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Professor Rob Hale of William & Mary's Virginia Institute of Marine Science is lead author of a new "Grand Challenges" paper commissioned to mark the 100th anniversary of the American Geophysical Union, the world's largest association of Earth and space scientists with more than 60,000 members in 137 countries.

The paper, "A Global Perspective on Microplastics," is co-authored by VIMS doctoral student Meredith Seeley and senior research scientist Dr. Mark LaGuardia, along with Drs. Lei Mai and Eddy Zeng of Jinan University in Guangzhou, China.

"Microplastics" are microscopic particles fabricated for products like facial scrubs, or produced when physical, chemical, and biological forces break down larger pieces of plastic debris. There has been widespread concern among scientists and the public that these minute synthetic fragments are impacting marine ecosystems.

AGU Executive Director/CEO Chris McEntee says the Grand Challenges "represent a special collection of open-access review papers with the shared goal of transforming Earth and space science to meet the challenges of today and the opportunities of tomorrow. They explore where major research and discovery are needed to address fundamental questions in our understanding of Earth and the solar system."

Not just an ocean problem

The team's paper appears in the January issue of the Journal of Geophysical Research: Oceans, but Hale is quick to stress that microplastics are a concern outside the marine environment as well.

"It's not just an ocean problem," says Hale. "There's growing evidence that microplastics are distributed across the land surface and in the air. We're finally opening up the other boxes and discovering a pretty substantial footprint."

Indeed, the broad nature of the microplastic threat is a main focus of the authors' manuscript. "We stress that microplastics are a global phenomenon that can't be adequately understood or addressed in the context of the marine environment alone," says Hale. "Plastics are produced, used, and discarded on land, and disperse through soils, rivers, and the atmosphere. The cat's already out of the bag if you're talking about dealing with these materials after they've reached the ocean."

The researchers note that the global scope of the issue extends to the social sphere as well. "We have to recognize that microplastic pollution is an international problem that doesn't respect political boundaries," says Seeley. "As with climate change and species management, developed and emerging nations will have to cooperate to find equitable solutions."

Not all plastic is the same

A second goal of the article is to gain broader recognition that "plastic" is a catch-all term for a complex array of materials that vary in chemical composition, size, texture, and shape--including pellets, fragments, and fibers. Adding further complexity is that plastics are often infused with additives, including flame retardants and UV inhibitors, which may themselves have environmental and health impacts.

"People often assume that all plastics are the same and behave identically in the environment," says Hale, "but that isn't the case at all. To resolve key questions and mitigate possible impacts, everyone--manufacturers, scientists, health-care specialists, engineers, economists, policymakers, and others--must collaborate to better understand the composition and nature of plastic products and their additives."

The researchers also stress that the characteristics of microplastics can and do change during and after use. "The complexity of microplastics becomes even more convoluted once they enter the environment and begin to intermingle and weather," says LaGuardia. "We have to better understand these complexities, especially in transition zones such as estuaries."

To gain that understanding, the authors recommend the research community move beyond studies of individual habitats, size ranges, polymer types, or forms; and into more holistic studies of the changing characteristics of microplastics and their impacts on ecosystem health and processes.

A need for better tools

The researchers' third main message is that comprehensive understanding of the microplastics issue, and the most effective responses, will require better analytical tools.

"To understand the real impacts of microplastics," says Hale, "we've got to improve our sampling and analytical capabilities, including the ability to study nanoplastics and weathered materials." Nanoplastics are particles even smaller than microplastics, with sizes ranging from 1 nanometer to 1,000 nanometers or a micron. A strand of DNA is about 2.5 nanometers across.

Hale says current state-of-the-art instruments, such as FTIR and Raman microscopes, "provide really great information when you zero in on a single microplastic particle." The problem, he says, is that many samples contain thousands of different particles, and many of these particles are really, really small.

"There's a disconnect," says Hale. "A lot of our technology can't get down to stuff below 10 microns, and in terms of effects on organisms, we think that smaller particles may be more toxic." Trying to bridge this gap, VIMS recently received funding from the NOAA Marine Debris program to investigate interactions between particles smaller than 10 microns and infectious disease in fish.

Effects on human health?

The authors' concerns regarding microplastics extend to potential impacts on human health.

"There have been concerns about ingesting microplastics from seafood, but the indoor environment is our biggest direct threat," says Hale. "Many people in developed countries spend almost all their time indoors, in spaces that are increasingly air-tight and insulated with things like polystyrene foam. Our exposure to microplastics from breathing and ingesting indoor dust may have toxicological consequences, but there's been very little research."

To address these concerns, Hale and colleagues at VIMS are acquiring a time-of-flight mass spectrometer, which will hopefully allow them to better analyze chemical contaminants associated with microplastics, as well as those found in other environmental samples.

"This will help us start going after all these unknown additives in plastics and open up that Pandora's Box a little better," says Hale. "I think that's where the action really is in terms of human health."

Philadelphia, February 24, 2020 - In a compelling article in Progress in Cardiovascular Diseases, published by Elsevier, Mark McCarty of the Catalytic Longevity Foundation, San Diego, CA, USA, and James DiNicolantonio, PharmD, a cardiovascular research scientist at Saint Luke's Mid America Heart Institute, Kansas City, MO, USA, propose that certain nutraceuticals may help provide relief to people infected with encapsulated RNA viruses such as influenza and coronavirus.

In the United States, influenza infects around 30 million people every year causing around 30,000 deaths. While there are medications approved for the treatment of influenza, they typically are costly, have side effects, and are not very effective. Additionally, vaccinations against influenza may only be effective in around 50 percent of those vaccinated. Thus, there is a need for safer and effective alternatives in those infected with influenza.

Over the past few months, a novel RNA coronavirus, now called COVID-19, has broken out in China and has spread to over two dozen countries and infected more than 76,000 people causing more than 2,000 deaths. This novel coronavirus is much more lethal than the typical flu, with a current mortality rate of about 2.92 percent. In other words, around 1 in 33 people who are infected with this novel coronavirus will die. Whereas the annual flu has a mortality rate of just 0.05 to 0.1 percent. This means that around 1 in 1,000 to 2,000 people infected with the annual flu will die. In other words, COVID-19 is around 30 to 60 times more lethal than the typical annual flu.

Both influenza and coronavirus cause an inflammatory storm in the lungs and it is this inflammatory storm that leads to acute respiratory distress, organ failure, and death. Certain nutraceuticals may help to reduce the inflammation in the lungs from RNA viruses and others may also help boost type 1 interferon response to these viruses, which is the body's primary way to help create antiviral antibodies to fight off viral infections.

The authors draw attention to several randomized clinical studies in humans that have found that over the counter supplements such as n-acetylcysteine (NAC), which is used to treat acetaminophen poisoning and is also used as a mucus thinner to help reduce bronchitis exacerbations, and elderberry extracts, have evidence for shortening the duration of influenza by about two to four days and reducing the severity of the infection. The authors also note several nutraceuticals such as spirulina, beta-glucan, glucosamine, and NAC have either been found to reduce the severity of infection or to cut the rate of death in half in animals infected with influenza. Furthermore, one clinical study in humans testing spirulina noted significant reductions in viral load in those infected with HIV.

"Therefore, it is clear that certain nutraceuticals have antiviral effects in both human and animal studies," commented Dr. DiNicolantonio. "Considering that there is no treatment for COVID-19 and treatments for influenza are limited, we welcome further studies to test these nutraceuticals as a strategy to help provide relief in those infected with encapsulated RNA viruses."

Editor-in-Chief of Progress Cardiovascular Diseases Carl "Chip" Lavie, MD, Ochsner Clinical School-The University of Queensland School of Medicine, New Orleans, LA, USA, added, "Considering the recent interests directed at serious viral infections, especially coronavirus and influenza, this material should be of interest to specialists in cardiovascular diseases but also to a wide range of clinicians outside of our typical readership."

Targeting overactive immune cells and dampening their effects may serve as a new treatment for treating a traumatic brain injury, according to new research in mice published in JNeurosci.

Time is of the essence when treating a traumatic brain injury (TBI). Triggered by trauma, microglia - the brain's immune cells - morph into an inflammatory state, which helps to protect the brain. However, long term inflammation may contribute to neurological degeneration after a TBI.

Henry et al. report that quelling such chronic inflammation, even months after the injury, could serve as a new treatment for TBI. One month after a TBI, the team inhibited a receptor microglia need to survive. The inhibition killed 95 percent of the mice microglia cells. However, the cells bounce back to normal levels once the inhibition ends. The researchers stopped the inhibition after one week and let the mice recover for a few months. The inhibition "reset" the mice's microglia: the new cells were in a more normal, less inflammatory state. The mice recovered better than the mice that didn't receive treatment, showing less brain damage, fewer neuron deaths, and better motor and cognitive performance. Targeting inflammation pathways could treat the chronic consequences of a TBI long after the initial injury.

Two recently approved leukemia drugs could be enlisted against treatment-resistant lung cancer, with a clinical trial expected to launch in Toronto and Zagreb, Croatia, later this year to evaluate one of them.

Researchers led by Igor Stagljar, a professor of molecular genetics and biochemistry at the Donnelly Centre for Cellular and Biomolecular Research, made the findings using a new live cell-based method developed by his team for identifying small molecules that target specific mutations in cancer cells.

"Drug resistance is a big problem for lung cancer patients," says Stagljar. "Our new technology allows us to find molecules that could be used against cancers for which no other treatment options are available."

The researchers identified gilteritinib and midostaurin, two drugs already approved for patients with a particular form of leukemia, as potential treatments for lung cancer patients with triple mutant epidermal growth factor receptor (EGFR). The tumours in these patients are highly resistant to available therapy.

The Toronto team hopes to demonstrate the efficacy of these drugs in patient trials, with the gilteritinib trial to launch first. If it proves successful, gilteritinib could in a few years become a new standard of care treatment for an estimated 60,000 lung cancer patients worldwide who have triple mutant EGFR.

"We already have a sense of gilteritinib doses that are safe to give to humans," says Dr. Adrian Sacher, an oncologist at Toronto's Princess Margaret Cancer Centre, at University Health Network, who will lead the trial. "We only need to demonstrate efficacy and hopefully make them a novel treatment option for lung cancer patients that have developed resistance to current targeted therapies."

The journal Nature Chemical Biology published the findings.

Lung cancer remains a leading cause of death from cancer in Canada and the world. Non-small cell lung cancer is the most common type of the disease with about one fifth of cases in North America caused by EGFR mutations.

EGFR is a cell surface receptor that regulates cell proliferation and belongs to a class of proteins known as receptor tyrosine kinases (RTKs). Oncogenic mutations make the receptor overactive, spurring on cell division.

There are dozens of approved kinase inhibitor drugs that target specific mutations in the receptor's catalytic domain, but tumours quickly gain new mutations and become drug resistant. A third of lung cancer patients on osimertinib, a last resort drug approved in 2017 against the double mutant EGFR, will develop the treatment-resistant C797S mutation within six to nine months.

In a bid to stay one step ahead of the disease, scientists seek to identify drugs that can target the mutations that arise in response to treatment. Most methods are test tube based and focus on finding new kinase inhibitors, however. Consequently, promising drug candidates are often not suitable as therapeutics either because they don't penetrate the cells or because their effects are altered by other cellular factors.

The tool developed by Stagljar's team overcomes these hurdles by testing potential drug molecules directly in living cells. Named MaMTH-DS, for Mammalian Membrane Two-Hybrid Drug Screen, the all-in-one method allows identification of drug candidates which both enter the cells and target the receptors in their natural environment.

"The advantage of our method is that we are doing it in living cells, where we have all the other molecular machineries present that are important for signal transduction," says Stagljar. "Also, the compounds are fished at very low dose, which allows us to test for both permeability and toxicity at the same time."

Furthermore, MaMTH-DS allows identification of drug molecules which target not only the receptor's kinase activity, but also its interactions with other cellular proteins.

In a proof of principle study, the team looked for small molecules that can target the resistance-conferring C797S mutation in the triple mutant EGFR. A screen of almost 3,000 molecules revealed four promising compounds that had no effect on the normal receptor, meaning the drugs would be less likely to harm healthy cells.

In addition to midostaurin and gilteritinib, the latter of which will be tested in a pilot trial of about 20 lung cancer patients whose tumours harbor the C797S mutation, the study also revealed two more promising molecules.

One of these molecules, known as EMI1, acts on the mutant EGFR in a completely new way, not by inhibiting its kinase activity, but by targeting the receptor for degradation with the help of other molecular machineries. The researchers think that EMI1's more complex mechanism of action will make it more difficult for tumours to develop resistance to it.

Stagljar is working with Rima Al-awar, Head of Therapeutic Innovation and Drug Discovery, and her medicinal chemistry team at the Ontario Institute for Cancer Research (OICR), to create an improved version of the EMI1 molecule before its ability to shrink tumours can be evaluated in animal cancer models and eventually patients.

"The unbiased screening approach by the Stagljar's group has the merit of identifying small molecule inhibitors that could act via new mechanisms of action that would otherwise escape detection by conventional drug development strategies, as shown in this proof of principle study, " says Marino Zerial, Managing Director of the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany and one of Stagljar's collaborators.

Interacting contagious diseases like influenza and pneumonia follow the same complex spreading patterns as social trends. This new finding, published in Nature Physics, could lead to better tracking and intervention when multiple diseases spread through a population at the same time.

"The interplay of diseases is the norm rather than the exception," says Laurent Hébert-Dufresne, a complexity scientist at the University of Vermont who co-led the new research. "And yet when we model them, it's almost always one disease in isolation."

When disease modelers map an epidemic like coronavirus, Ebola, or the flu, they traditionally treat them as isolated pathogens. Under these so-called "simple" dynamics, it's generally accepted that the forecasted size of the epidemic will be proportional to the rate of transmission.

But according to Hébert-Dufresne, professor of computer science at University of Vermont, and his co-authors, Samuel Scarpino at Northeastern University, and Jean-Gabriel Young at the University of Michigan, the presence of even one more contagion in the population can dramatically shift the dynamics from simple to complex. Once this shift occurs, microscopic changes in the transmission rate trigger macroscopic jumps in the expected epidemic size--a spreading pattern that social scientists have observed in the adoption of innovative technologies, slang, and other contagious social behaviors.

STAR WARS AND SNEEZING

The researchers first began to compare biological contagions and social contagions in 2015 at the Santa Fe Institute, a transdisciplinary research center where Hébert-Dufresne was modeling how social trends propagate through reinforcement. The classic example of social reinforcement, according to Hébert-Dufresne, is "the phenomenon through which ten friends telling you to go see the new Star Wars movie is different from one friend telling you the same thing ten times."

Like multiple friends reinforcing a social behavior, the presence of multiple diseases makes an infection more contagious that it would be on its own. Biological diseases can reinforce each other through symptoms, as in the case of a sneezing virus that helps to spread a second infection like pneumonia. Or, one disease can weaken the host's immune system, making the population more susceptible to a second, third, or additional contagion.

When diseases reinforce each other, they rapidly accelerate through the population, then fizzle out as they run out of new hosts. According to the researchers' model, the same super-exponential pattern characterizes the spread of social trends, like viral videos, which are widely shared and then cease to be relevant after a critical mass of people have viewed them.

DENGUE AND ANTIVAXXERS

A second important finding is that the same complex patterns that arise for interacting diseases also arise when a biological contagion interacts with a social contagion, as in the example of a virus spreading in conjunction with an anti-vaccination campaign. The paper details a 2005 Dengue outbreak in Puerto Rico, and Hébert-Dufresne cites an additional example of a 2017 Dengue outbreak in Puerto Rico where failure to accurately account for the interplay of Dengue strains reduced the effectiveness of a Dengue vaccine. This in turn sparked an anti-vaccination movement--a social epidemic--that ultimately led to the resurgence of measles--a second biological epidemic. It's a classic example of real-world complexity, where unintended consequences emerge from many interacting phenomena.

Although it is fascinating to observe a universal spreading pattern across complex social and biological systems, Hébert-Dufresne notes that it also presents a unique challenge. "Looking at the data alone, we could observe this complex pattern and not know whether a deadly epidemic was being reinforced by a virus, or by a social phenomenon, or some combination."

"We hope this will open the door for more exciting models that capture the dynamics of multiple contagions," he says. "Our work shows that it is time for the disease modeling community to move beyond looking at contagions individually."

And the new study may shed light on the spread of coronavirus. "When making predictions, such as for the current coronavirus outbreak occurring in a flu season, it becomes important to know which cases have multiple infections and which patients are in the hospital with flu--but scared because of coronavirus," Hébert-Dufresne says. "The interactions can be biological or social in nature, but they all matter."

CHICAGO--February 24, 2020--Hospitals can dramatically reduce the length of a patient's stay (by up to 67%) when their provider teams hold integrated care conferences (ICCs), a daily meeting for providers to share information at once. However, the seemingly obvious concept is rarely implemented, according to researchers in The Journal of the American Osteopathic Association.

Admitted patients require multidisciplinary teams to provide care, including nurses, social workers, pharmacists and more. Most hospitals leave it up to the primary physician to do the leg work of coordinating that care via individual emails, phone calls and in-person meetings.

"When I first encountered a hospital with ICCs, I was awestruck by how much easier and efficiently everything ran," says Ryan Shilian, DO, an adult and pediatric allergy/immunology fellow with University Hospitals Cleveland Medical Center, and lead author on this study. "At the vast majority of hospitals, it is left up to the primary physician to physically seek out and coordinate supporting services."

An intuitive practice with dramatic results

Dr. Shilian set out to quantify the efficiency of ICCs by comparing the lengths of stay for COPD patients at two University Hospital facilities. Each had similar staffing and resources, as well as patient populations. The key difference was one maintained a daily ICC in which representatives from each care provider team met to discuss patient progress and address barriers to a safe discharge. The other did not.

The average length of stay for patients with COPD at the hospital with ICCs was 3.37 days, compared to 5.55 days in the hospital without them. Additionally, in the hospital with daily ICCs, patients aged 40 to 69 years old had a 67% shorter admission, and patients aged 70 to 99 years or older had a 36% shorter length of stay compared with patients at the hospital without those meetings.

Dr. Shilian says that the more common model of care coordination--without ICCs--is not only slower but allows more opportunities for miscommunication and gaps in treatment. He adds that reducing the length of hospital stays will save money and improve patient outcomes as patients will have less exposure to risks like secondary infections and other complications.

The vast majority of hospitals conduct multidisciplinary rounds (MDRs) in which the attending physician visits each patient with an entourage of residents, medical students, nurses, ancillary clinicians and staff to discuss the diagnoses and treatment plans. Dr. Shilian notes that MDRs are often held at the bedside, leaving little space and time for the large group to have meaningful discussion and/or input.

He adds that ICCs are held in a conference room that can accommodate the required staff, but also provide a more collaborative environment that dedicates time for every team member's input. ICCs are typically led by nursing supervisors, who represent the most direct point of care, and are focused on the patients' progress and identifying the necessary steps to getting each patient healthy enough to discharge.

MIAMI, FL (February 18, 2020)--Jose Romano, Chief of the Stroke Division at the University of Miami Miller School of Medicine, co-authored a recently published international study that shows that visual rehabilitation is effective for patients who have suffered vision loss related to stroke or traumatic brain injury.

The study titled "Efficacy and predictors of Recovery of Function After Eye Movement Training in 296 Hemianopic Patients," was recently published in the journal Cortex. It is the largest neuro-visual study of its kind.

The research team found that the NeuroEyeCoach visual rehabilitation therapy applied after stroke or other traumatic brain injury (TBI) improved vision in over 80 percent of patients, helping them with everyday tasks and improving their quality of life. The results showed that the treatment improved vision even in an 90-year-old patients.

"Up to recently, there was very little treatment available to restore vision loss in this population," said Romano, noting that while stroke and TBI patients regain some vision on their own, "very few regain it completely."

Blindness among these patients usually stems from injury to the back of the brain where images are interpreted. "Patients have very poor quality of life as they often bump into things, cannot drive or read," said Romano.

The study involved almost 300 patients, the largest number of patients to participate in a study of this nature. Conducted in Europe, involving U.S. and European patients, the study revealed that patients achieve major improvements within 2-3 weeks of therapy. The findings showed that 87 percent of patients improved in search time and 80 percent had made fewer errors leading to reduced disability.

Blindness after brain injury is common and its effect on patient's daily life is sudden. Those affected have great difficulties navigating their way around and avoiding obstacles. The significance of this study is that the use of NeuroEyeCoach can lead to improved eye movements allowing better interaction with the environment. Not only are patients reducing their errors following the therapy, they are also seeing things much faster and state in their self-assessment that the therapy improves their activities of daily living, such as exploring their surroundings better, identifying obstacles and avoiding collisions.

Improvements were not dependent on age, gender, side of blindness, nor the time elapsed since the brain injury. The study also found that there was no upper age limit to the success of the treatment. This is the first time that a treatment of this kind has been shown to be effective in both old as well as young adults.

The study, which was funded by industry partner NovaVision Inc., also demonstrated that the therapy is highly beneficial to patients that state they have high levels of disability: 79 percent of these patients said they had less disability after doing NeuroEyeCoach.

"Our results show that rehabilitation of vision loss after brain injury is possible and can drastically improve patients' quality of life," said Arash Sahraie, professor and chair in Psychology at the University of Aberdeen.

"The larger scale of this study has provided answers to important questions as to whether rehabilitation outcome is affected by how old people are when they suffer their injury or how long ago they had their vision loss, or even whether they are male or female."

An international research team has been able to describe the overall structure of the antibody type IgE, which is the key molecule in allergic diseases. This is a scientific breakthrough which provides important insights into basic mechanisms of allergic reactions and may pave the way for more effective allergy medicine. The new research results have now been published in the scientific journal Allergy.

Antibodies are fundamental and versatile molecules of the human immune system. Different types of antibodies existing in humans share general features that include binding to potentially harmful antigens and the ability of inducing proper responses of the immune system. One of the tenets of immunobiology is that antibodies are flexible in order to maximise their efficacy.

The team of researchers from Aarhus, Denmark, and Marburg, Germany, used EM microscopy and small angle x-ray scattering for their analysis. At Aarhus University, Scientist Michaela Miehe and Postdoc Rasmus K Jensen worked closely together the past two years to achieve the results. Based on this work, the research team can now describe the three-dimensional structure of IgE. The results they obtained were very surprising to the scientists involved.

"For the first time, we could show that IgE antibodies are unique and are violating the dogma of antibody flexibility. My work with electron microscopy demonstrated directly that IgE is a highly rigid molecule with a defined architecture of the allergen-binding moieties, which is different from the behavior of the other antibody isotypes we know," explains Postdoc Rasmus K Jensen.

The researchers also analyzed the structural and functional impact of a therapeutic antibody currently tested in clinical trials on the IgE molecule. This therapeutic antibody, which is of a different type than IgE, binds to IgE and prevents allergic reactions.

"Our new results describe the structural changes that IgE undergoes when neutralized by this anti-IgE antibody. This also allows us to understand better, how IgE recognizes allergens and the two IgE receptors sitting on the surface of the immune cells we have in our body," explains Associate Professor Edzard Spillner.

Antibody features revised

Generally, an allergic person produces high levels of IgE molecules directed against external allergens when exposed to them. These IgE antibodies circulate in the blood and are loaded onto the effector cells of the immune system. Upon exposure to allergens, these armed cells harnessed with IgE are triggered to release large amounts of mediators and histamine and thereby cause an immediate allergic reaction in the body.

"We now realise that the picture we and other researchers have puzzled together through decades by studying IgE fragments differs compared to the new results obtained with intact IgE. It was also most satisfying that we could visualize how the anti-IgE antibody changes the IgE architecture including the antigen binding arms," explains Professor Gregers Rom Andersen.

The researchers conducted their experiments with different recombinant IgE molecules they produced in the lab. These IgE molecules recognize specifically a house dust mite allergen and sugar groups found on allergens. However, the method can be transferred to virtually all types of IgE molecules.

Hope for better medicine

Allergic diseases are affecting the lives of more than one billion people worldwide, and their prevalence is expected to reach up to 4 billion in 2050. The prevalence of allergic diseases and socioeconomic impact are particularly on the rise in urbanizing regions and globalizing world in association with environmental and lifestyle changes. Apart from individual suffering of patients, allergic diseases present a very high cost for the health care systems. The current treatments cannot control all types of allergy, but the researchers now hope that their scientific results will pave the way for the development of new types of allergy medicine.

"We now understand much better and in much more detail the IgE molecule that we want to control and the way it behaves upon treatment of patients with allergy medicine. This also allows us to envision new strategies for developing medicine of the future," says Edzard Spillner.

While the obtained knowledge will finally benefit the individual patient, the team will also broaden the ongoing research in the field.

"The extraordinary characteristics of IgE makes it an exciting object for more detailed studies in concert with molecules within and outside the allergic immune response," says Gregers Rom Andersen.

TAMPA, Fla. (February 24, 2020)- Neuroscientists at the University of South Florida have become the first to definitively prove pressure in the eye is sufficient to cause and explain glaucoma. They come to this conclusion following the development of a method that permits continuous regulation of pressure without damaging the eye.

Researchers were able to manipulate pressure by implanting a tiny tube in the eye of an animal model and connecting the tube to a pressure source and pressure sensor. The pressure source infused fluid into the eye via a saline reservoir or a portable micropump built by the researchers. The pressure sensor took measurements every few seconds around-the-clock for up to two months, during which time the tube remained fixed in place even though the eye blinked and rotated and the animal freely moved. The study, published in Scientific Reports, found that raising pressure of an otherwise healthy eye resulted in patterns of retina and optic nerve damage like that seen in human glaucoma.

"The technique offers a significant advancement in glaucoma research," said Chris Passaglia, PhD, professor of medical engineering at USF. "All studies to date have elevated pressure by blocking fluid outflow from the eye, whereas ours adds fluid as necessary to produce a desired pressure without damaging outflow pathways. Now researchers can have direct knowledge and control of eye pressure."

A longstanding challenge with existing methods of glaucoma induction is that eye pressure changes are unpredictable and generally irreversible. Pressure may rise to unrealistic levels or not change at all if induction procedures are unsuccessful. Pressure can also settle at a stable value, fluctuate irregularly over time, or return abruptly to normal. Passaglia says the new tools can help speed research progress by removing such experimental variability and by enabling systematic studies of unanswered questions like the role of eye pressure history in disease onset and progression. Putative glaucoma drugs can also be concurrently infused by the system into the eye of animal models and screened for therapeutic effectiveness.

The viral infections of the upper respiratory tract are an important cause of morbidity and mortality worldwide and, among them, influenza is one of the most important ones, with severe cases ranging from three and five million cases, and between 290,000 and 650,000 deaths per year. This is why a proper supervision of the disease is crucial. Two studies led by the UB analyzed several aspects involved in the detection of the disease: the utility of the definition of the illness considering clinical manifestation and complementarity of supervision systems based on severe ambulatory cases that require hospitalization in Catalonia. Moreover, they also studied the features of the cases that were detected in Catalonia among children and teenagers who are under eighteen years old.

Experts from the Research Group on Epidemiology, Prevention and Control of Communicable Diseases of the UB, from the Institute of Biomedical Research of Lleida, the Public Health Agency of Catalonia and the Barcelona Public Health Agency, led by Professor Àngela Domínguez, from the Faculty of Medicine and Health Sciences of the UB and the Epidemiology and Public Health Networking Biomedical Research Centre (CIBERESP, Carlos III Health Institute), took part in the three studies.

In the study published in the journal Viruses the researchers analyze in a retrospective way the behavior in different definitions of case and different symptoms for the flu to identify properly the cases of laboratory-confirmed-influenza between 2008 and 2018 in Catalonia. Researchers analyzed the case definitions of the World Health Organization (WHO) and the European Centre for Disease Prevention and Control (ECDC), as well as different symptoms that can appear. "Clinical definitions for influenza are important because they can have a more homogeneous recount of the impact caused by the virus in the community and make comparisons within the same community to see variations that occur over time, as well between seasons and even between communities and countries that use similar surveillance systems", notes Professor Àngela Domínguez.

Results show the WHO definition (based on temperature and cough) is the most sensitive one to predict cases that are really caused by influenza virus instead of other respiratory viruses. "The definition of the case that predicted best the laboratory-confirmed-influenza was the WHO definition of influenza syndrome, both considering every week of the year and considering only epidemic weeks. The symptoms that behaved as predictors of confirmed-influenza were temperature, cough, myalgia, headache, general discomfort and symptoms that emerged of a sudden. Temperature was the most predicting symptom for confirmed influenza", note the authors.

All the case definitions predicted best the confirmed influenza when the patients presented comorbidity. The ability of different symptoms to predict confirmed-influenza varied depending on the age groups: temperature got the highest value in people aged over 65 and cough got the highest value in children aged from 5 to 14. In patients with comorbidity, the temperature showed its highest ability to predict confirmed influenza. According to the authors of the study, these results can confirm that the case definition used in Catalonia to analyze clinical samples from certain patients could be affected by the influenza virus and not other viruses is accurate.

Complementary epidemiologic supervision systems for influenza

The second study carried out by the research team, published in the journal BMC Public Health, assessed two complementary surveillance systems for the flu. The objective was to analyze the cases of laboratory-confirmed-influenza syndrome in primary care and hospitalized cases of laboratory-confirmed-influenza. The study was carried out during seven influenza seasons (2010-2017) in Catalonia, with different series of data. On the one hand, data from primary care doctors informing about treated influenza syndrome and laboratory-confirmed-influenza cases. On the other hand, data obtained by twelve hospitals on the severe cases of laboratory-confirmed-influenza that were hospitalized.

Results show the information coming from primary care doctors predicts an average of 1.6 weeks before the rest of the sources, but researchers defend to keep the current supervision structure: "We have to continue with the supervision that combines data from primary care in people who do not need hospitalization together with data from severe cases that require hospitalization. According to what the article suggests, it is important for the surveillance system to include data from hospitalization cases despite not presenting a severe influenza, which was already done in the 2017-2018 season", researchers say.

Higher risk for children under two

Researchers also analyzed the clinical and epidemiological features of patients aged from zero to seventeen that were hospitalized in Catalonia for presenting severe forms of influenza during the 2010-2016 period. The study, published in the journal Scientific Reports, concluded confirming that children under two years old are those with a higher risk of showing severe forms of influenza which can even lead to death.

Out of the 291 registered cases, 79.4% of them were caused by the type A influenza virus and the 20.6% by the virus of type B influenza. Most of the studied cases (56.7%) corresponded to patients under two years old, and 24.4% of them were children aged less than one. The most common complication (62%) was pneumonia. The 21.3% of patients required hospitalization in the intensive care unit, most of them (54.8%) being children under two years old. Three detected deaths during these period were caused by the type A influenza virus.

Regarding the results, the authors recommend to "strengthen the supervision in children population to better know the real impact of the illness and vaccine those kids with risk conditions for they present certain diseases that show predisposition to complications".

SILVER SPRING, Md.--Researchers are proposing a new scientifically correct and medically actionable disease classification system for obesity, according to a paper published online in Obesity, the flagship journal of The Obesity Society.

The proposed disease classification system is based on the concept Adiposity-Based Chronic Disease (ABCD). The diagnostic term reflects both the pathophysiology and clinical impact of obesity as a chronic disease. The proposed coding system has four domains: pathophysiology, body mass index (BMI) classification, complications, and complication severity; and incorporates disease staging, specific complications that impact health, the basis for clinical intervention, individualized treatment goals and a personalized medicine approach.

"The coding reflects 'what we are treating' and 'why we are treating it', and, hopefully, will provide impetus for greater access of patients to evidence-based treatments," said W. Timothy Garvey, MD, Butterworth Professor in the Department of Nutrition Sciences and Director of the Diabetes Research Center at the University of Alabama at Birmingham. Garvey is also a GRECC investigator and staff physician at the Birmingham Department of Veterans Affairs Medical Center. Garvey is the corresponding author of the study.

The diagnosis of obesity is currently based only on BMI that conveys no indication of the impact of excess adiposity on a person's health. The International Classification of Diseases (ICD) code for obesity reads "obesity due to excess calories," which experts say is not medically meaningful and does not reflect obesity pathogenesis.

"These inadequacies contribute to lack of access of patients to evidence-based therapies and appreciation of obesity as a chronic disease," said Garvey.

The American Association of Clinical Endocrinologists (AACE) and the European Association for the Study of Obesity (EASO) have both embraced the concept of ABCD.

"There is increasing recognition globally that BMI and other simple metrics of obesity do not accurately reflect the complexity of the disease or the circumstances of patients. The Garvey and Mechanick proposal for a scientifically accurate and medically actionable four domain classification system is most welcome, and builds on previous initiatives of the AACE and EASO, explaining obesity as an 'adiposity-based chronic disease.' It is time for obesity to enter the era of precision medicine, with novel classification systems based on functionally established endpoints," said Gema Frühbeck, first author of the EASO paper on ABCD.

"AACE has historically supported efforts in advancing the clinical evaluation and therapy of obesity beyond just a disease of weight based upon BMI, including guidelines recommending more nuanced diagnosis based upon exam and clinical evaluation to classify and stage the severity of disease. It is critical to match the intensity of therapy to the severity of disease and pathophysiology of disease, thus AACE followed its guidelines with a position statement proposing ABCD as a new diagnostic term for obesity. This proposed ICD coding structure supports the clinical efforts of personalizing individual diagnoses with more precision and nuance, which will benefit customized therapeutic plans for patients with obesity," said Karl Nadolsky, DO, FACE, chair of the Nutrition and Obesity Disease State Network at AACE.

"The framework provides a well-organized way to help practitioners and payers conceptualize obesity beyond an erroneous framework of this patient eats too much and is not active enough," said Jamy Ard, MD, professor of epidemiology and prevention at Wake Forest School of Medicine and co-director of the Weight Management Center at Wake Forest Baptist Health in Winston-Salem, NC. Ard was not associated with the research.

Ard added that the biggest challenge he foresees with this approach is that providers currently underdiagnose obesity using the simple BMI-based coding. "This more advanced approach will require a significant amount of education and outreach to change providers' behaviors. However, if better reimbursement is tied to this type of coding system as the authors aspire, it may help to drive broader adoption and implementation," said Ard.

Tempe, Ariz. –Two Arizona physicians are trying to improve care for patients with chronic kidney disease by pioneering a minimally invasive procedure that provides easier access to a patient’s bloodstream for life-saving dialysis treatments.

Kidney specialist Randy Cooper, MD, of SKI Vascular Center, presented his experience with the Ellipsys® Vascular Access System at the meeting of the American Society for Diagnostic and Interventional Nephrology (ASDIN), February 21-23, in Las Vegas.

His initial four-year follow-up data indicates this new type of dialysis access may last longer and require fewer interventions than the current standard of care, which requires an open surgical procedure. Dr. Cooper, a board member of the Phoenix chapter of the National Kidney Foundation, is also a co-author on a recent position paper from ASDIN regarding patient selection for this revolutionary approach to dialysis patient care.

In Arizona, more than 10,000 people are currently on dialysis as a result of kidney failure - an increase of nearly 50 percent in the last decade. For these patients, many of whom must visit a dialysis center several times a week for their life-saving treatments, any improvement in quality of life can have a significant impact.

“The ability to create a minimally invasive dialysis access means no incisions, no scars and less trauma for the patient. Most people want to avoid surgery at all costs, but for patients with kidney failure who already spend so much of their life under a doctor’s care, this technology offers a considerable quality of life impact,” said Dr. Cooper. “As soon as we learned about this novel technology, we knew we wanted to be able to offer this to our patients.”

Nearly 100 kidney patients have now undergone the Ellipsys procedure at SKI Vascular Center.
In 2015, Dr. Cooper and his partner Umar Waheed, MD, were among the first physicians to participate in the U.S. clinical trial and later co-authored an article on the study results showing the safety and efficacy of the Ellipsys system. SKI was the first surgery center in the United States to offer the Ellipsys System following its FDA approval in 2018.

Using a minimally invasive approach, Ellipsys replaces surgery with a single needlestick in order to create a fistula (a type of vascular access for dialysis). For the past 50 years, the only way to create a fistula was with a complex surgery that subjects patients to discomfort and long recovery times. In contrast, the Ellipsys procedure can be done in an outpatient setting and requires little to no recovery time.

Chandler-based data analyst Alex Kaplan, a 32-year old father of one, had his fistula created with Ellipsys in September 2019 and has been successfully using the fistula for dialysis three times a week since December 2019.

“Ellipsys just seemed like the better option in every way. It was a lot less invasive and I had virtually no recovery. With having a young child, I needed to be back in action as soon as possible for my family,” he said. “The procedure was quick, with no complications, and I returned to work the next day. My fistula has very little impact on my daily life.”

In addition to being more patient-friendly, recently published two-year data has shown this type of access may function better and last longer than the surgical method. Dr. Cooper’s ASDIN presentation also suggests Ellipsys fistulas heal faster and can be ready to use for dialysis access sooner than surgical ones - potentially reducing the time from fistula creation to dialysis from six months to four to six weeks.

“For patients with kidney failure, this innovative procedure eliminates a lot of the hurdles they
face in getting a fistula and actually being able to use it for dialysis,” said Dr. Waheed. “Patients
come in for a consultation and within a matter of days they are having the Ellipsys fistula
created, and in some cases they’ve begun dialysis with that fistula in about a month.”

LOS ANGELES, Feb. 21, 2020 -- Treatment with the blood thinner apixaban was associated with a lower risk of bleeding, death and hospitalization compared with warfarin, regardless of history of prior stroke or blood clot, according to a secondary analysis presented as late breaking science today at the American Stroke Association's International Stroke Conference 2020. The conference, Feb. 19-21 in Los Angeles, is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

The AUGUSTUS trial, first published in March 2019, found that treatment with apixaban without aspirin resulted in less bleeding and fewer deaths and hospitalizations than treatment with a vitamin K antagonist (like warfarin) plus aspirin among patients with atrial fibrillation and acute coronary syndrome and/or percutaneous coronary intervention treated with a P2Y12 inhibitor. The current study is a secondary analysis of the efficacy and safety outcomes of those treatments.

"We divided the AUGUSTUS study population into two groups: patients with prior stroke/transient ischemic attack/thromboembolism and those with no prior stroke/transient ischemic attack /thromboembolism," said lead study author Maria Cecilia Bahit, M.D., chief of cardiology at INECO Neurociencias in Rosario, Santa Fe, Argentina. "Apixaban was safer than warfarin - causing less major bleeding - and more effective, resulting in less death or hospitalization in both groups."

In the AUGUSTUS trial - a global, multi-center study - 4,614 patients with atrial fibrillation and an acute coronary syndrome or those under­going percutaneous coronary intervention (PCI) with planned treatment with a P2Y12 inhibitor were randomly assigned to receive apixaban or a vitamin K antagonist and to receive aspirin or matching placebo for six months. Of the 4,581 patients with information available about prior stroke, 13.8% had prior stroke/transient ischemic attack or thromboembolism.

This analysis found:

Patients with prior stroke were at increased risk of ischemic stroke, bleeding, hospitalization or death compared with those with no prior stroke;

Apixaban without aspirin was associated with the lowest rate of bleeding, death or hospitalization, regardless of history of prior stroke;

The highest rate of bleeding was seen in patients who received the combination of a vitamin K antagonist plus aspirin;

The risk of bleeding was higher with aspirin than placebo among patients with no prior events; and

There was no significant difference between aspirin and placebo observed between patients with and without prior stroke for other clinical outcomes.

"These results reinforce the main results of the AUGUSTUS trial by assuring physicians that even in a high-risk group of patients with prior stroke 'less is more.' In other words, a strategy of apixaban plus a P2Y12 inhibitor without aspirin has the most favorable outcomes, and triple therapy -- a vitamin K antagonist plus aspirin plus a P2Y12 inhibitor -- should be avoided," said Bahit.

PITTSBURGH, Feb. 21, 2020 - Although 1 in 7 adults smoke cigarettes the year prior to undergoing weight-loss surgery, nearly all successfully quit at least a month before their operation. However, smoking prevalence steadily climbs to pre-surgery levels within seven years, according to new research led by the University of Pittsburgh Graduate School of Public Health.

The findings -- reported today in the Annals of Surgery -- suggest that there may be missed opportunities to engage patients in interventions to improve long-term smoking cessation rates, particularly at regular post-surgery checkups.

"Smoking cessation prior to surgery is strongly recommended to reduce surgical complications," said lead author Wendy King, Ph.D., associate professor of epidemiology at Pitt Public Health. "But there isn't the same emphasis on maintaining cessation after surgery. Our findings show that there is a need for ongoing support in order to reduce and quickly respond to relapses."

King and her colleagues followed 1,770 adults who underwent Roux-en-Y gastric bypass surgery -- a procedure that reduces the size of the stomach and bypasses part of the small intestine -- for seven years post-surgery, annually surveying them about their smoking habits. The participants were enrolled in the National Institutes of Health-funded Longitudinal Assessment of Bariatric Surgery-2 (LABS-2), a prospective, observational study of patients undergoing weight-loss surgery at one of 10 hospitals across the United States.

More than 45% of the participants reported a history of smoking prior to surgery, with 14% still smoking in the year before surgery, which fell to 2% in the month before surgery. The rate rebounded to nearly 10% in the year following surgery and steadily climbed back to 14% by seven years post-surgery.

"Interestingly, the people who picked up smoking post-surgery weren't just the people who quit smoking in the year prior to surgery, presumably to prepare for the operation. Many had never smoked to begin with," said co-author Gretchen White, Ph.D., assistant professor in Pitt's School of Medicine, explaining that 2 out of 5 people who smoked after surgery had quit more than a year before their operation or hadn't ever smoked.

Additionally, people who identified as smokers post-surgery smoked more, going from an average of a dozen cigarettes per day in the year before surgery to more than 15 cigarettes per day seven years post-surgery. These findings contrast with concurrent reductions in smoking prevalence and intensity in the general U.S. population.

The researchers hypothesized that weight control would be a key reason weight-loss patients took up smoking after surgery, but found that the prevalence of smoking for weight control was actually fairly stable over time, at about 2% pre- and post-surgery, and did not appear to be related to smoking more cigarettes. King noted that "this surprised everyone, as there is a general assumption that weight control is a main motivator for smoking."

While the study was not designed to find a biological reason for the results, the researchers did observe that gastric bypass patients were more likely to smoke post-surgery than patients who underwent gastric banding, where a silicone belt is surgically inserted around the stomach to reduce the amount of food it can hold. A recent study showed that gastric bypass increases exposure to the psychoactive nicotine metabolite cotinine. Just as gastric bypass increases the risk of alcohol use disorder due to changes in alcohol metabolism that lead to higher and quicker elevation of blood alcohol levels, it may also increase risk of smoking via nicotine metabolism, King suggested.

The scientists identified several factors that predict which patients would be most likely to take up smoking after surgery. Not surprisingly, a prior history of smoking was the greatest risk factor. In addition, younger age, poverty, being married or living as married, and drug use were each associated with increased risk.

LOS ANGELES, Feb. 21, 2020 -- Adding phone-based lifestyle counseling to home blood pressure telemonitoring is an effective strategy to improve long-term blood pressure control among minority stroke survivors with uncontrolled high blood pressure, according to late breaking science presented today at the American Stroke Association's International Stroke Conference 2020. The conference, Feb. 19-21 in Los Angeles, is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

Uncontrolled high blood pressure, or hypertension, is a major predictor of racial disparities in stroke outcomes in the United States. Improving blood pressure control among minority stroke survivors is key to secondary stroke prevention. Although home blood pressure telemonitoring and lifestyle counseling by nurses have proven effective in controlling blood pressure, this study is the first time this strategy has been tested specifically among minority stroke survivors.

Researchers randomly assigned 450 black and Hispanic stroke survivors with uncontrolled blood pressure (average age 62; 51% black; 44% women) to home blood pressure telemonitoring alone with monthly feedback to primary care providers, or home blood pressure telemonitoring plus telephone-based counseling by nurses. The nurses counseled patients via telephone on lifestyle behaviors and strategies to improve their blood pressure and reported the blood pressure readings to the patient's doctor.

After 12 months, patients who received the home blood pressure telemonitoring plus lifestyle counseling by nurses, experienced a 14-point reduction in their systolic blood pressure, while those who received only home blood pressure telemonitoring had only a 5-point drop in their systolic blood pressure.

"The magnitude of reduction in systolic blood pressure for those who received lifestyle counseling and support was much larger than we expected," said Gbenga Ogedegbe, M.D., M.P.H., lead study author, director, Division of Health and Behavior and the Center for Healthful Behavior Change in the Department of Population Health at NYU Grossman School of Medicine in New York City. "The reduction in systolic blood pressure of 14 mmHg among these patients would be expected to translate to at least a 20% decrease in stroke deaths and 34% fewer secondary strokes. These are pretty robust findings."

Ogedegbe said, "The results suggest that hypertension management in patients at high risk for recurrent stroke should involve telephone-based lifestyle counseling by a non-physician health worker coupled with home blood pressure telemonitoring. The role of the nurse case manager could be played by the patient's pharmacist or other trained non-physician health workers."