Culture

February 26, 2020 (Toronto) - In a first-of-its-kind study using advanced brain imaging techniques, a commonly used anti-psychotic medication was associated with potentially adverse changes in brain structure. This study was the first in humans to evaluate the effects of this type of medication on the brain using a gold-standard design: a double-blind, randomized, placebo-controlled trial.

The study, conducted across several North American centers, and just published in the journal JAMA Psychiatry, could have an immediate impact on clinical practice according to lead author Dr. Aristotle Voineskos, Chief of the Schizophrenia Division, and Head of the Kimel Family Translational Imaging-Genetics Laboratory at the Centre for Addiction and Mental Health (CAMH) in Toronto, Canada.

Until the 1990s, antipsychotic medications were primarily administered to people with schizophrenia. But since then their use has expanded to major depression and a range of pediatric, adult and geriatric disorders, including anxiety, insomnia and autism, for which one in five patients are prescribed anti-psychotics.

"With the increased off-label prescribing of antipsychotic medications, especially in children and the elderly, our findings support a reexamination of the risks and benefits," said Dr. Voineskos.

Because it is believed that antipsychotics protect against the harmful effects of untreated psychosis in the brain, they remain the foundation of treatment for schizophrenia. But the authors state that the adverse changes in brain structure found in this study are an important consideration for prescribing for psychiatric conditions where alternatives are possible.

The study examined patients with major depression who also experience psychosis who were prescribed antipsychotic medications olanzapine and sertraline for 12 to 20 weeks. For those who went into remission, participants were divided into a randomized double-blind phase -- where one group continued with both medications and one was given a placebo instead of olanzapine. Magnetic Resonance Imaging (MRI) scans were taken before and after the placebo was introduced.

The study found evidence that sustained use of olanzapine verses a placebo was associated with potentially adverse changes in brain structure, namely a thinning of the cortex. These changes were even more prominent in the elderly study participants. But participants who experienced a relapse of psychotic symptoms also had potentially adverse changes in brain structure, emphasizing the essential role antipsychotics play in treating disorders where psychosis is present.

"When psychosis is present, the life-threating effects of untreated illness outweigh any adverse effects on brain structure," said Dr. Voineskos. "But given that half the patients in the trial sustained remission after switching from olanzapine to placebo, future studies could provide a predictive model for which patients need long-term anti-psychotic treatment and which patients can safely discontinue them."

What The Study Did: Researchers in this observational study evaluated dimensions of the aorta in 442 older competitive runners and rowers (ages 50 to 75) to examine the association between long-term endurance exercise and enlargement of the artery.

Authors: Aaron L. Baggish, M.D., of Massachusetts General Hospital in Boston, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamacardio.2020.0054)

Editor's Note: The article includes conflict of interest disclosures. Please see the articles for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

MADISON -- Sand dunes, like many ecosystems, have more than one comfort zone. Variations in moisture, especially, can shift them from active, blowing waves of dry sand to rolling mounds with soils held down by grass and low shrubs.

But those changes are not always smooth and uniform, and new research on dunes in China describes how even neighboring dunes can long remain in different and seemingly conflicting states -- confounding the assessment of stabilization efforts and masking the effects of climate change.

For more than 15 years, University of Wisconsin-Madison geography professor Joe Mason and researchers at Nanjing University, China, have worked to date layers of sand and soils at dune sites across more than 1,000 kilometers in northern China. They compared their results to records of temperature and rainfall. Working with ecologists who have studied other dryland ecosystems, they published their analysis of 144 study sites today in the journal Science Advances.

"At each site we can reconstruct times when the dunes were active and bare at that location and when they were vegetation-stabilized," says Mason. "We can show that there was this kind of patchwork of active and stable sand going back over the past 12,000 years."

At the beginning of that time period, the Mu Us, Otindag, and Horqin dune fields were almost uniformly bare sand, but over about five millennia the region's annual precipitation increased by nearly half. By about 6,000 years ago, almost all the dune fields were carpeted -- and protected from wind erosion -- by plants.

In the last 6,000 years, estimated precipitation has fallen back to annual rates similar to those from 12,000 years ago, and all but about 35 percent of the dunes have returned to sandy states. But the changes have been anything but uniform.

"There's change over time in the proportion of active, sandy sites, but not a pattern spatially within the dune fields that we can relate to climate," Mason says. "If there was a single threshold, or just a gradual transition from one state to another, we'd expect to see the whole dune field move fairly quickly from one state to another and back as climate changed. Instead we see each local site kind of doing its own thing in terms of when it switches from active to stable."

To change a bare, active dune into one stabilized by grass and shrubs requires more moisture than the switched dune needs to maintain the stabilized state. Similarly, it takes a sharper dry shock to remove vegetation and turn a dune into active sand than it takes to keep it from re-growing plant cover.

"There are feedbacks that tend to keep the system in a particular state," says Mason, whose work was funded by the U.S. National Science Foundation. "For example, an active, sandy dune is an extra hard place for a seed to settle and germinate and spread. And when dust falls out of the air onto a vegetation-stabilized dune, it gets trapped under the plants and helps hold in more moisture and keep those plants in place."

Combined with those feedbacks, local factors -- differences in the size of sand grains, elevation above the water table, a human disturbance or particularly strong winds -- can be powerful enough on a local scale to keep a group of dunes in one stable state while all its neighbors flip.

"Rainfall is typically patchy and highly spatially variable, especially in a dry region like this," Mason says. "So, one major rainstorm might allow a patch that was under that storm to survive through a short dry period that triggers a shift to sand activity in lots of other patches around it."

Though the region is sparsely populated, the Chinese government has invested since the 1970s in projects meant to stabilize the dunes. Sprawling grids of plants or sticks jabbed into the ground are meant to keep blowing sand from swallowing stretches of highway, ranchland and train tracks.

"You can change the environmental conditions even deliberately with these massive dune stabilization programs, and you still won't get a uniform response in the dune field because each local patch is going to respond at a different time," Mason says. "So it can look like failure of the dune stabilization programs."

Patchy changes can also mask the expected effects of rapid changes in climate.

"Today, you could argue that the dunes are more stable than they should be relative to where they were 12,000 years ago when the estimated precipitation was actually slightly higher," Mason says. "Partly because climate change is also slowing wind speeds in this region, there are areas that haven't hit that tipping point to become the active, sandy dunes we might expect."

Administering stem cell or enzyme therapy in utero may be a path to alleviating some congenital diseases that often result in losing a pregnancy, according to a new study in mice by UC San Francisco researchers, who showed that stem cells can enter the fetal brain during prenatal development and make up for cells that fail to make an essential protein.

Each year, about 24,000 women in the US lose a pregnancy. One of the major contributors to this problem is a group of congenital diseases that can cause a condition called hydrops, in which fluid accumulates in the fetus, often to a fatal extent.

"This group of vulnerable patients has been relatively ignored in the fetal surgery world," said UCSF's Tippi MacKenzie, MD, senior author of the new study who has worked for a decade developing novel therapies for heritable diseases that can be treated before birth. "We know these patients could potentially benefit from a number of medical therapies. So this is our first foray into treating one of those diseases."

The new study was aimed at exploring treatments for MPS7, also known as Sly syndrome, a disorder caused by a mutation in a single gene. In this disease the body's cells lack an enzyme to properly process large chains of sugar molecules that are necessary for proper cell function. Sly syndrome is part of a family of related metabolic disorders that can potentially be treated before birth using similar approaches.

The incidence of MPS7 is difficult to determine, because it is believed that many fetuses with the disorder die before birth. Those that survive are treated with regular injections of the enzyme that their cells do not produce on their own.

While these injections can provide some benefit, the enzyme cannot enter the brain through the bloodstream after birth. In some related metabolic diseases, clinicians need to infuse the enzyme directly into the brain to treat neurological aspects. But because the so-called blood-brain barrier -- which protects the brain from potentially damaging substances in the blood -- is not fully developed before birth, MacKenzie believed the enzyme would successfully enter the brain at this stage.

Another problem with repeated enzyme infusions for metabolic disorders is that patients can develop an immune response to the enzyme, which their bodies view as "foreign." Infusing the protein before birth could prevent this immune response, since the fetal immune system tends to view new proteins as "friendly," without rejecting them.

MacKenzie, who co-directs UCSF's Center for Maternal-Fetal Precision Medicine, is among the first to attempt enzyme replacement of any sort at the fetal stage. Led by co-first author Russell Witt, MD, these experiments proved to be successful, and the researchers discovered that in utero treatment with the enzyme dramatically improved the survival of the mice to birth.

The researchers continued to give the enzyme after birth, which ultimately resulted in immune tolerance of the enzyme and improvements in multiple organs, including the brain and liver. Moreover, in comprehensive testing of the mice conducted in collaboration with the UCSF lab of Saul Villeda, PhD, the researchers noted significantly improved strength in the grip of MPS7 mice -- which is generally weak -- and in some cases their grip strength approached that of normal mice.

All told, the research team found that in utero enzyme replacement conferred three major improvements, MacKenzie said. "It will enter the brain, the mice develop immune tolerance for it, and the treatment helps sustain the fetus through birth."

These combined advantages, she said, overcome the main limitations of the current approach of delivering enzyme treatment after birth -- but not all of them. Even if the treatment were successfully delivered in the womb, challenges would still arise. Because the enzyme only lasts about two weeks in the body, patients would still require regular injections after birth. And at that point, the blood-brain barrier is fully developed, so the enzyme can't cross into the brain.

Ultimately, MacKenzie said, the answer may lie in giving fetuses stem cells, which could differentiate into new cells -- in both the brain and the rest of the body -- that could produce the enzyme that the faulty ones don't.

To explore this possibility, MacKenzie worked with research fellow and surgery resident Quoc-Hung Nguyen, MD, to transplant blood-forming stem cells from normally developing mice into fetal mice carrying a genetic mutation that causes MPS7. The researchers were most interested to see whether these cells could reach the brain, and whether they would change into cells called microglia, immune cells that originate from blood-forming stem cells. In a normally developing fetus, once matured, microglia produce and store the necessary enzyme, as well as regulate the immune environment of the brain.

Others have tried transplanting these stem cells, but usually after birth, said Nguyen, and it has been challenging to obtain fully functioning microglia. "We wanted to test this transplant before birth, using the environment of the fetal brain where, in a normal fetus, the stem cells are migrating into the brain to become microglia," he said. "One of our big findings is that these cells truly do become microglia, so there's a huge advantage to transplanting them before birth."

Nguyen tagged the transplanted cells with a fluorescent marker so he could easily identify them and verify that they had successfully crossed the blood-brain barrier and migrated into the brain. To confirm that the transplanted cells were acting as functional microglia, Nyugen sequenced the RNA that the cells were producing and saw that it matched the proper signature of protein production by microglia.

He also confirmed that the stem cells had also made their way to the liver, kidney, and other organs, and that they became the appropriate cell type needed to produce the needed enzyme in those organs.

The researchers saw that once the stem cells had engrafted in the brain and body and differentiated, they were able to deliver the enzyme to nearby cells and restore their function, a process called cross-correction. The transplanted cells thus fended off the liver disease and other complications associated with MPS7 for the lifespan of the animals.

"We found that even if you have only one or two percent healthy cells circulating, you can drastically improve, for example, liver disease," said MacKenzie. "One good cell can, in effect, correct multiple other cells."

Another advantage of the proposed treatments is that, in humans, they would be performed using the same techniques now used for fetal blood transfusions, which have been performed for decades in hospitals all around the country. "That means that if we do get to a stage of performing fetal therapy for these diseases in humans, the treatments could someday be offered at multiple centers around the world, and the family doesn't necessarily have to travel a long distance to get the care they need," said MacKenzie.

There are a large number of other heritable metabolic disorders that arise from similar faulty single genes, and Nyugen and MacKenzie agree that their approach may be a useful one for these conditions as well.

"These exciting findings are just the tip of the iceberg," said Nyugen. "They open up a whole new approach to treating a range of diseases. At the same time, there's also a lot of work to do to optimize the treatment for humans."

To that end, MacKenzie is applying to the U.S. Food and Drug Administration to launch a clinical trial of enzyme replacement therapy that will ultimately enroll 10 patients with MPS7 and related metabolic disorders. She already has a similar trial underway, transplanting mothers' stem cells into developing fetuses to treat a blood disorder called alpha thalassemia. With the proposed trial of enzyme replacement therapy, she hopes to expand the scope of fetal molecular therapies to treat metabolic disorders as well as blood disorders in humans.

MacKenzie points out that while fetal molecular therapies are not yet common, the environment and resources at UCSF allow her team to broaden the field, even as it is developing. "With this work, we're pushing the frontiers of fetal surgery into newer, less invasive therapies. At the same time, colleagues at UCSF are performing genetic sequencing of fetuses with hydrops, so that one day we can identify and treat these genetic conditions before birth," she said. "It's exactly this sort of clinical and research environment that can accelerate moving a therapy like this one into humans."

BOSTON - It's long been known that endurance athletes have larger hearts on average than the rest of the population and that cardiac enlargement is a healthy adaptation to exercise.

But what wasn't known until now was whether the aorta -- the main artery leaving the heart and supplying the body with oxygenated blood -- followed suit, and if it did, whether that might pose problems as athletes aged. "The prevailing wisdom is that the aorta is a relatively stable structure with minimal plasticity," said Aaron L. Baggish, MD, investigator in Massachusetts General Hospital's (MGH) Cardiovascular Performance Program. "But this concept comes from studies done almost exclusively on young competitive athletes -- typically under 25 years of age."

As a sports cardiology fellow at MGH's Cardiovascular Performance Program, Timothy W. Churchill, MD, noticed that a surprisingly high number of master athletes -- the rapidly growing population of aging men and women who continue to train and compete into middle age and beyond -- were coming in for evaluation of aortic enlargement. Churchill proposed pinning down the actual prevalence of this characteristic.

So in 2018 Baggish, Churchill, and their team undertook a cross-sectional study evaluating aortic size in 442 veteran endurance athletes aged 50 to 75 years who were taking part in athletic competitions across the United States. "We set up study sites at several large-scale rowing and running events that attract high-caliber masters athletes, and did cardiac ultrasounds at the race venues," Churchill said. They found that a high percentage of athletes -- 20 to 25 percent -- had aortas larger than the upper limit of clinical normality. "It was proof of concept for us because while we'd been seeing it in the clinic for a long time, it had never been studied in an isolated fashion," said Baggish.

The question of whether this is a good thing or a bad thing -- dilated aortas in non-athletic populations put patients at increased risk for a leak or rupture, and acute events involving the aorta have mortality rates as high as 50 percent -- remains open. "We want to know whether this enlargement means the same thing in an athlete as in a nonathlete," said Churchill.

"The findings from the study are pushing us to do more science," said Baggish, "as there are two viable yet unresolved implications of our work. The first option is that aortic enlargement among masters athletes is a benign adaptation and another feature of the so-called athlete's heart, where big is good. "The alternative is that being a lifelong exerciser may cause dilation of the aorta with the sort of attendant risk seen in nonathletes."

To find out, the MGH team plans to turn this cross-sectional study into a longitudinal one, checking outcomes for the same cohort four to five years from their initial ultrasounds. "We're now halfway through that waiting period, so it won't be too long until we have a touchpoint," said Baggish. "If we find that big aortas are a benign adaptation, doctors can be reassured when they see it and not put patients through unnecessary testing and surgery. If we find that they really are an indicator of risk, then we have to think about screening people who fit this bill. So regardless of what the next step tells us, it has very important clinical implications. For now, our goal is to alert athletes and their doctors about this evolving story"

A novel blood test that uses gold nanoparticles to detect cancer has also been shown to identify signals released by cancer cells which could result in earlier diagnosis and better treatment.

New research has revealed the nanotechnology developed by University of Queensland scientists can detect and monitor extracellular vesicles (EVs) in the bloodstream.

Australian Institute for Bioengineering and Nanotechnology (AIBN) researcher Jing Wang said the discovery could lead to more effective, personalised cancer therapy by allowing oncologists to rapidly determine how treatment is progressing.

"EVs are an exciting next-generation of potential biomarkers in blood," she said.

"They are nanoparticles that are constantly emitted by health cells and cancer cells to enable cell-to-cell communication.

"They are like tiny bubbles that transport cargoes such as DNA, proteins and other molecules between cells, and this cargo reveals a lot about what's going on inside the cell.

"Cancer cells use the EV nanoparticles in order to manipulate the cells around them, as well as to suppress and manipulate the immune system."

In collaboration with oncologists Dr Andreas Behren and Professor Jonathan Cebon at the Olivia Newton John Cancer Research Institute (ONJCRI), the technology has been tested on blood samples from melanoma patients and was able to detect the presence of cancer-derived EVs and could also track critical changes during and after treatment.

AIBN researcher Dr Alain Wuethrich said cancer EVs have been difficult to distinguish from EVs emitted from healthy cells, which are more abundant in the bloodstream.

"The technology brings together two entirely new approaches within a clinical setting for potential treatment monitoring," Dr Wuethrich said.

"We used an electrically activated nano-fluidic chip that helps capture only cancer emitted EVs.

"We coupled this with a special type of gold nanoparticle attached to antibodies that stick to molecules found only on the surface of cancer EVs."

The gold nanoparticles emit a unique signal when hit with laser light and this can be used to detect an EV fingerprint specific to the patient.

With the help of the collaborators at the ONJCRI, the technology was tested on blood samples from 23 melanoma patients.

The new device accurately detected cancer EVs in the blood samples, and successfully tracked how the cancer EV fingerprint changed in response to therapy for each patient.

"Our technology can reveal changes in the cancer EV fingerprint, so it could be used to quickly find out whether a therapy is working or if drug resistance is happening," Ms Wang said.

"This could guide cancer therapy in real-time."

The AIBN team lead by Professor Matt Trau has previously demonstrated that gold nanoparticles can be used to detect Circulating Tumour Cells (CTCs) and unique fragments of DNA released by cancer cells.

By showing that EVs can also be detected with the help of these nanoparticles adds a critical new weapon to the cancer-detection arsenal.

"This technology could complement and eventually replace more costly cancer imaging technologies, and could potentially become regularly used at point-of-care in a doctor's surgery," Ms Wang said.

Melbourne researchers have uncovered important differences between the male and female immune system which may explain why men are more susceptible to obesity and metabolism-related associated diseases, such as heart disease, stroke and diabetes.

It has long been known that men are more likely than women to develop unhealthy obesity and related metabolic diseases, while women are more prone to certain autoimmune diseases such as arthritis. These findings suggested the male and female immune systems differ, but until now scientists weren't sure how.

Researching male and female adipose tissue - commonly referred to as body fat - a team at the Doherty Institute and the Walter and Eliza Hall Institute discovered striking differences in the numbers and function of an immune cell population called regulatory T cells, or Treg cells, between male and female mice.

Treg cells play a central role in the body by dampening inflammation, autoimmunity and maintaining the health of many tissues, including the adipose tissue.

Importantly, the adipose tissue is not only a storage for energy, but also an endocrine organ that plays a crucial part in regulating metabolism, appetite and inflammation. It also produces a range of different hormones.

Published today in Nature, the team systematically examined every cell type in the adipose tissue and discovered a novel type of stromal - or connecting - cell that communicates with Treg cells and is found only in males. These stromal cells determine how many Treg cells can be recruited to the adipose tissue and how they are being activated.

University of Melbourne Dr Ajithkumar Vasanthakumar, Doherty Institute postdoctoral researcher and first author of the study, said finding these differences between male and female Treg cells was a remarkable breakthrough, as scientists have previously been unable to understand the differences between male and female immune systems.

"Not only did we discover dramatic differences in Treg cells, we also discovered a stromal cell type that responds directly to the male sex hormone, testosterone, and is therefore specific to males," Dr Vasanthakumar said.

"This stromal cell makes a signalling molecule, IL-33, which is what Treg cells depend on. So, you have a completely novel chain of events that is regulated in a sex-specific manner."

With the unprecedented worldwide rise of obesity and metabolic disease, University of Melbourne Professor Axel Kallies, senior author and laboratory head at the Doherty Institute, said the findings are important when considering new therapeutic approaches to this global challenge.

"We are now exploring whether similar mechanisms are at play in autoimmune diseases and in cancers," Professor Kallies said.

"For too long the male physiology and the male immune system was considered the 'norm' in research and in clinical studies. Our work shows that important differences exists between the sexes. This means that the strategies to treat a range of diseases may have to be different between men and women."

This work was done in collaboration with researchers at Monash University and the Peter MacCallum Cancer Centre.

A recent study published in Nature has reported two conserved epigenetic regulators as novel anti-aging targets. The research, by scientists from Dr. CAI Shiqing's Lab at the Center for Excellence in Brain Science and Intelligence Technology, Institute of Neuroscience of the Chinese Academy of Sciences (CAS), and Dr. JIANG Lubing's team at Institut Pasteur of Shanghai of CAS, identified conserved negative regulators of healthy aging by using multiple modalities and systems, thus providing insights into how to achieve healthy aging.

Aging is associated with progressive decline in physiological functions over time and is a major risk factor for a number of chronic diseases, such as Alzheimer's disease, cancer, and diabetes. Over the past decades, the understanding of longevity regulation has progressed greatly, and a number of longevity pathways conserved from yeast to mammals have been delineated.

However, increasing longevity is not often accompanied by an extended healthspan, despite global increases in life expectancy. Thus, how to achieve healthy aging (i.e., an extension of healthspan) is one of the most important and challenging heath issues nowadays. Despite its extreme importance, the biological mechanisms underlying healthy aging, as defined by the preservation of normal behavioral capabilities, remains to be elucidated.

Previous studies from Dr. CAI's lab have revealed that behavioral performance in aged animals can be improved by increasing neurotransmitters. They also showed that variation in levels of neurotransmitters may contribute to different rates of age-related decline among individuals.

In the current study, the researchers used the animal models C. elegans and mouse, along with human datasets to identify novel anti-aging targets and unravel a mechanism for regulating cognitive aging. C. elegans is a tiny free-living nematode, about 1 mm in length. Due to its short lifespan and clear genetic background, C. elegans has been widely used in aging research.

To identify aging modulators, the researchers performed a genome-wide RNAi screen for genes that regulate behavioral deterioration in aging C. elegans. They identified 59 genes that potentially regulate the rate of age-related behavioral deterioration. By constructing a co-expression network of these screening hits, they found that a neuronal epigenetic reader BAZ-2 and a neuronal histone 3 lysine 9 (H3K9) methyltransferase SET-6 appeared as a key node in the network. Deletion of baz-2 and set-6 prevented age-related deterioration in the worm's food-induced behavior, food intake, and male virility.

By analyzing published databases, the researchers found that the expression levels of their human homologues BAZ2B and EHMT1 increase with age in human brains, and positively correlate with Alzheimer's disease (AD) progression. Strikingly, ablation of Baz2b, the mouse ortholog of baz-2, attenuated age-dependent body weight gain and prevented cognitive decline in aging mice. Their findings suggest that BAZ2B and EHMT1 are key aging modulators and appear to be novel anti-aging targets.

In addition, the researchers demonstrated that these epigenetic modulators repressed the expression of nuclear genes encoding mitochondrial proteins by occupying the promoter regions and hence reduced mitochondrial function, a mechanism conserved in mouse brain tissues. Deletion of baz-2/BAZ2B and set-6/EHMT1 delayed the aging process by improving mitochondrial function.

Mitochondrial dysfunction has been implicated in the pathogenesis of Alzheimer's disease (AD). By analyzing gene expression in the brains of AD patients, they found that the expression levels of BAZ2B and EHMT1 negatively correlate with the expression of key mitochondrial function-related genes, suggesting that BAZ2B and EHMT1 can regulate mitochondrial function in aging human brains.

The researchers in this study performed a genome-wide RNAi screen and provided the first view of genes that modulate behavioral aging. They showed that two conserved epigenetic factors modulate the aging of the nervous system by regulating mitochondrial function. This newly discovered epigenetic regulation of mitochondrial function is critical for achieving healthy aging of the brain. Given the reversible nature of epigenetic regulation, BAZ2B and EHMT1 emerge as promising drug targets for combating behavioral and cognitive aging.

Entrepreneurs seeking funds on business-oriented crowdfunding platforms should avoid over-emphasising the social or environmental benefits of their start-ups or products if they are to maximise potential investment, a new study from the University of Bath and Polytechnic University of Milan shows.

Language emphasising the social good of a product can be highly effective on micro-lending platforms, such as Kiva.org that target investors with social consciences, but can be counterproductive on more business-focused platforms such as Kickstarter where potential backers look more to the potential return, effectiveness or usefulness of the product.

"Conventional wisdom suggests that, in general, backers appreciate projects that go beyond proponents' pure self-interest. However, our results show that too much pro-social orientation may be detrimental," said Dr Daniela Defazio of the University of Bath's School of Management.

"A 'too much of a good thing' effect can be at work in crowdfunding platforms that do not specifically target a pro-social audience," she said. "Entrepreneurs should be aware of it when preparing the description - or 'framing' - of their projects. A moderate emphasis on pro-social framing is beneficial but too much emphasis can backfire."

Defazio said the study focused on technology and design projects in Kickstarter, categories where investors' self-interest in returns and benefits and functional values were deemed to be important. She said it was important that social benefits should not obscure the business value, product functionality, or the potential for financial return.

"Some platforms have a clear pro-social mission and the results from studies based on platforms like Kiva.org consistently show that pro-social motives are a plus. On the other side, results of the effect of pro-social framing on reward-based platforms like Kickstarter are mixed," Defazio said.

"Evidence suggests that even the most socially conscious individuals continue to be driven by their self-interest. They appreciate products' pro-social attributes but only when they are provided in combination with - and not at the expense of - product functionality," she added.

The study, by Bath's Defazio, and Dr Chiara Franzoni and Professor Christina Rossia-Lamastra of the Polytechnic University of Milan's School of Management, showed that too strong an emphasis on social benefits may also raise questions in investors' minds about credibility and the financial prospects of a project, as well as obscuring key messages about project's financial effectiveness. This latter problem is exacerbated by the issue that space provided by a platform to describe a project may be limited and entrepreneurs may be seeking funds amongst a crowd of competitors.

"Because the title and blurb are made only of a few words - approximately 10 - placing pro-social cues in those may overshadow other project attributes," she said.

Defazio said there were some indications that the platform's 'crowdedness' - the number of projects vying for funds - might change the effect of pro-social emphasis. As the number of competing projects rose, the study found that pro-social angles might actually help a project stand out from the crowd. More work needed to be done to pinpoint this effect, she added.

Defazio said the study's results would help entrepreneurs seeking funds but also direct the attention of crowdfunding platform managers to the importance of how textual information about projects - the title and the blurb - are organised in large, crowded platforms.

The study examined the title, short description, and project description of 8631 technology and design projects posted on Kickstarter from January 2016 to September 2017. It analysed the probability of success of the crowdfunding campaigns in relation to the emphasis given to the pro-social orientation of the business idea.

The latest U.S. Preventive Services Task Force evidence report on screening for cognitive impairment in older adults raises many questions, but provides few answers for healthcare providers, patients, and families. The recommendation findings, published in JAMA, state that the tools to accurately identify cognitive impairment in older adults exist, but that there is insufficient evidence to assess the value of using them routinely in older people.

There is great benefit in providing quality care for people with cognitive impairment and dementia. A lot that needs to be done to care for these patients, and they and their loved ones benefit from and are grateful for early diagnosis, proper treatment, and education and counseling," said Howard Fillit, MD, Founding Executive Director and Chief Science Officer at the Alzheimer's Drug Discovery Foundation, a neuroscientist and geriatrician who has been caring for people with dementia for over 40 years.

The ADDF has invested more than $150 million to support research into finding effective treatments to prevent and treat Alzheimer's disease and related dementias. While we are making much progress, we do not yet have effective disease-modifying medications for Alzheimer's disease. Currently, we only have safe and modestly-effective medications to treat symptoms. But early detection and appropriate care and management care still provide tremendous value to physicians, patients, and their caregivers.

Even though the Task Force report does not imply people with memory or related cognitive problems should forego assessment, there is a risk that some will interpret the report's no evidence finding as negative evidence. In the accompanying editorials, Ronald Petersen, M.D., Ph.D. and Kristina Yaffe, Ph.D., warn "the absence of evidence for benefit may lead to inaction" and that it would be "a terrible mistake if clinicians did not consider the value of screening for cognitive impairment on a case-by-case basis."

"Physicians are trained to practice medicine in the care of each individual patient. If a patient has a memory complaint, or if a loved one or other related person reports a memory issue, or a change in personality, then a cognitive assessment should be done," said Dr. Fillit. "Cognitive assessments are valuable. For example, about 10% of people with cognitive impairment have a reversible cause; delayed diagnosis leads to poor medical and psychosocial outcomes, including major effects on caregivers."

Early diagnosis of dementia also has benefits. Currently, half of people with dementia in the U.S. (mostly related to Alzheimer's disease) are diagnosed two years after onset of symptoms and up to 50% are not diagnosed until the moderate stage of dementia. According to Dr. Fillit, this often leads to unnecessary hospitalizations from accidents/falls, poor medical management of common chronic diseases like diabetes, and many other avoidable medical outcomes.

"Evidence-based medicine is the holy grail and in the perfect world we could precisely quantify the benefits and risks (and costs) of each test, treatment, and non-pharmacologic intervention before we decide to use it, but sometimes that just isn't possible," explained Dr. Fillit. "In this case, we need to trust our medical experts. Individual patients with the warning signs of cognitive impairment and dementia should be properly assessed, diagnosed, treated, and managed just as they are for other chronic diseases of old age. Early diagnosis is critical to quality of care."

Mount Sinai Health System physicians--the first experts in the country to analyze chest computed tomography (CT) scans of patients from China with coronavirus disease (COVID-19)--have identified specific patterns in the lungs as markers of the disease as it develops over the course of a week and a half. The finding, published in the February issue of Radiology, could lead to quicker diagnosis in patients who come in with possible COVID-19 symptoms, and help keep patients isolated in early stages when the lung disease may not show up in initial scans.

"This work augments our initial study, which was the first published research study on the imaging findings of COVID-19, and now we are able to provide a more comprehensive evaluation of how lung disease in coronavirus patients manifests and develops. If coronavirus should continue to spread and impact the United States or elsewhere more significantly, this study equips radiologists with the knowledge to recognize and more confidently suggest if a patient has COVID-19 or pneumonia due to another cause," said co-author Michael Chung, MD, Assistant Professor of Diagnostic, Molecular and Interventional Radiology at the Icahn School of Medicine at Mount Sinai. "This is necessary for prompt diagnosis for any individual patient (which will lead to more rapid and effective care), but also for patient isolation to prevent the spreading of the highly contagious disease."

The study encompassed scans of 94 patients that Mount Sinai received from institutional collaborators at hospitals in China. The patients were admitted to four medical centers in four Chinese provinces between January 18 and February 2. Most either had recently traveled to Wuhan, China, where the outbreak began, or had contact with an infected COVID-19 patient. The cardiothoracic radiologists from Mount Sinai's BioMedical Engineering and Imaging Institute and its Department of Radiology evaluated each case, took notes of imaging findings, and correlated them with infection time course based on the number of days between symptom onset and the CT scan. Of the 36 patients scanned zero to two days after reporting symptoms, more than half showed no evidence of lung disease--an important finding suggesting that CT scans cannot reliably rule out COVID-19 early in the disease course. For the 33 patients scanned three to five days after symptoms developed, radiologists started to see more patterns of "ground glass opacities" (hazy findings in the lungs), and the abnormalities became more round in shape and more dense. In the 25 patients scanned six to 12 days after symptoms, the scans analysis showed fully involved lung disease. Patterns seen in these images are similar to patterns in related coronavirus outbreaks earlier this century, including SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome).

The conclusions from this study are crucial for prompt diagnosis of COVID-19 as well as for efficient patient isolation. When patients first report symptoms of possible COVID-19, they are nonspecific, often resembling a common cold, so it can be difficult to diagnose. A chest X-ray does not reveal lung disease as well as a CT scan does, and confirmatory tests by the Centers for Disease Control and Prevention can take several days. The study allows hospitals in the United States and worldwide to confirm or rule out COVID-19 based on CT images. Additionally, if lung scans for patients with early symptoms are inconclusive, doctors can consider holding the patient in isolation for a few days until the disease can be properly ruled in or ruled out.

"Just as clinicians are evaluating more patients suspected of COVID-19, radiologists are similarly interpreting more chest CTs in those suspected of infection. Chest CT is a vital component in the diagnostic algorithm for patients with suspected infection, particularly given the limited availability and in some cases reliability of test kits," said lead author Adam Bernheim, MD, Assistant Professor of Diagnostic, Molecular and Interventional Radiology at the Icahn School of Medicine at Mount Sinai. "These investigative efforts not only show patterns of imaging findings in a large number of patients, but they also demonstrate that frequency of CT findings is related to disease time course. Recognizing imaging patterns based on infection time course is paramount for not only understanding the disease process and natural history of COVID-19, but also for helping to predict patient progression and potential complication development."

"Mount Sinai's imaging programs are leaders in the development and application of novel technologies to improve patients' diagnosis and treatment, and we hope the findings from this study will help advance care for coronavirus patients," added Zahi Fayad, PhD, Director of the BioMedical Imaging and Engineering Institute at the Icahn School of Medicine at Mount Sinai.

According to a February 13 report from the World Health Organization, the Wuhan coronavirus has stricken more than 46,000 people and has caused over 1,300 deaths since the first cases in Wuhan, China, in December 2019. Now, researchers reporting in ACS' Journal of Medicinal Chemistry have designed compounds that block the replication of similar coronaviruses, as well as other disease-causing viruses, in the lab. The compounds have not yet been tested in people. 

The Wuhan coronavirus, also known as SARS-CoV-2 or 2019-nCoV, is a close relative to the severe acute respiratory syndrome (SARS) virus that caused an outbreak in 2003 (SARS-CoV-1), as well as the Middle-East respiratory disease virus (MERS-CoV) that emerged in 2012. All of these viruses cause flu-like symptoms and, frequently, pneumonia. However, no effective treatments have been developed, in part because the relatively small number of cases have not warranted large expenditures by pharmaceutical companies. Hong Liu, Rolf Hilgenfeld and colleagues envisioned a possible solution in the form of broad-spectrum antiviral drugs that target all coronaviruses, as well as enteroviruses -- some of which cause conditions like the common cold; hand, foot and mouth disease; and the "summer flu." All of these viruses share a similar protein-cutting enzyme, called the "main protease" in coronaviruses and the "3C protease" in enteroviruses, that is essential for viral replication.

The researchers examined X-ray crystal structures of the proteases and then made a series of α-ketoamide compounds that were predicted to fit snugly in the enzymes' active sites, interfering with their function. By testing the molecules in the test tube and in human cells in petri dishes, they identified one versatile inhibitor that blocked multiple coronaviruses and enteroviruses, including SARS-CoV-1. Another molecule showed very strong activity against MERS-CoV, with moderate activity against the other viruses. Because the main proteases of SARS-CoV-2, MERS-CoV and SARS-CoV-1 are very similar, the inhibitors will most likely show good antiviral activity against the Wuhan coronavirus, the researchers say. Their next step will be to test the inhibitors in small-animal models of disease.

Today, phenols are used to produce medicines, paints, and inexpensive furniture made of chipboard or MDF panels and also to process food. Some of them are capable of imparting a pleasant smoky aroma to food, so they are often added to sausage or fish. But if we eat something that is high in phenols, it can have a deleterious effect on our health, so at factories they pay close attention to their concentrations in food. During tests, more often than not meat samples are dissolved in alkalis (in which phenols are very soluble), but the resulting emulsions require additional purification from the fats contained in sausage.

'Our method is based on application deep eutectic solvents - very promising compounds that have been studied extensively over the last fifteen years,' said Andrei Shishov, the project leader, who has a PhD in Chemistry and is an associate professor in the Department of Analytical Chemistry at St Petersburg University. 'Usually, such solvents formed from two substances, which are then used to extract a third. But we got to thinking about it and wondered if it wouldn't be a good idea to try deriving this substance not through a solvent but by means of the way it is formed. After all, phenols themselves produce such compounds when they bond with choline chloride - it's the commonly known vitamin B4.'

This innovative approach involves only a few steps. First of all, a meat sample is minced and then mixed with organic solvent. After that, a piece of paper with a layer of choline chloride crystals, on which phenol is excreted, is immersed in the solution. The composition on the surface of the paper is washed off with water, and the concentration of phenols in it is determined by using, for example, a chromatograph - a special device for analysing a mixture of substances.

The paper membrane is impregnated in a special substance, choline chloride, which is used to discharge phenols. The meat sample is put in the solvent, in which the membrane has been placed on a needle. Phenols are excreted on its surface. After that, the phenols are washed off the surface of the membrane with water, and the resulting solution is analysed with the use of a special device.

Best of all, as the chemists in Professor Bulatov's research team note, this technique is perfect for solid products, which are easy to grind up. Among its advantages are safety - after all, vitamin B4 is nontoxic - and speed - if all of the instruments are properly adjusted, an analysis takes no more than half an hour. What is more, this new approach makes it possible to determine whether a sausage has really been smoke-cured or liquid smoke has simply been added to it.

'Besides, using this method, it is also possible to identify polyphenol compounds in edible oils, for example olive oil, and this is exactly what we are looking at now,' said Mr Shishov. 'It is known that these are the compounds that account for the antioxidant activity of edible oils, and they are beneficial for our health.'

As social insects, ants are particularly dependent on optimizing their communication in order to ward off enemies and to recognize individuals from their own colony. They must also protect themselves against desiccation. Their bodies are covered with wax-like substances known as cuticular hydrocarbons (CHCs) that serve both purposes - communication and protection against desiccation. However, while recognition of other ants requires the CHC layer to be not too solid, making it easier for other ants to sense the chemical signals in the layer, desiccation protection requires it to be as solid as possible. To resolve this conflict between the needs of communication and waterproofing, this layer is composed of CHCs with special physical properties, as biologists have now discovered. "We were surprised to find that the layer does not melt at a specific temperature or a narrow temperature range, but rather has a huge melting range: It starts melting at around minus 45 degrees Celsius and is only fully liquid above 30 to 40 degrees Celsius," explained Dr. Florian Menzel of Johannes Gutenberg University Mainz (JGU). "We found that the layer is, in fact, composed of a mixture of liquid and solid components, similar to ice cubes in a glass of water or liquid honey containing sugar crystals."

Conflicting functions: communication versus waterproofing

The CHC layer covering the bodies of almost all insects like an external skin has already been studied in detail. For instance, scientists already know that CHCs form a mixture of several dozens to over a hundred different compounds and that each species of ant has its own distinctive hydrocarbon blend. The chemical composition of the hydrocarbons determines not only their information content, but it also influences how well the layer prevents desiccation. "In other words, the substances have to serve different purposes simultaneously, which can, of course, be a problem," said Menzel.

Along with chemist Dr. Svenja Morsbach of the Max Planck Institute for Polymer Research in Mainz and physicist Dr. Bérengère Abou of the Centre national de la recherche scientifique (CNRS) in Paris, Menzel has now studied the physical properties of this wax-like layer, in particular the melting ranges of the hydrocarbons and their flow characteristics. To date, neither has been an issue in research.

Viscosity similar to that of motor oil

Finding suitable methods for investigating such tiny quantities of material was particularly challenging. Based on a formula developed by Albert Einstein, Abou had developed a novel microrheological technique to measure viscosity in this case, which allows to measure liquid drops as tiny as 100 pikoliters. The viscosity of the CHC layer was found to be similar to that of motor oil. Although the investigated hydrocarbon mixtures were completely different from each other - the CHCs of eleven different ant species were included in the study -, the viscosity was very similar for all species. The research team attributes this similarity to the fact that the exchange of communication signals may require a specific degree of viscosity or fluidity.

The chemical composition of the wax layer alone does not predict its waterproofing ability

Scientists at the Max Planck Institute for Polymer Research employed differential scanning calorimetry (DSC) to determine the melting behavior of the hydrocarbons. "We were astonished by the results. To date, this aspect has been largely neglected, while numerous studies implicitly assumed that the CHC layer is completely solid at ambient temperatures," said Menzel. Over the entire melting range, between minus 45 degrees Celsius and plus 40 degrees Celsius, the hydrocarbons take the form of a blend of liquid and solid components. According to Menzel, this liquid-solid mixture is essential to allow the CHC layer to fulfill both purposes. "There might be a fundamental conflict between the two functions of waterproofing and communication, which makes the evolution of CHCs particularly intriguing," the biologist added. If this is the case, the melting behavior of the CHCs, which directly depends on their chemical composition, would be one of the most important functional characteristics of the waxy CHC layer. It determines how effectively the CHC layer inhibits desiccation at different temperatures, while at the same time influencing how signals are exchanged. This not only applies to ants but most likely also to nearly all other insects.

Menzel and his team now plan to investigate how the viscosity and melting behavior of hydrocarbons change when ants can acclimate to different temperatures over several weeks. Insects may rely on such acclimation strategies to survive temperature fluctuations that are associated with a higher risk of desiccation.

Hamilton, ON (February 26, 2020) - McMaster University researchers have identified an antibacterial compound made by cannabis plants that may serve as a lead for new drug development.

An interdisciplinary team of McMaster researchers found that the chemical compound, or cannabinoid, called cannabigerol (CBG) is not only antibacterial but also effective in mice against a resilient family of bacteria known as methicillin-resistant Staphylococcus aureus (MRSA).

The findings were published in the journal American Chemical Society Infectious Diseases.

"In this study, we investigated 18 commercially available cannabinoids and they all showed antibiotic activity, some much more than others," said study lead Eric Brown, professor of biochemistry and biomedical sciences at McMaster.

"The one we focused on was a non-psychoactive cannabinoid called CBG, as it had the most promising activity. We synthesized that cannabinoid in mass quantity which gave us sufficient compound to go deep into the research."

The research team found that CBG had antibacterial activity against drug-resistant MRSA. It prevented the ability of that bacteria to form biofilms, which are communities of microorganisms that attach to each other and to surfaces; and it destroyed preformed biofilms and cells resistant to antibiotics. CBG achieved this by targeting the cell membrane of the bacteria.

These findings in the laboratory were supported when mice with an MRSA infection were given CBG.

"CBG proved to be marvellous at tackling pathogenic bacteria," Brown said. "The findings suggest real therapeutic potential for cannabinoids as antibiotics."

One caveat noted by the research team is the toxicity of CBG on the host cells which makes the study's findings an important lead rather than a likely final product, Brown said.

"It opens a therapeutic window, but a narrow one, to develop this into a drug," he said. "The next steps are to try to make the compound better in that it is more specific to the bacteria and has a lower chance of toxicity."

The Brown lab has been studying the antibiotic potential of cannabis for the past two years since the legalization of marijuana in Canada.

"This research became top of mind for us, in part, because we are in Canada," Brown said. "There has been some stigma of investing in this kind of research, but there's increasing anecdotal evidence of the medicinal use of cannabis. The stigma seems to be waning."

Brown said the study was reliant on his collaborator, Jakob Magolan, a McMaster associate professor of biochemistry and biomedical sciences who specializes in drug development using organic synthetic chemistry.

"The labs of Jake and I are just steps away from each other and our teams are talking to each other all the time," Brown said. "This is just one of many exciting projects we're involved with that combine scientists with very different but complementary expertise."