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Yale researchers have found a neural home of the feeling of stress people experience, an insight that may help people deal with the debilitating sense of fear and anxiety that stress can evoke, Yale researchers report May 27 in the journal Nature Communications.

Brain scans of people exposed to highly stressful and troubling images -- such as a snarling dog, mutilated faces or filthy toilets -- reveal a network of neural connections emanating throughout the brain from the hippocampus, an area of the brain that helps regulate motivation, emotion and memory.

The brain networks that support the physiological response to stress have been well studied in animals. Activation of brain areas such as the hypothalamus triggers production of steroid hormones called glucocorticoids in the face of stress and threats. But the source of the subjective experience of stress experienced by people during the COVID-19 pandemic, for instance, has been more difficult to pinpoint.

"We can't ask rats how they are feeling," said Elizabeth Goldfarb, associate research scientist at the Yale Stress Center and lead author of the study.

Goldfarb and co-authors, including senior author Rajita Sinha, the Foundations Fund Professor of Psychiatry, conducted a series of fMRI scans of subjects who were asked to quantify their stress levels when presented with troubling images.

The study reveals that neural connections emanating from the hippocampus when viewing these images reached not only areas of the brain associated with physiological stress responses, but also the dorsal lateral frontal cortex, an area of the brain involved in higher cognitive functions and regulation of emotions. The Yale team found that when neural connections between the hippocampus and frontal cortex were stronger, subjects reported feeling less stressed by the troublesome images.

Conversely, subjects reported feeling more stressed when the neural network between the hippocampus and hypothalamus was more active.

The authors note there is also evidence from other studies that those suffering from mental health disorders such as anxiety may have difficulty receiving calming feedback from the frontal cortex in times of stress.

"These findings may help us tailor therapeutic intervention to multiple targets, such as increasing the strength of the connections from the hippocampus to the frontal cortex or decreasing the signaling to the physiological stress centers," said Sinha, who is also a professor in Yale's Child Study Center and neuroscience department.

All study subjects were healthy, she said, and in some cases their responses during the experiment seemed to be adaptive -- in other words, the network connections with the frontal cortex became stronger as the subjects were exposed to the stressful images. Sinha and Goldfarb speculated that these subjects might be accessing memories that help moderate their response to stressful images.

"Similar to recent findings that remembering positive experiences can lower the body's stress response, our work suggests that memory-related brain networks can be harnessed to create a more resilient emotional response to stress," Goldfarb said.

Empowering people to intervene when they witness unacceptable behaviour can help to prevent domestic violence and abuse, a new study has found.

Specific training for bystanders makes them "significantly" more confident to take action when they see or hear wrongdoing related to domestic abuse in their community, according to the research.

A total of 81 per cent of participants reported being more likely to intervene when they saw wrongdoing after the training, this increased to 89 per cent four months later.

This is the first academic study to examine a bystander programme as a way to tackle domestic violence and abuse in UK communities. The study, published in the journal BMC Public Health, comes at a critical moment: during the current coronavirus lockdown there has been a sharp rise in calls to domestic abuse helplines.

Similar training has been used in universities in the UK and experts who developed the new programme hope bystander training will now play a key role in domestic violence prevention work across the country.

The training, entitled Active Bystander Communities, was led by Dr Rachel Fenton at the University of Exeter and Alexa Gainsbury at Public Health England, and is a collaboration between University of Exeter Law School, Public Health England, Devon County Council, Bristol County Council, Splitz and the Hollie Gazzard Trust. It was piloted with 70 people in Exeter, Torquay and Gloucester.

Active Bystander Communities, was designed to give people the knowledge and skills they need to be 'active bystanders' and intervene positively in potentially harmful situations. It was delivered in three two hour sessions by experienced facilitators. Participants learned how to notice harmful behaviour alongside developing the skills to be able to intervene safely and effectively.

Surveys of participants immediately after the training showed a significant increase in confidence and intent to take action as well as a significant improvement in their ability to spot and reject myths about domestic abuse. A total of 87 per cent of people who took part in the training were less likely to believe myths about domestic abuse afterwards. A total of 84 per cent of participants said they felt more confident about intervening following the training.

Researchers found further improvement four months after training when participants had had the opportunity to take their learning out into their communities and take action.

Dr Fenton said: "Bystander intervention is about empowering all members of the community to speak up and challenge gender inequality and the drivers of domestic abuse in a safe and situation-appropriate way. It's about helping people to find their own way to make an impact and make a difference. We hope others will now use our programme.

"People in the community are ideally placed respond to problematic behaviours and support individuals who are experiencing domestic violence and abuse because they have the relationships, insights and opportunities to make a real difference.

"During the coronavirus pandemic people can still be a bystander by keeping in touch with friends and neighbours, and signposting to services and reporting particularly if they think others are at risk of domestic violence and abuse."

One participant said: "I found the courage to voice my ideas, ideas that previously I was able to share with friends and family, but never with strangers on social media, and I did it in spite of how scared I was of the possible reactions. I just knew that challenging certain behaviours could make the difference, that we can tackle big problems by performing small acts, and therefore could not keep silent."

Another participant said: "I have felt empowered by the bystander intervention to feel confident to intervene and show my disapproval at sexist and toxic behaviours towards women, potentially within a male dominated environment in which I work

"This has given me an insight into different ways to challenge domestic abuse and also made me aware of thinking of the impact my actions could have if I challenged behaviour for the victim. I now feel I have more tools to help me use appropriate responses that will support the victim."

Ms Gainsbury at Public Health England said: "Preventing violence is everyone's business and we are all aware of the devastating impact domestic abuse has on individuals, families and communities. Whilst we are clear that domestic violence and abuse should never happen, it is not always clear what we can do to stop it. The Active Bystander Communities is at the forefront of developing the evidence base for bystander interventions in the UK."

"Our follow-up research has found participants have been quick to put their training into action and have already carried out a wide range of bystander interventions from calling out sexist behaviour to supporting victims of domestic abuse within their communities."

"From spreading the word that bystanders can make a difference to calling out harmful behaviours they see in everyday life and being a source of support to those experiencing abuse, the range of ways in which participants have enacted interventions since undertaking the training has been inspirational."

Simon Kitchen, Head of Communities at Devon County Council said: "The Council has been pleased to be part of the development and learning from this innovative and challenging project. Ending domestic abuse and sexual violence in Devon is a longstanding ambition for the Council and our key partners and bystander intervention offers an important tool for people and communities to challenge thinking, behaviour and attitudes at an early stage. I think it can also teach us about being better, kinder and informed citizens, and personally has given me tools and knowledge to be a better father, partner, colleague and friend."

Dame Vera Baird QC victims' commissioner for England and Wales said: "I had the pleasure of helping to launch active bystander communities at Exeter City football club in October of last year.

"It had obvious potential to influence bystanders better to recognise problematic attitudes, beliefs and behaviours around violence against women. It also empowers them to intervene when they see harmful things occurring. Interestingly, participants who heard discriminatory comments made by others found that if they spoke out many others listening shared their concerns. The point is to utter these concerns, empower themselves and each other and, one hopes, at the same persuade the person they are critical of that their attitudes are unacceptable.

"It is excellent to see that the evaluation is as good now as the potential was then. I congratulate the University of Exeter Law School and Public Health England on this endeavour. I would enthusiastically recommend that other universities and organisations take on bystander projects."

People who believe more strongly that depression is biologically caused also tend to think it is more severe and long lasting, compared to those who see less of a role for biological causes, a new Rutgers study finds.

At the same time, people who believe that biological factors cause depression also tend to be more optimistic that treatment will have a positive effect, said Sarah Mann, a former doctoral student at Rutgers University-New Brunswick who led the study.

The study, published in Journal of Mental Health, also found that people who think depression runs in the family genetically or occurs because of a change in the brain are less likely to hold negative attitudes toward those with depression.

The researchers surveyed 319 people online and assessed their beliefs, attitudes and experiences with depression and its treatment. Nearly half (48.6%) reported prior depression. Using a Likert scale, a measurement of how much people agree or disagree with a statement, and an illness perception questionnaire, researchers analyzed their perceptions of the causes, duration, consequences and treatability of depression.

"Scientifically, very little is known about people's understanding of depression and their feelings about those affected by this disorder. From a practical standpoint, those beliefs and attitudes may influence decisions people make about whether to seek treatment for their own depression. They may also affect their reactions toward depressed individuals, including prejudice and discrimination," said co-author Richard Contrada, a professor of psychology.

Participants were asked, after reading a description of depression, whether they believed they had experienced depression and, in a separate question, whether they believed a "spouse, romantic partner, parent, sibling or close friend" had.

If people reported previous experience with their own depression or with someone close to them, they tended to report less negative attitudes toward depressed people and greater acceptance, said Mann. Among these individuals, there was also a significant link between believing that depression has a biological cause and holding more accepting attitudes toward people with depression.

Researchers asked the participants their views about depression's impact and whether treatment is effective; their willingness to be in specific situations with people with depression, such as recommending them for a job or introducing them to friends; their own attitudes and other people's attitudes about depression, and other questions.

The findings suggest that the way people respond to public health announcements highlighting biological causes of depression depends partly on their previous experiences with depression. Though the effects of messages on public attitudes toward people with depression may be mixed, the researchers said, they may decrease affected individuals' self-blame and encourage them to seek treatment.

A Canadian case series of all patients with COVID-19 admitted to six intensive care units (ICUs) in Metro Vancouver found patient outcomes were substantially better than reported in other jurisdictions. The paper is published in CMAJ (Canadian Medical Association Journal).

Researchers looked at outcomes for 117 patients with COVID-19 admitted to one of six hospitals in Metro Vancouver between February 21 and April 14, 2020. Patients ranged in age from 23 to 92 years, with a median age of 69 years. Two-thirds (67.5%) were male. As of May 5, 85% of patients were still alive and 61% had been discharged home. The overall mortality rate was 15%.

"The overall mortality was appreciably lower than in previously published studies, despite comparable baseline patient characteristics and a higher proportion of patients with completed hospital courses," writes Dr. Donald Griesdale, a critical care physician at Vancouver General Hospital and associate professor at the University of British Columbia's Faculty of Medicine, Vancouver, BC, with coauthors.

Data from Lombardy, Italy, showed a 61% mortality rate for patients admitted to an ICU, a case study of 24 people in Seattle had a 57% mortality rate among patients in the ICU, and a case series from Wuhan, China, reported a mortality rate of 80% in patients admitted to the ICU.

Fewer patients in the Canadian series (63%) received mechanical ventilation than in Lombardy (88%), Seattle (75%) and New York (90%), but in Wuhan even fewer (42%) received mechanical ventilation. Very few patients received unproven treatments for COVID-19; one patient received hydroxychloroquine, four received tocilizumab, and none recived remdesivir.

"Despite the observed differences between patients and critical care interventions in these studies, it is unclear whether these solely account for the marked lower mortality that we report," write the researchers. "We hypothesize that these encouraging results may be due to a broader system-level response that prevented an overwhelming surge of critically ill patients with COVID-19 from presenting to our hospitals and ICUs."

HUNTINGTON, W.Va. - New findings reveal the importance of the Na/K-ATPase protein in stem cell differentiation and organogenesis, in a study led by scientists at Marshall University that involves the scaffolding function of the Na/K-ATPase.

The research, published today in Science Advances, indicates that a sequence in the Na/K-ATPase, also known as the sodium pump, that is not involved in the ion pumping function of this protein is critical to stem cell differentiation and organogenesis across the animal kingdom.

"The goal of this study was to reveal a novel role of this protein in animal biology and physiology," said first and corresponding author, Xiaoliang Wang, M.D., Ph.D., a postdoctoral research fellow at the Marshall University Joan C. Edwards School of Medicine. "Embryonic development represents one of the most amazing processes of biology. Na/K-ATPase is prevalently expressed in every single cell in our body."

The study builds upon the seminal work of the late Zijian Xie, Ph.D., who, along with collaborators, discovered the signaling & scaffolding function of the Na/K-ATPase in the late 1990s. Xie's discovery has had tremendous applications in both cell biology and medicine and opened the door to this new area of research.

Wang along with co-first author, Liquan Cai, Ph.D., and researchers at the Marshall Institute for Interdisciplinary Research and Joan C. Edwards School of Medicine, used a mutagenesis technique to generate three different models in order to explore the essential role of Na/K-ATPase in organogenesis and embryonic development.

Findings from this study provide the first genetic evidence that a specific sequence on Na/K-ATPase is evolutionally conserved, not for the enzymatic activity of Na/K-ATPase, but for the formation of a signaling circuitry essential for the rapid organogenesis in a time- and space-specific manner during animal embryonic development. The researchers conclude from these new findings that the Na/K-ATPase is not just an ion pump but a critical multi-functional protein. This whole functionality underlies a previously unrecognized common mechanism essential for stem cell differentiation and organogenesis in multi-cellular organisms within the animal kingdom.

"In addition to potential relevance to human health and disease, which has been the focus of this research group, this particular work may be of critical importance to basic biology," said contributing author, Joseph I. Shapiro, M.D., dean of the Marshall University Joan C. Edwards School of Medicine, who has been Xie's primary research partner for the past two decades.

When it comes to the great civilizations of human history, the pen really might have been mightier than the sword.

That's according to a new paper in Nature Communications that shows the ability to store and process information was as critical to the growth of early human societies as it is today.

"There's a fundamental relationship between the way in which societies process information and how large they are able to become," said Tim Kohler, an archaeologist at Washington State University and a corresponding author of the paper.  "Early innovations in information processing such as writing and coinage appear to be as important to the sociopolitical development of our ancestors as something like the internet is to us today."

For their study, Kohler and colleagues at the Santa Fe Institute set out to discover more about the role information technology played in the growth of human societies from the Neolithic to the last millennium.

They dug into what's called the Seshat Global History Databank, a massive assembly of historical and archaeological information spanning more than 400 societies, six continents and 10,000 years of human history.

The databank enabled the researchers to quantitatively analyze things like how large were civilizations when they developed writing, systems of coinage and other innovations in information processing and what were the effects of these advances on the growth of the overall state.

Their findings show that sociopolitical development historically underwent three phases. Initially, population growth was the dominant force in a society's complexity.

Then, once a civilization reached a certain size, it needed to develop more sophisticated ways of dealing with information and economic transactions, through inventions like writing and currency. Once these innovations were discovered, the society could once again continue growing in size and scale.

"Our findings show that ancient civilizations ran into an information bottleneck when they reached a certain size, a point we call the scale threshold," Kohler said. "Without innovations like writing or a system of currency, further expansion became very rare. However, once these advances in information processing and storage were achieved, you start to see the big empires of history emerge."

One of the more intriguing findings of Kohler and colleagues' study is a possible explanation for the technology gap that existed between old and new world societies.

Their work shows very few civilizations in the ancient Americas ever crossed the scale threshold. Consequently, there was less pressure to develop writing and other forms of information processing in the Americas that spurred further technological development in Europe and Asia.

"One of the main reasons we think the vast majority of Native American civilizations never reached the scale threshold was the absence of horses, oxen and other large animals capable of carrying people or sizeable loads," Kohler said. "Such animals helped create agricultural surplus, facilitated trade and generally facilitated the expansion of empire in Europe and Asia."

Moving forward, the researchers hope to use the Seshat database to investigate other intriguing, long-standing questions from history such as why did some civilizations collapse when there weren't any apparent external causes such as natural disaster, famine or war.

"We think as the Seshat database gets larger and larger there will be more data points and we will be able investigate these kinds of questions," Kohler said.

The researchers' work could also have interesting implications for the study of contemporary society.

"We have enormous new capabilities for storing and processing data that are just well beyond the scope of anything in the past," Kohler said. "Does this imply that we're going to have another growth in scale for human civilizations? And if so, what would that look like?"

Volume 11, Number 21 of @Oncotarget reported that eligible patients with stable or responding mPDA after 6 months on chemotherapy were randomized 1:1 to metformin alone or with rapamycin, stratified by prior treatment with FOLFIRINOX. Metformin +/ rapamycin maintenance for mPDA was well-tolerated and several patients achieved stable disease associated with exceptionally long survival.

Dr. Dung T. Le from The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, 21287 said, "Pancreatic ductal adenocarcinoma (PDA) is aggressive cancer with high mortality at all stages and limited treatment options in the advanced setting."

"Pancreatic ductal adenocarcinoma (PDA) is aggressive cancer with high mortality at all stages and limited treatment options in the advanced setting." - DR. DUNG T. LE, THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER AT JOHNS HOPKINS

Metformin is an antidiabetic drug in the biguanide class of agents which inhibits mTOR complex 1 primarily through AMP-kinase activation.

A synergistic effect of the combination of metformin with rapamycin was suggested by preclinical studies demonstrating enhanced inhibition of mTOR in a pancreatic cancer cell line and better growth inhibition of pancreatic cancer cells in a xenograft tumor model with the combination than either agent alone.

Based on this, they conducted an exploratory study of metformin with or without rapamycin in patients with mPDA in the maintenance setting.

The Le Research Team concluded in their Oncotarget Research Article, "the administration of metformin with or without rapamycin in patients with mPDA who achieve a response to chemotherapy is well-tolerated and was associated with better than expected overall survival in this study. Additional studies are needed to prospectively evaluate the role of these agents compared to a maintenance chemotherapy or observation only approach."

Researchers at the University of Queensland may have found a way to improve treatment of triple-negative breast cancer.

The team found that triple-negative breast tumours with the highest energy usage respond best to chemotherapy because the 'recycling stations' that deal with metabolic by-products, called proteasomes, also make cancer more 'visible' to the immune system.

Lead researcher Dr Jodi Saunus said the discovery could improve a patient's response to treatment of the aggressive cancer.

"Previous research has indicated that inhibiting proteasomes could be effective in triple-negative breast cancer, but we have found the opposite to be true," Dr Saunus said.

"If we can figure out how to boost the activity of tumour proteasomes, we could improve the effectiveness of chemotherapy, and potentially increase the prospects for immunotherapy."

Until recently, chemotherapy has been the main drug therapy for triple-negative breast cancer, but research now suggests immunotherapy - which activates the body's in-built cancer defences - may also work.

Triple-negative breast cancer is negative for three receptors commonly found in breast cancer cells - oestrogen, progesterone and HER2 receptors.

This means hormone therapies are ineffective and treatment usually involves surgery, radiotherapy and cytotoxic chemotherapy that produce harrowing side-effects.

It affects 15 per cent of patients and is one of the most severe breast cancers because it tends to grow and spread faster, with many patients experiencing relapse in the lungs, liver or brain.

Dr Saunus' research team analysed the molecular features of 3,500 breast tumours over two years to make this finding.

With funding from the National Breast Cancer Foundation, the team is working on the next phase of the research, which it hopes will lead to the development of experimental 'cancer vaccines' that can help the immune system fight the cancer if it spreads to the brain.

DALLAS – May 25, 2020 – Scientists have known for a decade that cells that fuse with others to perform their essential functions – such as muscle cells that join together to make fibers – form long projections that invade the territory of their fusion partners. But how the thin and floppy polymers involved in this process propel mechanically stiff protrusions has been unknown.

In a new study published online today in Nature Cell Biology, UT Southwestern scientists outline the mechanisms behind the formation of these projections, focusing on the interaction between two proteins known as actin and dynamin. The findings, they say, offer insight on a key cellular process that’s essential for the conception, development, regeneration, and physiology of multicellular organisms and may eventually lead to new treatments for a rare muscle disease.

Cell fusion involves three main steps, explains study leader Elizabeth Chen, Ph.D., a professor in the departments of molecular biology and cell biology at UT Southwestern Medical Center whose research focuses on this process. First, adhesion molecules draw cell membranes together, but leave a gap between cells; next, one cell extends fingerlike projections that invade the other cell; finally, so-called fusogenic proteins bring the cells’ membranes even closer to touch and merge.

For that middle step, Chen says, research from her lab and others has shown that a protein called actin plays a key role in forming projections. However, actin forms floppy and thin polymers, known as actin filaments, each with a diameter of only 7 nanometers. How these thin filaments become mechanically rigid enough to push out projections that invade other cells was unclear.

To solve it, Chen and her colleagues studied actin’s interaction with dynamin, a protein that can release energy from specific chemical bonds found throughout cells. One of dynamin’s roles is to pinch off newly formed vesicles that bring cargo into cells, by forming a structure around the “neck” of the vesicles protruding in from the cell membrane. Although previous studies have shown that dynamin and actin were associated with each other in many cellular structures, how they work together has remained a mystery for two decades.

Using fruit fly muscle cells as a model system, Chen and her team started by observing muscle cell fusion in embryos genetically engineered to not make any functional dynamin. They found that without dynamin function, not only could these cells no longer merge, they also couldn’t form the normal projections, suggesting that dynamin plays a key role in this step of the process.

The researchers then used microscopy to take a closer look at how purified dynamin and actin proteins interacted when they were mixed in equal parts. They found that the actin filaments appeared to be organized into bundles held together at regularly spaced intervals by dynamin, the latter of which forms a helix when multiple dynamin molecules assemble together. Surprisingly, rather than the dynamin helix wrapping around the actin filaments, the filaments bind to the outer rim of the helix, with each helix capturing up to 16 filaments.

Although this experiment shows that dynamin has the capacity to capture and hold multiple actin filaments into stronger bundles, Chen says, fully occupied dynamin helices are unlikely to last long in cells, where ample energy sources that can cause these dynamin structures to dissolve into individual units is abundant. Sure enough, when the researchers added energy sources to the dynamin-actin mix, the dynamin helices did come apart, but not in a synchronized fashion. While fully assembled helices broke apart, others remained – keeping the actin bundles together while allowing new filaments to emanate from areas unbound by dynamin. Such a dynamic process ultimately leads to the formation of multiple interconnected parallel actin bundles, hence further increasing the mechanical strength of the actin network, says Chen. Experiments in cells showed that the dynamic actin bundling process was critical for cells to form projections and fuse with other cells.

Although Chen and her colleagues used muscle cells as their model system, Chen notes that the interplay between actin and dynamin they discovered here could play a key part in other types of cell fusion, such as between bone-resorbing cells or between immune cells. Defects in this process could also be responsible for some rare disorders such as centronuclear myopathy, a condition in which muscle cells form fibers that are too small. Previous research has shown that multiple genetic mutations in dynamin can cause this disease.

“We are interested in looking at how the human mutations are blocking the fusion process, which could eventually lead to novel ways to intervene and help these patients,” Chen says.

Spring is in full swing. Trees are leafing out, flowers are blooming, bees are buzzing, and birds are singing. But a recent study published in Proceedings of the National Academy of Sciences found that those birds in your backyard may be changing right along with the climate.

Clark Rushing, Assistant Professor in the Department of Wildland Resources and Ecology Center, Quinney College of Natural Resources at Utah State University, and colleagues at the U.S. Geological Survey wanted to know how climate change has already affected where birds breed. They used data from the Breeding Bird Survey - one of the oldest and longest citizen-science programs in the world - to conduct their research. "Thousands of devoted volunteers, cooperators, and a joint U.S.-Canadian wildlife management team have contributed to the success of the surveys for the last 54 years," said Andy Royle, a USGS senior scientists and co-author of the study. "The Breeding Bird Survey is fundamental to our understanding and management of wild bird populations in North America."

The research team combined Breeding Bird Survey data with powerful computer models to discover changes in breeding range for 32 species of birds found in eastern North America. What they found is surprising:

Some birds' ranges are expanding. Birds that both breed and winter in North America are extending their ranges north to take advantage of new, warm places to breed. These birds are also maintaining their southern ranges. These results bring hope that some bird populations, such as Carolina wrens and red-bellied woodpeckers, may be resilient to future climate change.

Some birds' ranges are shrinking. Neotropical migratory birds breed in North America during the summer and migrate to the Caribbean, Central America, and South America for the winter. Neotropical migrants include many species that people love and look forward to seeing each spring such as buntings, warblers, orioles, and flycatchers. The team's research shows that these birds are not expanding north and their southern ranges are shrinking.

To make matters worse, over the past 50 years Neotropical bird populations have decreased by about 2.5 billion individuals. Rushing explained, "There's a real risk that, if these declines continue at their current pace, many species could face extinction within this century. Neotropical migrants are vulnerable to future climate change, putting them at risk of greater declines."

Neotropical migrants already fly thousands of miles each year to breed, so why can't they go just a bit farther as the climate warms? The researchers suspect the conditions where the birds live during the winter might make this impossible. Migrations require immense reserves of energy, so migratory birds need high-quality winter habitat with abundant food and moisture. Unfortunately, many habitats in the Caribbean, Central America, and South America are being degraded. It is possible that Neotropical birds can't store enough energy during the winter, so they simply can't extend their journeys any farther.

"That's just one explanation," concluded Rushing, "and it highlights how little we know and how much more research is needed." And what the team does know wouldn't have been possible without the help of devoted citizen scientists.

Glioblastoma multiforme (GBM) is an aggressive form of cancer in the brain that is typically fatal. But new findings by VCU Massey Cancer Center and VCU Institute of Molecular Medicine (VIMM) researchers could help increase the effectiveness of the most common current treatments with the addition of lumefantrine, an FDA-approved drug used to treat malaria.

While the current standard of care involving radiation and temozolomide, an anti-cancer chemotherapy, can marginally extend the lives of patients with glioblastoma multiforme brain tumors, resistance of GBM to these therapies is a frequent occurrence. Additionally, the five-year survival rate of GBM patients treated with the standard of care is less than 6 percent, and no current therapies prevent recurrence.

The researchers have focused on discovering FDA-approved drugs and more uncommon agents that could potentially help counteract glioblastoma's resistance to and effectiveness of treatment. "Our studies uncovered a new potential application of the antimalarial drug as a possible therapy for glioblastoma multiforme resistant to the standard of care entailing radiation and temozolomide," said Paul B. Fisher, M.Ph., Ph.D., FNAI, the principal investigator of the study recently published in the journal Proceedings of the National Academy of Sciences.

Specifically, lumefantrine can inhibit a genetic element involved in cancer development and progression, Fli-1, which controls resistance of glioblastoma multiforme to radiation and temozolomide.

During in vitro studies (conducted with cells grown in culture) researchers found that incorporating lumefantrine while treating glioblastoma killed cancer cells and suppressed tumor cell growth. This occurred in both glioblastoma cells sensitive to and those that otherwise would be resistant to radiation and temozolomide. Furthermore, during in vivo studies (conducted using mice containing a transplanted human glioblastoma multiforme in their brains), lumefantrine inhibited tumor growth caused by both therapy-sensitive and therapy-resistant glioblastoma cells.

Discovering lumefantrine's ability to neutralize the body's resistance to radiation and chemotherapy came through genetic and molecular approaches that identified the new genetic element "Fli-1" as an important genetic element controlling resistance to therapy. This discovery became a focal point of the current research. Researchers found that "heat shock protein B1," also known as HSPB1, is prominent in glioblastoma tumors, and its expression is regulated by Fli-1. Innovative screening strategies for Fli-1 inhibitors identified lumefantrine as a prospective agent that could bind to Fli-1, inactivate it and thereby suppress expression of important genes regulating growth, survival and oncogenicity (ability to cause tumors) of glioblastoma multiforme.

In addition, two key processes essential for cancer invasion and spread known as extracellular matrix (ECM) remodeling and epithelial mesenchymal transition (EMT) are important factors that regulate glioblastoma's ability to respond and resist radiation and chemotherapy. Those two processes are regulated by Fli-1 and are inhibited by lumefantrine.

To help treat glioblastoma, researchers will further explore other means to counteract therapy resistance induced by Fli-1.

"These preclinical studies provide a solid rationale for Fli-1/HSPB1 inhibition with lumefantrine as a potential novel approach for glioblastoma management," Fisher said. "Identification of drugs like lumefantrine from FDA-approved therapeutic agents and from uncommon sources provides opportunities to broaden the breadth and versatility of current therapeutic regimens for glioblastoma multiforme patients."

Beyond glioblastoma, an elevated expression of Fli-1 can be seen in cancers such as melanoma, ovarian cancer, breast cancer and others, researchers said, suggesting that blocking the cancer-promoting effects of Fli-1 might help other cancer patients as well.

"The present results may have broader implications than just treating glioblastoma," Fisher said.

Researchers at Tel Aviv University have discovered evidence of ear infections in the skull remains of humans living in the Levant some 15,000 years ago.

"Our research seeks to determine the impact of our environment on illnesses in different periods," says lead author Dr. Hila May of the Department of Anatomy and Anthropology at TAU's Sackler Faculty of Medicine and the Dan David Center for Human Evolution and Biohistory Research at the Faculty of Medicine, located at the Steinhardt Museum of Natural History. "Using advanced technologies and unique methods developed in our lab, we have been able to detect signs of prolonged inflammation in the middle ear."

Dr. Katrina Floranova of the Dan David Center and Sackler Faculty of Medicine and Dr. Ilan Koren of the Sackler Faculty of Medicine also contributed to the study, which was published on March 25 in the International Journal of Osteoarchaeology.

The researchers found a decline in morbidity as a result of ear infections following the transition from hunting and gathering to farming because of changes in living conditions. But a peak in morbidity was observed in a sedentary population living about 6,000 years ago, in the Chalcolithic period.

Dr. May says the reason for this is twofold: social and environmental. "We know from archaeological excavations of this period, similar to preceding periods, that people lived in a communal area where all activities, from cooking to raising livestock, took place. As a result, the population density in the 'home' was high, hygiene was poor and they suffered from indoor air pollution. Two other factors known about this period - dietary change, the advent of dairy consumption; and climate change, a dip in temperature and a rise in rainfall - also contributed to the prevalence of ear infections."

Until the advent of antibiotics in the 20th century, ear infections developed into chronic conditions. They could also lead to permanent loss of hearing or even death.

"Ear infections are still a very common childhood ailment, with over 50 percent of young children today still suffering from an ear infection at one point or another," explains Dr. May. "The tubes that channel fluid from the middle ear to the pharynx are underdeveloped in young children, so fluids that accumulate in the ear ultimately cause inflammation.

"A prolonged ear infection would cause permanent damage to the bony wall of the middle ear, which is preserved into adulthood. So when we sought to investigate changes in communal health over time in our region, we chose to focus on ear infections, developing a special method for doing so," she adds.

Scientists inserted a videoscope, a tiny camera mounted at the end of a flexible tube, through the skull's ear canal to the middle ear to observe its bony walls. In addition, they scanned skull remains with a high-resolution micro-CT and examined the middle ear's bony wall using a light microscope.

As living conditions improved, morbidity as a result of ear infections dropped, according to the study. "Houses were larger and featured several rooms, including separate areas for specific activities, i.e. the kitchen was set up in a separate room or outside, and livestock were kept in a separate area," Dr. May says. "The change in lifestyle and climate is reflected in a decline in morbidity.

"Our study deals with the impact of the environment and social behavior on morbidity rates. To explore this, we examined a common disease that has accompanied humanity since inception - the ear infection," Dr. May continues. "Understanding how diseases appear, spread and disappear throughout human history can help prevent and find solutions to contemporary illnesses. The study clearly points out risk factors and shows how lifestyle changes can affect the incidence of the disease.

"In both ear infections and COVID-19, social distancing and adherence to hygiene reduced the spread of infection, while close quarters and unhygienic living conditions saw infections spike," Dr. May concludes.

By Sunday, May 24, Tropical Cyclone Mangga had already transitioned to an extra-tropical storm and was affecting the southwestern coast of Australia.

When a storm becomes extra-tropical, it means that a tropical cyclone has lost its "tropical" characteristics. The National Hurricane Center defines "extra-tropical" as a transition that implies both poleward displacement (meaning it moves toward the north or south pole) of the cyclone and the conversion of the cyclone's primary energy source from the release of latent heat of condensation to baroclinic (the temperature contrast between warm and cold air masses) processes. It is important to note that cyclones can become extra-tropical and retain winds of hurricane or tropical storm force.

The Australian Bureau of Meteorology issued Severe Weather Warnings in Western Australia on Sunday as the extra-tropical system tracked in a southeasterly direction.

The final warning for Mangga came on May 23 at 5 pm EDT (2100 UTC), when it was located near latitude 21.6 south and longitude 104.7 east, about 525 nautical miles west of Learmonth, Australia. Mangga was moving southeast at a speedy 44 knots (51 mph/81 kph) and had maximum sustained winds of 35 knots (40 mph/65 kph).

NASA's Aqua satellite provided a visible look at the extra-tropical low-pressure area along the southwestern coast of Western Australia on May 24. The center of circulation was difficult to pinpoint in the visible image, captured by the Moderate Resolution Imaging Spectroradiometer, an instrument that flies aboard Aqua.

On May 24, the Australian Bureau of Meteorology's Severe Weather Warning called for "Damaging, locally destructive winds and abnormally high tides for people in Central West, Lower West, South West, South Coastal, South East Coastal, Great Southern, Central Wheat Belt and parts of Gascoyne and Goldfields districts."

The extra-tropical low-pressure area passed over the southwestern part of the state on Monday, May 25 as it continued to weaken and move back over open waters of the Indian Ocean.

What The Study Did: Postmortem records from the National Violent Death Reporting System were used to determine how common being bullied was among lesbian, gay, bisexual, transgender and queer (LGBTQ) youth ages 10 to 19 who died by suicide compared with non-LGBTQ young people who died by suicide.

Authors: Kirsty A. Clark, Ph.D., M.P.H., of the Yale School of Public Health in New Haven, Connecticut, 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/jamapediatrics.2020.0940)

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

What The Study Did: Whether the amount of blood pressure medications taken by older adults could be reduced safely and without a significant change in short-term blood pressure control was the objective of this randomized clinical trial that included 534 adults 80 and older. For some older adults the potential risks of continuing treatment with multiple medications may outweigh the benefits.

Authors: James P. Sheppard, Ph.D., of the University of Oxford in the United Kingdom, 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/jama.2020.4871)

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