Culture

Minimally invasive percutaneous treatment for osteoid osteoma of the spine

This research defines the new mini-invasive technique for the treatment of osteoid osteomas, which are benign but painful bone-forming tumors that usually involve long bones, with 10-20% of the cases having localization at the spine.

The most common symptom in osteoid osteomas is back pain which is generally responding to nonsteroidal anti-inflammatory drugs, but in some cases, also radicular pain can be present. The best treatment, for years, has been known to be surgical excision for cases with unresponsive pain. It has been practiced with much success but it also has a high rate of fusion with instrumentation.

In the recent years, percutaneous radiofrequency ablation has been suggested as a new mini-invasive technique for the treatment of osteoid osteomas.

Credit: 
Bentham Science Publishers

New printing process advances 3D capabilities

image: This tensile object was created using 3D injection printing, a new technology invented by UMass Lowell Plastics Engineering Prof. David Kazmer.

Image: 
David Kazmer

LOWELL, Mass. - More durable prosthetics and medical devices for patients and stronger parts for airplanes and automobiles are just some of the products that could be created through a new 3D printing technology invented by a UMass Lowell researcher.

Substances such as plastics, metals and wax are used in 3D printers to make products and parts for larger items, as the practice has disrupted the prototyping and manufacturing fields. Products created through the 3D printing of plastics include everything from toys to drones. While the global market for 3D plastics printers is estimated at $4 billion and growing, challenges remain in ensuring the printers create objects that are produced quickly, retain their strength and accurately reflect the shape desired, according to UMass Lowell's David Kazmer, a plastics engineering professor who led the research project.

Called injection printing, the technology Kazmer pioneered is featured in the academic journal Additive Manufacturing posted online last week.

The invention combines elements of 3D printing and injection molding, a technique through which objects are created by filling mold cavities with molten materials. The marriage of the two processes increases the production rate of 3D printing, while enhancing the strength and properties of the resulting products. The innovation typically produces objects about three times faster than conventional 3D printing, which means jobs that once took about nine hours now only take three, according to Kazmer, who lives in Georgetown.

"The invention greatly improves the quality of the parts produced, making them fully dense with few cracks or voids, so they are much stronger. For technical applications, this is game-changing. The new process is also cost-effective because it can be used in existing 3D printers, with only new software to program the machine needed," Kazmer said.

The process took about 18 months to develop. Austin Colon of Plymouth, a UMass Lowell Ph.D. candidate in plastics engineering, helped validate the technology alongside Kazmer, who teaches courses in product design, prototyping and process control, among other topics. He has filed for a patent on the new technology.

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University of Massachusetts Lowell

Academic achievement is influenced by how pupils 'do' gender at school

Pupils' achievements at school are often shaped by the way that they 'act out' specific gender roles, according to a new study which warns against over-generalising the gender gap in education.

The study, by researchers at the University of Cambridge, suggests that young people's attainment is linked to their ideas about what it means to be male or female. Those who defy traditional gender stereotypes appear to do better in the classroom.

Annual GCSE results in the UK, in common with many western countries, typically show that boys lag behind girls academically, but the research argues that this broad pattern masks a more nuanced picture. In particular, the researchers warn that a large sub-group of girls, who conform fairly rigidly to some traditional 'feminine' norms, could be academically at-risk. They point out that these girls are often 'invisible' in broad surveys of attainment by gender that show girls performing well as a group.

The researchers examined the English and Maths results of almost 600 GCSE candidates at four schools in England. On average, the girls did significantly better in English, while boys were slightly better at Maths. Girls outperformed boys overall.

But the study then went a step further, analysing sub-groups of boys and girls according to how they expressed their gender identity. This revealed that around half of the girls displayed 'maladaptive patterns of motivation, engagement and achievement'. By contrast, around two-thirds of boys were motivated, engaged and did well in exams. The pupils' academic performance corresponded closely to their sense of gender.

Dr Junlin Yu, a researcher at the Faculty of Education, University of Cambridge, said: "There has been a lot of justifiable concern about low attainment among boys, but we really need to move on from looking at averages, and ask which specific groups of boys and girls are falling behind. These findings suggest that part of the answer is linked to how pupils 'do' gender at school."

The study asked pupils to complete questionnaires which measured their motivation and engagement, and also examined how far they conformed to certain gender 'norms'.

These norms were drawn from two widely-used scales that identify the characteristics which people in western countries consider 'typically' masculine or feminine. The supposedly 'masculine' traits were emotional control, competitiveness, aggression, self-reliance, and risk-taking. The 'feminine' traits were thinness, an interest in appearance, concern with relationships, and an inclination towards domesticity.

In reality, most people exhibit a combination of masculine and feminine traits and the researchers found that pupils typically belonged to one of seven gender profiles that blended these characteristics. They classified these as:

'Resister boys' (69% of boys): typically resist traditional ideas about masculinity.

'Cool guys' (21%): competitive risk-takers, but concerned with appearance and romantic success.

'Tough guys' (10%): have an emotionally 'hard' image, self-reliant.

'Relational girls' (32% of girls): shun appearance norms, comfortable connecting with others emotionally.

'Modern girls' (49%): concerned with appearance, but also self-reliant and emotionally distant.

'Tomboys' (12%): uninterested in feminine qualities, often regarded as 'one of the lads.'

'Wild girls' (7%): embrace masculine behaviours, but also display an exaggeratedly 'feminine' appearance.

These profiles were then cross-referred with the pupils' GCSE results.

On average, the sample group performed as international trends predict. Girls had an average grade of 6.0 (out of 9) in English, compared with the boys' average of 5.3. In Maths boys averaged 5.9; slightly higher than the girls' 5.5.

But the researchers also found strong correlations between the specific gender profiles and patterns of engagement, motivation, and attainment. The two groups who resisted conventional gender norms - resister boys and relational girls - were found to be 'better academically adjusted' and typically did well in exams. The lowest overall performers were the 'cool guys' and 'tough guys'.

This significantly affected the average patterns of attainment by gender. In English, for example, relational girls far outperformed all other pupils in the cohort (averaging 6.3), almost single-handedly raising the girls' average.

The 'modern' and 'wild' girls typically had more mediocre GCSE results. More worryingly, these groups also displayed signs of low engagement and motivation: they gave up easily when faced with difficult tasks, and generally put less effort into their work. Collectively, these girls represented 56% of the total, but their underachievement was partially obscured by the high attainment average for girls.

The study suggests that one reason for the close correspondence between gender profile and academic achievement is that adolescents tend to express strong and inflexible ideas about gender, which influences their attitude towards school. For example, 'cool guys', who prize risk-taking and winning, consistently admitted to not trying hard at school - probably because doing so maintained the illusion that they would succeed if they put in more effort.

Attitudes towards gender probably also influence pupils' engagement with certain subjects. Previous studies have, for example, shown that Maths is often perceived as 'male'. Tellingly, within the sample, tomboys - girls who rejected 'feminine' traits - earned higher grades than the other girls in Maths.

The study's main recommendation is that efforts to close the gender gap in attainment need to focus less on 'girls versus boys' and more on these nuanced profiles. However, the researchers also suggest that schools could support pupils by encouraging them to think beyond traditional gender stereotypes.

"Among boys in particular, we found that those who resist gender norms were in the majority, but at school it often doesn't feel that way," Yu said. "Teachers and parents can help by encouraging pupils to feel that they won't be ridiculed or marginalised if they don't conform to traditional gender roles. Our findings certainly suggest that resistance to stereotypes is fast becoming less the exception, and more the rule."

Credit: 
University of Cambridge

Experts make weak recommendation for remdesivir in severe COVID-19

In The BMJ today, a panel of international experts make a weak recommendation for the use of remdesivir in patients with severe covid-19, and strongly support continued enrolment of patients into ongoing clinical trials of remdesivir.

Their advice is part of The BMJ's Rapid Recommendations initiative - to produce rapid and trustworthy guidelines for clinical practice based on new evidence to help doctors make better decisions with their patients.

The antiviral medication remdesivir has received worldwide attention as a potentially effective treatment for severe covid-19 and is already being used in clinical practice.

Today's recommendation is based on a new evidence review comparing the effects of several drug treatments for covid-19 up to 20 July 2020.

It shows that remdesivir may be effective in reducing recovery time in patients with severe covid-19, although the certainty of the evidence is low. But remdesivir probably has no important effect on the need for mechanical ventilation and may have little or no effect on length of hospital stay.

The authors stress that "the effectiveness of most interventions is uncertain because most of the randomised controlled trials so far have been small and have important study limitations."

After thoroughly reviewing this evidence, the expert panel says that most patients with severe covid-19 would likely choose treatment with remdesivir given the potential reduction in time to clinical improvement.

But given the low certainty evidence, and allowing for different patient perspectives, values, and preferences, they issued a weak recommendation with strong support for continued recruitment in trials.

They suggest that future research should focus on areas such as optimal dose and duration of therapy, and whether there are specific groups of patients most likely to benefit from remdesivir.

The authors also sound a note of caution about the potential opportunity cost of using remdesivir while the evidence base is still uncertain. As a relatively costly drug that is given intravenously, use of remdesivir may divert funds, time, attention, and workforce away from other potentially worthwhile treatments.

The study that today's recommendation is based on is called a living systematic review.

In a linked editorial, The BMJ editors explain that living systematic reviews are useful in fast moving research areas such as covid-19 because they allow authors to update previously vetted and peer reviewed evidence summaries as new information becomes available.

This is the second living systematic review published by The BMJ this year, and it will be updated to reflect emerging evidence. Several more are planned, including one on pregnancy outcomes among women infected with covid-19.

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BMJ Group

New risk tool developed for cardiac arrest patients

Experts have developed a risk score to predict cardiac arrest patient outcomes.

The study published today in European Heart Journal, by a team of researchers from King's College London and King's College Hospital, details a novel risk score for heart attack centres to predict brain damage in patients who have had an out of hospital cardiac arrest.

Out of hospital cardiac arrest is a major public health challenge and can lead to considerable morbidity and mortality. Patients have an extremely high risk of long-term brain damage after cardiac arrest, but this can be difficult to predict early on after admission.

The risk score, known as MIRACLE2, has been developed to help clinical decisions, improve selection of appropriate treatments and inform family discussion early after admission.

The study examined data on 400 patients who have had an out of hospital cardiac arrest and been treated at King's College Hospital and then identified characteristics of patients that developed brain injury. The team then performed prediction modelling to create a score that could be readily applied by clinicians on arrival to a heart attack centre.

The MIRACLE2 predicted brain injury with high accuracy and when validating the performance of the score in nearly 500 patients from two other heart attack centres from Europe, the score performed equally well.

The risk score will now be validated in a larger number of patients and potentially across different healthcare settings, for example by ambulance staff in the community. Once the performance of the score has been checked in these settings, it could be incorporated into future clinical trials and potentially into national guidance.

Nilesh Pareek from King's College Hospital said: "MIRACLE2 is the first practical score which can provide objective risk stratification to support clinicians in making critical decisions for patients with OOHCA. This could be a major step forward in understanding which OOHCA patients to select for invasive treatments, to guide the application of novel therapies and for standardising care across all healthcare settings."

Professor Ajay Shah, BHF Professor Cardiology at King's College London and Director of the King's BHF Centre of Research Excellence, said: "People who suffer a cardiac arrest in the community are among the most serious and complex emergency patients to manage, with a wide range of possible outcomes from complete recovery to possible long-term brain damage. The new risk score developed in our study should greatly aid ambulance teams and emergency heart doctors to make early decisions about the best treatment option for each patient."

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King's College London

Gut feelings can be good for us

New research has found that paying greater attention to internal bodily sensations can increase our appreciation of our own bodies.

The study, led by Jennifer Todd of Anglia Ruskin University (ARU) and published in the journal Body Image, focused on gastric interoception, which are the feelings of hunger or fullness that originate in the gut.

The researchers carried out an experiment involving 191 adults in the UK and Malaysia fasting and then consuming water.

They measured both the quantity of water consumed in relation to stomach capacity, and the feelings and experiences of the adults during the task. This included completing questionnaires examining different aspects of body image, such as appreciation of the body and appreciation of the body's functionality.

Body image refers to appearance-related thoughts and feelings, and positive body image refers specifically to an active love, respect, and appreciation for one's body.

The study found that a greater change in the intensity of feelings in the gut after consuming water was associated with significantly higher levels of appreciation of the body and appreciation of the body's functionality for adults in both the UK and Malaysia.

Lead author Jennifer Todd, a Psychology PhD student at Anglia Ruskin University (ARU), said: "Our study shows a clear link between bodily awareness, in this case the feeling of fullness, and body image. In other words, people who are more in tune with their body's internal workings have a greater appreciation of their body in general. Interestingly, we found that this link exists in two very different countries.

"We think that greater sensitivity to gastric signals might increase awareness of the positive functions the body performs and improve the ability to respond to the body's needs, both of which promote positive body image.

"Individuals who are less in tune with internal stimuli, such as feeling full, could be more at risk of developing negative body image, due to an over-reliance on external, appearance-related characteristics such as shape and size.

"It is possible that body image can be promoted by encouraging people to be more aware of internal sensations, such as feeling full. Gut feelings can be good for you!"

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Anglia Ruskin University

Stay or leave? A tale of two virus strategies revealed by math

image: Using a model to fit experimental data measured for cells infected with two strains of hepatitis C in the lab, researchers have quantified the viruses' preferences to adopt either a stay or leave strategy. The stay strategy emphasizes keeping copies of genetic code in the cell to accelerate replication, while the leave strategy focuses on packaging and sending out genetic code to infect more cells.

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Kyushu University

As small and relatively simple as they may be, even viruses have strategies. Now, researchers in Japan report that they can evaluate two of these strategies through a combination of biology and math, providing a new tool for insight into viruses that could be used to develop better treatments.

Unable to reproduce on their own, viruses replicate by infecting a living organism's cells and getting the cells to make copies of them. Two main options exist for copies of a virus's genetic structure made in the cell: stay in the cell as a template for making even more copies or get packaged as a new virus and leave in an attempt to infect other cells.

Each option comes with trade-offs, so an individual virus's strategy of how much weight to place on each one should directly influence the progression of an infection and any health problems it may cause.

"While such strategies are expected to be in play, showing the existence of the strategy itself has been difficult," says Shingo Iwami, associate professor of the Faculty of Science at Kyushu University and associate investigator of the Institute for the Advanced Study of Human Biology (WPI-ASHBi) at Kyoto University.

However, as reported in the journal PLOS Biology, collaborative research led by Shoya Iwanami and Iwami at Kyushu University and Koichi Watashi at the National Institute of Infectious Diseases to mathematically model the behavior of two hepatitis C virus strains now provides a means to evaluate two such strategies.

While one of the studied virus strains causes severe and sudden symptoms, the other is a genetically modified version developed in the laboratory to increase virus production, which is important for creating stocks of viruses for the development of treatments and vaccines.

As an experimental base for the modeling, Watashi's group measured characteristics of each virus's behavior--such as number of infected cells and the amount of viral genetic code inside and outside of the cells--over several days for cells grown and infected in the lab.

Iwami and his group then developed a mathematical model with parameters to take into account key processes like the replication and release rates of the viral genetic information to explain the experimental data.

By finding the range of model parameters that reasonably reproduce the experimentally observed results, they could quantify differences in behavior between the two strains. In particular, they estimated that the fraction of replicated genetic code packaged by the lab-developed strain to make new viruses was three times that for the other strain, indicating the preference of a leave strategy for the former and a stay strategy for the latter.

"The stay strategy initially produces copies of the genetic code faster, while the leave strategy emphasizes newly infecting cells," explains Iwami. "Though other mathematical models exist, ours is the first to evaluate these opposing evolutionary strategies."

The current model does have some limitations, such as assuming some processes are constant and excluding some of the detailed biological processes, but for now, it provides a relatively simple way to gain an overall insight into two virus strategies.

"Such strategies may be common in other chronic virus infections, and understanding them could help us develop effective therapeutic methods to counter individual virus strategies," Iwami comments.

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Kyushu University

Despite decline, distribution of air pollution highlights socioeconomic disparities

While the level of fine particulate air pollution has declined considerably over the last several decades, a new study finds that its distribution has remained largely unchanged. According to the results, the most and least polluted U.S. neighborhoods in 1981 remained the most and least polluted more than 30 years later, with disadvantaged communities far more likely to have higher levels of particulate pollution at any given time. The findings reveal persistent socioeconomic disparities in access to clean air and highlight the perpetual problem of environmental inequality. Overall, the concentration of fine particulate air pollution (PM2.5) - airborne particulate matter less than 2.5 microns in diameter - has decreased by roughly 70% since 1981 in the U.S., leading to improvements in air quality and, by extension, human health and economic well-being. But air pollution is not evenly distributed. Like other types of pollution and environmental hazards, increased levels of air pollution are often associated with disparities between different racial, ethnic and economic groups. However, little is known about how the spatial distribution of PM2.5 has evolved over time. Jonathan Colmer and colleagues combined measurements of PM2.5 spanning 1981-2016 with geographic, economic, and demographic data from 65,000 neighborhoods across the U.S. Colmer et al. found that the differences in PM2.5 between more and less polluted areas declined over time. However, the neighborhoods and subpopulations most exposed to pollution in 1981 remained the most exposed in 2016. In contrast, areas that were less polluted in 1981 were still less polluted in 2016. "Colmer et al.'s findings highlight outstanding issues relevant to implementing environmental justice in practice," writes Lala Ma in a related Perspective. "Further investigation to determine what caused the downward shift in the pollution distribution and the preservation of rankings over time could inform policies that avoid undesirable distributional consequences."

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American Association for the Advancement of Science (AAAS)

How global responses to COVID-19 threaten global food security

The ongoing COVID-19 pandemic has forced nations worldwide to implement unprecedented social measures to stem the rapid spread of the virus. In a Policy Forum, David Laborde and colleagues discuss how the economic fallout from these efforts and impacts on food supply chains worldwide puts global food security at risk. Laborde et al. argue that these new threats need to be acknowledged and addressed by governments worldwide to prevent the COVID-19 health crisis from becoming a global food crisis as well. According to the authors, COVID-19's most direct impacts on food security stem from the economic damage associated with the extreme measures designed to contain the virus, which has caused many around the world to lose their incomes and ability to buy food - particularly for the world's most poverty-stricken populations. What's more, disruptions to agricultural supply, production, and distribution of foods due to labor shortages, widespread industry closures, and restrictions on the movement of people and goods have placed further strain on the global food system. To address these emerging threats to global food security, Laborde et al. suggest that governments of both rich and poor nations should first focus on ways to provide income support to protect food access for their most vulnerable citizens. Novel strategies to enact safe social distancing in ways that facilitate food production and trade and allow for the movement of food-sector workers could also minimize disruptions to food systems and prevent looming food shortages as the COVID-19 pandemic progresses.

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American Association for the Advancement of Science (AAAS)

Hengduan Mountain alpine flora history shown to be longest on Earth

image: Rhododendron nivale subsp. boreale Shrubland in the Qinghai- Tibet Plateau (QTP), Himalaya, and Hengduan Mountains (THH).

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Image by DING Wenna

The alpine biome harbors distinctive communities adapted to stressful environmental conditions. For plants, the world's most species-rich temperate alpine biota occurs in the Qinghai-Tibet Plateau (QTP), Himalaya, and the Hengduan Mountains (THH).

Threatened by global warming, alpine species are vulnerable. To understand how alpine biotas formed in response to historical environmental change may improve our ability to predict and mitigate threats.

In a study published in Science, researchers from the Xishuangbanna Tropical Botanical Garden (XTBG) of the Chinese Academy of Sciences showed that the alpine flora of the Hengduan Mountains has continuously existed far longer than any other alpine flora on Earth. They also illustrated how modern biotas have been shaped by past geological and climatic events.

The researchers from XTBG and the Field Museum of the U.S. connected the dynamic tectonic and climatological history of the THH region to the biological processes that have driven the development of its alpine biota. The scientists especially focused on whether phylogenetic estimates of alpine ancestry are temporally and spatially consistent with geological evidence of alpine habitat availability.

By using a joint model of biome occupation, evolution of geographic range, and lineage diversification, they analyzed time-calibrated phylogenies of 18 groups of flowering plants.

"Our historical reconstructions indicate that an alpine flora had emerged in the THH region by the early Oligocene. This is much earlier than estimated origins of other extant alpine floras," said Prof. XING Yaowu from XTBG.

In addition, the researchers tested whether major tectonic events in the QTP, Himalaya, and Hengduan Mountains left discernible imprints on the tempo and mode of alpine biotic assembly.

They found that overall rates of in situ alpine speciation began to increase from the early Miocene and were jointly driven by the uplift of Himalaya and the Hengduan Mountains as well as intensification of the Asian monsoon.

"Our results, derived from analyses of time-scaled molecular phylogenies and not in situ fossil evidence of alpine ancestry, are nevertheless temporally consistent with the latest geological evidence that active orogeny associated with widespread crustal shortening and thickening established highlands from eastern Tibet to the Hengduan Mountains by the end of the Eocene," said DING Wenna, first author of the study.

"The rich alpine flora of the THH region has been shaped by a long and complex history of colonization, local recruitment and in situ diversification driven by mountain building and climate change. The Hengduan Mountains are not only the cradle of alpine plants. They are also the primary source of alpine lineages colonizing the Himalaya and QTP, which need urgent conservation in this temperate biodiversity hotspot," said Prof. XING.

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Chinese Academy of Sciences Headquarters

Challenging a central dogma of chemistry

Steve Granick, Director of the IBS Center for Soft and Living Matter and Dr. Huan Wang, Senior Research Fellow, report together with 5 interdisciplinary colleagues in the July 31 issue of the journal Science that common chemical reactions accelerate Brownian diffusion by sending long-range ripples into the surrounding solvent.

The findings violate a central dogma of chemistry, that molecular diffusion and chemical reaction are unrelated. To observe that molecules are energized by chemical reaction is "new and unknown," said Granick. "When one substance transforms to another by breaking and forming bonds, this actually makes the molecules move more rapidly. It's as if the chemical reactions stir themselves naturally."

"Currently, Nature does an excellent job of producing molecular machines but in the natural world scientists have not understood well enough how to design this property," said Wang. "Beyond curiosity to understand the world, we hope that practically this can become useful in guiding thinking about transducing chemical energy for molecular motion in liquids, for nanorobotics, precision medicine and greener material synthesis."

The unexpected ripples generated by chemical reactions, especially when catalyzed (accelerated by substances not themselves consumed), propagate long-range. For chemists and physicists, this work challenges the textbook view that molecular motion and chemical reaction are decoupled, and that reactions affect only the nearby vicinity. For engineers, this work shows a powerful new approach to design nanomotors at the truly molecular level.

Screening 15 organic chemical reactions, the researchers study chemical reactions that are workhorses with wide application within the organic chemical, pharmaceutical and materials industries. For example, "click" reactions assist the assembly of libraries of biomedical compounds for screening and the "Grubbs" reaction used for plastic manufacture. Their economic impact is major. Estimates indicate that a majority of all products manufactured require catalysis somewhere in their production sequence.

Wang remarked with enthusiasm: "Now, we're like a baby taking her first steps and there's so much exciting opportunity to grow this baby."

In designing their study, the researchers were bio-inspired by noticing that motion can be powered by enzymes and other molecular motors that are prevalent in living systems. Pioneering earlier work by Dr. Ah-Young Jee in the same research center showed this. But there was no consensus among scientists if these reports could be correctly extended outside biology. Analyzing the problem, the researchers made a high-risk, high-payoff argument. They hypothesized that the phenomenon would form an approach to understand molecular machines in the real world.

Testing their hypothesis, the team developed new analytical techniques. Professor Tsvi Tlusty, a theorist, predicted that catalysts in reaction gradients should migrate "uphill" in the direction of lesser diffusivity. Professor Yoon-Kyoung Cho, a microfluidics expert, designed a tailor-made microfluidics chip to test this idea. Dr. Ruoyu Dong, a Research Fellow, performed numerical computer simulations. "Our interdisciplinary team responded incredibly quickly to the research opportunities thanks to the research freedom of the Korean Institute for Basic Science," said Granick.

The team presents guidelines showing that the magnitude of diffusion increase in different systems depends on the energy release rate. These guidelines can be useful practically to estimate the effect in as-yet untested reactions. Beyond this, the study is very useful for expanding understanding of active materials, a collective term that traditionally refers to things like cells and microorganisms.

Granick concluded: "The field of active materials, quite new and growing fast, is enriched by this discovery that chemical reactions behave as nanoswimmers made of individual molecules that stir up the reaction soup. The concept of active materials has shown its value in challenging a central dogma of chemistry."

These findings were published in the July 31, 2020 issue of Science magazine. The study was performed at the IBS Center for Soft and Living Matter by authors Huan Wang, Myeonggon Park, Ruoyu Dong, Junyoung Kim, Yoon-Kyoung Cho, Tsvi Tlusty, and Steve Granick.

Credit: 
Institute for Basic Science

Presenting a SARS-CoV-2 mouse model to study viral responses and vaccine candidates

Researchers who generated a strain of SARS-CoV-2 that can infect mice used it to produce a new mouse model of infection that may help facilitate testing of COVID-19 vaccines and therapeutics. Notably, they used their mouse model to test and confirm the protective efficacy of a COVID-19 vaccine candidate. The ongoing COVID-19 pandemic has prioritized the development of small animal models for SARS-CoV-2. As SARS-CoV-2 does not use mouse ACE2 - the entry point for this virus in humans - mice are thought to be less susceptible. To date, efforts to study virus infection and to evaluate vaccines in mice have required mice to be engineered to express human ACE2. Here, in a different approach, Hongjing Gu and colleagues adapted a strain of SARS-CoV-2 seen in the clinic in the mouse respiratory tract, developing a mutant version (MASCp6) that was able to replicate and cause disease in young and aged mice; both groups showed pneumonia and inflammatory responses after intranasal infection, clinical features seen in human patients. Deep sequencing of the genome of MASCp6 compared to SARS-CoV-2 revealed that a mutation in the spike protein in the virus's receptor binding domain may be responsible for MASCp6's ability to enter mouse ACE2 cells, the authors say. To show their new model's utility for testing vaccine candidates, the researchers immunized female mice with two doses of a recombinant subunit vaccine candidate and then infected them with the adapted virus. Viral loads were lower and no visible clinical symptoms were identified in the vaccinated mice, compared to non-vaccinated controls, they say. Their new mouse-adapted strain of SARS-CoV-2 and the corresponding mouse model of infection add to the repertoire of animal models for studying SARS-CoV-2 transmission. This is important as no single animal model of SARS-CoV-2 currently recapitulates all aspects of human disease.

Credit: 
American Association for the Advancement of Science (AAAS)

Obesity linked to social ties in older women, more so than in men

image: Principal investigator Annalijn Conklin, assistant professor in the faculty of pharmaceutical sciences at UBC

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UBC

Women who lack social ties have a greater likelihood of being obese, according to new UBC research published today in PLOS One. Men, on the other hand, were less likely to be obese if they lived alone and had a smaller social network.

Using data from the Canadian Longitudinal Study on Aging, researchers analyzed the social ties of 28,238 adults aged 45 to 85 and how these link to waist circumference, body mass index and general obesity.

They found that women who were single, widowed, divorced or separated had higher odds of abdominal and general obesity. There were higher odds if they had limited social participation--women who were not married, lived alone and had no monthly social activities had the highest average waist size.

In comparison, among men, the average waist size was greatest among those who were widowed, co-living and had a large social network. For example, men whose social network had more than 219 contacts were more likely to be obese than those with smaller networks.

"There is a lot of literature suggesting that marriage is health-promoting for men and potentially less so for women, so our results about marital status were kind of surprising," said principal investigator Annalijn Conklin, assistant professor in the faculty of pharmaceutical sciences at UBC and researcher with the Centre for Health Evaluation and Outcome Sciences. "The different types of social ties that we looked at had a more consistent relationship with obesity for women. Those patterns in men were less obvious and seemed to sometimes even be reversed to what we saw in women."

The study did not investigate why these gender differences exist. However, Conklin suggested the findings may be partly due to differing gender roles and different social expectations around those roles.

"You would think that having small social networks would be a kind of social stress and that would have consequences for obesity, but we found that it was potentially protective for men," Conklin said. "It could be that managing very large networks becomes a source of stress for men, as research has shown that men often assign to their wives the emotional labour of keeping track of birthdays, special events and organizing family or social gatherings." An earlier study of the Korean population by other researchers obtained similar results.

More research is needed to understand the factors at work, says lead author Zeinab Hosseini, who did the work as a former postdoctoral research fellow at UBC's Collaboration for Outcomes Research and Evaluation.

"Not only did we find that minimal social participation was associated with obesity in older women, but also that social participation altered the levels of obesity in widowed women," said Hosseini. "These findings call for studies that will follow the participants over time to understand the possible causal links between different social connections and the health of older women and men."

The study results do suggest that health care providers may want to begin including social activities alongside healthy diet and exercise when treating non-partnered older women, added the researchers.

"Clinicians could be encouraging older women patients who are non-partnered, especially widowed women, to participate in social community interventions as a way to address obesity. This would require clear implementation strategies, and a focus on social connection interventions by health care researchers and decision-makers," said Hosseini.

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University of British Columbia

LSU health pathologists publish first report on likely MIS involving the heart

New Orleans, LA - A team of LSU Health New Orleans pathologists published what is believed to be the first case report on pathologic findings of vasculitis of the small vessels of the heart, which likely represents multisystem inflammatory syndrome (MIS). The report was published online in the Annals of Internal Medicine, available here.
The LSU Health New Orleans pathologists identified microscopic evidence of inflammation involving the small cardiac vessels during the autopsy of a patient who died weeks after initially recovering from COVID.
MIS is a severe illness featuring severe inflammation of multiple organs that occurs after the resolution of COVID symptoms. Similar to Kawasaki disease, MIS cases have been increasingly reported among children and young adults. Although vascular damage seems to be a component of both diseases, the pathologic features of MIS have not yet been described.

"We also found new pulmonary blood clots in a background of otherwise reparative changes in the lungs," notes Sharon Fox, MD, PhD, Associate Director of Research and Development in the Department of Pathology at LSU Health New Orleans School of Medicine. "These clots indicate a potential for increased clotting affecting the pulmonary blood vessels beyond the initial course of COVID-19, as well as the need for continued monitoring of laboratory markers and possible anticoagulation."

"Our report highlights the potential for serious complications due to damage to the lining of the vessels in the heart after COVID-19," adds Richard Vander Heide, MD, PhD, Professor and Director of Pathology Research at LSU Health New Orleans School of Medicine.

The team concludes, "Careful monitoring of laboratory markers of cardiac and systemic inflammation, as well as therapeutic intervention to target this inflammatory process, may improve patient outcomes."
Authors also include Drs. Elizabeth Rinker and Fernanda Lameira in the Department of Pathology at LSU Health New Orleans School of Medicine.

Credit: 
Louisiana State University Health Sciences Center

Your brain parasite isn't making you sick -- here's why

image: Tajie Harris, PhD, is part of UVA's Department of Neuroscience, the interim director of the Center for Brain Immunology and Glia (BIG), and a member of UVA's Carter Immunology Center.

Image: 
Dan Addison | UVA Communications

More than 30 million Americans are infected with a brain parasite spread by cats and contaminated meat, but most will never show symptoms. A new discovery from the University of Virginia School of Medicine explains why, and that finding could have important implications for brain infections, neurodegenerative diseases and autoimmune disorders.

The UVA researchers found that the parasite, Toxoplasma gondii, is kept in check by brain defenders called microglia. These microglia release a unique immune molecule, IL-1α, that recruits immune cells from the blood to control the parasite in the brain, the scientists discovered. This process works so well that very few people develop symptomatic toxoplasmosis, the disease the parasite causes.

Understanding the role of microglia is essential because they are normally the only immune cells inside the brain. The new finding reveals how they recruit help when needed, and that discovery could apply to any brain condition with an immunological component - including brain injury, neurodegenerative disease, stroke, multiple sclerosis and more.

"Microglia must die to save the brain from this infection," said researcher Tajie Harris, PhD, of UVA's Department of Neuroscience and the interim director of the Center for Brain Immunology and Glia (BIG). "Otherwise the IL-1α remains stuck inside the microglia and wouldn't alert the immune system that something is wrong."

The Brain and the Immune System

UVA's Department of Neuroscience and BIG center have in recent years completely rewritten our understanding of the brain's relationship with the body's immune system. For decades, textbooks taught that the brain was disconnected from the immune system. UVA research, however, showed that was not the case, to the shock of the scientific community. Many researchers are now exploring the implications of that major discovery.

One area of focus is microglia and their role in defending the brain. This has been a difficult question to answer because microglia are closely related to other immune cells elsewhere in the body. Until recently, laboratory tools made to target microglia have also targeted these other cells, making it hard to distinguish between the two.

UVA researcher Samantha J. Batista, a graduate student in Harris' lab, used an elegant approach that leveraged the long-lived nature of microglia to understand their role in brain infection. She and her colleagues found that infection caused microglia to die in an inflammatory fashion - a way that the closely related immune cells do not.

The microglia burst, the researchers determined, to recruit immune cells called macrophages to control the Toxoplasma gondii infection. This finding helps explain why most people have no trouble controlling the parasite, while some - especially people who are immunocompromised - can become very sick.

"Understanding pathways like this could be beneficial for other diseases involving neuroinflammation," Batista said. "We can ask whether promoting this pathway is helpful in situations where you need more of an immune presence in the brain, such as infections or cancers, and also whether inhibiting this molecule could be helpful in diseases driven by too much neuroinflammation, like multiple sclerosis. Targeting one specific pathway like this one could have less off-target effects than targeting inflammation more broadly."

In the future, Harris, Batista and their collaborators are interested in understanding how microglia detect the parasites in the brain. Microglia could recognize the parasite's presence directly, or they could recognize damage to brain tissue, a phenomenon that occurs in many diseases.

"The immune system must enter the brain to fight dangerous infections," said Harris, who is part of UVA's Carter Immunology Center. "We now understand how microglia sound the alarm to protect the brain. We suspect that similar signals are missed or misinterpreted in Alzheimer's disease, opening up an exciting new research avenue in the lab."

Credit: 
University of Virginia Health System