Culture

Nearly one-third of students who reported misusing prescription opioids as high school seniors between 1997 and 2000, but did not have a history of medical use, later used heroin by age 35, according to a University of Michigan study.

The research also found that 21% of seniors in the same period, who misused prescription opioids and later received an opioid prescription, went on to use heroin by age 35, said lead researcher Sean Esteban McCabe, professor and director of the Center for the Study of Drugs, Alcohol, Smoking and Health at the U-M School of Nursing.

"It is a very timely study given the number of adolescents and young adults who were overprescribed opioids and who are now aging into adulthood," he said. "We need to follow these generations to assess their risk for developing later problems."

Researchers focused on 25 cohorts of high school seniors between 1976 and 2000, following them from age 18 to age 35. They used data from 11,012 individuals from the national Monitoring the Future study, funded by the National Institute on Drug Abuse.

Unlike earlier cohorts, individuals from the 1997-2000 cohorts who reported prescription opioid misuse had a dramatically increased risk for later heroin use, compared to students who didn't misuse prescription opioids. The 1997-2000 cohorts included 1,059 individuals.

This likely reflects the trend of overprescribing opioids, said study co-author Philip Veliz, research assistant professor at the School of Nursing.

"There was an increase in opioid prescribing in the 1990s and 2000s that contributed to the opioid epidemic," he said. "Health professionals and the larger public health community owe it to these individuals to understand the downstream effects of overprescribing and develop effective interventions."

The researchers were surprised by the large uptick in heroin use among the more recent cohorts, and the findings partially explain why opioid overdoses have skyrocketed, Veliz said.

"These prevalence estimates of heroin use are very high, considering the general population annual estimates are less than 1%," McCabe said. "And anyone in the study with a history of heroin use at baseline was excluded, which makes the findings more conclusive."

Based on national estimates, the number of people in the United States using heroin has increased from 373,000 in 2007 to 808,000 in 2018. The largest increase in heroin use over this time period has occurred among adults aged 26 and older.

Although the vast majority of prescription opioid exposure does not lead to heroin use, heroin incidence and prevalence rates were significantly greater among those who reported prescription opioid misuse, the researchers say.

Previous data show that only 1% of individuals who reported past-year prescription opioid misuse had used heroin before prescription opioids, whereas approximately 80% of those who reported past-year heroin use had misused prescription opioids before starting heroin.

So what's the takeaway for parents and health care professionals?

"There are several generations who were overprescribed controlled medications with high misuse potential, such as opioids," McCabe said. "Prescribing fewer opioids and the correct dosage is only one piece to the puzzle.

"The solution requires a much more comprehensive plan that includes better education, screening and interventions to reach high-risk individuals who often fly under the radar in many health care settings. We all played a role in creating the opioid crisis and we owe it to these individuals to address the problem."

It has recently been described that infection by some enteroviruses - a genus of viruses that commonly cause diseases of varying severity - could potentially trigger diabetes, although its direct effect 'in vivo' as well as its mechanism of action at the molecular level were unknown. Now, a team of researchers from the Growth Factors, Nutrients and Cancer Group, led by Nabil Djouder at the Spanish National Cancer Research Centre (CNIO), demonstrates for the first time in Cell Reports Medicine how the enterovirus coxsackievirus type B4 (CVB4) could induce diabetes. These findings can be a fundamental step to open the way to the search of new therapeutic strategies.

The researchers also point out that the finding could be of relevance for the COVID-19 pandemic, since clinical information indicates a possible relationship between SARS-CoV-2 viral infection and diabetes. Djouder and his team suggest that since receptor of SARS-CoV-2 is expressed in the endocrine pancreas, it could operate and lead to diabetes in a similar way that CVB4 does, independently of immune reactions.

Molecular mechanisms of failure in insulin production

Coxsackieviruses belong to the family of Enterovirus, which also includes poliovirus and echovirus, and which can cause from mild flu-like illnesses to more serious illnesses such as myocarditis, pericarditis, meningitis, or pancreatitis. It was suspected that these viruses can cause diabetes in humans, but molecular mechanisms were unknown.

With the aim of finding and describing these mechanisms, the CNIO researchers worked with animal models engrafted with human pancreatic cells infected by CVB4, as well as with human and mouse insulin-producing cells, also infected with this virus.

What they observed was that CVB4 infection induces deregulation of URI, a protein that regulates the normal functions of numerous cellular activities. "In this case, URI downregulation triggers a cascade of molecular events leading to modification of the genome via hypermethylation and silencing of Pdx1. This is a gene critical for the identity and the function of beta cells present in the endocrine pancreas, at the so-called Islets of Langerhans, and responsible for the production and secretion of insulin, a hormone that decreases blood glucose levels," explains Nabil Djouder, lead author of the work published in Cell Reports Medicine. "PDX1 silencing causes the loss of the identity and function of the beta cells, which become more like alpha cells, in charge of increasing blood glucose levels, and hence leading to hyperglycemia and subsequent diabetes, independently of any immune reactions."

The researchers demonstrated their findings by using various genetically engineered mouse models and genomic studies. They show that loss of URI in mouse pancreata alters beta cell identity and function, leading to diabetes. Furthermore, they observed that diabetic mice that overexpress URI in beta cells are more tolerant to glucose. Finally, they demonstrated in several pancreata from diabetic patients that expression of URI, PDX1 and viral particles correlates in beta cells, highlighting a causal link between enterovirus infection and diabetes in humans.

The CNIO results could help advance knowledge about the pathological effects of the virus causing the current pandemic: "Similarly to our investigations on enteroviruses, some recent clinical observations have associated SARS-CoV-2, the virus responsible for COVID-19, to diabetes in infected patients," explains Djouder. "Since the receptor of SARS-Co-V2 is present in beta cells, it would be interesting to study if this virus also alters URI function and silences the expression of PDX1 to affect beta-cell function, promoting diabetes."

The researchers also suggest that, following these results, a possible prevention and therapeutic strategy would be to use, in combination with anti-viral therapies, inhibitors against DNA methylase transferase, a protein responsible for the hypermethylation of the genome and silencing of Pdx1. Indeed, Djouder's team demonstrated that this class of inhibitors reinstated PDX1 expression and glucose tolerance in diabetic mice. Several of these inhibitors have already been licensed for clinical use in cancer treatments, which could speed up their application in these cases.

How can the partisan divide be bridged when conservatives and liberals consume the same political content, yet interpret it through their own biased lens?

Researchers from the University of California, Berkeley, Stanford University and Johns Hopkins University scanned the brains of more than three dozen politically left- and right-leaning adults as they viewed short videos involving hot-button immigration policies, such as the building of the U.S.-Mexico border wall, and the granting of protections for undocumented immigrants under the federal Deferred Action for Childhood Arrivals (DACA) program.

Their findings, published today in the Proceedings of the National Academy of Sciences journal, show that liberals and conservatives respond differently to the same videos, especially when the content being viewed contains vocabulary that frequently pops up in political campaign messaging.

"Our study suggests that there is a neural basis to partisan biases, and some language especially drives polarization," said study lead author Yuan Chang Leong, a postdoctoral scholar in cognitive neuroscience at UC Berkeley. "In particular, the greatest differences in neural activity across ideology occurred when people heard messages that highlight threat, morality and emotions."

Overall, the results offer a never-before-seen glimpse into the partisan brain in the weeks leading up to what is arguably the most consequential U.S. presidential election in modern history. They underscore that multiple factors, including personal experiences and the news media, contribute to what the researchers call "neural polarization."

"Even when presented with the same exact content, people can respond very differently, which can contribute to continued division," said study senior author Jamil Zaki, a professor of psychology at Stanford University. "Critically, these differences do not imply that people are hardwired to disagree. Our experiences, and the media we consume, likely contribute to neural polarization."

Specifically, the study traces the source of neural polarization to a higher-order brain region known as the dorsomedial prefrontal cortex, which is believed to track and make sense of narratives, among other functions.

Another key finding is that the closer the brain activity of a study participant resembles that of the "average liberal" or the "average conservative," as modeled in the study, the more likely it is that the participant, after watching the videos, will adopt that particular group's position.

"This finding suggests that the more participants adopt the conservative interpretation of a video, the more likely they are to be persuaded to take the conservative position, and vice versa," Leong said.

Leong and fellow researchers launched the study with a couple of theories about how people with different ideological biases would differ in the way they process political information. They hypothesized that if sensory information, like sounds and visual imagery, drove polarization, they would observe differences in brain activity in the visual and auditory cortices.

However, if the narrative storytelling aspects of the political information people absorbed in the videos drove them apart ideologically, the researchers expected to see those disparities also revealed in higher-order brain regions, such as the prefrontal cortex. And that theory panned out.

To establish that attitudes toward hardline immigration policies predicted both conservative and liberal biases, the researchers first tested questions out on 300 people recruited via the Amazon Mechanical Turk online marketplace who identified, to varying degrees, as liberal, moderate or conservative.

They then recruited 38 young and middle-aged men and women with similar socio-economic backgrounds and education levels who had rated their opposition or support for controversial immigration policies, such as those that led to the U.S.-Mexico border wall, DACA protections for undocumented immigrants, the ban on refugees from majority-Muslim countries coming to the U.S. and the cutting of federal funding to sanctuary cities.

Researchers scanned the study participants' brains via functional Magnetic Resonance Imaging (fMRI) as they viewed two dozen brief videos representing liberal and conservative positions on the various immigration policies. The videos included news clips, campaign ads and snippets of speeches by prominent politicians.

After each video, the participants rated on a scale of one to five how much they agreed with the general message of the video, the credibility of the information presented and the extent to which the video made them likely to change their position and to support the policy in question.

To calculate group brain responses to the videos, the researchers used a measure known as inter-subject correlation, which can be used to measure how similarly two brains respond to the same message.

Their results showed a high shared response across the group in the auditory and visual cortices, regardless of the participants' political attitudes. However, neural responses diverged along partisan lines in the dorsomedial prefrontal cortex, where semantic information, or word meanings, are processed.

Next, the researchers drilled down further to learn what specific words were driving neural polarization. To do this, they edited the videos into 87 shorter segments and placed the words in the segments into one of 50 categories. Those categories included words related to morality, emotions, threat and religion.

The researchers found that the use of words related to risk and threat, and to morality and emotions, led to greater polarization in the study participants' neural responses.

An example of a risk-related statement was, "I think it's very dangerous, because what we want is cooperation amongst the cities and the federal government to ensure that we have safety in our communities, and to ensure that our citizens are protected."

Meanwhile, an example of a moral-emotional statement was, "What are the fundamental ethical principles that are the basis of our society? Do no harm, and be compassionate, and this federal policy violates both of these principles."

Overall, the research study's results suggest that political messages that use threat-related and moral-emotional language drive partisans to interpret the same message in opposite ways, contributing to increasing polarization, Leong said.

Going forward, Leong hopes to use neuroimaging to build more precise models of how political content is interpreted and to inform interventions aimed at narrowing the divide between conservatives and liberals.

EAST LANSING, Mich. - Strategies meant to motivate people in the workplace may have unintended consequences -- depending on who's in charge. Recent research from Michigan State University and Ohio State University shows that empowerment initiatives aren't necessarily the answer for business leaders hoping to motivate their employees.

"People tend to think of empowerment in uniformly positive ways," said Nicholas Hays, study co-author and associate professor of management in MSU's Eli Broad College of Business. "After all, humans crave independence and control so giving it to them at work should be a good thing. However, as people feel increasingly autonomous, they can also become unmoored from others' needs, expectations and social norms."

Hays explained that, in recent decades, companies have increasingly implemented various forms of empowerment initiatives that assume empowered leaders will translate into empowered workers.

The paper -- published in Journal of Applied Psychology -- found that, when properly implemented, empowerment initiatives can lead to heightened motivation, productivity and creativity. However, whether these initiatives are effective at all levels of the organization depends on the management style of the person implementing them.

Hays - along with Broad College of Business colleague, Russell E. Johnson, MSU Foundation Professor of management, and Hun Whee Lee, assistant professor of management at Ohio State University and lead author of the study -- found that superiors who value being respected will respond to empowerment initiatives by, in turn, empowering their workers. But, superiors who value being in charge will, somewhat ironically, respond to empowerment initiatives by closely controlling, dominating and managing their employees.

The researchers conducted three separate studies measuring outcomes of empowerment initiatives that considered personality trait data and leader behavior.

"We found that leaders who really care about being respected by their subordinates tend to react to empowerment initiatives by 'paying it forward' with certain behaviors. This could include things like allowing subordinates to set their own goals or decide how to accomplish tasks," Lee said. "In contrast, leaders who prefer to be in control and tell others what to do tend to react to these initiatives by doubling down on their desire for control. This is when we see things like micromanaging or setting specific goals for subordinates."

If an employee is uncomfortable with a superior's leadership style, the researchers say it may be beneficial to have a candid conversation between worker and boss.

"Many leaders are receptive to feedback and want to provide employees what they need to succeed at work," Hays said. "If that doesn't work, looking for different groups to join - either within an organization and with a different supervisor or even by changing organizations altogether - is sometimes the best option."

And in the unprecedented workplace environment of 2020, Hays also offered insight into what he believes the paper's findings may indicate for employees in real time.

"To the extent that leaders prioritize dominance and being in charge, they may go out of their way to micromanage employees by, for example, monitoring their online status and requesting frequent check-ins," Hays said. "I wouldn't necessarily characterize this as abusing an empowerment initiative, but certainly could rub employees the wrong way."

On the southern exterior wall of the Dome of the Rock, a very important Islamic shrine in Jerusalem's Old City, there are two marble slabs, both carved from the same stone and placed side by side to form a symmetrical pattern, that depicts two birds. In a recent article published in the Journal of Near Eastern Studies, "Solomon and The Petrified Birds on the Dome of the Rock," author Elon Harvey explores the history of this marble decoration and describes how different narratives about Solomon and two birds contributed to the multiple understandings of this imagery.

According to this article, there are six factors that contribute to the significance of the birds' imagery: (1) it breaks the symmetry that characterizes the Dome of the Rock's southern wall; (2) it is placed in the southern entrance, which is the main entrance to the Dome of the Rock; (3) there are no other depictions of animals or living creatures on the Dome of the Rock; (4) the imagery bears resemblance to carved depictions of birds in Frankish structures in the region; (5) the imagery has remained in the same spot for at least 350 years in spite of extensive renovations; and (6) the techniques for producing symmetrical imagery from marble point suggest a Byzantine and, perhaps, Christian origin.

In terms of narratives that describe the significance of the two birds, the earliest account is attributed to Evliya Celebi in 1672, who described it as an imagery that shows a "miracle of God." In the 18th century, Elzear Horn, a Franciscan missionary, described local accounts that tells the story of a stonecutter who found the two birds "formed... by nature itself."

A main departure from these two accounts, however, is found in later narratives that emphasize the story of Solomon and the two birds. Two 19th century accounts by Lievin de Hamme and Ermette Pierotti, respectively, describe the birds as magpies who defied Solomon's orders to contribute to the building of the Temple, and, as a result, were petrified as a punishment. In the beginning of the 20th century, James Edward Hanauer noted a local tale that describes how Solomon punished a male bird for boasting to a female bird: because the male bird boasted that he himself could tear down all of Solomon's edifices, Solomon turned both birds into stone. Later on, Haim Schwarzbaum, a 20th century folklorist, demonstrated that Hanauer's tale is a narrative with Sufi origins dating back to the beginning of the 10th century CE.

According to this article, however, Schwarzbaum's work points towards older Sufi narratives that date back to, at the latest, the 9th century C.E. These Sufi narratives are recorded by three figures: al-Qushayr, al-Kahra'iti, and Abu Tahir al-Silafi. In these versions, the birds were not petrified as a punishment. Rather, even after a male bird boasted to a lover that he can single-handedly topple the Dome of Solomon, Solomon acknowledged the bird's plea that the words of lovers should not be held against them. Afterall, those attempting to impress their love interests tend to get carried away with their words.

In conclusion, this article suggests that the legend of Solomon and the birds developed over time until it was finally associated with the Dome of the Rock. As the author argues, stories about the two birds demonstrate that "Sufi traditions and the figure of Solomon were still very influential in shaping the appearance and conception of the Dome of the Rock."

Artificial light abnormally increases mosquito biting behavior at night in a species that typically prefers to bite people during the day, according to research from the University of Notre Dame that was published in The American Journal of Tropical Medicine and Hygiene.

Increased biting by Aedes aegypti mosquitoes, which normally fly and bite in the early morning and during the afternoon, highlights the concern that increasing levels of light pollution could impact transmission of diseases such as dengue fever, yellow fever, chikungunya and Zika.

"This is potentially a very valid problem that shouldn't be overlooked," said Giles Duffield, associate professor in the Department of Biological Sciences, who is also affiliated with the Eck Institute for Global Health and the Neuroscience and Behavior Program. Unlike other species that may emerge from the forest to feed on humans and animals, Aedes aegypti evolved with humans and prefers to feed on them.

"They live and breed in the vicinity of houses, so the chances of Aedes aegypti being exposed to light pollution are very likely," he added.

To conduct the experiment, the study's first author, Samuel S. C. Rund, a staff scientist in the Department of Biological Sciences, allowed mosquitoes in cages to bite his arms under controlled conditions, including during the day, at night or at night while exposed to artificial light. The female mosquitoes -- the only ones that bite -- were twice as likely to bite, or blood-feed, at night when they were exposed to artificial light. Twenty-nine percent of the mosquitoes in the control group, which had no light, fed at night, while 59 percent of the mosquitoes exposed to artificial light blood-fed.

The findings will help epidemiologists better understand the true risk of disease transmission by this species. The discovery could also lead to more recommendations for bed net use. Usually mosquito bed nets are used at night to ward off bites from a different genus of mosquitoes, Anopheles, but because Aedes aegypti were shown to be stimulated by artificial light, mosquito nets could also be used in areas with a likelihood of disease transmission even with limited Anopheles activity.

"The impact of this research could be huge, and it probably has been overlooked," Duffield said. "Epidemiologists may want to take light pollution into account when predicting infection rates."

Duffield and his collaborators plan to experiment with additional variables of artificial light to further study Aedes aegypti biting activity. These variables include the duration of light, its intensity and color, and the timing of the biting -- whether early at night or later. The team is also interested in the molecular genetic pathways that might be involved with biting activity, after noticing that not every mosquito in the population under study was interested in biting at night even with artificial light.

"So, we think there is a genetic component within the Aedes aegypti species," Duffield said.

The COVID-19 pandemic has left many people with chronic health conditions relying on telemedicine rather than seeing their doctor in person when necessary or putting off important visits entirely because they fear being infected.

Ann M. Nguyen, an assistant research professor at Rutgers Center for State Health Policy at the Institute for Health, Health Care Policy and Aging Research, who recently published a paper on safety measures at physician offices, discusses what people should know about visiting their doctor and why putting off appointments that need to be done in person could lead to other health problems.

What can patients do to assess the safety of their doctor's office when making an appointment?

The physician's office should be appointment-only and have clear safety protocols posted online, outside of their office or described over the phone. While making an appointment, the office staff should walk patients through those safety protocols, such as asking them to wear a mask to the in-person visit and to come alone unless a companion is necessary for their physical or emotional health. Staff should ask COVID-19 screening questions over the phone. Any information that can be collected over the phone or online, such as insurance information, should be done before the appointment.

What are doctors' offices doing to ensure safety during in-person visits?

Contact is limited as much as possible. Intake forms are completed online or over the phone. Offices offer early-morning appointments for high-risk patients to lessen exposure, discourage or stop walk-in appointments and stagger in-person visits to allow time for rooms and equipment to be cleaned.

Patients wait outside or in their car until the doctor is ready to see them. While they wait, an office staff member asks COVID-19 screening questions and checks their temperature. The office staff member also offers to do part of the visit at the curbside or in the parking lot if possible, such taking blood pressure. If patients must go into a waiting room, the offices limit the number of people to allow for social distancing. During the visit, office staff and the doctor maintain a six-foot distance when possible. Equipment and rooms are marked as sanitized. Hand sanitizer is available. Everyone in the office is wearing personal protective equipment, including other patients.

What precautions should people take for lab work?

Patients should call labs before booking appointments since many have slowed response times and capacity or have focused on coronavirus testing. People with chronic conditions especially should ask the labs and/or their doctors for tips on the best times to visit and how the lab separates patients seeking routine lab work from those with appointments for coronavirus testing.

How have doctors' offices otherwise restructured operations for safety?

Following every patient visit, the equipment and examination rooms are sanitized. To reduce contact, offices have set up patient portals for questions. Doctor's office staff who can perform their jobs at home are not in the office. Also, since primary care clinics need to have a close pulse on their community, they can keep in direct communication with local and state health agencies to monitor evolving conditions.

A review of dozens of studies by researchers at Oregon Health & Science University and Oregon State University suggests that people may shed virus for prolonged periods, but those with mild or no symptoms may be infectious for no more than about 10 days. People who are severely ill from COVID-19 may be infectious for as long as 20 days.

That's in line with guidance provided by the U.S. Centers for Disease Control and Prevention, confirming recommendations for the length of time people should isolate following infection with SARS-CoV-2.

The review published in the journal Infection Control and Hospital Epidemiology.

"Detection of viral RNA may not correlate with infectivity since available viral culture data suggests shorter durations of shedding of viable virus," the authors write.
"Additional data is needed to determine the duration of shedding of viable virus and the implications for risk of transmission."

Researchers decided to conduct the review to gain more information on transmission and to help inform infection control practices, said co-author Monica Sikka, M.D., assistant professor of medicine (infectious diseases) in the OHSU School of Medicine.

"Even though people can shed virus for a prolonged period of time, the studies we reviewed indicated that live virus, which may predict infectiousness, was only detected up to nine days in people who had mild symptoms," Sikka said.

The researchers identified 77 studies worldwide, including 59 that had been peer-reviewed, and combed through the results. All studies reported assessments of viral shedding using standard methods to identify the virus by replicating it through a process called polymerase chain reaction, or PCR.

"Although PCR positivity can be prolonged, culture data suggests that virus viability is typically shorter in duration," the authors write.

Boston, MA - Air pollution was significantly associated with an increased risk of hospital admissions for several neurological disorders, including Parkinson's disease, Alzheimer's disease, and other dementias, in a long-term study of more than 63 million older U.S. adults, led by researchers at Harvard T.H. Chan School of Public Health.

The study, conducted with colleagues at Emory University's Rollins School of Public Health and Columbia University's Mailman School of Public Health, is the first nationwide analysis of the link between fine particulate (PM2.5) pollution and neurodegenerative diseases in the U.S. The researchers leveraged an unparalleled amount of data compared to any previous study of air pollution and neurological disorders.

The study will be published online October 19, 2020 in The Lancet Planetary Health.

"The 2020 report of the Lancet Commission on dementia prevention, intervention, and care has added air pollution as one of the modifiable risk factors for these outcomes," said Xiao Wu, doctoral student in biostatistics at Harvard Chan School and co-lead author of the study. "Our study builds on the small but emerging evidence base indicating that long-term PM2.5 exposures are linked to an increased risk of neurological health deterioration, even at PM2.5 concentrations well below the current national standards."

Researchers looked at 17 years' worth (2000-2016) of hospital admissions data from 63,038,019 Medicare recipients in the U.S. and linked these with estimated PM2.5 concentrations by zip code. Taking into account potential confounding factors like socioeconomic status, they found that, for each 5 microgram per cubic meter of air (μg/m3) increase in annual PM2.5 concentrations, there was a 13% increased risk for first-time hospital admissions both for Parkinson's disease and for Alzheimer's disease and related dementias. This risk remained elevated even below supposedly safe levels of PM2.5 exposure, which, according to current U.S. Environmental Protection Agency standards, is an annual average of 12 μg/m3 or less.

Women, white people, and urban populations were particularly susceptible, the study found. The highest risk for first-time Parkinson's disease hospital admissions was among older adults in the northeastern U.S. For first-time Alzheimer's disease and related dementias hospital admissions, older adults in the Midwest faced the highest risk.

"Our U.S.-wide study shows that the current standards are not protecting the aging American population enough, highlighting the need for stricter standards and policies that help further reduce PM2.5 concentrations and improve air quality overall," said Antonella Zanobetti, principal research scientist in Harvard Chan School's Department of Environmental Health and co-senior author of the study.

Traditionally, neuroscience regards the brain as being made up of two basic tissue types. Billions of neurons make up the grey matter, forming a thin layer on the brain's surface. These neuronal cells are interlinked in a mindboggling network by hundreds of millions of white matter connections, running in bundles, deeper in the brain. Until very recently, not much was known about the interface between the white and grey matter - the so-called superficial white matter - because methods were lacking to study it in living human brains. Yet, previous investigations had suggested the region to be implicated in devastating conditions such as Alzheimer's disease and autism. Now a multidisciplinary team led by Nikolaus Weiskopf from the Max Planck Institute for Human Cognitive and Brain Sciences has succeeded in making the superficial white matter visible in the living human brain.

"We demonstrated that the superficial white matter contains a lot of iron. It is known that iron is necessary for the process of myelination," explains Evgeniya Kirilina, first author of the study published in Science Advances. Myelin is what makes the white matter white. It's the fatty coating of nerve cell axons that speeds up transmission of information through the brain. The myelination process can occur throughout the lifespan but is predominant during development. In fact, the largest concentration of iron the researchers found was in the superficial white matter in regions of the frontal cortex, which happens to be the slowest developing structure in the human brain. Incredibly, the human frontal cortex is not fully myelinated until the forth decade of life.

The key to the new method is MRI (Magnetic Resonance Imaging) but at very high field strength. While typical clinical MRI scanners work at 1.5 or 3 Tesla, in terms of the strength of the magnetic field, the Max Planck Institute for Human Cognitive and Brain Sciences houses a powerful 7 Tesla scanner. This, in combination with advanced biophysical model, allowed the team to create very high resolution maps of the white-grey matter border across the entire living brain. The accuracy of their submillimetre maps was assessed against classic and advanced histological methods involving physical dissection and analysis of post mortem brains.

The new method promises many further insights into the organisation of the interface between white and grey matter. Evgeniya Kirilina adds, "We hope the method can be used to increase our understanding of brain development as well as pathological conditions involving the superficial white matter."

NEW YORK - October 18, 2020 - A large subgroup analysis of a randomized clinical trial showed neither a mortality risk nor benefit associated with the use of paclitaxel drug-coated devices (DCD) in the treatment of peripheral artery disease (PAD). The study also found that the benefit of rivaroxaban use on reducing ischemic limb and cardiovascular outcomes was consistent regardless of whether a DCD was used.

Findings were reported today at TCT Connect, the 32nd annual scientific symposium of the Cardiovascular Research Foundation (CRF). TCT is the world's premier educational meeting specializing in interventional cardiovascular medicine.

Paclitaxel drug-coated devices (DCD) improve patency of lower extremity revascularization (LER) in patients with peripheral artery disease (PAD). However, meta-analyses of randomized trials of DCD have reported increased long-term mortality compared with non-DCD. These concerns have led to warnings from regulatory agencies about the use of DCD in patients with PAD.

VOYAGER PAD was a double-blind, placebo-controlled trial of PAD patients undergoing lower extremity revascularization (LER) randomized to rivaroxaban 2.5 mg twice daily or placebo on a background of aspirin 100 mg daily. Clopidogrel was allowed per operator discretion. The primary results of this trial, presented earlier this year at ACC and published in the New England Journal of Medicine, found that rivaroxaban at a dose of 2.5 mg twice daily plus aspirin was associated with a significantly lower incidence of the composite outcome of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes than aspirin alone.

This analysis examined the long-term safety of DCD and evaluated whether rivaroxaban 2.5 mg twice daily plus low dose aspirin versus low dose aspirin alone on the primary efficacy endpoint was consistent with versus without DCD use.

Deaths were prospectively collected and adjudicated. All-cause mortality, a prespecified secondary outcome, was the primary outcome for this analysis. Device type was collected at enrollment in patients undergoing endovascular LER.

Among 6,564 randomized patients, 66% (n=4,316) underwent endovascular index LER and were included in this analysis; median follow-up was 31 months (IQR 25, 37), and complete ascertainment of vital status was available for 99.6% of patients. During the qualifying endovascular LER, DCD was used for 31% (n=1,358) of patients. Patients receiving DCD more frequently had prior endovascular LER, had higher baseline use of dual antiplatelet therapy and statins, and were more often treated for claudication than non-DCD patients.

In the unweighted analysis, lower associated mortality was observed among patients receiving DCD versus non-DCD (2.9 vs. 3.9 per 100 patient-years; 3.5-year Kaplan-Meier cumulative incidence of 10.2% vs.13.8%). After weighting, there was no association between DCD use and mortality (3.5-year cumulative incidence 12.1% vs. 12.6%, HR 0.95, 95% CI 0.83-1.09, p=0.49). The benefit of rivaroxaban 2.5 mg twice daily with aspirin compared to aspirin alone on reducing ischemic limb and cardiovascular outcomes was also consistent regardless of whether a DCD was used.

"Inverse Probability Treatment Weighting (IPTW) successfully adjusted for known confounders and showed no mortality risk or benefit associated with DCD, including in subgroups by device type," said Connie N. Hess, MD, MHS. Dr. Hess is an Associate Professor of Medicine (Cardiology) at the University of Colorado School of Medicine, Aurora. "This analysis from VOYAGER PAD addresses many of the limitations of currently available data regarding mortality and paclitaxel and adds to the literature examining the safety of drug-coated devices."

Not too little, not too much - Goldilocks' 'just right' approach can now assess children's daily activities as new research from the University of South Australia confirms the best make up of a child's day to maximise bone health and function in children.

Examining 804 Australian children aged between 11 and 13 years old, the world-first study found that children need more moderate-to-vigorous physical activity, more sleep and less sedentary time to optimise bone health.

The study found the ideal balance of a child's activities across a 24-hour period comprises:

1.5 hours of moderate-to-vigorous physical activity (sports, running around)

3.4 hours of light physical activity (walking, doing chores)

8.2 hours of sedentary time (studying, sitting at school, reading)

10.9 hours of sleep.

Lead researcher, UniSA's Dr Dot Dumuid say that the findings provide valuable insights for parents, caregivers and clinicians.

"Children's activities throughout the whole 24-hour day are important for their bone health, but until now, we haven't known the perfect combination of exercise, sleep and sedentary time," Dr Dumuid says.

"Higher levels of physical activity are known to be good for children's bone health, yet we can't just increase children's exercise without impacting their other activities.

"In this study, we looked at the interrelating factors of physical activity (both light, and moderate-to-vigorous physical activity), sedentary time and sleep, finding an ideal combination that delivers the best daily balance.

"The 'Goldilocks Day' tells us the durations of physical activity, sleep and sitting that are 'just right' for children's optimal bone health."

"Up to 90 per cent of peak bone mass is achieved by age 18-20, which makes this especially important during childhood and adolescence.

"Optimising bone health in children is a key protector against osteoporosis, the leading preventable cause of fracture in adults and a major public health problem with considerable economic and societal costs.

Osteoporosis is common in Australia, with 1.2 million people estimated to have the condition and a further 6.3 million with low bone density. Globally, osteoporosis affects 200 million people, with 75 million cases across Europe, USA and Japan.

In this study, participants were selected from the Child Health CheckPoint study within the Longitudinal Study of Australian Children. Activity data was collected through accelerometer readings (worn for 24 hours a day over an eight-day period), supplemented by self-recorded logs for bed and wake times. Bone measures were recorded via peripheral QCT scans of the leg (ankle and shin) to identify bone density and geometric parameters.

Dr Dumuid says the study also highlights the importance of sleep, especially for boys.

"We always talk about getting enough exercise to help build bones, but for children, it's vital that they also get enough sleep.

"Curiously, the study also showed that sleep is more important for boys' bone health than for girls, with boys needing an extra 2.4 hours of sleep a day. However, boys tended to be at earlier stages of pubertal development than girls, causing us to speculate that the need for longer sleep is related to rapidly changing hormonal processes rather than gender.

"By knowing the best balances and interrelations of sleep, exercise and rest, parents and caregivers can guide their child's daily activities to put them in good stead for future bone health."

According to data published by the Organization for Economic Co-operation and Development (OECD), female participation in the labour market has risen over the past 35 years, with women now accounting for 52.5% of the total workforce. Despite this increase, gender equality in the workplace is still far from a reality. In traditionally male-dominated fields, such as those known by the STEM acronym (for science, technology, engineering and mathematics), only two of every ten positions are occupied by women.

This underrepresentation distances women from accessing leadership positions and results in the exclusion of the feminine perspective in creating and developing solutions in the digital transformation era. It also leads to an absence of role models that showcase the contributions made by women in these areas, which may in turn cause children and teens to mistakenly think that the talent and skills required to pursue STEM careers are correlated with masculinity.

As such, in a study published in the open access journal Frontiers in Psychology, a team of researchers led by the director of the GenTIC (Gender and ICT) research group at the Universitat Oberta de Catalunya (UOC) Internet Interdisciplinary Institute (IN3), Milagros Sáinz, have demonstrated the impact of female role models in influencing girls' preferences for studying STEM subjects.

The researchers evaluated the effectiveness of an intervention implemented in sixteen schools in various cities around Spain, involving the participation of 304 girls aged between twelve and sixteen. The intervention formed part of a programme developed by the Inspiring Girls Foundation to promote scientific and technological vocations for girls. This programme involves recruiting successful women working in STEM fields as volunteers to go into schools to talk to the children about their careers. The hope is that this contact with female role models will serve to prevent the perpetuation of gender stereotyping in relation to STEM subject competency and encourage girls to opt to study on university programmes in these fields.

"From a very early age, around the age of six, girls are conditioned to think that they are not as good at maths as their male counterparts. This programme, however, focuses on girls in secondary education aged between twelve and seventeen, as this represents a crucial time during which they have to make choices about which academic path to follow," explained Sáinz.

Dismantling gender stereotypes

The youngsters who participated in the study, which examined their perceptions in relation to mathematics, were asked to complete a questionnaire both before and after the talks in which they needed to rate the validity of statements, such as 'Maths is more important for boys', 'Boys are better at maths than girls,' and 'I am talented at maths.'

The aim was to analyse the extent to which the intervention - attending the talks given by successful women working in STEM - changed the girls' perceptions about whether women are able to succeed in these fields and whether it increased the likelihood of them choosing to go on to study a STEM subject at university.

"We observed how effective the sessions were in neutralizing the negative effects of gender stereotypes, which advocate that girls have less of an affinity for mathematics, in relation to their predisposition to choose to study STEM subjects," stressed Sáinz.

Thus, according to the results of the study, coming into contact with successful women working in traditionally male-dominated STEM fields helps promote an interest in these areas of study for girls. "The sessions with the role models also showed the girls a reality that was contrary to established gender stereotypes regarding the kind of people that supposedly work in these sectors and the requirements needed to enter them," the UOC researcher pointed out.

The role played by families and teachers

Sáinz has also recently published another study, again in the Frontiers in Psychology journal, on how the assessments made, often unconsciously, by parents and teachers with regard to the academic skills of adolescents help to reinforce gender stereotypes and roles. Surprisingly, the researchers identified a discrepancy between the actual academic performance of students and the perception of their abilities by parents and teachers.

In fact, the study, which involved eight focus groups made up of 39 parents and 34 secondary school teachers, showed that many adults are unaware that girls achieve higher grades across all subjects, including those traditionally associated with masculine roles, such as maths, technology, physics and chemistry.

Many of them also continue to attribute academic performance to biological or genetic differences, without reflecting on the implications of this or on how these misconceptions contribute to replicating gender biases and perpetuating a socialization process based on emphasizing the differences between men and women.

"Although some parents and teachers are aware of this, they don't possess the strategies to combat these gender biases," said Sáinz. As such, the researcher suggests that efforts still need to be made to seek strategies to effectively combat these biases through training and intervention programmes aimed at families and the educational community.

A new study from the University of Eastern Finland is the first in the world to show that the serum metabolite profile can be used to identify individuals likely at risk of developing an alcohol-related disease in the future. The finding also opens up new avenues for preventing alcohol-related adverse effects. The study was published in Alcoholism: Clinical and Experimental Research.

Alcohol is the cause underlying many severe diseases, such as alcohol dependence, liver cirrhosis and different types of cancer. It is estimated that alcohol accounts for approximately five per cent of the global burden of disease, and the WHO has listed the reduction of excessive consumption of alcohol as one of its most important priorities.

"However, it is challenging to identify individuals most in need of an intervention, i.e., people who will go on to develop an alcohol-related disease," Senior Researcher Olli Kärkkäinen says.

The new study from the University of Eastern Finland discovered that changes in the serum metabolite profile are visible years before an individual is diagnosed with an alcohol-related disease. The researchers used metabolomics methods to analyse serum samples collected from middle-aged Finnish men in the 1980s as part of a prospective study focusing on risk factors of coronary artery disease. They analysed baseline serum samples from individuals who were diagnosed with an alcohol-related disease in the course of a 30-year a follow-up. On average, the diagnosis was made 13.6 years after the sample was taken. The study had two control groups: one group consisted of individuals whose consumption of alcohol at baseline was equally heavy, but who were not diagnosed with an alcohol-related disease later on. The other control group consisted of individuals whose consumption of alcohol at baseline was moderate, allowing the researchers to analyse alcohol-related changes.

There were significant differences in the groups' serum metabolite profiles. After controlling for self?reported alcohol use and gamma?glutamyl transferase levels, which is a biomarker of alcohol use, the researchers found that individuals who would later develop an alcohol-related disease had significantly lower serum levels of serotonin and asparagine than individuals in the control groups.

"Serotonin is an important mediator that regulates the function of the nervous system, and lower levels of asparagine may be related to an increased risk of alcohol-induced organ damage," Senior Researcher Kärkkäinen says.

Heavy alcohol use in itself was associated with considerable changes in the blood metabolite profile, e.g., in the levels of amino acids, steroid hormones and fatty acids.

"Our study is the first to show that the serum metabolite profile could be used to identify, already in advance, individuals who are likely to develop an alcohol-related disease in the future. This would have far-reaching consequences: if we can identify these individuals sufficiently early, we can target preventive measures at them. Successful prevention of alcohol-related adverse effects and diseases is highly significant both on the individual and societal levels," Senior Researcher Kärkkäinen says.

A limitation of the study is that it only analysed middle-aged Finnish men who belonged to a risk group for alcohol-related diseases.

"Future research should focus on analysing whether these findings can be generalised to other population groups, including women, younger people and people who are not Finnish," Senior Researcher Kärkkäinen says.

A team of scientists from the Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW), the Australian Museum and the Max Delbrück Center for Molecular Medicine (MDC) report a new method for identifying any genome sequence located next to a known sequence. It is often difficult to precisely determine unknown sequences close to small known fragments. Whole genome sequencing can be a solution, but it's a very cost intensive approach. In order to find a more efficient technique, the scientists developed Sonication Inverse PCR (SIP): First, DNA is cut into random pieces using ultrasound waves. After DNA fragmentation, long-range inverse PCR is performed followed by long-fragment high-throughput sequencing. SIP can be used to characterise any DNA sequence (near a known sequence) and can be applied across genomics applications within a clinical setting as well as molecular evolutionary analyses. The results are reported in the scientific journal Methods in Ecology and Evolution.

Many methods have been developed to identify sequences next to a determined sequence of interest. Inverse PCR based methods are among the most common methods and have been used for decades but suffer from bias because of the way DNA is cut apart by enzymes: They need to find specific sequence motifs that are not evenly spread across the DNA. Therefore, many neighbouring sequences to a target cannot be characterised without technical difficulty or without the expense and effort of whole genome sequencing. "Sonication Inverse PCR (SIP) circumvents this problem by using high-frequency sound waves to randomly cut the DNA, eliminating the bias resulting from the use of enzymes", Prof Alex Greenwood from Leibniz-IZW explains. "The fragments are then turned into circles and the so-called inverse PCR is applied." With the development of long-fragment sequencing, the authors were able to target 4-6 thousand base long inverse PCR fragments and sequenced them at high-throughput on the PacBio RS II sequencing platform.

The new method was tested on a complex model, the koala retrovirus (KoRV), a high copy retrovirus found in the koala (Phascolarctos cinereus) genome. Targeting the ends of the integrated virus, the full spectrum of viral integrations in the genome could be determined using a small 'known' piece of viral DNA. Mapping the integrations against reference genomes provided precise genomic locations for each integration at a resolution that would otherwise require a large sequencing effort. "Applying this method allowed us to discover a koala specific defense mechanism against KoRV", says Dr Ulrike Löber from the MDC (see also Löber et al. 2018 [1]).

"SIP is economical and can be simultaneously applied to many samples by including barcodes to the PCR primers, making the method cost efficient", adds Dr David Alquezar, former member of the Leibniz-IZW team and now manager of the Australian Centre for Wildlife Genomics at the Australian Museum. The authors continue to apply SIP to address different problems, such as how viruses become integrated into genomes and how they cause diseases. In conclusion, SIP provides a new protocol for high-throughput profiling of flanking sequences next to any region of interest coupled with long-range sequencing, allowing scientists to study complex biological systems such as mobile genetic elements.