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None of the mutations currently documented in the SARS-CoV-2 virus appear to increase its transmissibility in humans, according to a study led by UCL researchers.

The analysis of virus genomes from over 46,000 people with COVID-19 from 99 countries is published today in Nature Communications.

First and corresponding author Dr Lucy van Dorp (UCL Genetics Institute) said: "The number of SARS-CoV-2 genomes being generated for scientific research is staggering. We realised early on in the pandemic that we needed new approaches to analyse enormous amounts of data in close to real time to flag new mutations in the virus that could affect its transmission or symptom severity.

"Fortunately, we found that none of these mutations are making COVID-19 spread more rapidly, but we need to remain vigilant and continue monitoring new mutations, particularly as vaccines get rolled out."

Coronaviruses like SARS-CoV-2 are a type of RNA virus, which can all develop mutations in three different ways: by mistake from copying errors during viral replication, through interactions with other viruses infecting the same cell (recombination or reassortment), or they can be induced by host RNA modification systems which are part of host immunity (e.g. a person's own immune system).

Most mutations are neutral, while others can be advantageous or detrimental to the virus. Both neutral and advantageous mutations can become more common as they get passed down to descendant viruses.

The research team from UCL, Cirad and the Université de la Réunion, and the University of Oxford, analysed a global dataset of virus genomes from 46,723 people with COVID-19, collected up until the end of July 2020.

The researchers have so far identified 12,706 mutations in SARS-CoV-2, the virus causing COVID-19. For 398 of the mutations, there is strong evidence that they have occurred repeatedly and independently. Of those, the researchers honed in on 185 mutations which have occurred at least three times independently during the course of the pandemic.

To test if the mutations increase transmission of the virus, the researchers modelled the virus's evolutionary tree, and analysed whether a particular mutation was becoming increasingly common within a given branch of the evolutionary tree - that is, testing whether, after a mutation first develops in a virus, descendants of that virus outperform closely-related SARS-CoV-2 viruses without that particular mutation.

The researchers found no evidence that any of the common mutations are increasing the virus's transmissibility. Instead, they found most common mutations are neutral for the virus. This includes one mutation in the virus spike protein called D614G, which has been widely reported as being a common mutation that may make the virus more transmissible. The new evidence finds that this mutation is in fact not associated with significantly increasing transmission.

The researchers found that most of the common mutations appear to have been induced by the human immune system, rather than being the result of the virus adapting to its novel human host. This situation is in contrast with another analysis by the same team of what happened when SARS-CoV-2 later jumped from humans into farmed minks.

Dr van Dorp said: "When we analysed virus genomes sourced from mink, we were amazed to see the same mutation appearing over and again in different mink farms, despite those same mutations having rarely been observed in humans before."

Lead author Professor Francois Balloux (UCL Genetics Institute) added: "We may well have missed this period of early adaptation of the virus in humans. We previously estimated SARS-CoV-2 jumped into humans in October or November 2019, but the first genomes we have date to the very end of December. By that time, viral mutations crucial for the transmissibility in humans may have emerged and become fixed, precluding us from studying them."

It is only to be expected that a virus will mutate and eventually diverge into different lineages as it becomes more common in human populations, but this does not necessarily imply that any lineages will emerge that are more transmissible or harmful.

Dr van Dorp said: "The virus seems well adapted to transmission among humans, and it may have already reached its fitness optimum in the human host by the time it was identified as a novel virus."

The researchers caution that the imminent introduction of vaccines is likely to exert new selective pressures on the virus to escape recognition by the human immune system. This may lead to the emergence of vaccine-escape mutants. The team stressed that the computational framework they developed should prove useful for the timely identification of possible vaccine-escape mutations.

Professor Balloux concluded: "The news on the vaccine front looks great. The virus may well acquire vaccine-escape mutations in the future, but we're confident we'll be able to flag them up promptly, which would allow updating the vaccines in time if required."

Bottom Line: The U.S. Preventive Services Task Force (USPSTF) recommends offering or referring adults with cardiovascular disease risk factors to behavioral counseling interventions to promote a healthy diet and physical activity. Adults who adhere to national guidelines for a healthy diet and physical activity have a lower risk of cardiovascular disease and death than those who do not. The USPSTF routinely makes recommendations about the effectiveness of preventive care services. This statement is mostly consistent with its 2014 recommendation, although it no longer includes adults with impaired glucose tolerance or type 2 diabetes because this population is now included in a separate USPSTF recommendation.

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

(doi:10.1001/jama.2020.21749)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Note: More information about the U.S. Preventive Services Task Force, its process, and its recommendations can be found on the newsroom page of its website.

Sophia Antipolis, 24 November 2020: Cardiovascular disease remains the leading cause of mortality in Europe, and World Health Organization (WHO) heart disease goals will not be achieved by 2025 unless urgent action is taken. That is the finding of a European Society of Cardiology (ESC) report published today.

"Cardiovascular Realities 2020" is a compendium of the latest statistics on cardiovascular disease (CVD) in Europe.1 The document provides numbers of people with heart conditions, death rates, and levels of risk factors including obesity, diabetes, and high blood pressure.

Comparisons of data over time show alarming trends which suggest it is unlikely that WHO noncommunicable disease (NCD) targets for global cardiovascular health will be met.2

Dr. Hans Henri Kluge, WHO Regional Director for Europe said: "We cannot be complacent. Healthcare disruption during the COVID-19 pandemic highlighted the importance of maintaining services to prevent and treat cardiovascular disease. Access to essential CVD medicines and technologies varies widely across Europe and more work is needed to achieve universal health coverage. I look forward to collaborating with European cardiologists and policymakers to tackle these issues."

In Europe, cardiovascular disease accounts for 47% and 39% of all deaths in women and men, respectively. The WHO has called for a 25% relative reduction in premature mortality from CVD by 2025 (compared to 2010). Today's report shows that in high-income countries, premature death from CVD (below age 70 years) has declined by 9% in women and 11% in men since 2010. But in middle-income countries, rates have fallen by just 8% in women and 2% in men, making it improbable that the target will be reached.

Major risk factors for CVD including obesity and diabetes are becoming more prevalent. More than one in five European adults are obese.3 The WHO has called for a halt to rises in both diabetes and obesity (between 2010 and 2025). However, from 2010 to 2016, the prevalence of obesity increased from 20.4% to 22.8% in women and from 19.2% to 22.3% in men - unless these trends are reversed, the goal will not be achieved.

Meanwhile, the median prevalence of diabetes increased from 3.2% in 2010 to 4.2% in 2015 - a rise of 28.5%. Middle-income countries suffered most: here the prevalence of diabetes increased by 37% (compared with 12.4% in high-income countries). These statistics make it unlikely that the WHO diabetes target will be met, particularly in middle-income countries.

High blood pressure is the leading global cause of premature death, accounting for almost 10 million deaths in 2015, of which 4.9 million were due to ischaemic heart disease and 3.5 million were due to stroke.4 The WHO target is a 25% relative reduction in high blood pressure between 2010 and 2025. The median prevalence of elevated blood pressure in Europe declined by 8.4% for women and by 5% for men in 2010 to 2015, making it unlikely that the target will be met unless these trends change.

Despite the immense burden of CVD, it does not receive the attention that decision-makers give to other diseases. This is why the ESC is calling for the development of national strategies covering all aspects of cardiovascular health: prevention, detection, treatment, and rehabilitation - this action is essential to meet the WHO's targets. Today's report enables local policymakers to take stock of their country's performance and identify areas demanding greater attention.

ESC President Professor Stephan Achenbach said: "Improvements in treatment and management of heart disease and stroke are being offset by a growing and ageing population, alongside worsening epidemics of obesity and type 2 diabetes. We must make sure that everyone has access to guideline-directed cardiovascular care and importantly, unhealthy lifestyles including poor diet and lack of physical activity must be addressed. Preventing an even greater burden of heart disease and stroke requires a major effort by a broad coalition of stakeholders: join us in the effort."

New Rochelle, NY, November 23, 2020--During the COVID-19 pandemic, most science and medical faculty began working from home, with women reporting a significant decrease in manuscript submissions. Women also report providing 77.6% of the childcare themselves, compared to 61.3% for men, according to the Journal of Women's Health. Click here (http://doi.org/10.1089/jwh.2020.8710) to read the article now.

A study of faculty in science, technology, engineering, mathematics, and medicine (STEMM) found that those individuals with children younger than 6 years worked significantly fewer hours after the COVID-19 pandemic. Women reported a significant decrease in first- and co-author manuscript submissions, whereas no significant differences in productivity were reported by men.

"Overall, significant disparities were observed in academic productivity by gender and child age during COVID-19 'stay-at-home' orders and, if confirmed by further research, should be considered by academic institutions and funding agencies when making decisions regarding funding, hiring, promotion, and tenure," state Rebecca Krukowski, PhD, University of Tennessee Health Science Center, and coauthors.

"The COVID-19 pandemic has forced many STEMM faculty to work from home and, especially when young children are in the home, has put a strain on work hours. Publishing is crucial when seeking grant support for research, looking for a job, and seeking promotion and tenure," says Journal of Women's Health Editor-in-Chief Susan G. Kornstein, MD, Executive Director of the Virginia Commonwealth University Institute for Women's Health, Richmond, VA.

The correlation between the high concentration of fine particles and the severity of influenza waves is well known to epidemiologists. An interdisciplinary team from the University of Geneva (UNIGE) and the ETH Zürich spin-off Meteodat investigated possible interactions between acutely elevated levels of fine particulate matter and the virulence of the coronavirus disease. Their results, published in the journal Earth Systems and Environment, suggest that high concentrations of particles less than 2.5 micrometers in size may modulate, or even amplify, the waves of SARS-CoV-2 contamination and explain in part the particular profile of the COVID-19 pandemic. The increase in fine particles is generally favored by air temperature inversions, characterized by fog situations, or by Saharan dust intrusions. The study provides preventive measures related to air pollution to limit future outbreaks of morbidity and mortality due to the coronavirus.

Epidemiologists widely agree that there is a correlation between acute and locally elevated concentrations of fine particles and the severity of influenza waves. «We have investigated whether such a link also exists with the virulence of COVID-19 disease,» says Mario Rohrer, researcher at the Institute for Environmental Sciences of the Faculty of Sciences of UNIGE and director of Meteodat.

A surprising time lag

COVID-19 studies conducted in Italy and France suggest that SARS-CoV-2 was already present in Europe at the end of 2019, while the sharp increase in morbidity and mortality was only recorded in spring 2020 in Paris and London. «This time lag is surprising, but also suggests that something else than just the mere interaction of people may promote the transmission of the virus, and particularly the severity of the infection,» says Mario Rohrer. His research team has been able to show that these increases in cases followed phases where the levels of fine particles in the air were higher.

The team made similar observations in the Swiss canton of Ticino, where fine-particle pollution increased sharply during a period of shallow fog on the Magadino plain and the Sotto Ceneri, observed at the end of February 2020. «Shortly afterwards, an explosive increase in hospital admissions due to COVID-19 was recorded in Ticino. The fact that a large carnival event with some 150,000 visitors took place at the same time probably had an additional impact on the spread of the virus,» says Mario Rohrer.

The information is important for Switzerland because the increase in fine particle concentrations is particularly frequent during thermal inversions, i.e. when fog forms on the Swiss Plateau, thus limiting the exchange of air masses. In these situations, emissions accumulate in the layer of air underneath the fog. Switzerland is also frequently swept by dust from Saharan sandstorms, also pointed out in this study.

Aggravating factor

The Swiss research team shows that acute concentrations of fine particles, especially those smaller than 2.5 micrometers, cause inflammation of the respiratory, pulmonary and cardiovascular tracts and thicken the blood. «In combination with a viral infection, these inflammatory factors can lead to a serious progression of the disease. Inflammation also promotes the attachment of the virus to cells,» he says. In addition, the coronavirus may also be transported by the fine particles. «This has already been demonstrated for influenza and an Italian study found coronavirus RNA on fine particles. All this remains to be demonstrated, of course, but it is a likely possibility,» adds Rohrer.

A multifactorial pandemic

Nonetheless, the researchers also emphasize that, although particulate matter pollution can influence the virulence of the virus and possible severe disease progression, physiological, social or economic factors will clearly also influence the further course of the pandemic. Mario Rohrer concludes that the findings of this study offer the possibility of taking preventive measures in the event of future increases in fine particulate matter concentrations, thus limiting a new flare-up of Covid-19 morbidity and mortality.

University of Cincinnati researchers have discovered new clues into why some people with head and neck cancer respond to immunotherapy, while others don't.

Findings published in the Journal for ImmunoTherapy of Cancer show that it could all come down to "channeling" the power and function within one particular type of immune cell.

Laura Conforti, PhD, professor in the Department of Internal Medicine at the UC College of Medicine and corresponding author on the study, says understanding these mechanisms could help in creating combination treatments to more effectively treat some patients with cancer.

She points out that head and neck cancers are the sixth most common cancers in the world, affecting about 53,000 Americans every year. To combat the deadly disease, doctors often turn to immunotherapy, which boosts the body's own immune system in an effort to identify and kill cancer cells.

"Our immune cells are naturally programmed to distinguish between our body's 'normal' cells and what they see as 'foreign' cells and attack only the foreign cells," explains Conforti.

She says the immune cells -- called T cells -- lead the body's attack against cancers but the impact of that attack can be proven futile if a molecule in cancer cells is able to bind to an immune checkpoint in the T cells and effectively "turn them off like a light switch." As a result, the T cells leave the cancer cells alone, which Conforti says is "a major problem," especially for head and neck cancers.

A known immunotherapy treatment (pembrolizumab) targets the checkpoint molecule and blocks the "off switch" of the T cells, but scientists are trying to determine why this method works in some people and not in others.

Conforti further explains that the ability of these T cells to attack and destroy cancer cells relies on molecules called potassium ion channels, which are present in T cells and are responsible for a variety of functions, including killing cancer cells.

Conforti's team includes co-lead authors Hannah Newton, PhD, a recent UC doctoral graduate; Vaibhavkumar Gawali, PhD, postdoctoral fellow; and Ameet Chimote, PhD, research scientist in Conforti's lab.

The team found that when patients with head and neck cancer were given immunotherapy at UC Medical Center, T cells in these patients showed increased activity in these channels, allowing them to more effectively reach the cancer cells and kill them.

The team also found that after the treatment was delivered to patients, these channels in the T cells circulating in their blood were more active, meaning they were more equipped to continue fighting off the cancerous cells.

"We also saw that head and neck cancer patients who were responding to this immunotherapy, meaning their tumors were shrinking, had greater channel activity in their T cells soon after treatment, and the T cells had more ability to enter into the tumors to continue killing cancer cells," Conforti adds. "However, patients who did not respond lacked this increased activity.

"Immunotherapy is not one-size-fits all, since some patients respond to immunotherapy, while others don't, but our research shows that ion channels within T cells of these patients play a crucial role in the response of immunotherapy. Now that we know the benefits of these channels, more research is needed to look at ways we can activate them or create combination therapies to help patients increase their chance of survival."

Team member Newton, who recently completed her doctorate at UC and is now working at the National Institutes of Health-sponsored Frederick National Laboratory for Cancer Research, says that working on this study at UC was invaluable.

"This research allowed me to collaborate with diverse professional individuals including medical oncologists, clinical coordinators and other researchers and gave me the opportunity to better understand the bench-to-bedside procedure for drug development," Newton says. "Most importantly, it could help clinicians determine more personalized and effective treatment combinations for patients with head and neck cancer."

Scientists have developed a lung-on-chip model to study how the body responds to early tuberculosis (TB) infection, according to findings published today in eLife.

TB is a disease caused by the bacterium Mycobacterium tuberculosis (M. tuberculosis) and most often affects the lungs. The model reveals that respiratory system cells, called alveolar epithelial cells, play an essential role in controlling early TB infection. They do this by producing a substance called surfactant - a mixture of molecules (lipids and proteins) that reduce the surface tension where air and liquid meet in the lung.

These findings add to our understanding of what happens during early TB infection, and may explain in part why those who smoke or have compromised surfactant functionality have a higher risk of contracting primary or recurrent infection.

TB is one of the world's top infectious killers and affects people of all ages. While it mostly affects adults, there are currently no effective vaccines available to this group. This is partly due to challenges with studying the early stages of infection, which take place when just one or two M. tuberculosis bacteria are deposited deep inside the lung.

"We created the lung-on-chip model as a way of studying some of these early events," explains lead author Vivek Thacker, a postdoctoral researcher at the McKinney Lab, École polytechnique fédérale de Lausanne (EPFL), Lausanne, Switzerland. "Previous studies have shown that components of surfactant produced by alveolar epithelial cells can impair bacterial growth, but that the alveolar epithelial cells themselves can allow intracellular bacterial growth. The roles of these cells in early infection are therefore not completely understood.

"We used our model to observe where the sites of first contact are, how M. tuberculosis grows in alveolar epithelial cells compared to bacteria-killing cells called macrophages, and how the production of surfactant affects growth, all while maintaining these cells at the air-liquid interface found in the lung."

The team used their lung-on-chip model to recreate a deficiency in surfactant produced by alveolar epithelial cells and then see how the lung cells respond to early TB infection. The technology is optically transparent, meaning they could use an imaging technique called time-lapse microscopy to follow the growth of single M. tuberculosis bacteria in either macrophages or alveolar epithelial cells over multiple days.

Their studies revealed that a lack of surfactant results in uncontrolled and rapid bacterial growth in both macrophages and alveolar epithelial cells. On the other hand, the presence of surfactant significantly reduces this growth in both cells and, in some cases, prevents it altogether.

"Our work shines a light on the early events that take place during TB infection and provides a model for scientists to build on for future research into other respiratory infections," says senior author John McKinney, Head of the Laboratory of Microbiology and Microtechnology at EPFL. "It also paves the way for experiments that increase the complexity of our model to help understand why some TB lesions progress while others heal, which can occur at the same time in the same patient. This knowledge could one day be harnessed to develop effective new interventions against TB and other diseases."

The authors add that they are currently using a human lung-on-chip model to study how our lungs may respond to a low-dose infection and inoculation of SARS-CoV-2, the virus that causes COVID-19.

While there are therapies to aid in overall heart health, there are very few preventative therapies for heart failure after a significant heart attack, a serious condition that has a very significant mortality. However, researchers at Baylor College of Medicine have found a potential treatment that has shown promising results in mice.

The findings, published in the latest edition of the Proceedings of the National Academy of Sciences, showed that stimulation of a steroid receptor coactivator, SRC-3, by a molecule known as MCB-613 after a heart attack prevented the scar and maladaptive repair of heart tissue that can lead to heart failure.

"Heart failure after a significant heart attack is a leading cause of death in humans. It often occurs over a few years; a person becomes weaker and weaker and eventually they die," said Dr. Bert O'Malley, professor of molecular and cellular biology at Baylor and lead author of the study. "In the mouse model, our team has been able to show that MCB-613 decreases damaging remodeling when given within hours after a myocardial infarction, thereby inhibiting the subsequent development of heart failure."

Researchers had previously discovered and characterized MCB-613 as a small molecule stimulator for SRCs. The family of SRCs are responsible for cellular plasticity and cell growth pathways during both normal and abnormal tissue growth. After a heart attack, the damaged tissue scars. This results in tissue loss and increased inflammation, fibrosis and a progressive decrease in cardiac function, all of which are hallmarks of myocardial infarction-induced heart failure.

The molecule works by stimulating SRC-3, thus initiating a complex cascade of events in tissue repair and modulation of the inflammatory response. O'Malley and his team also found that after treating the mice model with MCB-613, there were no significant signs of toxicity.

"The clinical implications of this discovery are significant. I have cared for many patients with advanced heart failure, and if we can modulate the natural history of this disease at all, we will lessen the No. 1 cause of human death and avoid a significant amount of human suffering," said Dr. Clifford Dacso, professor of molecular and cellular biology and medicine.

"Our findings show us that this molecule acts directly on heart tissue repair and regeneration after a severe heart attack; however, more studies are needed to fully understand the safety and efficacy before we are able to use this as a therapy in humans," O'Malley said.

"Our study shows promise to address the unmet need for treatments to prevent damage to heart tissue following a heart attack. These findings pave the way for discovery of additional treatments to target chronic heart disease progression," said Dr. Lisa Mullany, assistant professor of molecular and cellular biology and first author on the study.

"This is a remarkable discovery that may lead to an effective and safe treatment to prevent the progression to heart failure after a heart attack. Heart failure is a devastating disease that is more lethal than all cancers combined, and currently there are no definitive therapies other than heart transplantation. MCB-613 is a great candidate to help solve this huge clinical problem," said Dr. James Martin, Vivian L. Smith professor of regenerative medicine, molecular physiology and biophysics.

COLUMBUS, Ohio - There's one group of essential workers who especially enjoy being called a "hero" during the COVID-19 pandemic: narcissists.

In a new study, researchers found that essential workers (including those in restaurants, grocery and retail stores) who scored higher on measures of narcissism shared more than others about their work. And this sharing on social media, in person and elsewhere increased their narcissistic feelings in the moment.

"The word 'hero' is a trigger for narcissists," said Amy Brunell, co-author of the study and associate professor of psychology at The Ohio State University Mansfield campus.

"Having their work elevated to hero status provides them with an opportunity to shine in front of others and feel even better about themselves."

Brunell conducted the study with Stephanie Freis, assistant professor of psychology at Presbyterian College, who received her doctorate from Ohio State. Their work was published this week in the journal Personality and Individual Differences.

They conducted two identical online studies, one worldwide and one restricted to the United States, with a total of 312 people who reported being "essential workers" during the pandemic. The most common job position listed was working in a convenience/grocery store.

Participants completed measures of narcissism and reported on how much they shared with others about their work.

Results suggested that people who scored higher on two specific types of grandiose narcissism - called communal and agentic - were more likely than others to share about their work on social media and elsewhere.

Communal narcissists are those who think they are better than others at being helpful and were more likely to strongly agree with statements like "I will be known for the good deeds I will have done."

Agentic narcissists are those that people usually picture when they think of narcissism: They strongly agreed with statements like "I will usually show off if I get the chance."

It is easy to see why people who score higher on communal narcissism would enjoy being known as an essential worker and want to share their experiences on Facebook and Instagram, Brunell said.

"They think they are the best at being helpful and caring for others. The pandemic gave them a chance to stand out," she said.

Agentic narcissists don't usually like to share the spotlight, but they likely thrived from the attention and the status boost they received from being called a "hero," according to Brunell.

"That's why they likely shared about their work. Their 'hero' status gave them a way to feel admired and distinct from others," she said.

Sharing about their experiences as essential workers on social media and elsewhere made people who scored higher on measures of narcissism feel even better about themselves in the moment, the study found.

They were more likely to strongly agree with statements like "Right now, I greatly enrich others' lives" and "Right now, I feel like I am a special person."

There was one kind of narcissist who didn't tend to feel better about themselves during the pandemic, findings showed.

Vulnerable narcissists don't feel good about themselves in general, but do feel self-absorbed and believe they aren't getting the attention they deserve. They are more likely to agree with statements like "I feel that I have enough on my hands without worrying about other peoples' troubles."

"Perhaps being an essential worker made vulnerable narcissists feel more exposed to others' judgments or anxious about their own well-being," Brunell said.

Overall, she said the results suggest that some narcissists are finding a way to use the COVID-19 pandemic to benefit themselves.

"It is a way for them to feel even more self-important because they are seen as essential to society."

Our lungs are exposed to a multitude of hazardous airborne particles on a daily basis. Nanoparticles, due to their small size, may reach the sensitive alveolar region of the human lung and trigger inflammation even after a single inhalation leading to severe diseases such as heart disease, brain damage and lung cancer for prolonged exposure. In manufacturing, toxic nanoparticles may be released into the environment during the production, processing, degradation or combustion of materials. Despite advances in models for nanotoxicology, currently neither in vitro nor in silico testing tools can reliably predict adverse outcomes or replace in vivo testing. In order to facilitate the introduction of safer materials into our lives, novel testing strategies are needed to predict the potential toxicity of industrial nanoparticles before and during the manufacturing process.

Unlocking the cellular mechanisms

At Helmholtz Zentrum München, the research group of Dr. Tobias Stöger is focusing on an improved mechanistic understanding of the interactions between nanoparticles and lung cells, especially in view of the resulting inflammation. In cooperation with partners from the SmartNanoTox EU project, the research group discovered that for certain materials the long-lasting inflammatory response to a single exposure to a nanoparticle can originate from two cellular key events which were so far unknown: First, the quarantining process which is the deposition of excreted immobile composites of the nanoparticles wrapped with biological molecules on the cell surface. Second, the so-called nanomaterial cycling which entails the movement of the nanoparticles between different alveolar lung cell types.

"With these new insights, we developed a deeper comprehensive approach on how an inflammatory response in the lung originates from particle-cell interactions. Being able to pinpoint the origin to these two key events and quantitatively describe them was a breakthrough as it helped us built our prediction method", says Stöger.

A step closer to safe-by-design material development

Using only a small set of data from in vitro measurements and by combining it with in silico modeling, the researchers gathered insights on the toxicity of nanoparticles and managed to predict the spectrum of lung inflammation (from acute to chronic) associated with a range of 15 selected materials. Stöger adds: "Being able to make such a prediction means that we can move a step closer to a safe-by-design material development. This will have profound implications on the safety, speed and cost-effectiveness of new materials."

Additional benefit: Animal-free testing

Currently, safety testing relies heavily on animal studies. While animal experimentation is still indispensable for mechanistic and chronic toxicological studies, they are less suited for predictive tests within a safe-by-design production of new materials. This study introduces an alternative animal-free testing strategy, capable for high-throughput testing and connectable with in silico modelling.

UNIVERSITY PARK, Pa. -- Don't be afraid to toss a handful of raisins or dried apples in your Thanksgiving stuffing this year -- a new Penn State study has found that dried fruit may be connected with better health.

The researchers found that people who ate dried fruit were generally healthier than those who did not, and on days when people ate dried fruit they consumed greater amounts of some key nutrients than on days when they skipped. However, they also found that people consumed more total calories on days when they ate dried fruit.

Valerie Sullivan, postdoctoral researcher at Johns Hopkins Bloomberg School of Public Health and a Penn State grad student at the time of the study, said the findings suggest that dried fruit can be part of a healthy diet -- with some caveats.

"Dried fruit can be a great choice for a nutritious snack, but consumers might want to be sure they're choosing unsweetened versions without added sugar," Sullivan said. "Portion sizes can also be tricky, because a serving of dried fruit is smaller than a serving of fresh since the water has been taken out. But the positive is that dried fruit can help people potentially consume more fruit because it's portable, it's shelf-stable, and can even be cheaper."

Previous research has found that poor diet contributes to nearly half of deaths from cardiovascular disease in the U.S., with a lack of fruit being a major factor. According to the researchers, fruits provide an abundance of nutrients, including fiber, potassium and several heart-healthy bioactives.

However, despite these benefits, other studies have found that people may not eat enough fruit for a number of reasons -- including limited availability, cost and the fact that it can spoil quickly, among others. In the current study, the researchers wanted to examine whether dried fruit could be a healthful alternative to fresh fruit, since it could be cheaper.

"Minimally processed forms of fruit, including frozen, canned, and dried, have some advantages over fresh fruits," said Kristina Petersen, an assistant professor of nutritional sciences at Texas Tech University and assistant research professor of nutritional sciences at Penn State at the time this work was done. "They are available year round, are relatively consistent in quality, and can be stored for far longer than fresh. Many are also less expensive per serving than their fresh counterparts."

For the study, the team used data on 25,590 participants in the National Health and Nutrition Examination Survey. Participants provided data about all the foods they had consumed in the previous 24 hours, including dried fruit. Data were also gathered about participants' cardiometabolic health -- including body mass index, waist circumference and blood pressure -- and their overall diet quality.

After analyzing the data, the researchers found that on average, people who reported consuming dried fruit in the survey had healthier diets than those who did not. They also tended to have lower body mass index, waist circumference, and systolic blood pressure.

Because some of the participants reported eating dried fruit on one day of the survey but not the second, the researchers were also able to examine what people's diet looked like on days they ate dried fruit versus days when they didn't.

"What I also found interesting was that people tended to eat more total fruit on the days they ate dried fruit than on days they didn't," Sullivan said. "On days when dried fruit was not eaten, however, fresh fruit intake was not higher. So dried fruit could be a way to boost overall fruit intake in people that aren't eating the recommended amounts."

Additionally, the researchers found that on days they ate dried fruit, participants consumed more total carbohydrates, dietary fiber, potassium, polyunsaturated fat, and overall total calories.

"In our study, people who consumed dried fruits had a higher calorie intake but a lower BMI and waist circumference which suggests they were more physically active," said Penny Kris-Etherton, Evan Pugh University Professor of Nutritional Sciences. "So, when incorporating dried fruits, pay attention to calories and be sure to substitute out calories from low-nutrient foods for dried fruits to get the greatest benefit of eating dried fruits."

Aurora, Colo. (Nov. 24, 2020) - Eighty to 90% of adolescents benefit from lasting weight loss following bariatric surgery, and most experience the remission of obesity-related complications such as elevated blood pressure, high cholesterol, type 2 diabetes and musculoskeletal pain, among others. In a new study published in Obesity, researchers at Children's Hospital Colorado (Children's Colorado) have shown that, with the exception of cholesterol and triglyceride levels, remission of obesity-related complications was not dependent on major sustained weight loss. Rather, a majority of adolescents benefited from remission of obesity-related complications, an observation that was independent of whether or not they lost a significant amount of weight.

"We view the findings of this study to be very encouraging," said Sarkis Christopher (Chris) Derderian, MD, pediatric surgery fellow at Children's Colorado. "Because the amount of weight loss does not seem to impede the sustained remission of many obesity-related complications, the study supports the myriad benefits of bariatric surgery for severely obese teens. These patients are often able to stop taking medications for Type 2 diabetes and high blood pressure following surgery. In doing so, not only does their quality of life dramatically improve, but no longer incurring the cost of managing such complications can offset the cost of surgery over time."

In the study, Derderian and colleagues compared rates of remission of obesity-associated complications among two groups of patients: those who experienced less than 20% total body weight loss five years after surgery and those who experienced 20% or greater total body weight loss over the same time period. All 192 study participants were part of a multi-center study led by researchers at Children's Colorado known as the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS).

Specifically, researchers found that 40.6% of study participants exhibited 20% total body weight loss at five years. While the latter group saw greater improvement in their cholesterol levels, the remission of other complications appeared to be independent of whether or not the participants achieved major sustained weight loss.

"In looking at the relationship between the extent of weight loss and health benefits obtained, it is clear that patients' health improves regardless of whether or not they sustain high levels of weight loss long-term following surgery," said Thomas H. Inge, MD, PhD, Teen-LABS principal investigator, and director of pediatric surgery and the bariatric center at Children's Colorado. "While this study is incredibly promising, additional research is needed to determine if the same benefits are seen in patients who only sustain weight loss of five to 10% over time. Nevertheless, this study supports the recognition of bariatric surgery as the most effective intervention to promote significant and durable weight loss in adolescents with severe obesity."

PHILADELPHIA (November 24, 2020) - In-hospital cardiac arrests (IHCA) represent catastrophic and often terminal events. Despite investments to improve the quality of resuscitation efforts, fewer than 25% of all patients that experience cardiac arrests in hospitals survive to discharge, and survival varies significantly across hospitals and by race. Until now, few have been able to specify reasons for the between-hospital differences.

A new study from the University of Pennsylvania School of Nursing's (Penn Nursing) Center for Health Outcomes & Policy Research is the first of its kind to describe the relationship between medical-surgical nurse staffing and its association with racial disparities in survival after IHCAs. It suggests that while the likelihood of survival to discharge after an IHCA is lower for black patients than for white patients in both poorly staffed and well-staffed hospitals, the survival difference produced by better staffing is more pronounced for black patients than for white patients.

"The effect of being cared for in hospitals with better medical-surgical staffing has a greater effect on black patients than white patients, and differences in survival to discharge after an IHCA between black and white patients are more pronounced in poorly staffed hospitals than in well-staffed hospitals," says J. Margo Brooks Carthon, PhD, RN, FAAN, Associate Professor of Nursing at Penn Nursing and lead author of the study. "The findings are consistent with a growing number of studies that suggest that hospital-based disparities may be related to variation in nursing care quality in the settings where black patients receive care."

A Cleveland Clinic study shows that among patients who have obesity and who tested positive for COVID-19, a past history of bariatric surgery was significantly associated with a lower risk of hospital and intensive care unit admission. The results were published in the journal of Surgery for Obesity and Related Diseases.

In the past months, researchers worldwide have identified obesity as a risk factor for developing a severe form of COVID-19, which may require hospital admission, need for intensive care and use of ventilator support. The Centers for Disease Control and Prevention reported that more than 70% of U.S. adults are overweight or have obesity, which may increase the risk of severe illness from the coronavirus.

Obesity is a complex disease caused by multiple factors that weaken the immune system. Obesity creates a chronic inflammatory state that causes excessive production of cytokines, which are small proteins involved in the immune response.

"Infection with the coronavirus also triggers the immune system to release cytokines, which may lead to excessive cytokine production that damages organs. That may partly explain the severity of infection in patients with obesity," says Ali Aminian, M.D., Director of the Bariatric & Metabolic Institute at Cleveland Clinic and principal investigator of the research.

In addition, obesity increases the risk for cardiovascular disease, hypertension, diabetes, kidney disease and blood clot formation. Those conditions can lead to poor outcomes after an infection with SARS-CoV-2, which is the virus that causes COVID-19. Obesity may also affect the respiratory system. Many patients with obesity have underlying lung conditions, such as sleep apnea and obesity hypoventilation syndrome, that can worsen the outcomes of COVID-19 pneumonia.

"Dr. Aminian's study provides further evidence of the important link between obesity and poor outcomes from coronavirus infection. The study shows for the first time that substantial weight loss via bariatric surgery may actually reduce the risk from severe illness in these patients," says co-author Steven Nissen, M.D., Chief Academic Officer of the Heart, Vascular and Thoracic Institute at Cleveland Clinic.

Looking at 4,365 patients who tested positive for SARS-CoV-2 between March 8, 2020 and July 22, 2020, researchers identified 33 patients who had a prior history of weight-loss surgery (20 patients had a sleeve gastrectomy and 13 patients had a Roux-en-Y gastric bypass). The 33 surgical patients were carefully matched 1:10 to nonsurgical patients with obesity to assemble a cohort of 330 control patients with a body mass index of 40 or higher at the time of SARS-CoV-2 testing.

This matched cohort study of 363 patients showed that sustained weight loss and improvement of diabetes and hypertension in the bariatric surgical group prior to contracting COVID-19 was associated with a much lower rate of hospital and ICU admission.

Eighteen percent of patients in the weight-loss surgery group and 42 % of patients in the control group required hospitalization after contracting COVID-19. In addition, 13 % of patients in the control group required ICU admission, 7 % required mechanical ventilation, and 2.4 % died. None of these occurred in the surgical group.

"Patients after bariatric surgery become significantly healthier and can fight the virus better," adds Dr. Aminian. "If confirmed by future studies, this can be added to the long list of health benefits of bariatric surgery such as improvement of diabetes, hypertension, fatty liver disease, sleep apnea, and prevention of heart attack, stroke, kidney disease and death."

Another Cleveland Clinic study showed that weight-loss surgery was associated with a 40 % reduction in risk of death and heart complications in patients with diabetes and obesity.

A research team at the RIKEN Center for Biosystems Dynamics Research (BDR) in Japan has succeeded in experimentally evolving the common bacteria Escherichia coli under pressure from a large number of individual antibiotics. In doing so, they were able to identify the mechanisms and constraints underlying evolved drug resistance. Their findings, published in the scientific journal Nature Communications, can be used to help develop drug-treatment strategies that minimize the chance that bacteria will develop resistance.

Counteracting multidrug-resistant bacteria is becoming a critical global challenge. It seems that every time we develop new antibiotics, novel antibiotic-resistant bacteria emerge during clinical use. To win this cat-and-mouse game, we must understand how drug resistance evolves in bacteria. Naturally, this process is very complicated, involving numerous changes in genome sequences and cellular states. Therefore, a comprehensive study of resistance dynamics for large numbers of antibiotics has never been reported.

"Laboratory evolution combined with genomic analyses is a promising approach for understanding antibiotic resistance dynamics," explains Tomoya Maeda, a researcher at RIKEN BDR who led this study. "However, laboratory evolution is highly labor-intensive, requiring serial transfer of cultures over a long period and a large number of parallel experiments." Additionally, Maeda says that identifying the genes that allow resistance to antibiotics is not always easy because of the large number of genetic features that are contained within the data.

To overcome these limitations, the team developed an automated robotic culture system that allowed them to successfully perform high-throughput laboratory evolution of E. coli for more than 250 generations under pressure from 95 different antibiotics. With this new ability, they were able to quantify changes in the bacteria's transcriptome--the set of all messenger RNAs and their transcripts, which is the record of which genes are actually expressed. As a result, the system produced resistance profiles for 192 of the evolved strains. The researchers also developed a machine-learning method for analyzing this large amount of data, allowing them to identify both novel and well-known genes that contribute to the prediction of resistance evolution.

"We found that E. coli's evolutionary dynamics is attributable to a relatively small number of intracellular states, indicating that it is likely equipped with only a limited number of strategies for antibiotic resistance," says Maeda. By being able to quantify the constraints that affect evolution of antibiotic resistance in E. coli, the team hopes they can predict, and thus control, antibiotic resistance.

For example, by using this new system, they were able to test 2162 pairs of drug combinations and discovered 157 pairs that have the potential to suppress antibiotic resistance acquisition in E. coli. As Maeda says, "We believe that our results can be applied to the development of alternative strategies for suppressing the emergence of drug-resistant bacteria."