implies that an individual has had a prior medical condition and has undergone surgery. However, when the epidemiological findings are considered along with rodent studies such as this one, which unequivocally demonstrate that exposure to anesthetics during key periods of brain development results in worsened performance on behavioral tests of learning and memory, a causal link in humans seems likely. The FDA safety advisory calls for further research on this topic to clarify the risk to patients.

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Preschoolers learn from math games, to a point

What is the best way to help poor schoolchildren succeed at math? A study co-authored by researchers at MIT, Harvard University, and New York University now sheds light on the ways preschool activities may — or may not — help children develop cognitive skills.

The study, based on an experiment in Delhi, India, engaged preschool children in math games intended to help them grasp concepts of number and geometry, and in social games intended to help them cooperate and learn together.

The results contained an unexpected wrinkle. Children participating in the math games did retain a superior ability to grasp those concepts more than a year later, compared to children who either played only the social games or did not participate. However, the exercises did not lead to better results later, when the children entered a formal classroom setting.

“It’s very clear you have a significant improvement in the math skills” used in the games, says Esther Duflo, the Abdul Latif Jameel Professor of Poverty Alleviation and Development Economics at MIT and co-author of the study. “We find that the gains are persistent … which I think is quite striking.”

However, she adds, by the time the children in the study were learning formal math concepts in primary school, such as specific number symbols, the preschool intervention did not affect learning outcomes.

“All the kids [in primary school] had learned, but they had learned [those concepts] equally,” says Duflo, who is a co-founder of MIT’s Abdul Latif Jameel Poverty Action Lab (J-PAL), which conducts field experiments, often in education, around the globe.

A paper detailing the results of the study, “Cognitive science in the field: A preschool intervention durably enhances intuitive but not formal mathematics,” is being published in the journal Science.

The authors are Duflo; Moira R. Dillon, an assistant professor in New York University’s Department of Psychology; Harini Kannan, a postdoc at J-PAL South Asia; Joshua T. Dean, a graduate student in MIT’s Department of Economics; and Elizabeth Spelke, a professor of psychology and researcher at the Laboratory for Developmental Studies at Harvard University.

It’s a numbers game

The results bear on the question of how early-childhood educational interventions can help poor children access the same educational concepts that more privileged children have before entering primary school.

Spelke, an expert in cognitive development among children, notes that around age 5, children “transition from developing knowledge in a common-sense, spontaneous manner, to going to school, where they have to start grappling with formal subjects and building formal skills.” She adds that this can be a highly challenging transition for children living in poverty whose parents had no schooling themselves.

To address that, the researchers developed a field experiment involving 1,540 children, who were 5 years old on average and enrolled in 214 Indian preschools.

Roughly one-third of the preschool children were put in groups playing math games exposing them to concepts of number and geometry. For instance, one game the children played allowed them to estimate numbers on cards and sort the cards on that basis.

Another one-third of the preschool children played games that focused on social content, encouraging them to, for instance, estimate the intensity of emotional expressions on cards and sort the cards on that basis. In all, the games were “fun, fast-paced, and social” and “encouraged a desire to play together,” Dillon says.

Meanwhile, the final one-third of the preschoolers had no exposure to either type of game; these children formed another control group for the study.

The researchers then followed up on the abilities of children from all three groups, soon after the intervention, as well as six and 12 months later. They found that even after the first year of primary school, children who had played the math games were better at the skills that those games developed, compared to children from the other groups. The intervention using social games had effects on social skills but did not produce a comparable effect on math skills; the effects of the math games were specific to their math content.

Despite these effects, the early exposure to numerical concepts such as one-to-one correspondence, and geometrical concepts such as congruence and parallelism did not produce an advantage for the first group of students when it came to achievement in primary school. As the paper states, “Although the math games caused persistent gains in children’s non-symbolic mathematical abilities, they failed to enhance children’s readiness for learning the new symbolic content presented in primary school.”

Not adding up

The researchers have been analyzing why the intervention did not produce improvements in school results. One possibility, Duflo observes, is that children in Delhi primary schools learn math in a rote style that may not have allowed the experiment’s set of games to have an effect. Kids in these schools, she observes, “are [only] learning to sing ‘1 times 1 is 1, 1 times 2 is 2.'” For this reason, Duflo notes, the greater understanding of the concepts provided by the preschool math games might be more beneficial when aligned with a different kind of curriculum.

Or, Spelke puts it, “the negative thing that we learned” from the study is that lab work is not necessarily “sufficient to establish what actually causes knowledge to grow in the mind of a child, over timespans of years in the environments in which children live and learn.”

With that in mind, the research team is designing follow-up studies in which the games will segue more seamlessly into the curriculum being used in a particular school district.

“We want to include in the games themselves some element of bridging between the intuitive knowledge of mathematics and the formal knowledge they will be actually exposed to,” Duflo says. J-PAL is currently engaged in developing projects along these lines in both India and the U.S.

The larger goal of helping disadvantaged preschool children remains intact, Duflo emphasizes: “If we could take the poorest kids and instead of sending them to school with a [learning deficit], because they haven’t been to preschool or been to very good preschools, or their parents have not been able to help them out in the schoolwork, why couldn’t we try to use the best cognitive science available and bring them to school with a slight advantage?”

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New genetic syndrome identified; may offer some answers for puzzled parents

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Researchers have identified a rare genetic syndrome characterized by intellectual disability, seizures, an abnormal gait and distinctive facial features. The scientists pinpointed variants in the WDR26 gene as causes for this distinctive, yet unnamed condition. Their early research provides initial information for counseling patients and families coping with uncertainties for children with the rare, poorly recognized condition.

Finding what's right with children who grow up in high-stress environments

A new research article proposes that more attention be given to what’s right with children who grow up in high-stress environments so their unique strengths and abilities can be used to more effectively tailor education, jobs and interventions to fit them.

Stress-adapted children and youth possess traits — such as heightened vigilance, attention shifting and empathic accuracy — that aren’t tapped in traditional learning and testing situations. In addition, these skills may actually allow at-risk children to perform better than their peers from low-risk backgrounds when faced with uncertainty and stress.

Most research to date has focused on detrimental effects of growing up under stressful conditions and the deficits in cognitive development that can result, said Bruce J. Ellis, lead author.

“We’re not arguing that’s wrong, but that it is only part of the picture,” said Ellis, a University of Utah psychology professor. “The other part is that children fine-tune their abilities to match the world that they grow up in, which can result in enhanced stress-adapted skills. We’re trying to challenge a world view and give consideration to an alternative adaptation-based approach to resilience.”

The study “Beyond Risk and Protective Factors: An Adaptation-based Approach to Resilience” is forthcoming in the July issue of Perspectives on Psychological Science.

Co-authors include JeanMarie Bianchi, University of Arizona; Vladas Griskevicius, University of Minnesota; and Willem E. Frankenhuis, Radboud University Nijmegen.

The prevailing view is that children who experience high-stress environments are at risk for impairments in learning and behavior and that interventions are needed to prevent, reduce or repair the damage that has been done to them.

These high-stress environments include neighborhood danger; exposure to environmental chemicals; bad housing conditions; neglectful and abusive parenting; low-quality childcare; and peer and school violence. Research has shown that the more stressors children are exposed to, the more their performances in traditional learning and testing situations is compromised.

Most interventions are aimed at countering these deficits and getting “children and youth from high-risk backgrounds to act, think, and feel more like children and youth from low-risk backgrounds,” the authors say.

In other words, the dominant approach assumes at-risk youth are somehow broken and need to be fixed.

Virtually no research attention has been paid to what strengths and abilities youth possess as a result of growing up in high-risk environments, Ellis said.

Although there is a rich body of literature examining adaptive responses in birds and rodents to stressful environments, the first theoretical work related to humans was published in 2013 by co-author Frankenhuis, followed by the first experiments in 2015 by co-author Griskevicius, Ellis said.

That research showed repeated or chronic stress does not exclusively impair cognition and can improve forms of attention, perception, learning, memory and problem-solving.

“Our argument is that stress does not so much impair development as direct or regulate it toward these strategies that are adaptive under stressful conditions,” Ellis said. “Stress-adapted children and youth may perform better on tasks that involve situations and relationships that are relevant to them, such as social dominance. They also may perform better in settings that do not attempt to minimize the reality of daily stressors and uncertainties.”

These stress-adapted skills should be understood, appreciated and seen as building blocks for success, Ellis said. A first, essential step is that researchers catalog the strengths and abilities of people who grow up in high-stress environments and focus on how to leverage those abilities to enhance learning, intervention and developmental outcomes.

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Gene that could play key role in depression identified

Globally, depression affects more than 300 million people annually. Nearly 800,000 die from suicide every year — it is the second-leading cause of death among people between the ages of 15 to 29. Beyond that, depression destroys quality for life for tens of millions of patients and their families. Although environmental factors play a role in many cases of depression, genetics are also crucially important.

Now, a new study by researchers at the University of Maryland School of Medicine (UM SOM) has pinpointed how one particular gene plays a central role — either protecting from stress or triggering a downward spiral, depending on its level of activity.

The study, published in the Journal of Neuroscience, is the first to illuminate in detail how this particular gene, which is known as Slc6a15, works in a kind of neuron that plays a key role in depression. The study found the link in both animals and humans.

“This study really shines a light on how levels of this gene in these neurons affects mood,” said the senior author of the study, Mary Kay Lobo, an assistant professor in the Department of Anatomy and Neurobiology. “It suggests that people with altered levels of this gene in certain brain regions may have a much higher risk for depression and other emotional disorders related to stress.”

In 2006, Dr. Lobo and her colleagues found that the Slc6a15 gene was more common among specific neurons in the brain. They recently demonstrated that these neurons were important in depression. Since this gene was recently implicated in depression by other researchers, her lab decided to investigate its role in these specific neurons. In this latest study, she and her team focused on a part of the brain called the nucleus accumbens. This region plays a central role in the brain’s “reward circuit.” When you eat a delicious meal, have sex, drink alcohol, or have any other kind of enjoyable experience, neurons in the nucleus accumbens are activated, letting you know that the experience is pushing the proper buttons. In depression, any kind of enjoyment becomes difficult or impossible; this symptom is known as anhedonia, which in Latin means the inability to experience pleasure.

The researchers focused on a subset of neurons in the nucleus accumbens called D2 neurons. These neurons respond to the neurotransmitter dopamine, which plays a central role in the reward circuit.

They studied mice susceptible to depression; when subjected to social stress — exposure to larger, more aggressive mice — they tend to withdraw and exhibit behavior that indicates depression, such as social withdrawal and lack of interest in food that they normally enjoy. Dr. Lobo found that when these animals were subjected to chronic social stress, levels of the Slc6a15 gene in the D2 neurons of the nucleus accumbens was markedly reduced.

The researchers also studied mice in which the gene had been reduced in D2 neurons. When those mice were subjected to stress, they also exhibited signs of depression. Conversely, when the researchers enhanced Slc6a15 levels in D2 neurons, the mice showed a resilient response to stress.

Next, Dr. Lobo looked at the brains of humans who had a history of major depression and who had committed suicide. In the nucleus accumbens of these brains, the gene was reduced. This indicates that the link between gene and behavior extends from mice to humans.

It is not clear exactly how Slc6a15 works in the brain. Dr. Lobo says it may work by altering neurotransmitter levels in the brain, a theory that has some evidence from other studies. She says her research could eventually lead to targeted therapies focused on Slc6a15 as a new way to treat depression.

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Learning with music can change brain structure

Using musical cues to learn a physical task significantly develops an important part of the brain, according to a new study.

People who practiced a basic movement task to music showed increased structural connectivity between the regions of the brain that process sound and control movement.

The findings focus on white matter pathways — the wiring that enables brain cells to communicate with each other.

The study could have positive implications for future research into rehabilitation for patients who have lost some degree of movement control.

Thirty right-handed volunteers were divided into two groups and charged with learning a new task involving sequences of finger movements with the non-dominant, left hand. One group learned the task with musical cues, the other group without music.

After four weeks of practice, both groups of volunteers performed equally well at learning the sequences, researchers at the University of Edinburgh found.

Using MRI scans, it was found that the music group showed a significant increase in structural connectivity in the white matter tract that links auditory and motor regions on the right side of the brain. The non-music group showed no change.

Researchers hope that future study with larger numbers of participants will examine whether music can help with special kinds of motor rehabilitation programmes, such as after a stroke.

The interdisciplinary project brought together researchers from the University of Edinburgh’s Institute for Music in Human and Social Development, Clinical Research Imaging Centre, and Centre for Clinical Brain Sciences, and from Clinical Neuropsychology, Leiden University, The Netherlands.

The results are published in the journal Brain & Cognition.

Dr Katie Overy, who led the research team said: “The study suggests that music makes a key difference. We have long known that music encourages people to move. This study provides the first experimental evidence that adding musical cues to learning new motor task can lead to changes in white matter structure in the brain.”

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False-positive mammogram results linked to spike in anxiety prescriptions

Women who experience a false-positive mammogram result are more likely to begin medication for anxiety or depression than women who received an immediate negative result, according to a study led by Penn State researcher Joel Segel. The finding highlights the importance of swift and accurate follow-up testing to rule out a breast cancer diagnosis.

The study found that patients who receive a false-positive mammogram result are also prescribed anxiety or depression medication at a rate 10 to 20 percent higher than patients who receive an immediate negative result. These prescriptions are new and not continuations of previously prescribed medicines.

A false-positive result is one where a suspicious finding on the screening mammogram leads to additional testing that does not end up leading to a breast cancer diagnosis.

Additionally, within that group of patients who required more than one test to resolve the false-positive there was a 20 to 30 percent increase in those beginning to take anxiety or depression medications. The increase was particularly noticeable among women with commercial insurance who required multiple tests to rule out a breast cancer diagnosis.

“The results suggest that efforts to quickly resolve initially positive findings including same-day follow-up tests may help reduce anxiety and even prevent initiation of anxiety or depression medication,” said Segel, assistant professor of health policy and administration at Penn State.

This study demonstrates that some women who experience a false-positive mammogram may need additional follow-up care to effectively handle the increased anxiety that may accompany the experience, Segel said.

More importantly, from a practitioner standpoint, the study identifies sub-populations who may be most at risk of increased anxiety following a false-positive mammogram, Segel said. Specifically, women whose false-positive result requires more than one follow-up test to resolve, women with commercial insurance who undergo a biopsy, women who wait longer than one week to receive a negative result, and women who are under age 50 may all be at higher risk of experiencing clinically significant anxiety or depression.

“Regular breast cancer screening is critical to early detection,” Segel said. “Patients should continue to work with their providers to ensure they are receiving guideline-appropriate screening and should follow up with their providers if they experience either anxiety or depression following screening or any type of care.”

Researchers studied commercial- and Medicaid-claims databases to identify women ages 40 to 64 who underwent screening mammography with no prior claims for anxiety or depression medications.

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Scientists lay the groundwork for a reliable marijuana breathalyzer

Marijuana is now legal for recreational or medicinal use in at least 28 states and the District of Columbia. But driving under the influence of marijuana is illegal no matter which state you’re in. To enforce the law, authorities need a simple, rigorous roadside test for marijuana intoxication.

Although several companies are working to develop marijuana breathalyzers, testing a person’s breath for marijuana-derived compounds is far more complicated than testing for alcohol.

But scientists at the National Institute of Standards and Technology (NIST) have taken an important step toward that goal by measuring a fundamental physical property of the main psychoactive compound in marijuana, delta-9 tetrahydrocannabinol (THC). Specifically, they measured the vapor pressure of this compound — a measurement that, due to the compound’s chemical structure, is very difficult and has not been accomplished before. The results were published in Forensic Chemistry.

“Vapor pressure describes how a compound behaves when it transitions from a liquid to a gas,” said Tara Lovestead, a NIST chemical engineer and the lead author of the study. “That’s what happens in your lungs when a molecule leaves the blood to be exhaled in your breath. So if you want to accurately measure blood levels based on breath, you need to know the vapor pressure.”

Law enforcement agencies are interested in a breathalyzer because roadside collection of blood or urine would be impractical and invasive. Lovestead is not designing a breathalyzer herself. Rather, by measuring this fundamental physical property, she and her colleagues are laying the technical groundwork for manufacturers to develop accurate devices.

While this research is an important step forward, more research will still be needed to understand how breath levels of THC correlate with blood levels, and what blood levels of THC indicate that a person is too impaired to drive.

What is Vapor Pressure?

Vapor pressure tells you how adventurous a molecule is. Even when they are in solid or liquid form, molecules are in a constant state of jiggly motion, and some will escape as a gas. Molecules with a high vapor pressure, such as ethyl alcohol, are constantly escaping. That’s why when you open a bottle of whiskey, you can instantly smell the alcohol molecules that have collected in the air space beneath the cap.

Ethyl alcohol escapes so easily because it is a small molecule with a simple shape. But THC molecules are large and complex, with loops and spurs that cause them to stick together. This results in a very low vapor pressure — so low that you can’t measure it the usual way, which would involve putting THC in a closed container and waiting for the pressure to equalize.

“You’d be waiting a very long time,” Lovestead said.

A New Technique

The researchers overcame that obstacle by using a technology called PLOT-cryo — short for porous layer open tubular cryogenic adsorption. “PLOT-cryo is an extremely sensitive technique for capturing and analyzing things in the vapor phase,” said Tom Bruno, a NIST research chemist and co-author of the study. “It was a natural candidate for this type of problem.”

Bruno invented PLOT-cryo in 2009 for use with airport puffer machines that blow air onto passengers or luggage, then sniff the air for traces of explosives. At the time, existing technology could detect the explosive traces in the air, but could not precisely identify which compounds were present. PLOT-cryo solved that problem. The technology has since been used to sniff fire debris for evidence of arson and to find clandestine graves by following the faintest scent of decomposition.

PLOT-cryo is so sensitive that it can capture and analyze even the relatively few molecules of THC that escape into the vapor phase. In this experiment, the researchers used pure THC, purchased in compliance with a DEA research license. They swept an inert gas across the sample to capture escaping molecules, then chilled the gas to collect them (that’s where the “cryo” part of the name comes from). By measuring the mass of the recovered molecules in a known volume and temperature of sweep gas, the researchers calculated the vapor pressure.

The researchers also calculated the vapor pressure of a second compound, cannabidiol, which is considered less psychoactive than THC.

Measurements are Fundamental

When it comes to alcohol breathalyzers, NIST helps ensure accurate results by manufacturing ampules of ethyl alcohol mixed to extremely precise concentrations. Police agencies use these as reference standards to calibrate their breathalyzers. This ensures that different devices used in different jurisdictions produce consistent results — something that’s particularly important when guilt or innocence hangs in the balance.

Similarly, accurate vapor pressure measurements for THC will help ensure that marijuana breathalyzers are calibrated to a consistent standard.

“Fundamental measurements are the basis of standardization,” Bruno said. “We’re laying the foundation for the reliable systems of the future.”

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Controlled temperature change inside ear can prevent migraines

The application of gentle cooling and warming currents inside the ear canal can provide relief for migraine sufferers, new research at the University of Kent has helped show.

Volunteers in the study who had a history of migraines experienced a significant reduction in the number of migraines they normally experienced in a month after using a technique known as caloric vestibular stimulation (CVS).

CVS activates the balance organs which are believed to alter activity in the area of the brain, known as the brainstem, associated with the onset of migraine headaches.

Dr David Wilkinson, of the University’s School of Psychology, helped lead the randomised, double-blinded, placebo-controlled trial. It was carried out across the US and UK, involving 81 volunteers with a history of between four and 14 migraine attacks per month.

The volunteers self-administered caloric vestibular stimulation daily for 20 minutes over a period of three months. The thermal currents were delivered by aluminium earpieces seated within padded headphones, powered and controlled by a small, hand-held device.

The findings demonstrated that the treatment reduced both the number of migraine days per month (the active treatment group experienced a reduction of 3.6 days compared to 0.9 days in the placebo group) as well as headache pain and the consequent need for migraine abortive prescription medications.

Dr Wilkinson said the results indicated that vestibular stimulation ‘may address the existing need for new preventative therapies for episodic migraine’.

The findings were presented at the American Headache Society’s annual meeting in June, where Professor Peter Goadsby, Chair of its Science Committee, said that ‘many patients want non-drug options, so developing a non-drug therapy such as this may provide that.’

A second, expanded study will begin this summer, involving another collaboration between the University of Kent and US medical device company Scion Neurostim, who produced the CVS delivery device and will again fund the study, as well as local GP surgeries and specialist headache centres across the UK and US.

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Materials provided by University of Kent. Note: Content may be edited for style and length.

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Bringing bacteria's defense into focus

By taking a series of near-atomic resolution snapshots, Cornell University and Harvard Medical School scientists have observed step-by-step how bacteria defend against foreign invaders such as bacteriophage, a virus that infects bacteria.

The process they observed uses CRISPR (clustered regularly interspaced short palindromic repeats) sites, where the cell’s DNA can be snipped to insert additional DNA.

Biologists use CRISPR for genetic engineering experiments, but cells may have evolved the mechanism as part of a defense system. The cell uses these locations to store molecular memories of invaders so that they can be selectively eradicated at the next encounter.

“The bug’s immunity system works just as efficiently as ours, except our system functions at the protein recognition level, whereas CRISPR works at the nucleic acid recognition level,” explained Ailong Ke, professor of molecular biology and genetics.

Upon first encounter, the bacteria insert a bit of an invader’s DNA into its own genome at the CRISPR location. When needed, an RNA transcript of the stored DNA, called guide RNA, can be assembled with other proteins into a complex called Cascade (CRISPR Associated Complex for Antiviral Defense). The system is so efficient and precise that researchers have thought of ways to re-tool it for genome editing applications, to introduce changes at precise locations of DNA. “A CRISPR revolution is sweeping through biology as we speak,” said Ke.

In previous research, Ke had defined the function of the protein-RNA complexes involved in the process and used the X-ray crystallography facilities of the Cornell High Energy Synchrotron Source (CHESS) to determine their structure. Yibei Xiao, a postdoctoral researcher in Ke’s lab worked out the entire immunity process, step by step. “The next step is to capture structural snapshots of these steps, to produce a high-definition movie of what’s going on,” said Ke.

Ke collaborated with Maofu Liao, assistant professor of cell biology at Harvard Medical School, who is an expert in using a cryo-electron microscope to determine high-resolution structures of macromolecules frozen in a thin layer of ice. Working with the bacteria Thermobifida fusca, used in fermentation, Ke’s lab prepared samples representing distinct stages of the immune response. Liao and his postdoctoral researcher Min Luo froze these samples and took high-resolution snapshots at each step. The study focused on a particular version of CRISPR-related defense known as Type I-E.

“We knew roughly how it works, but without the structures we didn’t have the details,” Ke said. “A picture is worth a thousand words.”

“Scientists hypothesized that these states existed but they were lacking the visual proof of their existence,” said Luo. “Now, seeing really is believing.”

The findings, published June 29 in the journal Cell, provide structural data that can improve the efficiency and accuracy of biomedical CRISPR operations. Aspects of this defense mechanism – particularly how it searches for its DNA targets – were unclear and have raised concerns about unintended off-target effects and the safety of using the CRISPR-Cas mechanism for treating human diseases.

“To solve problems of specificity, we need to understand every step of CRISPR complex formation,” said Liao.

“To apply CRISPR in human medicine, we must be sure the system does not accidentally target the wrong genes,” said Ke. “Our argument is that the Type I system is potentially more accurate than CRISPR-Cas9, because it checks a longer stretch of sequence before action, and the system divides target searching and degradation into two steps, with built-in safety features in between.”

Type I CRISPR so far offers limited utility for precision gene editing, but it may be used as a tool to combat antibiotic-resistant strains of bacteria.

Ke and Xiao co-authored another paper in the same issue of Cell, with Ilya Finkelstein, assistant professor of molecular biosciences at the University of Texas at Austin, to characterize how Cascade searches for targets at the single molecule level.

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Materials provided by Cornell University. Original written by Bill Steele. Note: Content may be edited for style and length.

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Binge drinking accelerates alcohol use disorder, but stable daily drinking may be just as risky in the long-term

Research Society on Alcoholism. “Binge drinking accelerates alcohol use disorder, but stable daily drinking may be just as risky in the long-term.” ScienceDaily. ScienceDaily, 5 July 2017. .

Research Society on Alcoholism. (2017, July 5). Binge drinking accelerates alcohol use disorder, but stable daily drinking may be just as risky in the long-term. ScienceDaily. Retrieved July 5, 2017 from www.sciencedaily.com/releases/2017/07/170705183937.htm

Research Society on Alcoholism. “Binge drinking accelerates alcohol use disorder, but stable daily drinking may be just as risky in the long-term.” ScienceDaily. www.sciencedaily.com/releases/2017/07/170705183937.htm (accessed July 5, 2017).

Sleep problems may be early sign of Alzheimer’s

Poor sleep may be a sign that people who are otherwise healthy may be more at risk of developing Alzheimer’s disease later in life than people who do not have sleep problems, according to a study published in the July 5, 2017, online issue of Neurology®, the medical journal of the American Academy of Neurology. Researchers have found a link between sleep disturbances and biological markers for Alzheimer’s disease found in the spinal fluid.

“Previous evidence has shown that sleep may influence the development or progression of Alzheimer’s disease in various ways,” said study author Barbara B. Bendlin, PhD, of the University of Wisconsin-Madison. “For example, disrupted sleep or lack of sleep may lead to amyloid plaque buildup because the brain’s clearance system kicks into action during sleep. Our study looked not only for amyloid but for other biological markers in the spinal fluid as well.”

Amyloid is a protein that can fold and form into plaques. Tau is a protein that forms into tangles. These plaques and tangles are found in the brains of people with Alzheimer’s disease.

For the study, researchers recruited 101 people with an average age of 63 who had normal thinking and memory skills but who were considered at risk of developing Alzheimer’s, either having a parent with the disease or being a carrier of a gene that increases the risk for Alzheimer’s disease called apolipoprotein E or APOE. Participants were surveyed about sleep quality. They also provided spinal fluid samples that were tested for biological markers of Alzheimer’s disease.

Researchers found that people who reported worse sleep quality, more sleep problems and daytime sleepiness had more biological markers for Alzheimer’s disease in their spinal fluid than people who did not have sleep problems. Those biological markers included signs of amyloid, tau and brain cell damage and inflammation.

“It’s important to identify modifiable risk factors for Alzheimer’s given that estimates suggest that delaying the onset of Alzheimer’s disease in people by a mere five years could reduce the number of cases we see in the next 30 years by 5.7 million and save $367 billion in health care spending,” said Bendlin.

While some of these relationships were strong when looking at everyone as a group, not everyone with sleep problems has abnormalities in their spinal fluid. For example, there was no link between biological markers in the spinal fluid and obstructive sleep apnea.

The results remained the same when researchers adjusted for other factors such as use of medications for sleep problems, amount of education, depression symptoms or body mass index.

“It’s still unclear if sleep may affect the development of the disease or if the disease affects the quality of sleep,” said Bendlin. “More research is needed to further define the relationship between sleep and these biomarkers.”

Bendlin added, “There are already many effective ways to improve sleep. It may be possible that early intervention for people at risk of Alzheimer’s disease may prevent or delay the onset of the disease.”

One limitation of the study was that sleep problems were self-reported. Monitoring of sleep patterns by health professionals may be beneficial in future studies.

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Materialsucaqcuavaybs provided by American Academy of Neurology. Note: Content may be edited for style and length.

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