Culture

Antiepileptic drugs are associated with a higher risk of mortality in persons with Alzheimer's

The use of antiepileptic drugs is associated with a higher risk of death among persons with Alzheimer's disease, according to a new study from the University of Eastern Finland. The results were published in Neurology. The mortality risk increased considerably during the first three months of treatment with antiepileptic drugs, and was higher among users of older antiepileptic drugs in comparison to users of newer antiepileptics. The risk of death remained elevated after exclusion of people with epilepsy in the sensitivity analyses.

The increased risk remained after controlling for comorbidities, sociodemographic factors and the use of other drugs. However, it is possible that the reasons for initiating an antiepileptic partially explain the results and, therefore, the findings should be confirmed in further studies.

These initial findings are concerning, as people with Alzheimer's disease used antiepileptic drugs more frequently than people without the disease, and the use of older antiepileptics is more common among them. The association between antiepileptic use and mortality in this population has not been studied before.

The results highlight caution in prescribing these drugs for indications other than epilepsy in this vulnerable group. Up to 1% of the population needs chronic antiepileptic treatment to control epilepsy. These drugs are also frequently used for other indications, including neuropathic pain and behavioural and psychological symptoms of dementia, although antiepileptics are not officially indicated for behavioural and psychological symptoms of dementia.

The studies are based on the Finnish nationwide MEDALZ dataset, which includes all community-dwelling persons with Alzheimer's disease in Finland during 2005-2011 (70,718 people). Data on antiepileptic drug use was extracted from the Prescription Register. The mortality risk was compared between antiepileptic drug users and matched non-users with Alzheimer's disease. The study, funded by the Academy of Finland, was conducted at the University of Eastern Finland.

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University of Eastern Finland

Did life emerge in the 'primordial soup' via DNA or RNA? Maybe both

Scientists have long debated which genetic information carrier - DNA or RNA - started life on Earth, but a new study suggests life could have begun with a bit of both. The research, led by scientists from the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB), in Cambridge, shows for the first time how some of the building blocks of both DNA and RNA could have spontaneously formed and co-existed in the 'primordial soup' on Earth.

The work challenges one of the leading hypotheses for the advent of life - the 'RNA world' theory, which arose in the 60s and has gained wide acceptance.

Today, all known living organisms use the same genetic molecules - called nucleic acids - to store information. There are two sorts of nucleic acids: DNA and RNA. DNA encodes instructions in genes. Genes are turned into messages using RNA, which carries instructions to make proteins. Proteins can make structures and act as molecular machines.

In the 'RNA world' theory, life started with RNA molecules, which can both store instructions and can act as a modest machine, potentially enabling them to self-replicate. It proposes that through evolution, life in the RNA world gave way to the era of DNA and proteins, because DNA is more stable and durable than RNA.

In the current study, published in Nature, the researchers simulated the conditions on a primordial rocky Earth with shallow ponds in the lab. They dissolved chemicals that form RNA in water, then dried them out and heated them, then they simulated the early sun's rays by exposing them to UV radiation.

In this recreation of early Earth geochemistry, intermediates in the synthesis of two of the building blocks of RNA were simultaneously also converted into two of the building blocks of DNA.

It is the first demonstration that reasonable amounts of a genetic alphabet made up of four building blocks, two for RNA and two for DNA - potentially sufficient to have encoded early life, which was far less complex than life today - may have been available on the primordial Earth.

Professor John Sutherland from the MRC Laboratory of Molecular Biology, who led the work, says: "The RNA world hypothesis suggests that life began with RNA, before a genetic takeover occurred involving primitive biosynthetic machinery and natural selection to result in DNA."

"Our work suggests that in conditions consistent with shallow primordial ponds and rivulets there was a mixed genetic system with RNA and DNA building blocks co-existing at the dawn of life. This fulfils what many people think is a key precondition for the spontaneous emergence of life on Earth."

The team's experiments to simulate early Earth geochemistry showed that four of the building blocks for DNA and RNA can arise from the same reagents and conditions. They produced cytidine and uridine, two of the building blocks of RNA, and deoxyadenosine, which is one of those of DNA. Deoxyadenosine was partly converted to deoxyinosine, which can take the role of another DNA building block.

They believe that these four building blocks may have coexisted before life evolved and were the beginnings of a primitive genetic alphabet.

Professor Sutherland adds: "The nucleic acids, RNA and DNA, are clearly related and this work suggests that they both derive from a hybrid ancestor, rather than one preceding the other."

"Since genetic information always flows from nucleic acids to proteins, and never in reverse - a principle called the 'central dogma' of molecular biology by Francis Crick - we now need to uncover how the information which can be stored and purveyed by these nucleic acids could have been first used to make to proteins."

Understanding the chemical origins of life is a fundamental aspect of natural science, and can inform the design of future synthetic biology.

Dr Megan Dowie, head of molecular and cellular medicine at the MRC commented: "This study shows that blue skies research can reveal fascinating insights into how the very beginnings of life may have emerged, and demonstrates the importance of supporting fundamental research. These underpinning discoveries in the life sciences could enable exciting future strategies for artificial biology."

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UK Research and Innovation

New TILDA research highlights online habits of older adults in the age of our 'new normal'

The COVID-19 pandemic has rapidly and dramatically changed how people interact, moving work and social communication online. Use of the internet to stay connected, socialise, shop and conduct business has expanded since the implementation of measures to curtail the spread of COVID-19.

Researchers from The Irish Longitudinal Study on Ageing (TILDA) at Trinity College have released a new report today (Wednesday, June 3rd, 2020) entitled ' Internet access and use among adults aged 50 and over in Ireland: Results from Wave 5 of The Irish Longitudinal Study on Ageing' that delves into the internet habits and behaviours of adults aged 50 and over in Ireland.

The report is part of concerted efforts by researchers at TILDA to refocus its research outputs to provide a better understanding of relevant aspects of Ireland's older population and help shape policy responses to the COVID-19 pandemic.

Given the restrictions introduced to minimise exposure to infection spread, technology plays a central role in enabling activities of daily living and in communication. Knowledge of the availability and use of technology by Irish adults is therefore key to policy decisions.

What does the report show?

The report analyses data from Wave 5 of TILDA (2018) to provide insights into internet use among older adults.

Some of the key findings reveal that:

71% of adults aged 50 and over (c. 1 million adults) have access to the internet in their homes.

Internet access decreases with age. Only 38% of those aged 80 and over have home internet access, compared to 86% aged 50-69 years, and 66% aged 70-79 years.

68% aged 50+ use the internet daily (700,000 adults), while 85% (870,000 adults) access the internet at least once a week.

64% of adults aged 50+ (approximately 900,000) have access to smartphones/tablets (and therefore to apps).

79% of older adults use the internet for information sharing, 72% for sending and receiving emails, 43% make audio and video calls online, while 40% engage with social media

30% of adults aged 50+ who live alone do not have internet access

74% aged 50+ living in urban areas have home internet access, compared to 67% in rural areas

The findings show a high level of access, and frequent and varied use of the internet among older adults in Ireland. The internet is a valuable resource to maintain social connections, access information and support services, and help adults carry out a variety of tasks from financial matters, to social and leisure activities.

The report outlines encouraging evidence that older adults are increasingly connected in the online world. Internet use offers positive engagement opportunities to keep older adults mentally stimulated and lessen feelings of isolation and loneliness. Nonetheless, 3 in 5 people aged 80 and older do not have access to the internet and alternative means of communication are required. For these individuals, particularly for those living alone and older age groups, more traditional forms of communication are likely to be essential. Communicating and accessing information through telephone, radio, television, and the national postal service remains important, in combination with ongoing family and community support.

Lead author of the report, Health Research Assistant at TILDA, Paul Doody said:

"These data indicate that among adults aged 50 and older in Ireland, there is a high prevalence of home internet access, with frequent and varied use. Particularly in light of the on-going COVID-19 pandemic, the internet provides a valuable resource for many to maintain social interactions, obtain information, access support services, and engage in online commerce. However, our data also indicates a relatively large section of the population are without home internet access. This is particularly the case for older age groups and those living alone. For these individuals, more traditional forms of communication and information distribution, in combination with ongoing family and community support, are likely to be essential.

Our findings may be of particular interest to organisations and institutions commonly engaged with older populations, especially given the recent need to reorientate many organisational structures and resources online. Furthermore, these findings may provide a valuable resource to aid planning around contemporary provision of online shopping, continuity of medical care, and ongoing development of optional contacting tracing apps."

Co-author of the report, Senior Data Manager, Minjuan Wang said:

''The data in the report suggests strong feasibility of the plan to use a contact tracing application to combat COVID-19, as the majority of adults aged 50 or above have access to the internet. Nevertheless, we should also bear in mind the continued importance of traditional forms of communication, as there is still a substantial section of the population that does not fully embrace modern technologies like the internet. The optimal approach would be to combine both traditional and modern methods of communication to ensure full coverage.''

Professor Rose Ann Kenny, Principal Investigator of TILDA said:

''The impact of this information goes beyond the current pandemic. More and more financial and commercial institutions rely on the internet and allied technologies to interact with customers. This leaves a significant number of citizens marginalised and disenfranchised. It is incumbent on Government and other organisations to ensure that all citizens can engage fully with organisations.''

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Trinity College Dublin

Wearable sensor may help to assess stress in healthcare workers

image: A wearable biosensor may help monitor stress experienced by healthcare professionals, according to a study published in Physiological Reports.

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Emma Chapron, University of South Wales

A wearable biosensor may help monitor stress experienced by healthcare professionals, according to a study published in Physiological Reports.

In the study of 12 healthy male volunteers, a wearable biosensor that is placed on the chest, called the VitalScout, provided an accurate assessment of physiological parameters--heart rate and respiration rate--that are used to calculate stress. Furthermore, the biosensor's metrics correlated strongly to those obtained using breathing analyses, and they could discriminate changes associated with stress from changes related to increased physical activity.

"A high prevalence of stress and burnout has been reported in healthcare professionals, however, the current tools utilized to quantify such metrics like smart watches or questionnaires are not in keeping with doctors' busy lifestyles and do not comply with infection prevention policies," said senior author Prof. Damian M. Bailey, PhD, of the University of South Wales, in the UK. "Given that increased stress can subsequently impact both the healthcare profession and the patient in care, we believe the wearable biosensor used in this study is a useful tool to monitor and manage stress experienced by healthcare professionals."

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Wiley

Certain personality traits may affect risk of 'pre-dementia'

A study published in the Journal of the American Geriatrics Society examined five personality traits--neuroticism, extraversion, conscientiousness, agreeableness, and openness--and their links to pre-dementia conditions called motoric cognitive risk (MCR) and mild cognitive impairment (MCI) syndromes.

Among 524 adults aged 65 years and older who were followed for a median of 3 years, 38 participants developed MCR and 69 developed MCI (some with memory loss, or amnestic MCI).

Openness was associated with a 6% reduced risk of developing MCR, whereas neuroticism was associated with a 6% increased risk of non-amnestic MCI. In non-amnestic MCI, memory remains intact, but one or more other cognitive abilities--such as language, visual-spatial skills, or executive functioning--are impaired.

None of the personality traits were associated with MCI overall or with amnestic MCI.

"While more studies are needed, our results provide evidence that personality traits play an independent role in the risk for or protection against specific pre-dementia syndromes," said lead author Emmeline Ayers, MPH, of the Albert Einstein College of Medicine. "From a clinical perspective, these findings emphasize the importance of accounting for aspects of personality when assessing for dementia risk."

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Wiley

The nature of glass-forming liquids is more clear

image: Researchers from The University of Tokyo revealed a key structural feature of glass-forming liquids that may help solve a decades-long physics debate

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Institute of Industrial Science, The University of Tokyo

Tokyo, Japan - Glass is such a common, everyday material that you probably don't think about it much. It may surprise you to learn that researchers today still don't understand how glass forms. Figuring this out is important for glass industries and many other surprising applications of glasses.

In a study published in Physical Review Letters, researchers from The University of Tokyo have revealed a structural origin of slow glassy dynamics that's aimed at understanding how a liquid becomes more viscous on cooling and can form a glass. The researchers found the correlation between the structure and motion of particles within simulated glass-forming liquids, on the level of individual particles and larger-scale particle assemblies.

A central puzzle in glass physics is why a glass-forming liquid becomes so viscous before forming a glass. Whether this unusually slow motion in a liquid is mainly attributable to changes in spatial structure remains unknown. A physical model that reproduces how glass forms would help resolve this debate.

"We used the concept of mutual information to understand the interrelationship between local particle arrangement and dynamics in glass-forming liquids," explains lead author of the study Hua Tong, who is now Assistant Professor in Shanghai Jiao Tong University. "Our results suggest that spatial structure controls the unique cooperative particle motion seen in glass-forming liquids."

The researchers based their simulations on a structural order parameter that quantifies how closely the particles can pack together. The simulations focused on particle motions attributable to the original state of the particles, i.e., on the spatial structure. With the concept of mutual information, the simulations showed that particles structurally organize into assemblies that move more slowly than the rest of the particles, as seen in a real glass.

"We found no clear relationship between particle-level potential energy and relaxation time," says Hajime Tanaka, senior author. "This suggests that slow glassy dynamics is fundamentally controlled by structural order formed by interparticle interactions, including both the repulsive and attractive parts."

This liquid-to-glass research has many applications, including window glasses, optical fibers, and improved smart touch screens. Ultrahigh viscosity of a glass-forming material is very useful to deform it to arbitrary shape. By understanding what controls the viscosity of glass-forming liquids, the shape processability may be much improved.

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Institute of Industrial Science, The University of Tokyo

COVID-19 spurs increase in self-care, new survey shows

WASHINGTON (June 3, 2020) - The vast majority of U.S. adults (80%) say they will be more mindful about practicing self-care regularly once the pandemic is over, according to a new survey conducted by The Harris Poll on behalf of Samueli Integrative Health Programs. Nearly half of Americans (46%) also report that they are struggling to find ways to maintain their whole health (i.e., physical, mental, and spiritual health) during the pandemic.

"The pandemic threatens the mental and physical well-being of every American. People are seeking ways to manage their stress, but it isn't enough," said Wayne Jonas, MD, executive director of Samueli Integrative Health Programs. "As we adjust to a new normal, we need to foster a robust, patient-centered healthcare system to better promote self-care."

More than one in four Americans report a lack of energy (30%), difficulty sleeping (29%), or exercising less (29%) during the pandemic. Nearly half of Americans (47%) report feeling socially isolated, according to the online survey of more than 2,000 adults over age 18 conducted in May 2020.

A majority (64%) say they are focused on their mental health now more than ever. Nearly half of Americans (44%) say they wish they had more guidance and support for practicing self-care during the pandemic. Self-care strategies include lifestyle changes, healthy diet, regular exercise, stress management, and other behavior changes such as smoking cessation.

Compared to before the pandemic, roughly one-third say they are practicing more creative activities (35%), praying more (31%), or engaging in more meaningful conversations with friends and family (31%). Most U.S. adults (83%) report that technology has been essential in helping them to stay connected with others. One in four also report that they are spending more time outdoors or eating healthy foods more.

However, a majority also cite disruptions in obtaining regular and preventative healthcare services: 55 percent say they are scared to get healthcare during the pandemic. This is felt most acutely by people who have had a household income reduction during the pandemic (64% vs. 46% of those whose household income has not decreased due to the pandemic). Nearly half (45%) of all U.S. adults say they have failed to get preventive healthcare (e.g., wellness visits, standard vaccinations, screenings, etc.) during the pandemic.

"At a time when healthcare is needed the most, a majority of people are scared to seek it out. This not only leaves them without critical immediate care, it also halts necessary preventative care that is vital to chronic disease prevention and management," said Jonas. "This change in healthcare access will likely have dangerous repercussions for the long-term health of our country. These are also the same risk factors that increase serious illness from COVID-19."

In summarizing the importance of the findings, Jonas said, "As the country begins our recovery, it will inevitably create questions about the future of the healthcare system. The findings from this study show the critical need for a system that empowers individuals to maintain healthy habits they formed and emphasizes strategies that support self-care--like good nutrition, exercising, and stress reduction--alongside guidance from physicians."

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The Reis Group

Solving the mysteries of water and air underground

image: PVC pipes painted with rust, known as IRIS tubes, help track how much oxygen is in the soil. When there isn't enough oxygen, microbes will turn the rust into regular iron, which washes away. These tubes are drying after being extracted from the experiments and rinsed.

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J.C. Fiola

Stand outside and look underneath your feet. There, perhaps under some grass, is the soil. On a dry day, all the spaces in the soil are filled with air. And some distance further down, those spaces are entirely water. So, what's in between?

That's the capillary fringe. And it might just be the most important -- and mysterious -- thing you've never heard of.

Like a paper towel wicking up water from a surface, water rises above its natural level in soils through capillary action. A lot of chemical and microbial activity in the soil varies based on how much water or air is around. So, the capillary fringe controls many important functions in the soil.

"Important processes like contaminant breakdown and carbon storage depend on the amount of water and oxygen available," says Jaclyn Fiola, now a graduate student at Virginia Tech. "Understanding the conditions in the capillary fringe will help us predict where certain soil processes will occur."

Fiola and her team set out to better understand this strange region. But that's no easy feat. With the entire fringe underground, it's invisible. And even scientists have a hard time agreeing on where the fringe begins and ends. That's where lab experiments come in handy.

The team gathered two kinds of soil, one sandy and one loamy. The scientists packed this soil into five-gallon buckets with holes near the bottom to allow water to enter.

To track the key events in the capillary fringe, Fiola turned to cleverly simple systems. To study how much oxygen was in the soil, the researchers painted PVC pipes with rust-embedded paint. They inserted these pipes into the soil.

Wherever there wasn't enough oxygen, microbes would "breathe" rust instead. That would turn the rust into a different form of iron, which washes away. By measuring how much rust was left, the team could get a glimpse beneath the soil.

The researchers were surprised to find that the water rose the entire height of the buckets in both types of soils. That means the capillary fringe extended at least 9 inches, more than they were expecting.

They were also surprised that the PVC pipes had lost their rust well above the water table. "This means the soil in the capillary fringe at least 2 inches above the water table is behaving like soil in the water table even though it's not fully saturated," says Fiola.

"Based on the findings, the soil directly above the water table behaves a lot like the saturated soil within the water table," says Fiola.

Wetlands are defined by the government as soils that are saturated near the surface. But if soils act like they're saturated even above the water table, that means more areas might act like wetlands and deserve protection.

Scientists also wanted to better understand how water and air in the capillary fringe can affect other soil processes. To track decomposition, they inserted wooden sticks into the soil. Researchers found that microbes eating the wooden sticks were finnicky.

"Our results suggest that the microbes that carry out decomposition require ideal conditions - not too wet and not too dry," says Fiola. The wood was most eaten away in the middle of the buckets where it was moist.

"The capillary fringe is far too complicated to define based on one single measurement," says Fiola. Even though her team measured many different aspects of the fringe, those measurements didn't always agree with one another.

Soils are complex, especially outside of the lab. So now the researchers are planning to study the capillary fringe in more realistic conditions and in the field.

That future work might give us a better understanding of -- and appreciation for -- the fuzzy, complex, and vital in-between spaces beneath our feet.

Credit: 
American Society of Agronomy

UMN trial shows hydroxychloroquine has no benefit over placebo in preventing COVID-19

MINNEAPOLIS, MN- June 3, 2020 - Today, University of Minnesota Medical School researchers published the results from the first randomized clinical trial testing hydroxychloroquine for the post-exposure prevention of COVID-19.

The trial results, which were published in the New England Journal of Medicine, determined that hydroxychloroquine was not able to prevent the development of COVID-19 any better than a placebo. Further, 40% of trial participants taking hydroxychloroquine developed non-serious side effects -- predominantly nausea, upset stomach or diarrhea. However, the trial found no serious side effects or cardiac complications from taking hydroxychloroquine.

The randomized placebo-controlled trial, which rapidly launched on March 17, tested if hydroxychloroquine could prevent COVID-19 infection in healthy persons after exposure to someone with COVID-19. The trial enrolled 821 non-hospitalized adults from across the U.S. and Canada, who were exposed to COVID-19 from someone living in their same household or as a healthcare worker or first responder. Half of the participants received five days of hydroxychloroquine while the other half received five days of a placebo. The trial was a double-blind trial, meaning that neither the participants nor the researchers knew what the participants received. Participants were followed for two weeks to see who developed symptomatic COVID-19.

Overall, approximately 12% of those given hydroxychloroquine developed COVID-19 versus approximately 14% given the vitamin placebo (folate). This was not a statistical difference, and even if there was a statistical difference, this would equate to treating 42 persons with hydroxychloroquine in order to prevent one infection. There was no further benefit to prevent infection among those who also took zinc or vitamin C.

David Boulware, MD, MPH, the senior investigator of the trial and infectious disease physician at the University of Minnesota, launched the trial with the hope that an inexpensive, widely-available, oral medication could prevent or treat coronavirus early in the disease before people are sick enough to need hospital care.

"Our objective was to answer the question of whether hydroxychloroquine worked to prevent disease or did not work," Boulware said. "While we are disappointed that this did not prevent COVID-19, we are pleased that we were able to provide a conclusive answer. Our objective was to find an answer."

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University of Minnesota Medical School

Mass general model projects sharp rise in alcohol-related liver disease

Alcohol-related liver disease is currently the most common reason for liver transplantation in the United States. In recent years, high-risk drinking of alcohol--defined as exceeding daily drinking limits (more than 4 or 5 standard drinks for women and men, respectively) at least weekly for a whole year--has increased in nearly all sociodemographic groups, especially in women.

A new analysis by researchers at Massachusetts General Hospital, Harvard Medical School and Georgia Tech indicates that cases of alcohol-related liver disease will rise dramatically in the coming years without drastic steps to reduce high-risk drinking rates.

To project the impact of alcohol-related liver disease over the next two decades, the team developed a model of drinking patterns and alcohol-related liver disease in individuals born in 1900 to 2012 in the United States, with projections up to 2040. The model relied on data from multiple sources: the National Epidemiologic Survey on Alcohol and Related Conditions, the National Institute of Alcohol Abuse and Alcoholism, the US National Death Index, the National Vital Statistics System and numerous published studies. The model was validated in that it closely reproduced the trends in deaths due to alcohol-related liver disease that were observed from 2005 to 2018.

In the Lancet Public Health analysis, future trends in alcohol-related liver disease were modelled under three potential scenarios based on the level of interventions to address high-risk drinking:

Without any changes in trends in alcohol consumption (status quo), more than 1 million people could die from alcohol-related liver disease by 2040, of whom 35% are projected to be younger than 55 years
Reducing high-risk drinking rates to 2001 levels could prevent 35,000 deaths during the same time period
In contrast, decreasing the high-risk drinking rate by 3.5% per year--similar to the decrease in the rate of tobacco consumption observed after implementation of policies and social interventions in the 1960s to reduce smoking in the U.S.--could prevent 299,000 deaths compared with the status quo scenario (a 30% decrease)

The analysis also projected that in comparison with status quo, decreasing the high-risk drinking rates by 3.5% per year could prevent alcohol-related liver cancer and decompensated cirrhosis (a form of advanced liver disease) by 30% from 2019 to 2040.

"Our study underscores the need to bring alcohol-related disease to the forefront of policy discussions and identify effective policies to reduce high-risk drinking in the U.S.," said senior author Jagpreet Chhatwal, PhD, a senior scientist at the MGH Institute for Technology Assessment and an assistant professor at Harvard Medical School.

Lead author Jovan Julien, MS, a PhD student at Georgia Tech, noted that the impact of high-risk drinking takes years to observe. "Our model highlights the long-term risk, especially for younger generations whose drinking continues to outpace older generations," he said. "Given the practical infeasibility of clinical trials to study long-term effects of increased alcohol consumption, data-driven modeling studies such as ours are valuable for understanding the implications of high-risk drinking and making informed policy decisions," added co-author Turgay Ayer, PhD, MSc, an associate professor at Georgia Tech.

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Massachusetts General Hospital

A potential new weapon in the war against superbugs

University of Melbourne researchers are finding ways to beat dangerous superbugs with 'resistance resistant' antibiotics, and it could help in our fight against coronavirus (COVID-19) complications.

As bacteria evolve, they develop strategies that undermine antibiotics and morph into 'superbugs' that can resist most available treatments and cause potentially lethal infections.

The Melbourne team has shown that a newly discovered natural antibiotic, teixobactin, could be effective in treating bacterial lung conditions such as tuberculosis and those commonly associated with COVID-19.

Their work could pave the way for a new generation of treatments for particularly stubborn superbugs.

Teixobactin was discovered in 2015 by a team led by Professor Kim Lewis at Northeastern University in Boston in 2015. His company is now developing it as a human therapeutic.

The new University of Melbourne research, published in mSystems journal, is the first to explain how teixobactin works in relation to the superbug Staphylococcus aureus - also known as MRSA.

MRSA is among bacteria responsible for several difficult-to-treat infections in humans, particularly post-viral secondary bacterial infections such as COVID-19 chest infections and influenza.

University of Melbourne Research Fellow in anti-infectives Dr Maytham Hussein and Associate Professor Tony Velkov's team synthesised an aspect of teixobactin to produce a compound that showed excellent effectiveness against MRSA, which is resistant to the antibiotic methicillin.

Dr Hussein said that there was no way to stop bacteria like MSRA from developing resistance to antibiotics as it was part of its evolution. This made combatting it extremely challenging.

"The rise of multi drug-resistant bacteria has become inevitable," Dr Hussein said. "These bacteria cause many deadly infections, particularly in immunocompromised patients such as diabetic patients or those with cancers, or even elderly people with post-flu secondary bacterial infections."

The University of Melbourne team is the first to find that teixobactin significantly suppressed mechanisms involved in resistance to vancomycin-based antibiotics that are recommended for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, and MRSA-caused meningitis.

The development could lead to new lung infection treatments and Associate Professor Velkov said it would greatly facilitate the pre-clinical development of teixobactin.

"Bacteria often develop resistance towards antibiotics within 48 hours after exposure," Associate Professor Velkov said. "The bacteria failed to develop resistance towards this compound over 48 hours.

"These novel results will open doors to develop novel antibacterial drugs for the treatment of multi-drug resistant Gram-positive infections - bacteria with a thick cell wall - which are caused by certain types of bacteria."

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University of Melbourne

Sharp drop in Australia's bad cholesterol levels -- but rising in Asia and Pacific

The proportion of Australians with bad cholesterol levels has dropped significantly, while Asian and Pacific countries recorded a sharp rise, according to the world's largest study on the condition.

University of Queensland researchers were part of an international team that analysed data from 102.6 million people in 200 countries, spanning the period from 1980 to 2018.

UQ's Professor Annette Dobson said the results showed total and non-HDL 'bad' cholesterol levels had fallen in high-income nations including Australia, North-western Europe and North America, but had risen in low and middle-income nations, particularly in East and Southeast Asia.

"Australian women ranked 146th highest in the world for non-HDL cholesterol in 2018, compared with 32nd highest in 1980," she said.

"While Australian men ranked 116th highest for non-HDL cholesterol in 2018, compared to 31st highest in 1980.

"High cholesterol is responsible for almost four million deaths worldwide each year with half of these being in East, South and Southeast Asia."

Cholesterol is a waxy, fat-like substance found in blood which helps create healthy cells, but too much of it can lead to build-ups in blood vessels.

High non-HDL cholesterol can block blood supply and lead to heart attacks and strokes.

This type of cholesterol is usually caused by diets high in saturated fat but can be lowered effectively through the use of statins.

The researchers believe the findings suggest a need for pricing and regulatory policies that shift diets from saturated to non-saturated fats, while health systems must be prepared to treat those in need with effective medicines.

The data showed countries with the highest levels of non-HDL cholesterol now included China, Tokelau, Malaysia, the Philippines and Thailand.

But Australia may not be off the hook.

"While the study showed that non-HDL cholesterol levels had fallen over decades, Australia doesn't have up-to-date national data as blood samples are no longer included in the National Health Surveys, so we are in the dark about recent trends," Professor Dobson said.

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University of Queensland

Terahertz radiation can disrupt proteins in living cells

Researchers from the RIKEN Center for Advanced Photonics, Tohoku University, National Institutes for Quantum and Radiological Science and Technology, Kyoto University, and Osaka University have discovered that terahertz radiation, contradicting conventional belief, can disrupt proteins in living cells without killing the cells. This finding implies that terahertz radiation, which was long considered impractical to use, may have applications in manipulating cell functions for the treatment of cancer, for example, but also that there may be safety issues to consider.

Terahertz radiation is a portion of the electromagnetic spectrum between microwaves and infrared light, which is often known as the "terahertz gap" because of the lack so far of technology to manipulate it efficiently. Because terahertz radiation is stopped by liquids and is non-ionizing--meaning that it does not damage DNA in the way that x-rays do--work is ongoing to put it to use in areas such as airport baggage inspections. It has generally been considered to be safe for use in tissues, though some recent studies have found that it may have some direct effect on DNA, though it has little ability to actually penetrate into tissues, meaning that this effect would only be on surface skin cells.

One issue that has remained unexplored, however, is whether terahertz radiation can affect biological tissues even after it has been stopped, through the propagation of energy waves into the tissue. The research group from RAP and the National Institutes for Quantum and Radiological Science and Technology recently discovered that the energy from the light cold enter into water as a “shockwave.” Considering this, the group decided to investigate whether terahertz light could also have an effect like this on tissue.

They chose to investigate using a protein called actin, which is a key element that provides structure to living cells. It can exist in two conformations, known as (G)-actin and (F)-actin, which have different structures and functions, as the (F)-actin is a long filament made up of polymer chains of proteins. Using fluorescence microscopy, they looked at the effect of terahertz radiation on the growth of chains in an aqueous solution of actin, and found that it led to a decrease in filaments. In other words, the terahertz light was somehow preventing the (G)-actin from forming chains and becoming (F)-actin. They considered the possibility that it was caused by a rise in temperature, but found that the small rise, of around 1.4 degrees Celsius, was not sufficient to explain the change, and concluded that it was most likely caused by a shockwave. To further test the hypothesis, they performed experiments in living cells, and found that in the cells as in the solution, the formation of actin filaments was disrupted. However, there was no sign that the radiation caused cells to die.

According to Shota Yamazaki, the first author of the study, published in Scientific Reports, "It was quite interesting for us to see that terahertz radiation can have an effect on proteins inside cells without killing them cells themselves. We will be interested in looking for potential applications in cancer and other diseases. He continues, “Terahertz radiation is coming into a variety of applications today, and it is important to come to a full understanding of its effect on biological tissues, both to gauge any risks and to look for potential applications.”

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RIKEN

Bees grooming each other can boost colony immunity

video: Honeybees engaging in allogrooming behavior.

Image: 
Dr Adele Bordoni, University of Florence

Honeybees that specialise in grooming their nestmates (allogroomers) to ward off pests play a central role in the colony, finds a new UCL and University of Florence study.

Allogroomer bees also appear to have stronger immune systems, possibly enabling them to withstand their higher risk of infection, according to the findings published in Scientific Reports.

Ectoparasites (parasites that live on the outside of a host's body, such as mites) are a growing threat to honeybees worldwide, so the researchers say that supporting allogrooming behaviour might be an effective pest control strategy.

Lead author Dr Alessandro Cini, who began the project at the University of Florence before moving over to UCL Centre for Biodiversity & Environment Research, said: "An ectoparasitic mite, Varroa destructor, represents a major global threat to bee colonies. By understanding how allogrooming practices are used to ward off parasites, we may be able to develop strategies to promote allogrooming behaviour and increase resilience to the parasites.

"Here, we found worker bees that specialise in allogrooming are highly connected within their colonies, and have developed stronger immune systems.

"We suspect that if more bees engaged in these allogrooming behaviours that ward off parasites, the colony as a whole could have greater immunity."

Among bees, allogrooming consists of a worker using its mouth to remove debris, which may include parasites and other pathogens, from the body of another member of its colony.

In bee colonies, different groups of worker bees conduct different activities - one such specialisation is allogrooming, although it was not previously known how specialised the groomer bees are, and how their physiology may be different.

The current study focused on Apis mellifera, commonly known as the western honeybee, which is the most common species of honeybee and also the world's most-used bee for both honey production and pollination in agriculture.

As allogrooming would likely put the grooming bees at an elevated risk of contracting pathogens and parasites, the researchers tested their immune systems, and found that their hemolymph (like blood, but for insects) could more effectively clear out potentially harmful bacteria than the immune systems of other bees in the colony.

Co-author Dr Rita Cervo from the University of Florence said: "By identifying a striking difference in the immune systems of the allogrooming bees, which are involved in tasks important to colony-wide immunity from pathogens, we have found a link between individual and social immunity."

The researchers found that allogroomer bees occupy a central position in the colony's social network, as they are more connected to bees across the colony than the average bee, enabling their grooming habits to benefit a large number of bees and keep the colony as pest-free as possible.

The researchers found that allogrooming is a relatively weak, transient specialty, as the groomer bees still devoted a similar amount of time to other tasks as the rest of the colony's worker bees. The researchers say this shows that bees can develop physiological differences narrowly tailored to specific tasks, while still maintaining a degree of plasticity enabling them to switch to other tasks as needed.

The researchers did not detect any differences in how well the allogroomer bees could detect when other bees needed grooming, as their antennae were not more finely-tuned to relevant odours. It is possible they can detect who needs grooming in other ways, such as by noticing the 'grooming invitation dance' whereby bees shake their whole body from side-to-side.

Credit: 
University College London

An optimal decision-making strategy emerges from non-stop learning

Unlike machines, the behaviour of animals and humans almost always has an element of unpredictability. Countless experiments have shown that our responses to the exact same challenge are sometimes faster, sometimes slower, sometimes correct and sometimes wrong.

In the field of neuroscience, this variability is often attributed to what is called "noise". An ever-present "neural babble" that influences the way brains process and respond to incoming information.

A new collaborative study in rodents by a team of scientists from the Champalimaud Centre for the Unknown in Portugal, Harvard Medical School in the US, and the University of Geneva in Switzerland, shows that, in fact, this variability could sometimes be wrongly interpreted as noise. Instead, it may actually be the reflection of a behavioural strategy that was overlooked due to prior assumptions about how the subject should behave. Their results - published today (June 2nd) in the scientific journal Nature Communications - call into question what "optimal behaviour" really means.

An unexpected strategy

"It all started with a simple experiment", recalls Maria Inês Vicente, who collected the experimental data as part of her graduate work at the Champalimaud Centre for the Unknown and is currently working at Leiden University . "We took two different odours and created several mixtures of the two. During the experiment, the different mixtures were presented to the rats, one at a time. On each trial, the rats had to report which of two odours was more dominant. If it thought the answer was odour A, it would approach a water spout on the right, and if it opted for odour B, it would go to the left. Some mixtures had much more of one odour compared with the other, making it easier to tell which was more salient. Whereas in other mixtures, the difference was more subtle. If the rat got the correct answer, it received a water reward."

The researchers recorded how quickly the rats responded and whether their answer was right or wrong. To their surprise, when they analyzed the data, they realized that the rats' behaviour didn't follow a common decision-making rule. "In these types of tasks we tend to see a clear dependency between difficulty and decision time: on the harder, more subtle trials, animals (and humans) take longer to decide than on easy trials", says André Mendonça of the Champalimaud Centre for the Unknown. "Instead, our rats would take, on average, the same amount of time to make both hard and easy decisions."

"The explanation for this unexpected observation wasn't easy to come by", adds Jan Drugowitsch, a co-author affiliated with Harvard Medical School. "Finally, we found it by constructing a mathematical model that united separate branches in the field of decision-making. In a sense, our goal was to replicate the rats' behaviour in a 'machine's brain' with the hope of discovering the underlying variables that produced this surprising result."

The model revealed an unexpected strategy. On each trial, the rat was readjusting its behaviour according to the results of the previous trial. If the rat was correct in one trial, it would be biased towards the same odour in the next one. And vice versa, an incorrect response in one trial would lead to switching in the next.

Why did the animals adopt this particular strategy? "This strategy is consistent with a world-view where the environment is continuously changing, which leads the animals to update their decision-making approach on a trial-by-trial basis. From the outside, their behaviour appears highly variable but in fact they were just adapting too quickly. That is why it would have been easy to wrongly interpret this variablity as 'just' noise", Drugowitsch points out.

Optimality is in the eye of the beholder

Why did the rats opt for a different strategy from the expected one? The authors explain that there are several reasons, the first is the nature of the task. "There isn't just one type of sensory discrimination task", says Mendonça. "Various elements in the design of the task may draw out different decision-making strategies. For instance, if we had asked rats to localize the side where a sound comes from instead of discriminating between odours, their strategy would have aligned with our initial expectation. This is because there is a 'built-in' right-left category in the brain for certain sensory modalities that are naturally spatially separated, but that's not the case for olfaction."

Another reason is confidence. "Just like humans, rats appear to evaluate their own decisions and change their behaviour accordingly. When you are very confident and end up making the correct decision, there's really not much to learn. But what happens when you're confident, but then find out that you're actually wrong? In this case, you should change your behaviour drastically. Which is precisely what we saw with our rats", says Zachary Mainen, one of the group leaders who headed the study and who is affiliated with the Champalimaud Centre for the Unknown.

According to the authors, another explanation for the rat's choice of strategy is their "hard-wired" circuitry for learning. "Ironically, if they would not constantly readjust their responses according to the outcome of the last trial, they would actually do better. In fact, what we were originally expecting them to do is to construct an 'odour A - odour B' category and implement it", points out Alex Pouget, who is a group leader at the University of Geneva and co-author of the study. "Still, the rats' strategy makes sense."

As the authors explain, this observation doesn't mean the rat is a maladapted animal, on the contrary, they claim that the scientific community should reconsider what they define as "optimal behaviour". "Rats have evolved over millions of years to search and explore an ever-changing environment. Therefore, when we assess the behaviour of these animals, we should remember that it's not necessarily only about performance per se. Optimality should depend both on the problem at hand and the nature of the problem-solver", Pouget argues.

"We believe that our work is a good starting point for exploring further how different subfields of decision-making may interact. We also hope that other scientists will use and refine our models in follow-up experiments. It would be fascinating and informative to see when, how and why our model starts to fail. Making an error is an opportunity for learning something new, and that is both the result and take-home message of our study", Mendonça concludes.

Credit: 
Champalimaud Centre for the Unknown