Culture

A cheaper, faster COVID-19 test

image: Co-first authors Ioanna Smyrlaki (right) and Anders Ekman (left) and Bjorn Reinius, principal investigator of the study.

Image: 
Stefan Zimmerman

Researchers at Karolinska Institutet have developed a method for fast, cheap, yet accurate testing for COVID-19 infection. The method simplifies and frees the testing from expensive reaction steps, enabling upscaling of the diagnostics. This makes the method particularly attractive for places and situations with limited resources. It is equally interesting for repeated testing and for moving resources from expensive diagnostics to other parts of the care chain. The study is published in Nature Communications.

"We started working on the issue of developing a readily available testing method as soon as we saw the developments in Asia and southern Europe, and before the situation reached crisis point in Sweden," says principal investigator Bjorn Reinius, research leader at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet. "Our method was effectively finished already by the end of April, and we then made all the data freely available online."

The spread of the new coronavirus at the end of 2019 in China's Wuhan region quickly escalated into a global pandemic. The relatively high transmission rate and the large number of asymptomatic infections led to a huge, world-wide need for fast, affordable and effective diagnostic tests that could be performed in clinical as well as non-clinical settings.

Established diagnostic tests for COVID-19 are based on the detection of viral RNA in patient samples, such as nasal and throat swabs, from which RNA molecules must then be extracted and purified. RNA purification constitutes a major bottleneck for the testing process, requiring a great deal of equipment and logistics as well as expensive chemical compounds.

Making the current methods simpler without markedly compromising their accuracy means that more and faster testing can be carried out, which would help to reduce the rate of transmission and facilitate earlier-stage care.

The cross-departmental research group at Karolinska Institutet has now developed methods that completely circumvent the RNA-extraction procedure, so that once the patient sample has been inactivated by means of heating, rendering the virus particles no longer infectious, it can pass straight to the diagnostic reaction that detects the presence of the virus.

According to the researchers, the most important keys to the method's success are both the above virus inactivation procedure and a new formulation of the solution used to collect and transport the sample material taken from the patients.

"By replacing the collection buffer with simple and inexpensive buffer formulations, we can enable viral detection with high sensitivity directly from the original clinical sample, without any intermediate steps," says Dr Reinius.

Institutions and research groups around the world have shown great interest in the method since a first version of the scientific article was published on the preprint server medRxiv. The article was read more than 15,000 times even before it was peer-reviewed by other researchers in the field and officially published in Nature Communications.

"Thanks to the low cost and the simplicity of the method, it becomes a particularly attractive option at sites and in situations with limited resources but a pressing need to test for COVID-19," he says and adds: "I would certainly like to see that this test used in Sweden too, for example for cheap periodic testing of asymptomatic people to eliminate the spread of infection."

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Karolinska Institutet

Boys' club barriers create issues for Australian boards

Pale, male and stale - it's certainly stereotypical, but it's a saying that still holds water when it comes to Australian boards, according to new research from the University of South Australia.

Assessing the influence of gender diversity on Australian boards, researchers found that a persistent boys' club mentality is impairing decision-making at the top, particularly in relation to corporate social responsibility (CSR) initiatives.

Lead researcher, UniSA's Dr Kathy Rao, says that many Australian boards suffer from a lack of gender diversity and a male pack mentality causes biased and unbalanced decisions.

"Women bring a unique set of values, perspectives and capabilities to top-level decision-making which can help boards address CSR issues in a more effective manner," Dr Rao says.

"But old-school attitudes tend to hold them back, partly because they don't have a critical mass to push new ideas over the line, but also because there are a few powerful older male directors who are so focussed on profit that they disregard CSR is 'soft' when it is raised by female directors.

"The challenge is, however, that CSR is incredibly important for ethical and sustainable business, so companies are essentially shooting themselves in the foot if they purposely, or inadvertently, avoid CSR strategies."

Despite an increasing focus on CSR and gender diversity in Australia and around the world - including a push for gender diversity targets and disclosures from key bodies such as ASIC, ASX and AICD - gender imbalances are compounded by 'like-attracting-like' recruitment practices.

Co-researcher, and Director of the UniSA Yunus Social Business Centre, Professor Carol Tilt, says unconscious bias is a massive issue for Australian boards.

"Board members' lack of awareness of their own bias is perhaps the single most damaging factor for effective leadership," Prof Tilt says.

"Australian companies need to be more proactive in offering training and incentives for more women to become actively involved in firm governance - and, to achieve this without regulatory pressures or token appointments simply to meet gender targets.

"Unfortunately, when boards look for new members, they're often reluctant to appoint female members or candidates who have different experiences to their own, defeating the capacity to recruit a diversity of views.

"Such a blinkered approach to governance is highly risky, and while members may not know they're operating in such a way, a lack of gender diversity almost guarantees this outcome.

"As you can appreciate, influence is king on boards; if you don't have it, you can't make much of an impact."

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University of South Australia

Don't sleep on the hypnotic potential of thalidomide

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University of Tsukuba

Tsukuba, Japan - Thalidomide is a medication with several different effects, one of which is promoting sleep in the context of insomnia. In a new study, researchers from the University of Tsukuba have discovered that thalidomide exerts its hypnotic effects through mechanisms distinct from those for the drug's notorious teratogenicity.

Thalidomide was first marketed under the trade name Contergan in the late 1950's in Europe to tackle anxiety, sleeplessness, and morning sickness in pregnant women. It was eventually removed from the market because of its teratogenic effects, which infamously led to phocomelia, or severe limb deformities. Today, thalidomide is used as a medication to modulate the immune system to fight off several types of cancer. The mechanism behind the teratogenic and immunomodulatory effects of thalidomide has been well-studied, whereby it was shown that the drug binds to the protein cereblon and blocks the cereblon-mediated ubiquitination pathway. This pathway is important for the degradation and removal of specific subsets of proteins within cells, and thus its blockage is expected to disrupt various cellular signaling mechanisms.

"Thalidomide is a powerful, yet controversial drug owing to its history," says corresponding author of the study Professor Masashi Yanagisawa. "The goal of our research was to investigate the as-yet undetermined molecular mechanism responsible for the hypnotic effects of thalidomide."

To achieve their goal, the researchers asked if cereblon-mediated ubiquitination is involved in the hypnotic effects of thalidomide or if thalidomide acts independently of cereblon to exert sleep-inducing effects. The researchers first treated normal mice with thalidomide, and recorded electroencephalography (EEG) and electromyography (EMG) to test whether the drug had an effect on the sleep of the animals. The researchers found that thalidomide increased non-REM (rapid eye movement) sleep without reducing REM sleep. Reduction of REM sleep is one of unwanted side effects of common sedatives.

The researchers then engineered a mutant mouse in which thalidomide no longer interacted with cereblon. Thalidomide had the same effects on the sleep of cereblon mutant mice as on that of normal mice, suggesting that thalidomide acts independently of cereblon to induce sleep (Figure). To corroborate these findings, the researchers investigated molecular pathways of known general anesthetics and sedatives in normal and cereblon mutant mice, and found that thalidomide acted on the same neurons as those drugs.

"These are striking results showing how thalidomide induces sleep independently of its known effects on the teratogenic cereblon pathway. Our findings could be helpful in developing novel thalidomide-like hypnotic drugs without thalidomide's teratogenic effects," says Professor Yanagisawa.

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University of Tsukuba

Faulty transportation of messenger RNA is the culprit in ALS

image: Model of ALS/FTLD pathology associated with abnormal deposition of TDP-43

Image: 
National Center of Neurology and Psychiatry

Osaka, Japan — As the current COVID-19 crisis has shown, the disruptions that occur when transportation cannot proceed as usual are system-wide, affecting individual lives, companies, and the global economy. Now imagine a similar problem inside your brain and spinal cord. A new study led by researchers from Osaka University and National Center of Neurology and Psychiatry reports that two common neurodegenerative diseases—ALS, also known as Lou Gehrig's disease, and frontotemporal lobar degeneration, or FTLD—result from reduced transportation of RNA by the protein TDP-43, which ultimately disrupts neuron function.

Because one of the biggest physiological changes in both ALS and FTLD is the disappearance of TDP-43 from the nucleoli of neurons, the team focused their research on finding out what TDP-43 normally does. TDP-43 is known to bind to RNA, and the team's first experiment showed that in neurons, TDP-43 attaches to RNA that codes for pieces of ribosomes, which are necessary for making proteins from RNA code.

At its core, transportation gets things where they need to be at the proper time, whether they're people, goods, or molecules. In the body, items being sent from one place to another are often a response to what's happening to you. For instance, in response to dehydration, your brain sends a hormone through your blood to the kidneys where it forces water to be reabsorbed. In cells like neurons, the situation is similar, but there are no roads or arteries. Instead, many molecules get to their destination by being carried by other molecules.

"We discovered TDP-43 in axons and that it binds to ribosomal protein messenger RNA," says first author Seiichi Nagano. "That was strong support for the idea that TDP-43 carries the RNA to the axon where it can be used to make ribosomal proteins. This would allow local synthesis of proteins at ribosomes built in axons." Indeed, further experiments confirmed that hypothesis and showed that when TDP-43 was missing, the RNA in question could not be transported to the axon.

But what happens if the RNA cannot be transported? The researchers examined axon growth in culture as well as in mouse embryos. They found that in both cases, axon extension and outgrowth were stunted when TDP-43 was missing. However, outgrowth could be restored by forcing the neurons to overproduce ribosomal proteins.

"Now that we understand TDP-43's role in transporting the ribosomal protein messenger RNA, it should help us develop new strategies and new targets for ALS and FTLD treatments," says co-author of the study Hideki Mochizuki. "Our results in reversing stunted axon extension in mouse embryos is promising, but is just a first step."

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Osaka University

Insomnia treatment offers relief

Insomnia causing sleepless nights, daytime fatigue and poor health outcomes is a cycle worth busting, experts say, with depression, anxiety and stress a common co-occurrence.

A study of more than 450 insomnia patients in Australia has confirmed some positive results for such patients with insomnia.

The Flinders University researchers found not only that a program of targeted cognitive behavioural therapy for insomnia help relieve insomnia - but also has a positive effect on symptoms of depression, anxiety and stress.

"With COVID-19 and many other stressors in life, treating the worst effects of insomnia may have a transformative effect on a person's wellbeing, mental health and lifestyle," says lead researcher Dr Alexander Sweetman, from Flinders University's sleep research clinic, the Adelaide Institute for Sleep Health.

"We studied the impact of depression, anxiety, and stress on response to CBTi, in 455 'real world' insomnia patients, from pre-treatment to three-month follow-up," Dr Sweetman says.

"Insomnia symptoms improved by a similar amount between patients with and without symptoms of depression, anxiety and stress."

Symptoms of depression, anxiety, and stress show moderate-to-large improvement following CBTi, the results published in Sleep Medicine show.

Flinders Professor Leon Lack, who runs the insomnia therapy service at the Adelaide Institute for Sleep Health at Bedford Park, says CBT for insomnia ('CBTi') is recommended as the most effective and first-line treatment of insomnia.

As well as face-to-face CBTi therapy available at the Adelaide Institute for Sleep Health, the expert treatment is also available via telehealth options around Australia.

"The revamped insomnia treatment program at Flinders includes a range of treatments provided by experienced psychologists and physicians specialising in the management of sleep disorders, and treatment approaches which are directly based on the highest quality available scientific evidence," says Professor Lack.

"In line with many health services during the COVID-19 pandemic, the Flinders University insomnia treatment program is also available through online and telehealth platforms to people living in rural or remote areas of Australia."

The sleep research team is also rolling out the evidence-backed insomnia CBT program for general practitioners to support people with their sleep problems and avoid the use of sedative hypnotic medication over time.

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Flinders University

New mouse model of tau propagation

image: A new mouse model of tau propagation established by Masuda-Suzukake at TMIMS and her colleagues. Intracerebral injection of synthetic tau filaments induced by dextran sulphate caused tau aggregation in wild-type mice. (Masuda-Suzukake et al., Brain Communications 2020).

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TMIMS

Accumulation of assembled tau protein in the central nervous system is characteristic of Alzheimer's disease and several other neurodegenerative diseases, called tauopathies. Recent studies have revealed that propagation of assembled tau is key to understanding the pathological mechanisms of these diseases. Mouse models of tau propagation are established by injecting human-derived tau seeds intracerebrally; nevertheless, these have a limitation in terms of regulation of availability of human samples. To date, no study has shown that synthetic assembled tau induce tau propagation in non-transgenic mice.

A study by researchers from TMIMS confirms that dextran sulphate, a sulphated glycosaminoglycan, induces the assembly of recombinant tau protein into filaments in vitro. As compared to tau filaments induced by heparin, those induced by dextran sulphate were shorter in length, and showed higher thioflavin T fluorescence and lower resistance to guanidine hydrochloride, which suggest that the two types of filaments have distinct conformational features. Unlike other synthetic filament seeds, intracerebral injection of dextran sulphate-induced assemblies of recombinant tau caused aggregation of endogenous murine tau in wild-type mice. Tau accumulation stained with a antibody against phosphorylated tau (AT8) was present at the injection site one month after injection, from where it spread to anatomically connected regions. Induced tau pathologies were also stained by anti-tau antibodies AT100, AT180, 12E8, PHF1, anti-pS396 and anti-pS422. They were thioflavin- and Gallyas-Braak silver-positive, indicative of amyloid. In biochemical analyses, accumulated sarkosyl-insoluble and hyperphosphorylated tau was observed in the injected mice.

In conclusion, this study revealed that intracerebral injection of synthetic full-length wild-type tau seeds prepared in the presence of dextran sulphate caused tau propagation in non-transgenic mice. These findings establish that propagation of tau assemblies does not require tau to be either mutant and/or overexpressed.

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Tokyo Metropolitan Institute of Medical Science

Sport and memory go hand in hand

If sport is good for the body, it also seems to be good for the brain. By evaluating memory performance following a sport session, neuroscientists from the University of Geneva (UNIGE) demonstrate that an intensive physical exercise session as short as 15 minutes on a bicycle improves memory, including the acquisition of new motor skills. How? Through the action of endocanabinoids, molecules known to increase synaptic plasticity. This study, to be read in the journal Scientific Reports, highlights the virtues of sport for both health and education. School programmes and strategies aimed at reducing the effects of neurodegeneration on memory could indeed benefit from it.

Very often, right after a sporting exercise - especially endurance such as running or cycling - one feels physical and psychological well-being. This feeling is due to endocannabinoids, small molecules produced by the body during physical exertion. "They circulate in the blood and easily cross the blood-brain barrier. They then bind to specialise cellular receptors and trigger this feeling of euphoria. In addition, these same molecules bind to receptors in the hippocampus, the main brain structure for memory processing," says Kinga Igloi, lecturer in the laboratory of Professor Sophie Schwartz, at UNIGE Faculty of Medicine's Department of Basic Neurosciences, who led this work. "But what is the link between sport and memory? This is what we wanted to understand," she continues.

Intense effort is more effective

To test the effect of sport on motor learning, scientists asked a group of 15 young and healthy men, who were not athletes, to take a memory test under three conditions of physical exercise: after 30 minutes of moderate cycling, after 15 minutes of intensive cycling (defined as 80% of their maximum heart rate), or after a period of rest. "The exercise was as follows: a screen showed four points placed next to each other. Each time one of the dots briefly changed into a star, the participant had to press the corresponding button as quickly as possible", explains Blanca Marin Bosch, researcher in the same laboratory. "It followed a predefined and repeated sequence in order to precisely evaluate how movements were learnt. This is very similar to what we do when, for example, we learn to type on a keyboard as quickly as possible. After an intensive sports session, the performance was much better."

In addition to the results of the memory tests, the scientists observed changes in the activation of brain structures with functional MRI and performed blood tests to measure endocannabinoid levels. The different analyses concur: the faster individuals are, the more they activate their hippocampus (the brain area of memory) and the caudate nucleus (a brain structure involved in motor processes). Moreover, their endocannabinoid levels follow the same curve: the higher the level after intense physical effort, the more the brain is activated and the better the brain's performance. "These molecules are involved in synaptic plasticity, i.e. the way in which neurons are connected to each other, and thus may act on long-term potentiation, the mechanism for optimal consolidation of memory," says Blanca Marin Bosch.

Improving school learning or preventing Alzheimer's disease

In a previous study, the research team had already shown the positive effect of sport on another type of memory, associative memory. However, contrary to what is shown here, they had observed that a sport session of moderate intensity produced better results. It therefore shows that, as not all forms of memory use the same brain mechanisms, not all sports intensities have the same effects. It should be noted that in all cases, physical exercise improves memory more than inaction.

By providing precise neuroscientific data, these studies make it possible to envisage new strategies for improving or preserving memory. "Sports activity can be an easy to implement, minimally invasive and inexpensive intervention. For example, would it be useful to schedule a sports activity at the end of a school morning to consolidate memory and improve learning?"

Improving academic learning or preventing Alzheimer's disease

In a previous study, the research team had already shown the positive effect of sport on another type of memory, associative memory. But, contrary to what is shown here, they had observed that a sport session of moderate intensity, not high intensity, produced better results. Thus, just as not all forms of memory use the same brain mechanisms, not all sports intensities have the same effects. It should be noted that in all cases, physical exercise improves memory more than inaction.

By providing precise neuroscientific data, these studies make it possible to envisage new strategies for improving or preserving memory. "Sports activity can be an easy to implement, minimally invasive and inexpensive intervention. Would it be useful, for example, to plan a moment of sport at the end of a school morning to consolidate school learning," Kinga Igloi wonders, who, with her colleagues at Sophie Schwartz's laboratory, aims to achieve such practical objectives.

Neuroscientists are currently pursuing their work by studying memory disorders, and in particular by studying populations at high risk of developing Alzheimer's disease. "Some people as young as 25 years of age may experience subtle memory deficits characterised by overactivation of the hippocampus. We want to evaluate the extent to which sports practice could help compensate for these early deficits that are precursors to Alzheimer's disease.», conclude the authors.

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Université de Genève

Prior abortion does not negatively affect feelings of parental competence

A recent study found that a prior induced abortion did not negatively impact a woman's psychological well-being or her thoughts about her competence as a parent when she later became a mother.

In the Acta Obstetricia et Gynecologica Scandinavica study, questionnaires were administered to 492 first-time mothers, 37 of whom had previously had an abortion, and their partners when their child was 18 months old.

A prior abortion was not predictive of maternal or paternal well-being or feelings of parental competence.

"Since induced abortion is the only type of pregnancy loss that women have influence over themselves, information about the consequences is crucial when the issue is under consideration," the authors wrote. They noted that Nordic countries are characterized by permissive abortion legislation, and an induced abortion is no longer considered a taboo in Finland.

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Wiley

Blood vessel growth in muscle is reduced in women after menopause

A new study from the University of Copenhagen's Department of Nutrition, Exercise and Sports demonstrates that formation of small blood vessels is impaired in the muscle tissue of postmenopausal women. The study's findings highlight the importance of physical activity for women prior to and during menopause, as a means to prevent the development of disease later in life.

The risk of developing cardiovascular disease generally increases with age. For most of their lives, women have a lower risk of cardiovascular disease than men, but the picture changes as menopause sets in. The exact reason has yet to be fully understood.

Spinning failed to stimulate blood vessel growth

A new study has demonstrated that postmenopausal women have a significantly reduced ability to form tiny blood vessels, called capillaries, in their muscles - compared to younger women. The study showed that older women were unable to increase the number of capillaries in skeletal muscle tissue after an eight-week period of spinning on stationary bikes, in contrast with what has previously been demonstrated in both younger and older men.

Capillaries are important for health as they are needed for absorbing sugar and fat into muscles. The loss of capillaries can also have an effect on insulin resistance and contribute to the development of type 2 diabetes.

Despite the absence of capillary growth, the women's health improved in a number of other ways after the eight weeks of spinning, including overall fitness.

Line Norregaard Olsen, a PhD student at the University of Copenhagen's Department of Nutrition, Exercise and Sports explains that the lack of improvement with regards to new capillary growth is most likely due to the permanent loss of estrogen after menopause:

"The study supports the idea that women benefit from being physically active prior to menopause, while their estrogen levels are high. It provides them with a better physical starting point as they enter menopause - which is important. Even though eight weeks of training of the post-menopausal women has a noteworthy effect on some parameters, it had no effect on capillary formation in muscle. A sufficient number of capillaries in muscle is important for muscle function and reduces the risk of developing type 2 diabetes."

Professor Ylva Hellsten, also of UCPH's Department of Nutrition, Exercise and Sports, and the principal investigator, elaborates on the study's potential implications: "It is important to emphasize that both men and women are greatly served by being physically active throughout life, regardless of their age. But the current study suggests that there are some crucial differences between men and women in the way that the cardiovascular system is affected by aging and physical activity. As a result, this study should lead to an adjustment of the training recommendations for women in this age group."

In future studies, the researchers will evaluate which training is most effective to develop the health of the postmenopausal women.

Facts about the study

Two groups of women participated in the study: 12 women 59-70 years of age (postmenopausal) and five women 21-28 years of age (premenopausal). Both groups had a biopsy taken from their thigh muscle. Furthermore, the older group was trained over an eight-week period, three times weekly, on spin bikes at moderate to high intensity.

The postmenopausal women took part in tests of their physical fitness and on a range of other parameters both before and after training. Both before and after the training, this group of participants had tissue samples taken from their thigh muscles, which were used to analyze the number of capillaries in their muscles, as well as to analyze several muscle-specific proteins.

After 8 weeks of aerobic exercise, in the form of spinning, the fitness of the postmenopausal women improved by 15%.

The process by which new capillaries are formed is called 'angiogenesis'. Capillaries are essential for the transport of oxygen and nutrients to the body's cells.

In the project, cells in capillaries called 'endothelial cells' were studied in the laboratory by isolating them from muscle samples obtained from the participating women. This has never been done before.

The study has ben published in the article "Angiogenic Potential is Reduced in Skeletal Muscle of Aged Women" in the renowned scientific journal 'Journal of Physiology'. 

The study is supported by Independent Research Fund Denmark and the Danish Ministry of Culture's Fund for Sports Research.

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University of Copenhagen - Faculty of Science

Bundled payment model reduces health disparities for Black patients

A new nationwide model of care for hip and knee joint replacements appears to reduce disparities in health outcomes for Black patients, according to new research led by Oregon Health & Science University.

Researchers examined health outcomes for about 700,000 patients who underwent joint replacement procedures through Medicare between 2013 and 2017. The study examined differences in outcomes before and after April 2016, when Medicare adopted a model called Comprehensive Care for Joint Replacement, a bundled payment model designed to reduce spending and improve outcomes for all joint replacement patients.

The review is published by the journal JAMA Network Open.

The retrospective study examined three key metrics: spending, discharges to institutional post-acute care and hospital readmission. It compared outcomes for patients self-identified as white, Black and Hispanic.

Taken together, the results showed improved outcomes for Black patients and mixed results for Hispanic patients compared with those who are white.

Although Black patients were discharged to institutional post-acute care more than white patients, the gap narrowed under the new bundled payment model. Readmission risk decreased about 3 percentage points for Black patients under the new model, and stayed roughly the same for Hispanic and white patients.

"I was surprised the readmission rate decreased for Black patients," said corresponding author Hyunjee Kim, Ph.D., a health economist with the OHSU Center for Health Systems Effectiveness. "When you combine it with lower rates of institutional post-acute care, you're seeing better overall care."

The bundled payment plan was enacted in April 2016 to reduce cost and improve care for the single most common inpatient procedure for Medicare beneficiaries. Hip and knee replacements alone account for 5% of total Medicare inpatient spending.

The OHSU-led retrospective study is the first to gauge the plan's comparative effect on Black and Hispanic patients, who have historically had worse outcomes compared with white patients.

Overall, the study found substantially reduced use of institutional post-acute care for all groups.

"These represent relative improvements, a notable finding given general concerns that value-based payment models may exacerbate care for racial/ethnic minorities," the authors concluded. "Nonetheless, racial/ethnic differences in joint replacement care still persist, indicating the need for additional and sustained efforts to create an equitable health care system."

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Oregon Health & Science University

COVID-19 and type 2 diabetes: do shared pathways have therapeutic implications?

During a special COVID-19 session at this year's online Annual Meeting of the European Association for the Study of Diabetes (EASD), Prof. Daniel J. Drucker (Lunenfeld Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, Canada) will present a new review the latest clinical findings linking diabetes to risk of infection and differential outcomes in people with COVID-19 infection.

The medications that are used to treat people with diabetes often include drugs that modulate the expression and activity of the protein ACE2, the principal receptor for SARS-CoV-2 (how the virus enters cells). Furthermore, observational data suggests that people treated with statins, a widely used class of cholesterol lowering drugs, may experience improved outcomes in the hospital.

He says: "I will review the importance of optimising management of risk factors in people with diabetes during the pandemic, and how to consider adjustment of glucose-lowering drugs in hospitalised patients with COVID-19 infection. Notably, some of the medicines, such as dexamethasone recently shown to be beneficial for severely ill people with COVID-19 may worsen blood sugar control requiring careful monitoring and preferential use of insulin in people with type 2 diabetes."

He will also discuss the reports of new onset type 1 diabetes and complications such as ketoacidosis in the context of SARS-CoV-2 biology, predisposition for viral infection of the endocrine pancreas, and the limitations of the available epidemiology so far. There continues to be controversy about whether the SARS-CoV-2 virus directly infects islets and insulin-producing beta cells, leading to insulin deficiency, and in some cases, new onset type 1 diabetes. Dr Drucker will highlight very new data in this area that illuminates our understanding of where the receptors for the virus are located in different cells within the pancreas.

Dr Drucker will underline that better control of blood sugar in people with type 1 and type 2 diabetes appears to be an important modifier of COVID-19 severity, further emphasizing the opportunity to optimise the management of diabetes in the community to mitigate the potential consequences of SARS-CoV-2 infection.

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Diabetologia

US cellphone data uncovers 'hotspots' where COVID-19 social distancing levels are low

U.S. cellphone data analysis finds "hotspots" where COVID-19 social distancing levels are low, as well as revealing how demographics and governmental restrictions interact. Rajesh Narayanan and colleagues at Louisiana State University, Baton Rouge, present these findings in the open-access journal PLOS ONE on September 22.

Maintaining physical distance from others can reduce the spread of COVID-19. People may engage in social distancing voluntarily or because of governmental restrictions, or some combination of the two. Understanding the interplay of these two factors could help inform strategies to reduce disease spread.

To better understand social distancing across geographic areas, Narayanan and colleagues developed a computational model of social distancing behavior across the U.S. The model uses cell phone tracking data to indicate the amount of time spent at home--a proxy for social distancing--in counties throughout the country.

The researchers used this model to explore how stay-at-home behaviors evolved over the first 21 weeks of the spread of COVID-19 in the U.S., from late January to June, 2020. They examined how these behaviors changed in relation to governmental restrictions and demographic factors that could influence social distancing, such as population density, the presence of children in households, education, race, and income.

The analysis suggests that stay-at-home behavior increased by over nine times from late January through late March, and then decreased by about half through mid-June. Demographic factors appear to have driven these changes to a substantially greater degree, suggesting the importance of(either due to voluntary distancing or to differential compliance with mandated distancing). Importantly, there was also a tendency for behaviors to cluster, creating hotspots of counties with low social distancing.

One implication of these findings is that encouraging voluntary distancing could potentially be an effective and lower-cost alternative to governmental restrictions. Such encouragement could boost acceptance of restrictions and thus increased compliance with distancing rules, resulting in an even greater degree of distancing.

Professor Naryanan adds: "Cell phone location and mobility data reveal that social distancing in the U.S. during the Covid-19 pandemic was initially voluntary rather than a response to governmental jurisdictional restrictions. As the pandemic progressed, both effects reinforced each other, increasing social distancing far more than what could be explained by the sum of the individual effects." -

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PLOS

Ecologists confirm Alan Turing's theory for Australian fairy circles

image: Drone image of the Australian fairy circles, taken at a flying altitude of 40 m above ground. The gaps have average diameters of 4 m and the spatially periodic pattern results from approximately equal distances between the centers of nearest-neighbouring gaps. This study plot burnt in 2014 and the recovering spinifex grasses were two years and eight months old.

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S Getzin, University of Göttingen

Fairy circles are one of nature's greatest enigmas and most visually stunning phenomena. An international research team led by the University of Göttingen has now, for the first time, collected detailed data to show that Alan Turing's model explains the striking vegetation patterns of the Australian fairy circles. In addition, the researchers showed that the grasses that make up these patterns act as "eco-engineers" to modify their own hostile and arid environment, thus keeping the ecosystem functioning. The results were published in the Journal of Ecology.

Researchers from Germany, Australia and Israel undertook an in-depth fieldwork study in the remote Outback of Western Australia. They used drone technology, spatial statistics, quadrat-based field mapping, and continuous data-recording from a field-weather station. With the drone and a multispectral camera, the researchers mapped the "vitality status" of the Triodia grasses (how strong and how well they grew) in five one-hectare plots and classified them into high- and low-vitality.

The systematic and detailed fieldwork enabled, for the first time in such an ecosystem, a comprehensive test of the "Turing pattern" theory. Turing's concept was that in certain systems, due to random disturbances and a "reaction-diffusion" mechanism, interaction between just two diffusible substances was enough to allow strongly patterned structures to spontaneously emerge. Physicists have used this model to explain the striking skin patterns in zebrafish or leopards for instance. Earlier modelling had suggested this theory might apply to these intriguing vegetation patterns and now there is robust data from multiple scales which confirms that Alan Turing's model applies to Australian fairy circles.

The data show that the unique gap pattern of the Australian fairy circles, which occur only in a small area east of the town of Newman, emerges from ecohydrological biomass-water feedbacks from the grasses. In fact, the fairy circles - with their large diameters of 4m, clay crusts from weathering and resultant water run-off - are a critical extra source of water for the dryland vegetation. Clumps of grasses increased shading and water infiltration around the nearby roots. With increasing years after fire, they merged more and more at the periphery of the vegetation gaps to form a barrier so that they could maximize their water uptake from the fairy circle's runoff. The protective plant cover of grasses could reduce soil-s­urface temperatures by about 25°C at the hottest time of the day, which facilitates the germination and growth of new grasses. In summary, the scientists found evidence both at the scale of the landscape and at much smaller scales that the grasses, with their cooperative growth dynamics, redistribute the water resources, modulate the physical environment, and thus function as "ecosystem engineers" to modify their own environment and better cope with the arid conditions.

Dr Stephan Getzin, Department of Ecosystem Modelling at the University of Göttingen, explains, "The intriguing thing is that the grasses are actively engineering their own environment by forming symmetrically spaced gap patterns. The vegetation benefits from the additional runoff water provided by the large fairy circles, and so keeps the arid ecosystem functional even in very harsh, dry conditions." This contrasts with the uniform vegetation cover seen in less water-stressed environments. "Without the self-organization of the grasses, this area would likely become desert, dominated by bare soil," he adds. The emergence of Turing-like patterned vegetation seems to be nature's way of managing an ancient deficit of permanent water shortage.

In 1952 when the British mathematician, Alan Turing, published his ground-breaking theoretical paper on pattern formation, he had most likely never heard of the fairy circles before. But with his theory he laid the foundation for generations of physicists to explain highly symmetrical patterns like sand ripples in dunes, cloud stripes in the sky or spots on an animal's coat with the reaction-diffusion mechanism. Now, ecologists have provided an empirical study to extend this principle from physics to dryland ecosystems with fairy circles.

Credit: 
University of Göttingen

Researchers find new way to protect plants from fungal infection

image: The differences are striking: both field bean plants were exposed to spores of the fungus Uromyces viciae-fabae. The plant on the left is untreated and the fungi are clearly visible. The right plant was treated with the acid, the fungus could not cause any damage.

Image: 
Perino et al. in Phytopathology

Widespread fungal disease in plants can be controlled with a commercially available chemical that has been primarily used in medicine until now. This discovery was made by scientists from Martin Luther University Halle-Wittenberg (MLU) and the University of the State of Paraná in Brazil. In a comprehensive experiment the team has uncovered a new metabolic pathway that can be disrupted with this chemical, thus preventing many known plant fungi from invading the host plant. The team reported on their study in the scientific journal Phytopathology.

The fungus Colletotrichum graminicola is prevalent around the world. It infects maize, causing anthracnose, a disease that causes the plant's leaves to turn yellow at first and then ultimately to succumb to toxins. The fungus multiplies through spores that initially land on the surface of the plant. There they find rather inhospitable conditions: a lack of most of the nutrients that fungi need to develop - in particular nitrogen. "The only option they have is to break down some of their own nitrogen-containing molecules, for instance purines, the building blocks of DNA or RNA," explains plant pathologist Professor Holger Deising from MLU.

The researchers on Deising's team have found a way to impede this transitional phase which the fungus relies on. To do this, the team administered acetohydroxamic acid onto the plants, a substance also used to treat harmful bacteria in the human stomach, and which is known to inhibit the breakdown of urea. "The acid prevents the harmful fungi from penetrating into the plants and from becoming infectious," says Deising.

The team also tested whether the findings from C. graminicola and maize could be transferred to other plants and fungi. The acid was also found to be effective against numerous other pathogens which cause, for example, powdery mildew in cereal crops, late blight in potatoes, as well as corn and bean rust. "We have been able to develop a completely new approach to pathogen control that uses an existing active ingredient and thus can be quickly used commercially," says Deising.

The scientists conducted extensive experiments in order to come to their conclusions. They wanted to understand the molecular details of how the fungus manages to obtain nitrogen at the onset of the infection. First, they generated a series of random mutations in the genome of the fungus C. graminicola. "Then we inoculated the different fungal mutants onto the plants to see which ones were no longer infectious," says Deising. One of these mutants had a defect in the purine degradation pathway. In order to check whether the mutants' failure to infect the plant was actually caused by a lack of nitrogen, the researchers then applied nitrogen to the plants. "Once nitrogen was added, even the harmless mutants became infectious again," says Deising. The team was able to induce the same defect they had observed in the mutants in wildtype fungi by applying acetohydroxamic acid because it blocks the purine degradation pathway, too.

Credit: 
Martin-Luther-Universität Halle-Wittenberg

Water on exoplanet cloud tops could be found with hi-tech instrumentation

University of Warwick astronomers have shown that water vapour can potentially be detected in the atmospheres of exoplanets by peering literally over the tops of their impenetrable clouds.

By applying the technique to models based upon known exoplanets with clouds the team has demonstrated in principle that high resolution spectroscopy can be used to examine the atmospheres of exoplanets that were previously too difficult to characterise due to clouds that are too dense for sufficient light to pass through.

Their technique is described in a paper for the Monthly Notices of the Royal Astronomical Society and provides another method for detecting the presence of water vapour in an exoplanet's atmosphere - as well as other chemical species that could be used in future to assess potential signs of life. The research received funding from the Science and Technologies Facilities Council (STFC), part of UK Research and Innovation (UKRI).

Astronomers use light from a planet's host star to learn what its atmosphere is composed of. As the planet passes in front of the star they observe the transmission of the stellar light as it skims through the upper atmosphere and alters its spectrum. They can then analyse this spectrum to look at wavelengths that have spectral signatures for specific chemicals. These chemicals, such as water vapour, methane and ammonia, are only present in trace quantities in these hydrogen and helium rich planets.

However, dense clouds can block that light from passing through the atmosphere, leaving astronomers with a featureless spectrum. High resolution spectroscopy is a relatively recent technique that is being used in ground-based observatories to observe exoplanets in greater detail, and the Warwick researchers wanted to explore whether this technology could be used to detect the trace chemicals present in the thin atmospheric layer right above those clouds.

While astronomers have been able to characterise the atmospheres of many larger and hotter exoplanets that orbit close to their stars, termed 'hot Jupiters', smaller exoplanets are now being discovered at cooler temperatures (less than 700°C). Many of these planets, which are the size of Neptune or smaller, have shown much thicker cloud.

They modelled two previously known 'warm Neptunes' and simulated how the light from their star would be detected by a high resolution spectrograph. GJ3470b is a cloudy planet that astronomers had previously been able to characterise, while GJ436b has been harder to characterise due to a much thicker cloud layer. Both simulations demonstrated that at high resolution you can detect chemicals such as water vapour, ammonia and methane easily with just a few nights of observations with a ground-based telescope.

The technique works differently from the method recently used to detect phosphine on Venus, but could potentially be used to search for any type of molecule in the clouds of a planet outside of our solar system, including phosphine.

Lead author Dr Siddharth Gandhi of the Department of Physics at the University of Warwick said: "We have been investigating whether ground-based high resolution spectroscopy can help us to constrain the altitude in the atmosphere where we have clouds, and constrain chemical abundances despite those clouds.

"What we are seeing is that a lot of these planets have got water vapour on them, and we're starting to see other chemicals as well, but the clouds are preventing us from seeing these molecules clearly. We need a way to detect these species and high resolution spectroscopy is a potential way of doing that, even if there is a cloudy atmosphere.

"The chemical abundances can tell you quite a lot about how the planet may have formed because it leaves its chemical fingerprint on the molecules in the atmosphere. Because these are gas giants, detecting the molecules at the top of the atmosphere also offers a window into the internal structure as the gases mix with the deeper layers."

The majority of observations of exoplanets have been done using space-based telescopes such as Hubble or Spitzer, and their resolution is too low to detect sufficient signal from above the clouds. High resolution spectroscopy's advantage is that it is capable of probing a wider range of altitudes.

Dr Gandhi adds: "Quite a lot of these cooler planets are far too cloudy to get any meaningful constraints with the current generation of space telescopes. Presumably as we find more and more planets there's going to be more cloudy planets, so it's becoming really important to detect what's on them. Ground based high resolution spectroscopy as well as the next generation of space telescopes will be able to detect these trace species on cloudy planets, offering exciting potential for biosignatures in the future."

Credit: 
University of Warwick