Culture

The fast-food industry spent $5 billion on advertising in 2019, and the advertisements disproportionately targeted Black and Hispanic youth, according to new research published today by the Rudd Center for Food Policy and Obesity at the University of Connecticut. The new report, Fast Food FACTS 2021, finds that the industry's annual ad spending in 2019 increased by over $400 million since 2012, and that children and teens were viewing on average more than two fast food TV ads per day.

Frequent and widespread exposure to fast-food marketing increases young people's preferences for, and consumption of fast-food, which is largely high in calories, sugar,
fat and sodium. Fast-food represents 40% of all food and beverage marketing expenditures targeted at children and teens (aged 2-17). Using 2019 Nielsen data, the study found that children aged 2-5 viewed an average of 830 TV ads for fast food over the course of the year, while children aged 6-11 viewed 787 ads, and teens and tweens aged 12-17 viewed 775 ads.

Nearly all of these ads promoted full-calorie regular menu items or the restaurants in general, while just 1% of ads viewed promoted restaurants' healthier menu items. Moreover, only 10% of ads viewed by children appeared during children's TV programming and fewer than 10% of ads promoted kids' meals. Further, many of the restaurants promoted their mobile apps or websites for digital orders in TV ads.

The study also shows that disparities in racial and ethnic targeted advertising are widening. Fast-food ad spending on Spanish-language television spiked, with a 33% increase from 2012 levels. Black youth viewed 75% more fast food ads than their White peers, up from a 60% difference found in 2012, even as TV viewership among all youth is down. On both Spanish-language and Black-targeted TV programming, restaurants advertised their low-cost large-portion value menu items and meal deals disproportionately more than on other types of programming, and no healthy menu items were advertised on Spanish-language TV.

"Fast-food consumption by children and teens has increased over the past decade, and fast-food advertising definitely plays a role in that rise," said Dr. Jennifer Harris, Senior Research Advisor for Marketing Initiatives at the Rudd Center and a co-author of the study. "Our findings show that these advertisements disproportionately target Black and Hispanic youth, groups who already face greater risk for obesity and other diet-related diseases. Moreover, many fast-food companies tout recent introductions of healthier menu items as evidence of their commitment to improving nutrition, but they rarely promote these items in their advertising."

More than 1 in 3 children eat fast-food on a given day in the United States. Fast-food restaurants have pledged to introduce healthier items on their regular menus and healthier drinks and sides to their kids' meals, but another recent study from the Rudd Center found that these voluntary policies have had little effect on purchases of kids' meals over regular menu items and selection of healthier kids' beverages. This new study shows that these purchasing patterns mirror the ads children see, with the vast majority of ads viewed by children promoting less healthy and higher portion items on their regular menus.

"Less time in front of TV screens is not protecting kids from fast-food TV ads," said Dr. Frances Fleming-Milici, Director of Marketing Initiatives at the Rudd Center and a co-author of the study. "Now more than ever parents need support in raising healthy children, and consistent exposure to ads featuring burgers, fries and pizza sabotages their best efforts. Media companies, policymakers and advocates can play a vital role in demanding an end to irresponsible advertising."

The study analyzed 2019 Nielsen data covering advertising spending and TV advertising exposure for 274 fast-food restaurants, including detailed analyses of the 27 top fast-food advertisers with the highest annual advertising spending and/or that targeted TV advertising to children, Hispanic, and/or Black consumers. The Rudd Center produces annual FACTS reports on the state of food and beverage advertising aimed at children, teens and Black and Hispanic youth. This study is a follow up to the Rudd Center's 2013 Fast-Food FACTS report.

The authors of the study make recommendations on concrete steps fast-food restaurants can take to limit such marketing, such as expanding voluntary industry self-regulation to restrict unhealthy food advertising to children up to age 14 at a minimum, discontinuing ads for regular menu items on children's TV channels and ending disproportionately high marketing to Hispanic and Black youth. They also offer suggestions for actions that federal, state and local governments can take such as creating nutrition standards for kids' meals and eliminating unhealthy food and beverage marketing to children as a tax-deductible expense. Lastly, their recommendations include how public health advocates and practitioners can push for changes to these marketing practices.

ANN ARBOR, Mich. - The price tag for giving birth in America may bring some families sticker shock - even for those with private insurance.

And when delivering moms require caesarians or their newborns need neonatal care, some families may spend as much as $10,000 out-of-pocket, according to a new Michigan Medicine-led study.

"Childbirth is the most common reason for hospitalization in the U.S.," said lead author Kao-Ping Chua, M.D., Ph.D.,a pediatrician and researcher at University of Michigan Health C.S. Mott Children's Hospital and the Susan B. Meister Child Health Evaluation and Research Center.

"Our findings show that some privately insured families are shouldering an astoundingly high financial burden for childbirth-related hospitalizations."

During 2016-2019, privately insured families paid an average of $3,000 out-of-pocket for maternal and newborn hospitalizations, according to the research in Pediatrics. But for one in 6 families, out-of-pocket spending exceeded $5,000. And when neonatal intensive care was required, the price climbed to over $10,000 for about 1 in 11 families.

"Many privately insured families believe that if they have health insurance, they're protected from the costs of childbirth hospitalizations. Unfortunately, this is simply not true for many families, particularly if their baby needs NICU care," Chua said.

"Having a healthy baby is expensive enough given the costs of diapers, childcare, and baby equipment. Adding a $10,000 hospital bill on top of this can devastate some families."

Researchers analyzed national data of 12 million privately insured enrollees across all states in the country. They identified 398,410 maternal deliveries that were linked to at least one newborn hospitalization covered by the same family plan. Overall, average out-of-pocket spending for the delivery and newborn hospitalizations was $3,068.

When cesarean birth occurred, the average bill was $3,389. When NICU care was needed, the average bill was $4,969. This bill exceeded $10,000 for 9% of instances when NICU care was needed.

About 30% of the time, deliveries and newborn hospitalizations were covered by high-deductible health plans, such as a health reimbursement arrangement or health savings account. Out-of-pocket costs were primarily driven by deductibles and co-insurance.

Chua said he was inspired to pursue the study because of his own personal experience that involved a $5,000 out-of-pocket bill after the birth of his second daughter.

"This is an issue that impacts millions of Americans at some stage in their lives," he said.

"Before delivery, clinicians can help privately insured families understand their childbirth benefits. If large bills are expected, clinicians should advise families to save money, assuming they have the means to do so. After delivery, clinicians should screen families for financial hardship, particularly those experiencing resource-intensive hospitalizations, such as NICU care, and connect them with local resources to address food, housing, and financial insecurity."

While substantial cost-sharing may be justified for low-value care, childbirth is a necessary, high value service, says senior author Michelle Moniz, M.D., M.Sc.,an obstetrician gynecologist at University of Michigan Health Von Voigtlander Women's Hospital. Moniz says policies should aim to alleviate the financial burden of childbirth on families.

Ideally, insurers would waive most or all cost-sharing for these hospitalizations, consistent with the approach taken by Medicaid programs and many peer, high-resource countries, she says.

The new study adds to Moniz' previous study examining the out-of-pocket costs of pregnancy, delivery, and postpartum care for mothers. .

"Maternal and childbirth hospitalizations are essential to families' health and wellbeing, with some babies needing longer stays because of complex or unexpected medical conditions," Moniz said.

"These services are vital to ensuring the best possible outcomes for moms and newborns. We should be looking at ways to improve childbirth coverage to avoid sending families home from the hospital with thousands of dollars in debt."

SPOKANE, Wash. - Many people likely lost sleep over COVID-19. A study of twins led by Washington State University researchers found that stress, anxiety and depression during the first few weeks of the pandemic were associated with less and lower quality sleep.

In a survey of more than 900 twins taken shortly after COVID-19 lockdown measures began, about half of the respondents reported no change in their sleep patterns, but around a third, 32.9%, reported decreased sleep. Another 29.8% reported sleeping more. In the analysis, the researchers found that any change in sleep was connected to self-reported mental health issues, though it was more strongly associated with decreased sleep.

"The results show that deviations from your typical sleep behavior may be associated with depression, anxiety and stress," said Siny Tsang, lead author on the study published in Frontiers in Neuroscience.

Tsang, a staff scientist with the WSU Elson S. Floyd College of Medicine, emphasized that this showed a connection, not a cause, but the study supports previous research that has found a two-way relationship between disrupted sleep patterns and poor mental health. In other words, when people don't sleep well, they are more likely to feel stress, anxiety and depression, and when they are dealing with those same problems, they are more likely to sleep less--and sometimes more--than the typical six to nine hours a night.

This study analyzes survey responses collected between March 26 and April 5, 2020 from participants in the Washington State Twin Registry. Since then, the same group has answered three more waves of survey questions. Researchers are particularly interested in studying twins, so they can investigate whether associations are mediated by genetic factors, shared environment, or both. The pandemic also offered an opportunity for a natural experiment to see how a stressful situation affects sleep amount and quality among individuals in the community, Tsang said.

The research relies on the self-reported perception of sleep length and quality, but the researcher said that when it comes to mental health, perception can matter more than the real amount of sleep.

"Even if your cell phone says you consistently sleep eight hours every day, you may feel that you slept less or slept poorly, and that may be linked to stressful or anxious feelings," Tsang said. "It may not matter whether or not the actual number has changed. It's how you are feeling that is associated with your mental health."

WSU researchers have also conducted twin-studies on COVID-19 lockdown effects on alcohol use and pandemic stress and exercise. These have all been initial studies taken at the early stages of the pandemic and associated social distancing measures. The scientists are still analyzing results of later surveys, but they are starting to see a common theme.

"A pattern that is consistent across these three studies is that people who reported change in physical exercise, alcohol use or sleep are more stressed, anxious and depressed than those who had said that they have had no change," Tsang said.

Ireland, June 17 2021: Popular video games have the potential to provide low-cost, easy access, effective and stigma-free support for some mental health issues, researchers at Lero, the Science Foundation Ireland Research Centre for Software, have found.

The team at Lero, a world leader in connected-health research, said video games could be used where conventional therapies are not available because of cost or location, or as an addition to traditional therapeutic treatments for depression or anxiety.

Lero researcher Dr Mark Campbell said there is mounting scientific evidence supporting the efficacy of commercial video games to improve mental health outcomes after the team reviewed existing academic research on the impact of video games on mental health issues, particularly depression and anxiety.

"It is worth considering commercial video games as a potential alternative option for the improvement of various aspects of mental health globally," he added.

Dr Campbell led a team attached to University of Limerick's Health Research Institute and Physical Education & Sport Sciences department to publish their latest research paper Gaming your mental health: A narrative review on mitigating depression and anxiety symptoms via commercial video games in academic journal JMIR Serious Games.

Dr Campbell said commercial video games are freely available or available for a one-time relative low cost and there are an estimated 2.7 billion video gamers worldwide.

"The overall accessibility and pervasiveness of commercial video games within modern society positions them as an invaluable means of reaching individuals with mental health disorders, irrespective of age and sex, and with limited access to mental health care, particularly relevant during the current COVID-19 pandemic," he said.

Lead author on the paper Magdalena Kowal of Lero and UL said their research was in the context of the financial and healthcare service burden of mental illness, affecting more than 14% of the world's population, with a significant proportion of people with mental health problems not receiving treatment.

"There is a heightened demand for accessible and cost-effective methods that prevent and facilitate coping with mental health illness. This demand has become exacerbated following the advent of the COVID-19 pandemic and subsequent increase in mental health disorders, depression and anxiety in particular," she said.

Magdalena Kowal said commercially available Virtual Reality (VR) video games have great potential in treating mental health issues also.

"These are well-suited for the implementation of cognitive behavioural techniques for the treatment of depression and anxiety disorders in the future. Given the immersive nature of VR technology and the controllability of the virtual environment, it could be particularly well-suited for use in exposure therapy," she added.

Singapore, 18 Jun 2021 - Scientists at Duke-NUS Medical School and National Heart Centre Singapore (NHCS), in collaboration with colleagues in Singapore and the UK, have shown that the human form of the signalling protein interleukin 11 (IL-11) has a damaging effect on human liver cells--overturning a prior hypothesis that it could help livers damaged by paracetamol poisoning. The finding, published last week in Science Translational Medicine, suggests that blocking IL-11 signalling could have a restorative effect.

Paracetamol, also called acetaminophen, is a widely available over-the-counter painkiller, and an overdose can lead to serious liver damage and even death. It is the most common pharmaceutical agent involved in toxic exposure in Singapore, while in the UK, 50,000 people a year show up at emergency departments with paracetamol poisoning. They can be treated with a drug called N-acetylcysteine if administered within eight hours of overdose. Any longer, however, and the only recourse may be a liver transplant.

To find treatments for the condition, scientists have been studying it in mice. Their investigations have shown that excessive doses of paracetamol deplete liver antioxidants. This leads to damage of mitochondrial proteins, triggering a cascade of events that lead to liver damage and liver cell death. Further studies showed that administration of anti-IL11 therapy in the form of an antibody drug not only reversed liver damage, but also supported liver regeneration and promoted survival in mice with liver injury. This led to the idea that anti-IL11 therapy could help treat humans with paracetamol poisoning.

"We recently found that IL-11 was actually detrimental for liver cell function in a fatty liver disease called non-alcoholic steatohepatitis (NASH)," said Assistant Professor Anissa Widjaja, from Duke-NUS' Cardiovascular and Metabolic Diseases (CVMD) Programme, the lead author of the study. "This made us want to look in more detail at what was happening in mouse models of paracetamol toxicity."

Employing an animal model conducted according to the National Advisory Committee for Laboratory Animal Research (NACLAR) guidelines, they found high serum levels of IL-11 in mice with paracetamol toxicity. Further investigations revealed that IL-11 was involved in activating pathways that led to liver cell death. Surprisingly, they found that mouse livers responded differently according to whether they were given human or mouse IL-11. The human form had a protective effect against liver damage while the mouse form caused liver cell death. When human IL-11 was administered in mice with paracetamol toxicity, it competed with the endogenous mouse IL-11, blocking its receptor. It was this blocking effect that protected against liver damage. Administering same-species IL-11 was damaging because it did not result in this competition and the resulting blocking effect.

"This means that IL-11 is actually a liver toxin," said Professor Stuart Cook, the senior author of the study, who is the Tanoto Foundation Professor of Cardiovascular Medicine at the SingHealth Duke-NUS Academic Medical Centre and Duke-NUS' CVMD Programme, and Senior Consultant at the Department of Cardiology at NHCS. "We found that blocking its cell receptors with an antibody can help the liver regenerate after it has been injured. This discovery could have implications for treating drug-induced liver failure, which can cause death if a liver transplant is not possible."

The study adds to the growing body of research on IL-11, led by Prof Cook, a leading expert who has dedicated years of study to this important signalling protein. In 2017, he co-founded Singapore-based Enleofen Bio as a spin-out from NHCS, SingHealth and Duke-NUS with the aim of developing first-in-class antibody therapeutics for the treatment of fibro-inflammatory human diseases. In 2019, Boehringer Ingelheim, a leading global pharmaceutical company in the treatment of fibrotic diseases and in therapeutic antibodies took an exclusive license to Enleofen's anti-IL11 platform.

Professor Patrick Casey, Senior Vice-Dean for Research at Duke-NUS, commented, "New insights from fundamental research enable scientists to not only test hypotheses, but also course-correct when the evidence overturns prior assumptions. Professor Cook and his team are among the leading experts on IL-11, and their latest findings yet again advance our understanding in this field of research."

The research team is now investigating whether IL-11 can stand in the way of the regeneration of other organs, like the kidneys, and whether it is involved in the loss of tissue function with advancing age.

Conservationists have long warned of the dangers associated with bears becoming habituated to life in urban areas. Yet, it appears the message hasn't gotten through to everyone.

News reports continue to cover seemingly similar situations -- a foraging bear enters a neighbourhood, easily finds high-value food and refuses to leave. The story often ends with conservation officers being forced to euthanize the animal for public safety purposes.

Now, a new study by sustainability researchers in the Irving K. Barber Faculty of Science uses computer modelling to look at the best strategies to reduce human-bear conflict.

"It happens all the time, and unfortunately, humans are almost always at fault," says study co-author Dr. Lael Parrott.

Looking to reduce the number of conflicts, Dr. Parrott and a team of researchers, including master's student Luke Crevier, built a computer model to simulate bears' journeys within a specific urban area.

Their goal was to find the best way to keep bears out.

Using the resort municipality of Whistler as their area of inquiry, the team partnered with Margo Supplies, a wildlife management technology solutions company based in High River, Alberta. Using agent-based computer modelling, researchers were able to simulate the movement of black bears in and around Whistler, identifying the potential attractants luring them in.

"Our model allows us to drop in large amounts of data, including the landscape's spatial characteristics, movement patterns collected from GPS tracking of real bears, and other important information to essentially create a virtual landscape," says Crevier.

The problem, he adds, is that bears are attracted to what researchers call anthropogenic food -- easily attainable food sources such as human garbage, berries or fruit.

"We were able to track the model bears as they moved through the landscape and interacted with different cells in the software that represented anthropogenic food, vegetation and human deterrents. The ability to input all of these proxies allowed us to better understand where they're roaming, why, and test different strategies within the simulation to find the most effective way to keep them out."

The study's findings reinforced the team's expectations that using attractant reduction and human deterrent strategies together was the most effective way to keep bears away. In cases where only one strategy could be applied, reducing attractants was the most effective.

"These results confirm that the most commonly used management strategies are indeed the most effective," explains Crevier. "What was really interesting was how the model allowed us to identify attractants that maybe otherwise wouldn't be considered -- like human garbage or large amounts of berries on private land within city limits."

A bear's intelligence and memory are largely the reasons why reducing the availability of anthropogenic food is considered more effective than reactive management strategies that aim to deter bears, when used alone.

"Using deterrents like bear bangers may be effective temporarily in that the bear will get frightened and run away, but they won't be gone for long," explains Dr. Parrott. "They'll remember being scared off, but their memories of the good meal will supersede their fear."

Though Whistler was selected as the study location because of the large number of black bears venturing into town, Crevier says this same type of modelling can be used for communities across Canada experiencing similar issues.

"What's cool about this model is it allows us to look at how different management strategies interact with each other, and this type of model can also be applied to better understand the movements of other large predators like cougars or wolves," he adds.

Dr. Parrott stresses it is important to learn how to co-exist with wildlife in a way that's safe for all -- including the animals. While some people may not think twice about a neighbourhood bear being destroyed, the practice has far-reaching implications.

"We know that bears who tend to come into communities are often juvenile or female bears with cubs, because the large males already have all the 'good spots' and have established their territories," she explains. "That's cause for concern because it means the females are teaching their cubs techniques to access anthropogenic food. It also means these are the bears who are most often put down, so we're selectively eliminating a particular part of their population.

The results of this study and similar agent-based models give conservationists another tool in the toolbox to help communities reduce the number of bears entering urban areas, ultimately reducing the number of bears destroyed, and putting the brakes on these problematic trends."

Osaka, Japan - Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and can progress to liver cirrhosis, liver failure or cancer. Currently, nonalcoholic steatohepatitis (NASH) diagnosis requires an invasive liver biopsy which can lead to procedural complications. Now, researchers at Osaka University working with international collaborators have identified a noninvasive biomarker that can identify patients at risk of NAFLD complications using a simple blood test.

Owing to the increasing prevalence of obesity worldwide, as many as one in four humans has NAFLD. Unrelated to alcohol intake by definition, the early stage - NAFL (nonalcoholic fatty liver) - is asymptomatic. Unfortunately, progression to NASH incurs inflammatory damage and eventually liver fibrosis occurs; this may further lead to adverse outcomes. Liver deterioration can be deferred by lifestyle modifications comprising diet and exercise; therefore, early diagnosis is key.

Diagnostic confirmation requires a needle biopsy; however, the disadvantages include expense and variability in sampling and interpretation. The research team investigated whether they could devise a diagnostic screen using transcriptomics, the emerging science of analyzing the 'transcriptome,' the entire array of an organism's messenger RNA molecules derived from expression of the genome.

"We obtained liver tissue from over 300 Japanese and European patients with biopsy-proven NAFLD and performed global RNA sequencing," co-first author Kazuhiro Kozumi explains. "Remarkably, from the protein patterns we could not only distinguish NASH from NAFL, but also determine the molecular hallmarks of NASH pathology. Specifically, we pinpointed that levels of thrombospondin-2 (TSP-2), a glycoprotein encoded by the THBS2 gene, were increased in both NASH and advanced fibrosis."

The researchers established that THBS2 expression in liver cells paralleled the clinical indicators conventionally used to categorize the pathological changes including serum enzyme levels, NAFLD Activity Score and NAFLD Fibrosis Score. "Serum levels of TSP-2 in NAFLD patients were significantly higher in NASH than in NAFL," co-first author Takahiro Kodama claims, "and, interestingly, the increase tallied with the degree of fibrosis."

Corresponding author Tetsuo Takehara explains the clinical relevance of their research findings. "Both hepatic THBS2 gene expression in the liver and serum protein levels of TSP-2 can diagnose cases of NASH and/or advanced fibrosis. A simple and convenient blood test can provide a clinically useful early warning system for complications of NAFLD and inform lifestyle modifications or other interventions that may alter the course of the disease and improve the prognosis."

Although plexiglass barriers are seemingly everywhere these days -- between grocery store lanes, around restaurant tables and towering above office cubicles -- they are an imperfect solution to blocking virus transmission.

Instead of capturing virus-laden respiratory droplets and aerosols, plexiglass dividers merely deflect droplets, causing them to bounce away but remain in the air. To enhance the function of these protective barriers, Northwestern University researchers have developed a new transparent material that can capture droplets and aerosols, effectively removing them from air.

The material is a clear, viscous liquid that can be painted onto any surface, including plastic, glass, wood, metal, stainless steel, concrete and textiles. When droplets collide with the coated surface, they stick to it, get absorbed and dry up. The coating also is compatible with antiviral and antimicrobial materials, so sanitizing agents, such as copper, could be added to the formula.

"Droplets collide with indoor surfaces all the time," said Northwestern's Jiaxing Huang, the study's senior author. "Right now, plexiglass dividers are deviating devices; they deflect droplets. If a surface could actually trap droplets, then every single droplet effectively removed from indoor air would be a successful elimination of a potential source of transmission."

The research will be published Wednesday (June 16) in the journal Chem. In the study, the researchers found that even when they bombarded surfaces with aerosol droplets -- at orders of magnitude higher concentration than typical for an indoor environment -- the coated surfaces still captured three times more aerosol droplets than uncoated surfaces.

Huang is a professor of materials science and engineering in Northwestern's McCormick School of Engineering. Zhilong Yu, Murak Kadir and Yihan Liu -- all members of Huang's laboratory -- co-authored the paper. The team embarked on this project during the stay-at-home order at the beginning of the pandemic.

The main ingredient in the Northwestern team's material is a polyelectrolyte polymer that is commonly used in a wide variety of cosmetic products. When applied with a blade or brush, the resulting formula yields uniform and conformal coatings on a broad range of indoor surfaces without damaging or discoloring the original material.

Huang's team found the surfaces also remained transparent and haze-free even when doused with droplets. In other words, the surfaces did not appear filthy or soiled after being showered with droplets. If used on plexiglass barriers, those coated barriers would not need to be cleaned more frequently than uncoated barriers.

Most infectious diseases spread through respiratory droplets and aerosols, which humans release constantly when talking, laughing, singing and exhaling. Because the coating is so versatile, Huang imagines that it could be used on plexiglass barriers and face shields as well as on no-touch or low-touch surfaces, such as walls or even curtains, to eliminate those droplets from the air.

"There are massive areas of indoor surfaces that are barely touched by people or pets. If we repurposed these 'idling' surfaces to capture respiratory droplets, then they could become functional 'devices' to help reduce air-borne transmission of infectious diseases," he said. "Surface-trapped pathogens can then be readily inactivated over time, which can be accelerated by pre-applied sanitization ingredients. They also can be removed during routine cleaning."

While Huang says that face masks are an irreplaceable public health tool to help preventing the spread of infectious droplets, he believes that trapping droplets on surfaces could be another effective tool.

"In a computer game, for example, you don't want to walk into a battlefield with only one piece of armor," he said. "It makes sense to leverage multiple layers of defense."

New York, NY (June 16, 2021) -- Immune cells that normally repair tissues in the body can be fooled by tumors when cancer starts forming in the lungs and instead help the tumor become invasive, according to a surprising discovery reported by Mount Sinai scientists in Nature in June.

The researchers found that early-stage lung cancer tumors coopt the immune cells, known as tissue-resident macrophages, to help invade lung tissue. They also mapped out the process, or program, of how the macrophages allows a tumor to hurt the tissues the macrophage normally repairs. This process allows the tumor to hide from the immune system and proliferate into later, deadly stages of cancer.

Macrophages play a key role in shaping the tumor microenvironment, the ecosystem that surrounds tumors in the body. By investigating this microenvironment, researchers can find key players that drive tumor growth that can be tested as targets for immunotherapy. But modifying macrophages therapeutically has proven difficult.

In this study, scientists studied tissue samples from lung cancer tumors and surrounding lung tissue in 35 patients to see the role of macrophages in the development of the tumors.

The study's lead author, Miriam Merad, MD, PhD, Director of the Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai, and a multidisciplinary team of thoracic surgeons, pathologists, and medical oncologists within the Institute of Thoracic Oncology devised a comprehensive study that began when patients went into surgery to have cancerous lesions removed. The patients' lung tumor samples, samples of surrounding healthy lung tissue, and blood samples were immediately analyzed on a cellular level at Mount Sinai's Human Immune Monitoring Center to map out the immune system components they contained.

Researchers identified the macrophages at play in the early development of lung cancer, identifying a potential target for future drug development. They also found that the process that allows the macrophages to help tumors invade lung tissues is present in mice as well, which will allow them to manipulate the macrophages in future mouse models knowing that the manipulation is relevant to humans.

Half of all early-stage lung cancers relapse, and once they do and reach later stages, it is deadly and irreversible. Knowing how to attack the cancer at an early stage could have huge impacts on the number of patients relapsing and their overall survival.

"These findings are very important for Mount Sinai in the future as we have a very strong lung cancer screening program that identifies patients with early lung cancer lesions before they become fully invasive," said Dr. Merad, who is also the Director of the Human Immune Monitoring Center and a member of the Institute of Thoracic Oncology and The Tisch Cancer Institute at Mount Sinai. "These findings will help devise immunoprevention strategies to prevent tumor progression in patients at risk by reprogramming macrophages and killing the tumor without surgery."

It sounds like a plot from a Quentin Tarantino movie -- something sets off natural killers and sends them on a killing spree.

But instead of characters in a movie, these natural killers are part of the human immune system and their targets are breast cancer tumor cells. The triggers are fusion proteins developed by Clemson University researchers that link the two together.

"The idea is to use this bifunctional protein to bridge the natural killer cells and breast cancer tumor cells," said Yanzhang (Charlie) Wei, a professor in the College of Science's Department of Biological Sciences. "If the two cells are brought close enough together through this receptor ligand connection, the natural killer cells can release what I call killing machinery to have the tumor cells killed."

It's a novel approach to developing breast cancer-specific immunotherapy and could lead to new treatment options for the world's most common cancer.

About one in eight women in the U.S. and one in 1,000 men will develop invasive breast cancer during their lives. Breast cancer is the second leading cause of cancer death in women in the U.S., trailing only lung cancer. The American Cancer Society estimates that about 43,600 U.S. women will die from the disease this year.

Immunotherapy harnesses the power of the body's immune system to kill cancer cells.

"Very simply, cancer is uncontrolled cell growth. Some cells will become abnormal and have the potential to become cancer," Wei said. "The immune system can recognize these abnormal cells and destroy them before they become cancer cells. Unfortunately for those who develop cancer, the immune system is not working very well because of gene mutations and environmental factors. The result is that the cancer cells won the fight between the immune system and the tumors."

Most breast cancer targeting therapies target one of three receptors: estrogen receptors, progesterone receptors or epidermal growth factor receptors. However, up to 20 percent of breast cancers do not express these receptors. These cancers are known as triple-negative breast cancer. Triple-negative is the most lethal subtype of breast cancer because of high heterogeneity, high metastasis frequency, early relapse after standard chemotherapy and lack of efficient treatment options.

In this novel research, Wei and his researchers targeted prolactin receptors. Prolactin is a natural hormone in the body and plays a role in breast growth and milk production during breastfeeding. Breast cancer cells overexpress prolactin receptors.

"When people are diagnosed with breast cancer, and it's called triple-negative, it is not good news," Wei said. "This has the potential to give patients another option."

Over 90 percent of breast cancer cells express prolactin receptors, including triple-negative breast cancer cells.

Wei and his team developed a bifunctional protein. One part is a mutated form of prolactin that can still bind to the prolactin receptor but blocks signal transduction that would promote tumor growth. The other part is an extracellular domain of major histocompatibility complex class I chain-related protein (MICA).

When the MICA binds to the prolactin receptor, it activates the natural killer cells.

"One of the things tumor cells do is to inhibit natural killer cell activation, so we use these artificial bifunctional proteins to connect natural killer cells and activate them to enhance the killing of the breast cancer cells without increased cytotoxicity," Wei said.

Wei is now seeking funding for an animal model study to confirm the results.

One big question is whether the bifunctional protein will bring natural killer cells to healthy cells in the body that also express prolactin receptors and kill them, too, causing severe side effects.

If the animal model studies are successful, the potential new treatment could move to human clinical trials.

"If we had the funding now and everything is what we expected in the animal model study, we could be in clinical trials in five or six years," he said. Wei said he expects the conversion from in-vitro and animal studies to clinical trials to be easier for this potential immunotherapy than others in the past because the protein created by the Clemson researchers uses human natural killer cells and breast cancer cells.

Developing new immunotherapy for cancer is nothing new to Wei. His research combining tumor cells with dendritic cells, an important part of the body's adaptive immune system, led to a dendritoma vaccine that proved effective in melanoma, renal cell carcinoma and neuroblastoma patients. The vaccine was patented and licensed to three biotech companies. Two companies are still pursuing the vaccine therapy or related therapy.

"It is my dream that someday we can create a group of these bifunctional proteins that could be used for other cancers by shifting the target molecule. We'd have the one part of the bifunctional protein that targets natural killer cells. The other part would target other cancer types that have unique markers," Wei said.

A group of researchers from the University of Jyvaskyla and Stanford University were part of an expedition to French Guiana to study tropical frogs in the Amazon. Various amphibian species of this region use ephemeral pools of water as their nurseries, and display unique preferences for specific physical and chemical characteristics. Despite species-specific preferences, researchers were surprised to find tadpoles of the dyeing poison frog surviving in an incredible range of both chemical (pH 3-8) and vertical (0-20 m in height) deposition sites. This research was published in the journal Ecology and Evolution in June 2021.

Neotropical frogs are special because, unlike species in temperate regions, many tropical frogs lay their eggs on the ground. This becomes an issue once tadpoles (who breathe using gills, like fish) hatch onto the forest floor, but poison frogs have developed innovative solutions to get their tadpoles to suitable aquatic habitats: piggy-back rides. In many of these terrestrial-breeding species, fathers will transport recently hatched tadpoles from the ground to pools of water formed by vegetation (like fallen trees or bromeliads).

PhD researcher Chloe Fouilloux and team leaders Dr. Bibiana Rojas from University of Jyvaskyla, Finland and Dr. Andrius Pasukonis from Stanford University wanted to know if different species (Dendrobates tinctorius, Allobates femoralis, and Osteocephalus oophagus) considered a combination of biological, physical, or chemical characteristics of pools when choosing nurseries for their young.

To find that out, this group of eight researchers sampled more than 100 pools over two years, which involved searching for suitable deposition sites that ranged from the ground to over 20 meter in vertical height (reached by climbing trees).

Of the three species, range and tolerance of D. tinctorius (dyeing poison frog) tadpoles was beyond what any of the researchers imagined physiologically possible: healthy tadpoles were found in a range of pools with a pH of around 3 to a pH of 8, which represents a 100,000x change of hydrogen ion concentration; in other words, these tadpoles were successfully developing in pools of what is chemically more acidic than orange juice to pools that have similar ionic concentrations to sea water!

The deposition choices of dyeing poison frogs confused researchers in other ways, too: tadpoles of this species are aggressive cannibals, which is why they are usually found to occur in low densities (1-2 tadpoles) per pool.

"However, in this study, we found several instances of more than 10 tadpoles of this species coexisting in the same nursery. The reason why fathers would deposit so many cannibals within the same pool, or if cannibalism occurs within these special pools, has yet to be tested", says PhD researcher Chloe Fouilloux from University of Jyväskylä.

Healthier males transporting their tadpoles to more suitable conditions?

From a parental perspective, dyeing poison frog fathers were found to carry their tadpoles more than 20 meters above the forest floor: for a frog that is about 4 centimeter long, 20 meters is 500 times their body length. In human terms, this physical feat would be equivalent to having a 1.65 meter person climbing up a giant (non-existent, obviously) tree of about 825 meters!

But why do fathers sometimes carry their tadpoles one meter away from where they hatched, and other times transport them to the tops of trees?

When looking at the chemical and biological trends, it appears that more biologically "comfortable" nurseries are found higher in trees. One possible explanation for this finding is that healthier males are able to invest more energy in transporting their tadpoles to more suitable conditions, but this is something that would need to be investigated in the future. Ultimately, there remains a lot to be learnt about the physiology and parental care of these animals; the degree of chemical flexibility found in these tadpoles is extremely unusual, and the secret underlying their resilience remains unknown.

"This work helps highlighting the amazing diversity observed between and among species in the wild: parents from different species prioritise unique characteristics when choosing pools to raise their offspring, which shapes both how species interact with each other and how they specialize in occupying different parts of the environment", states Dr. Bibiana Rojas from University of Jyväskylä.

This variation opens the door to future research that explores how species influence each other and how pool choice by parents affects tadpole development and survival.

Chemokine receptors, located at the surface of many immune cells, play an important role in their function. Chemokines are small proteins that bind to these receptors and control the movement and behaviour of white blood cells. However, despite the importance of this family of receptors, their activation mechanism remains poorly understood. In Switzerland, a research consortium from the University of Geneva (UNIGE), the Biozentrum of the University of Basel, and the Paul Scherrer Institute (PSI) in Villigen has succeeded in decoding the activation mechanism of the CCR5 receptor, a member of this family implicated in several diseases such as HIV/AIDS, cancer, and the respiratory complications of COVID-19. This discovery represents an important step in the understanding of chemokine receptor biology, providing valuable insights for improving new drugs that this important family of receptors. This work can be found in the journal Science Advances.

The CCR5 receptor plays a major role in inflammation and immune defence, and has long been an important target for anti-HIV drugs. "Research on CCR5 began almost 25 years ago as part of the fight against AIDS", explains Stephan Grzesiek, a professor at the Biozentrum of the University of Basel, who co-directed this work with Professor Oliver Hartley of the Department of Pathology and Immunology at UNIGE Faculty of Medicine, and colleagues from the Paul Scherrer Institute (PSI). "It is indeed fundamental to the HIV infection mechanism, but also seems to be very important in many other pathological processes, notably in cancers and inflammatory diseases. However, in order to better exploit it for therapeutic purposes, we needed to understand, at an atomic level, how activation through its binding to chemokines works."

Chemokines are small signalling molecules that play a central role in the circulation and activation of immune cells. By binding to receptors on the membrane of white blood cells, they act as guides, ensuring that the cells reach the right place at the right time, to both maintain the immune system and respond to infection or injury. But how is the receptor able to sense the docking of a chemokine at the outside the cell? And how is this activation message transmitted to the inside of the cell so that it can respond?

Visualising atomic structures in 3D

Until now, the study of this phenomenon has been hampered by the difficulty of observing the 3D structures of the receptors when bound to the molecules that activate them. To this end, the Basel team, which specialises in structural biology, used cryo-electron microscopy tools that make it possible to preserve and observe the structure of the smallest elements of living organisms. "However, in order to understand the entire process, it is necessary to make use of engineered chemokines that bind to receptors more stably than the natural ones", says Oliver Hartley. "For this, we were able to exploit the molecules that we had discovered in the course of our HIV drug research." And indeed, some of these variants over-activate the receptor while others block them entirely.

The right key to fit in the lock

The receptor, which is embedded in the cell membrane, works like a "lock and key" mechanism. A specific part of the chemokine structure must fit into the CCR5 lock to activate a change in the structure of the receptor, which then lets it trigger the activation and migration of white blood cells. "The activation capacity of chemokines is determined by certain amino acids (protein building blocks) that must arrange themselves in a specific pattern. If this part of the chemokine adopts a straight shape, it succeeds in activating the receptor. But if the amino acids are changed, the molecule adopts a slightly different shape which, although it maintains a very strong bond with the receptor, prevents its activation", explains Oliver Hartley. These small changes thus make the difference between receptor activators and inhibitors.

Better-targeted and therefore more effective drugs

Despite an almost identical architecture, minute structural differences between engineered chemokines determine their ability to activate or inhibit the receptor. A detailed understanding of this mechanism will allow for the improvement of drugs by developing new compounds capable of fine-tuning the the immune system.

Research published today in the Journal of General Virology has identified missed cases of SARS-CoV-2 by retrospective testing of throat swabs.

Researchers at the University of Nottingham screened 1,660 routine diagnostic specimens which had been collected at a Nottingham hospital between 2 January and 11 March 2020 and tested for SARS-CoV-2 by PCR. At this stage of the pandemic, there was very little COVID-19 testing available in hospitals, and to qualify patients had to meet a strict criterion, including recent travel to certain countries in Asia or contact with a known positive case.

Three previously unidentified cases of SARS-CoV-2 infection were identified by the retrospective screening, including one from a 75-year-old female whose positive swab was collected on 21 February 2020. This patient, referred to as Patient 1, died on 3 March; two days before the first official death from COVID-19 was recorded in the UK. Patient 1 had not recently travelled abroad or been in contact with anyone known to have COVID-19 and so did not qualify for a PCR test at the time. In addition to being the first death, the researchers believe that Patient 1 is also the earliest described case of community transmission in the UK.

The further newly-identified cases occurred in a 64-year-old male and a 66-year-old male, both of whom showed signs of chest infections, and both of whom recovered. The samples were collected on 2 March and 8 March 2020 respectively. International travel was only removed as an essential criterion for a SARS-CoV-2 test on 12 March 2020.

The research group collaborated with the COVID-19 Genomics UK Consortium (COG-UK) to sequence the SARS-CoV-2 isolates collected from the swabs used in the study, and found evidence of community transmission in Nottingham as early as February 2020. Through this genome sequence data, the group identified multiple introductions of the virus into Nottingham during late February and the month of March, many of which were a distinct lineage of the virus which dominated early phases of the outbreak within the region.

Based on the findings, the researchers suggest that testing should have been made available to hospital patients with compatible symptoms but no travel history earlier in the pandemic response.

The full research article, 'Retrospective screening of routine respiratory samples revealed undetected community transmission and missed intervention opportunities for SARS-CoV-2 in the United Kingdom' is free to read in the Journal of General Virology (doi: 10.1099/jgv.0.001595).

Tokyo, Japan - Colloids--mixtures of particles made from one substance, dispersed in another substance--crop up in numerous areas of everyday life, including cosmetics, food and dyes, and form important systems within our bodies. Understanding the behavior of colloids therefore has wide-ranging implications, yet investigating the rotation of spherical particles has been challenging. Now, an international team including researchers from The University of Tokyo Institute of Industrial Science has created particles with an off-center core or "eye" that can be tracked using microscopy. Their findings are published in Physical Review X.

Particles suspended in a liquid move from one place to another as a result of Brownian motion, which can be easily detected with a microscope. However, these particles also rotate, which is much more difficult to see if they are spherical.

The researchers overcame this by creating particles made from two different colors of the same material. The core sphere--which they call the eye--is set off-center at the surface of the particle. It provides a point that can be followed under a microscope to determine the orientation changes as the particle rotates.

"The rotation of a colloidal particle tells us about the surrounding hydrodynamics--the motion of the suspending liquid--and the contact forces, such as friction. However, to get the full picture in a dense suspension, all of the particles must be tracked at once," explains study corresponding author Professor Hajime Tanaka. "As well as providing a point to track over time, the density and refractive index of our particles can be matched so that the necessary 3D images can be acquired."

By tracking a dense suspension of charged particles forming a colloidal crystal--which has an ordered arrangement of particles--it was found that the rotation of neighboring spheres was coupled and moved in opposite directions, like meshed gears.

In addition, a system with uncharged particles showed that there was a relationship between local crystallinity--the ordering in the immediate surroundings--and the rotational diffusivity, which describes the process of the orientation regaining equilibrium.

The researchers also observed "stick-slip" rotational motion between particles that make contact, where a large neighbor could stop the motion of a particle through friction.

"Our system has provided much-needed insight into hydrodynamic and frictional coupling in very dense colloids," says other corresponding author Professor Roel Dullens. "We expect our findings to have a significant impact on the design of industrial processes involving colloids, as well as on the understanding of biological processes."

ENVIRONMENT Diesel-polluted soil from now defunct military outposts in Greenland can be remediated using naturally occurring soil bacteria according to an extensive five-year experiment in Mestersvig, East Greenland, to which the University of Copenhagen has contributed.

Mothballed military outposts and stacks of rusting oil drums aren't an unusual sight in Greenland. Indeed, there are about 30 abandoned military installations in Greenland where diesel, once used to keep generators and other machinery running, may have seeped into the ground.

This is the case with Station 9117 Mestersvig, an abandoned military airfield on the coast of East Greenland. Forty tons of diesel fuel contaminated the soil at Mestersvig. As a result, Danish Defence and NIRAS, an engineering company, initiated an experiment to optimize the conditions for naturally occurring soil bacteria to break down soil contaminants.

Bacterial populations and the biodegradation of diesel compounds were continuously monitored by scientists from the University of Copenhagen's Department of Plant and Environmental Sciences and the Geological Survey of Denmark and Greenland (GEUS). After five years, the researchers found that the bacteria had bioremediated as much as 82 percent of the 5,000 tons of contaminated soil.

"The bacteria have proven extremely effective at breaking down the vast majority of the diesel compounds. As such, this natural method can be applied elsewhere in the Arctic, where it would otherwise be incredibly resource-intensive to remove contaminated soil by way of aircraft or ship," explains Professor Jan H. Christensen of the University of Copenhagen's Department of Plant and Environmental Sciences. Christensen has been responsible for analyzing the chemical fingerprints in the diesel-contaminated soil.

Never thoroughly studied and documented

The method, known as landfarming, is most often associated with warmer climates around the world. Prior to this project, landfarming had never been tested on a large scale under Arctic conditions. Nor had the method ever been as thoroughly studied and documented as in this experiment.

Landfarming works by distributing contaminated soil in a thin layer, which is then ploughed, fertilized and oxygenated every year to optimize conditions for bacteria to degrade hydrocarbons.

Watering the field

Landfarming works by distributing contaminated soil in a thin layer, which is then ploughed, fertilized and oxygenated every year to optimize conditions for bacteria to degrade hydrocarbons. Photo: Anders Christian Vestergaard

According to Anders Risbjerg Johnsen,a microbiologist and senior research scientist at GEUS, the landfarming work resulted in regular explosions of soil bacteria, which he was able to keep track of from Denmark using advanced samples of soil bacteria.

"Having a wide variety of hydrocarbon-degrading bacteria is essential as the 10,000 various diesel compounds contaminating the soil require different degradation pathways to be broken down," explains Johnsen.

Ability to clean up abandoned bases

Warmer "summer" temperatures of between 0 and 10 degrees only last about three months in Mestersvig. For the rest of the year, the soil is frozen. Thus, it was uncertain whether Greenlandic soil bacteria could break down the leaked diesel as effectively as bacteria in warmer conditions.

Fortunately, the study demonstrated that the bacteria could easily degrade diesel contaminants in the soil, despite the frigid temperatures. In the future, the researchers hope that naturally occurring bacteria can be used to remediate contamination in the Greenlandic environment at roughly 30 other deserted installations. The lack of infrastructure has made it extremely expensive and resource-intensive to move soil around as, for example, might be done in Denmark.

"Some degree of diesel pollution can be found at nearly every Arctic site where there was once a weather station, research station or military installation. It is likely that the approach used in our experiments can be used at many of these sites," say Jan H. Christensen and Anders Risbjerg Johnsen.

The researchers are returning to Greenland this year to conduct new studies on the experiment. They hope to find that the bacteria have successfully degraded all remaining diesel contamination.