Culture

Historically, amphetamine-like drugs such as FDA-approved phentermine have been some of the most popular anti-obesity drugs that have ever been prescribed. They work in the brain by suppressing appetite but, besides being addictive, can also have dangerous side effects such as increased heart rate, hypertension and hyperthermia.

Despite being officially declared a chronic disease there are very few long-lasting and cost-effective treatments for obesity. Amphetamines are one of the few and they reportedly act in the brain to reduce appetite and increase locomotion or stamina. However, these drugs are also known for strongly activating the sympathetic nervous system, the peripheral part of the nervous system known to accelerate the heart rate, constrict blood vessels and raise blood pressure. Amphetamines are thus infamously coined as sympathomimetic. "It was always thought that amphetamine's noxious effects on the cardiovascular system resulted from a their direct stimulation of the cardiac sympathetic nerves themselves, rather than from an central action in the brain, where we know it acts, for instance, to supress appetite", highlights Ana Domingos, "despite the lack of experimental evidence favouring one mechanism over the other". However, the researchers suspected that the cardiac side effects of amphetamines could indeed originate in the brain. And if this was true, they imagined that if they could design a drug that did not pass the blood-brain barrier, they could avoid these unwanted outcomes, while perhaps retaining an anti-obesity action.

To test their hypothesis, they attached polyethylene glycol (PEG) polymer chains to amphetamine, in a process known as PEGylation. "PEGylation is often used to mask a drug from the body's immune system, or to increase the hydrodynamic size of molecules to alter their distribution in the body", explains Gonçalo Bernardes. Through this process, they created a larger, PEGylated amphetamine, which they dubbed PEGyAMPH. Because of its larger size, PEGyAMPH cannot penetrate the blood-brain barrier and the team showed that it is indeed absent is the brains of mice treated with PEGyAMPH, which did not show suppressed feeding nor increased locomotion. This lack of behavioural effects was another confirmation that the PEGyAMPH did not indeed cross the blood-brain barrier.

The team then used different drug delivery routes to confirm that the cardiovascular effects of amphetamines are not caused peripherally but centrally instead, originating from the brain. Either compounds, if directly delivered onto the brain, induce cardiovascular side effects. Conversely, and unlike amphetamine, these noxious side effects are gone if the brain-sparing PEGyAMPH is delivered systemically.

They also found that the activation of peripheral sympathetic neurons, which receive signals from the brain, is required for centrally-acting amphetamines to be effective in stimulating lipolysis and promoting weight loss. "This means that the anti-obesity effect of an amphetamine treatment is not as effective in the absence of an intact sympathetic nervous system, despite its behavioural effects on appetite and locomotion", explains Inês Mahú.

PEGyAMPH can still favour the activation of sympathetic neurons and increase peripheral sympathetic output onto adipose tissues. "And it does this in a different way of the unmodified amphetamine, namely by not entering the brain and by not binding to some of the well-known molecular targets of amphetamine", adds Gonçalo Bernardes. The researchers thus coined the compound as sympathofacilitator, to distinguish it from its chemical predecessor, the sympathomimetic class. They showed that the effect of PEGyAMPH is mainly mediated by the β2-adrenoceptor (ADRB2), which they show to facilitate the activation of peripheral sympathetic neurons. These neurons were previously shown by Domingos' team to make fat to burn if they are triggered by descending signals from the brain. The researchers then demonstrated that PEGyAMPH protected mice against obesity despite the absence of behavioural effects, such us decreased appetite and increased locomotor activity. "It was extremely exciting when we saw that, while untreated mice readily store excess fat the ones receiving treatment resisted weight gain" stated Inês Mahú, PhD student at the IGC and the first author of this study.

PEGyAMPH increased sympathetic-stimulated fat breakdown in the body, via a cellular process named lipolysis. It also increased thermogenesis, the process of heat production, which burns calories stored in fat. Importantly, although PEGyAMPH raises thermogenesis, unlike unmodified amphetamines, it does not cause higher core body temperature, because they have different actions on peripheral vasculature and thus on thermoregulation. Amphetamine is a vasoconstrictor, whereas PEGyAMPH promotes vasodilation via smooth muscle relaxation (known to involve ADRB2), allowing for higher heat-dissipation which normalizes core body temperature. Thus, the novel drug functions as an energy sink, whereby generation of heat is directly coupled to its dissipation. Ana Domingos adds "this is like turning on the heat and leaving the windows open during the winter: you'll see your gas bill go up!"

The newly designed drug has several advantages over traditional amphetamine treatments for weight loss. Because it does not pass the blood-brain barrier, PEGyAMPH is not addictive and it also does not affect cardiovascular function, thus avoiding the worrying side effects that amphetamines can cause. Moreover, it also improved blood glucose levels in mice by increasing sensitivity to insulin, thus preventing hyperinsulinemia, a condition that precedes the development of type 2 diabetes. Hence, PEGyAMPH reduces obesity with a size-effect comparable to that of AMPH, yet with a distinct mechanism in that it spares effects relating to brain action, overriding caloric intake by increasing energy expenditure.

Obesity is a major health issue across the world and is implicated in many serious health conditions such as diabetes, heart disease and cancer. Although PEGyAMPH is only validated pre-clinically, this new weight-loss drug brings hope for a safer and more cost-effective treatment than those currently available.

The IGC and IMM Innovation and Technology Transfer Units are working to license this technology, already patented, to industrial partners ensuring that this discovery reaches society.

How cells recognize pathogens and alert the immune system swiftly is a fundamental process of high importance for the survival of any species, including humans. A key role is ascribed to so-called adapters, that equal little molecular platforms inside cells where signals from pathogen detectors are integrated for safety and accuracy and conveyed to lasting signals leading to the activation of the major "red alarm" genes, like interferons. Researchers from the lab of Giulio Superti-Furga at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences in collaboration with Boehringer Ingelheim have identified a new key element of the multi-component machinery that is responsible for sorting out the nature and severity of the pathogen challenge. The new protein, named TASL, is indispensable for the signaling of so-called Toll-like receptors (TLR) in the endosomes leading to activation of the gene-activator IRF5 in certain immune cells. Sensitive "tuning" of the machinery is highly important as too much output causes inflammation also in the absence of the pathogen, as in auto-immune diseases. This particular version of the machinery seems particularly associated with disorders such as systemic lupus erythematosus (SLE). This discovery highlights a potential new target for the development of drugs to treat certain autoimmune diseases and possibly also overreaction to viral and other infections, and has been published in the renowned scientific journal Nature.

The immune system is the body's natural defense system and is made up of a network of cells, molecules, tissues, and organs working together to protect the body against infectious agents, such as viruses, bacteria or pathogenic fungi. The immune system is equipped with a sophisticated repertoire of sensing mechanisms which detect these pathogens and orchestrate an appropriate immune response. Autoimmune diseases originate when the immune system loses the ability to differentiate between itself and other foreign bodies.

Previous studies revealed that SLC15A4, a member of the body's biggest family of transporter proteins, was known as an essential component required for the correct function of these TLRs. Based on their strong research interests in pathogen-sensing by the innate immune system and the characterization of solute carriers, researchers in the group of CeMM Scientific Director Giulio Superti-Furga set out to investigate how SLC15A4 influences the ability of TLRs to sense pathogens, and, consequently, gain a better understanding on its implication in autoimmune conditions, and in particular SLE.

In their study, first author Leonhard Heinz and the team, including Boehringer Ingelheim researchers in Ridgefield, undertook a precise investigative work, not taking for granted previous findings on SLC15A4 and the connection to this group of specially located TLRs. They painstakingly determined by biochemistry and mass spectrometry the molecular interactions that involved SLC15A4. This led to the identification of an uncharacterized protein CXorf21, belonging to the functionally orphan genes that are merely numbered and assigned to the chromosome of origin. The gene, like SLC15A4, had been previously loosely associated with SLE.

The team demonstrated that the interaction between TASL and SLC15A4 was crucial for the localization and function of the TASL protein and could pinpoint the precise involved portions of both proteins. A eureka moment for the understanding of the protein came with the observation that TASL harbors a specific motif essential for the recruitment and activation of IRF5. "After STING, MAVS and TRIF, the new protein TASL is the fourth key innate immunity adaptor functioning as a platform for the encounter of a kinase and a gene activator of the IRF family", says Manuele Rebsamen, CeMM senior postdoctoral fellow and project leader of the study.

These findings raise the possibility that interfering pharmacologically with the SLC15A4/TASL complex could allow the regulation of TLR responses and, consequently, modulate inflammatory responses in the body. "It was clear to us that SLC15A4 plays a key role in endosomal TLR function and is involved in disease, but the underlying mechanism was not understood. These are exactly the exciting scientific questions that we love to address at our institute", says Giulio Superti-Furga, CeMM Scientific Director and responsible for the study. He adds: "We are happy that the vision we share with Boehringer Ingelheim regarding Solute Carriers being a group of disease-relevant proteins worthy of investigation was rewarded in this successful and exciting partnership."

Although COVID-19 commands the headlines today, tuberculosis (TB) remains the biggest infection killer in the world and multiple drug resistant TB, which does not respond to regular antibiotics, continues to be a major threat to global health.

TB is caused by bacteria (Mycobacterium tuberculosis) that most often affect the lungs. Tuberculosis kills over 4,000 individuals daily throughout the world; while here in Ireland resistant and highly complex cases of TB continue to rise year after year, with cases numbering over 300 annually.

Now, scientists at Trinity College Dublin and St James's Hospital, Dublin have discovered how the iron chelator, DFX, which functions by attaching to iron, drives the immune system to deal with tuberculosis (TB). The findings have been published today [Wednesday, 13th May 2020] in the prestigious immunity journal, Frontiers in Immunology here: https://bit.ly/3dH6eix.

Iron is crucial for daily human function but is also an essential element for the survival of viruses and bacteria. For some time, scientists have known that depriving infections of iron can limit bacterial burden and help improve patient outcomes.

The research team, led by Professor Joseph Keane, has shown for the first time how DFX supports lung immunity against TB by driving the activation of a key metabolic pathway called 'glycolysis'. The process of glycolysis helps immune cells make energy to fight infection which in turn drives several signals that improve the macrophages' (white blood cells) ability to address TB infection.

By helping immune cells turn on glycolysis, DFX has the potential to aid in developing more lung targeted treatment of pulmonary infection, which is the ultimate goal of this research group; by boosting the patient's immune response using the iron binding agent, DFX.

Dr James Phelan, Department of Clinical Medicine, Trinity College and Senior Author of the study said:

"Infectious disease experts globally agree on the important role metabolic processes play in eradicating a variety of infections; DFX helps infected immune cells to readily switch on metabolism which could help immune cells fight the infection."

Indeed, a clinical trial is underway using DFX to treat COVID-19, yet it is unclear how DFX might help the human lung fight infection; this research has the potential to greater understand this. In related experiments, the Trinity investigators demonstrate that DFX also works in a cellular model of sepsis, which broadens the appeal of this DFX strategy in fighting other infectious diseases and supports the clinical trial underway of DFX for COVID disease.

In the fight against the current pandemic, researchers of the Luxembourg Centre for Systems Biomedicine (LCSB) at the University of Luxembourg are coordinating an international collaboration to build a COVID-19 Disease Map: a comprehensive repository incorporating all current knowledge on the virus-host interaction mechanisms. This online tool will support research and improve our understanding of the disease.

In an article published this week in Nature Scientific Data, the researchers present their project and call for contributions from the R&D community worldwide.

Leveraging over a decade of expertise in disease maps and community building, the LCSB researchers are organising this project as a rapid response to the current epidemic. 162 contributors from 25 countries around the world are now participating in a collaborative effort. Extracting and assembling data from the existing literature and the fast-growing number of COVID-19 publications thanks to a rigorous and efficient organisation, they are building a reliable knowledge repository.

The disease map will provide a graphical, interactive representation of the disease mechanisms and a computational resource for analyses and disease modelling. "This platform will allow domain experts, such as clinicians, virologists, and immunologists, to collaborate with data scientists and computational biologists for a precise formulation of models and accurate data interpretation," explains Prof. Reinhard Schneider, head of the Bioinformatics Core at the LCSB.

The way the COVID-19 Disease Map is being built is unique as the researchers have to rely on a distributed, multi-tool, multi-group approach dictated by emergency time-constraints of the ongoing pandemic. Only a collaboration between several research institutions and the combination of multiple areas of expertise can allow to tackle this challenge fast enough. "The response from the research community is already impressive, but we want to gain more visibility and attract new contributors," underlines Dr Marek Ostaszewski, member of the Bioinformatics Core and one of the coordinators of the disease map. "We invite curators to join the project and help building the repository." The researchers are also seeking input from practising physicians, clinicians and domain experts. They can help to review the map - its content and its scope - and to improve quality and applicability.

Such an open collaboration between clinical researchers, life scientists, pathway curators, computational biologists and data scientists makes it possible to build a trusted, reliable, and useful resource for all projects that are looking into COVID-19 disease mechanisms. The gathered knowledge will improve our understanding of gender, age, and other susceptibility features of the host, disease progression, defence mechanisms, and response to treatment. It will facilitate the development of efficient diagnostics and treatment strategies.

"This project paves the way for long-term community-based development of high-quality models and knowledge bases that will be useful both for the current and future epidemics," concludes Prof. Schneider.

Scientists have identified a pair of neutralizing antibodies - isolated from a patient who recovered from COVID-19 - that bind to the glycoprotein spike of the SARS-CoV-2 virus, blocking the spike's ability to bind to the human ACE2 receptor and mediate viral entry into host cells. Preliminary tests of the two antibodies in a mouse model resulted in a reduction of virus titers, suggesting that the antibodies may offer therapeutic benefits - in addition to informing the design of small molecule therapeutics and vaccine candidates to fight COVID-19. Yan Wu and colleagues found that the antibodies, named B38 and H4, can each bind simultaneously to different epitopes on the spike's receptor binding domain (RBD), such that both antibodies together may confer a stronger neutralizing effect than either antibody on its own - a prediction supported by in vitro experiments. This feature also means that, should one of the viral epitopes mutate in a way that prevents the binding of one of the two antibodies (a phenomenon known as immune escape), the other antibody may yet retain its neutralizing activity. By imaging the structure of the viral spike's RBD bound to B38, Wu et al. confirmed that B38 binds to a subset of the amino acids bound by ACE2 in the RBD, providing an explanation for why B38 confers such strong neutralizing effects. The authors suggest that a "cocktail" containing both antibodies could provide direct therapeutic benefits for COVID-19 patients, while the new information regarding the viral spike epitopes could aid the development of small molecule antivirals and vaccine candidates to fight the SARS-CoV-2 virus.

By 11 May, when lockdown restrictions were eased in France, about 4.4% of the French population had been infected with SARS-CoV-2, a new modeling study suggests. These estimates are well short of what would be required for herd immunity, say the authors. Understanding the level of immunity to SARS-CoV-2 will be key to avoiding a rebound in the epidemic as populations around the world ease lockdowns. Serostudies - which detect anti-SARS-CoV-2 antibodies in patients' blood - are important to informing questions of immunity, but growing evidence suggests that many people, especially those who are asymptomatic, take a while to seroconvert. During this time, researchers seeking to understand virus immunity need to rely on indirect measures, including data on hospitalizations and deaths. France has been heavily affected by the SARS-CoV-2 epidemic and went into lockdown on March 17, 2020. Following the expected reduction in cases, the French government announced it would ease restrictions on 11 May. To better understand the underlying level of population immunity and infection at this time, Henrik Salje and colleagues studied de-identified hospital records of COVID-19 patients from all hospitals in France, along with surveillance data from these hospitals and from the Diamond Princess cruise ship. About 3.6% of infected individuals in France were hospitalized and 0.7% of those infected died, they say, with 10.1% of infected people over 80 dying. Across all ages, the authors report, men were more likely to be hospitalized than women. Applying their data to national models of disease transmission, Salje et al. estimate the lockdown in France resulted in a 78% reduction in transmission. By 11 May, when restrictions were eased in France, 4.4% of the population was likely infected, though infection rates were closer to 10% in two French regions most affected. However, because around 65% of the population would need to be immune for the epidemic to be controlled by immunity alone, population immunity appears insufficient to avoid a second wave, say the authors. Efficient control measures need to be maintained. The authors note their model projections can support healthcare planning of the French government by forecasting hospital bed capacity requirements.

It's a frustrating limitation of 3D printing: Printed objects must be smaller than the machine making them. Huge machines are impractical for printing large parts because they take up too much space and require excessive time to print. Now, a new material reported in ACS Applied Materials & Interfaces can be used to 3D print small objects that expand upon heating. The foam could find applications in architecture, aerospace and biomedicine. Watch a video here.

One type of 3D printing, stereolithography, creates objects by exposing sequential layers of light-sensitive resins to patterns of light, which cure the polymer into the desired shape. Large objects can be created with specialized stereolithography machines, but they are usually made by fastening smaller 3D-printed components together. David Wirth, Jonathan Pokorski and colleagues at the University of California, San Diego wanted to develop an expandable resin that could be used to print large objects with an inexpensive, commercially available 3D printer.

The researchers tested many different resin formulations to find one that allowed them to print an object that, when exposed to heat, expanded to a larger size. They used the formulation to 3D print a hollow, latticed sphere. Heating the sphere in an oven caused a volatile component of the resin to bubble out as a gas. This created a porous, polystyrene foam-like material that was up to 40 times larger in volume than the original printed object. With this method, the team also 3D printed many other shapes, including a boat, which could carry about 20 times more weight at its expanded size, and a wind turbine that could produce a small amount of electricity at its larger size. Although the new material isn't as strong as polystyrene foam, it could someday be used for cushioning, airfoils, buoyancy aids or even expandable habitats for astronauts, the researchers say.

In late May and early June, Earthlings may be able to glimpse Comet SWAN. The comet is currently faintly visible to the unaided eye in the Southern Hemisphere just before sunrise -- providing skywatchers with a relatively rare glimpse of a comet bright enough to be seen without a telescope. But Comet SWAN's initial discovery was made not from the ground, but via an instrument on board ESA (the European Space Agency) and NASA's Solar and Heliospheric Observatory, or SOHO, satellite.

The new comet was first spotted in April 2020, by an amateur astronomer named Michael Mattiazzo using data from a SOHO instrument called Solar Wind Anisotropies, or SWAN -- as seen here. The comet appears to leave the left side of the image and reappear on the right side around May 3, because of the way SWAN's 360-degree all-sky maps are shown, much like a globe is represented by a 2D map.

SWAN maps the constantly outflowing solar wind in interplanetary space by focusing on a particular wavelength of ultraviolet light emitted by hydrogen atoms. The new comet -- officially classified C/2020 F8 (SWAN) but nicknamed Comet SWAN -- was spotted in the images because it's releasing huge amounts of water, about 1.3 tons per second. As water is made of hydrogen and oxygen, this release made Comet SWAN visible to SOHO's instruments.

Comet SWAN is the 3,932nd comet discovered using data from SOHO. Almost all of the nearly 4,000 discoveries have been made using data from SOHO's coronagraph, an instrument that blocks out the Sun's bright face using a metal disk to reveal the comparatively faint outer atmosphere, the corona. This is only the 12th comet discovered with the SWAN instrument since SOHO's launch in 1995, eight of which were also discovered by Mattiazzo.

Comet SWAN makes its closest approach to Earth on May 13, at a distance of about 53 million miles. Comet SWAN's closest approach to the Sun, called perihelion, will happen on May 27.

Though it can be very difficult to predict the behavior of comets that make such close approaches to the Sun, scientists are hopeful that Comet SWAN will remain bright enough to be seen as it continues its journey.

Astronomers have detected elusive pulsation patterns in dozens of young, rapidly rotating stars thanks to data from NASA's Transiting Exoplanet Survey Satellite (TESS). The discovery will revolutionize scientists' ability to study details like the ages, sizes and compositions of these stars -- all members of a class named for the prototype, the bright star Delta Scuti.

"Delta Scuti stars clearly pulsate in interesting ways, but the patterns of those pulsations have so far defied understanding," said Tim Bedding, a professor of astronomy at the University of Sydney. "To use a musical analogy, many stars pulsate along simple chords, but Delta Scuti stars are complex, with notes that seem to be jumbled. TESS has shown us that's not true for all of them."

A paper describing the findings, led by Bedding, appears in the May 14 issue of the journal Nature and is now available online.

Geologists studying seismic waves from earthquakes figured out Earth's internal structure from the way the reverberations changed speed and direction as they traveled through it. Astronomers apply the same principle to study the interiors of stars through their pulsations, a field called asteroseismology.

Sound waves travel through a star's interior at speeds that change with depth, and they all combine into pulsation patterns at the star's surface. Astronomers can detect these patterns as tiny fluctuations in brightness and use them to determine the star's age, temperature, composition, internal structure and other properties.

Delta Scuti stars are between 1.5 and 2.5 times the Sun's mass. They're named after Delta Scuti, a star visible to the human eye in the southern constellation Scutum that was first identified as variable in 1900. Since then, astronomers have identified thousands more like Delta Scuti, many with NASA's Kepler space telescope, another planet-hunting mission that operated from 2009 to 2018.

But scientists have had trouble interpreting Delta Scuti pulsations. These stars generally rotate once or twice a day, at least a dozen times faster than the Sun. The rapid rotation flattens the stars at their poles and jumbles the pulsation patterns, making them more complicated and difficult to decipher.

To determine if order exists in Delta Scuti stars' apparently chaotic pulsations, astronomers needed to observe a large set of stars multiple times with rapid sampling. TESS monitors large swaths of the sky for 27 days at a time, taking one full image every 30 minutes with each of its four cameras. This observing strategy allows TESS to track changes in stellar brightness caused by planets passing in front of their stars, which is its primary mission, but half-hour exposures are too long to catch the patterns of the more rapidly pulsating Delta Scuti stars. Those changes can happen in minutes.

But TESS also captures snapshots of a few thousand pre-selected stars -- including some Delta Scuti stars -- every two minutes. When Bedding and his colleagues began sorting through the measurements, they found a subset of Delta Scuti stars with regular pulsation patterns. Once they knew what to look for, they searched for other examples in data from Kepler, which used a similar observing strategy. They also conducted follow-up observations with ground-based telescopes, including one at the W.M. Keck Observatory in Hawaii and two in the global Las Cumbres Observatory network. In total, they identified a batch of 60 Delta Scuti stars with clear patterns.

"This really is a breakthrough. Now we have a regular series of pulsations for these stars that we can understand and compare with models," said co-author Simon Murphy, a postdoctoral researcher at the University of Sydney. "It's going to allow us to measure these stars using asteroseismology in a way that we've never been able to do. But it's also shown us that this is just a stepping-stone in our understanding of Delta Scuti stars."

Pulsations in the well-behaved Delta Scuti group fall into two major categories, both caused by energy being stored and released in the star. Some occur as the whole star expands and contracts symmetrically. Others occur as opposite hemispheres alternatively expand and contract. Bedding's team inferred the alterations by studying each star's fluctuations in brightness.

The data have already helped settle a debate over the age of one star, called HD 31901, a member of a recently discovered stream of stars orbiting within our galaxy. Scientists placed the age of the overall stream at 1 billion years, based on the age of a red giant they suspected belonged to the same group. A later estimate, based on the rotation periods of other members of the stellar stream, suggested an age of only about 120 million years. Bedding's team used the TESS observations to create an asteroseismic model of HD 31901 that supports the younger age.

"Delta Scuti stars have been frustrating targets because of their complicated oscillations, so this is a very exciting discovery," said Sarbani Basu, a professor of astronomy at Yale University in New Haven, Connecticut, who studies asteroseismology but was not involved in the study. "Being able to find simple patterns and identify the modes of oscillation is game changing. Since this subset of stars allows normal seismic analyses, we will finally be able to characterize them properly."

The team thinks their set of 60 stars has clear patterns because they're younger than other Delta Scuti stars, having only recently settled into producing all of their energy through nuclear fusion in their cores. The pulsations occur more rapidly in the fledgling stars. As the stars age, the frequency of the pulsations slows, and they become jumbled with other signals.

Another factor may be TESS's viewing angle. Theoretical calculations predict that a spinning star's pulsation patterns should be simpler when its rotational pole faces us instead of its equator. The team's TESS data set included around 1,000 Delta Scuti stars, which means that some of them, by chance, must be viewed close to pole-on.

Scientists will continue to develop their models as TESS begins taking full images every 10 minutes instead of every half hour in July. Bedding said the new observing strategy will help capture the pulsations of even more Delta Scuti stars.

"We knew when we designed TESS that, in addition to finding many exciting new exoplanets, the satellite would also advance the field of asteroseismology," said TESS Principal Investigator George Ricker at the Massachusetts Institute of Technology's Kavli Institute for Astrophysics and Space Research in Cambridge. "The mission has already found a new type of star that pulsates on one side only and has unearthed new facts about well-known stars. As we complete the initial two-year mission and commence the extended mission, we're looking forward to a wealth of new stellar discoveries TESS will make."

May 13, 2020, NEW YORK CITY — Researchers from MSK Kids at Memorial Sloan Kettering Cancer Center (MSK) found that children with cancer are not at a higher risk of being affected by COVID-19. This new research led by Andrew Kung, MD, PhD, Chair of MSK Kids and his colleagues was published today in JAMA Oncology. MSK Kids is one of the largest pediatric cancer programs in the United States with a patient population that includes children, adolescents and young adults with cancer and a small proportion with non-oncological diseases such as bone marrow failure and immunodeficiencies.

Bottom Line: Pediatric cancer patients are no more vulnerable than other children to COVID-19 infection or morbidity resulting from COVID-19. Of all children with cancer infected with COVID-19, 95 percent had mild symptoms and did not require hospitalization. MSK Kids clinicians also tested asymptomatic children with cancer finding only a 2.5 percent rate of positivity compared to nearly 15 percent in their adult caregivers. Only half of the children with COVID-19 positive caregivers were themselves also COVID-19 positive. The researchers also found a very significant sex skewing with the vast majority of COVID-19 infections occurring in males. Together, these results suggest that children with cancer are not more susceptible than other children to infection or symptoms resulting from COVID-19, and that children are not an unrecognized reservoir of asymptomatic COVID-19 infection.

Methods and Findings: From March 10 through April 12, 2020, MSK Kids researchers instituted a screening and testing plan to mitigate risk associated with infection with COVID-19. MSK Kids patients were screened for exposure to contacts with known COVID-19 infection or for the presence of symptoms of COVID-19 illness at MSK. Researches performed COVID-19 testing on pediatric patients and their adult caregivers. Of the 178 unique pediatric cancer patients tested, the rate of positivity for COVID-19 was 29.3 percent in children with symptoms, but only 2.5 percent in asymptomatic children. Of the 20 patients who tested positive for COVID-19, only 3 were female.

Only one patient with COVID-19 illness required non-critical care hospitalization for COVID-19 associated symptoms. All other pediatric patients had mild disease symptoms and were managed at home. Of the 74 adult caregivers tested, 13 caregivers of 10 patients were found to be positive for COVID-19, including a 14.7 percent rate of COVID-19 infection in asymptomatic caregivers. Only half of the patients with COVID-19 positive caregivers were themselves also COVID-19 positive, suggesting low infectivity in children despite close household contacts.

While the overall numbers in the study are small, the data confirms that the overall morbidity of COVID-19 illness in pediatric cancer patients is low with only 5 percent requiring hospitalization for symptoms of COVID-19 infection; and that the rate of COVID-19 infection among asymptomatic pediatric patients is very low.

Journal: “COVID-19 in Children with Cancer in New York City” was published in the May 13, 2020 edition of JAMA Oncology.

Author Commentary: “We are encouraged by these latest findings that kids with cancer are not more endangered by COVID-19 and their symptoms are mild like in healthy children,” said Andrew Kung, MD, PhD, and corresponding author on the study. “These findings allow us to continue lifesaving cancer-directed therapy with standard precautions and safeguards but without heightened concern about adverse effects from COVID-19 infection.”

BLOOMINGTON, Ind. -- During the current pandemic, panicked overbuying of products such as toilet paper, cleaning products and similar items often has led to limited options for consumers and empty store shelves. What's often left are generic or lower-priced branded products.

According to new research from the Indiana University Kelley School of Business, it may not be because consumers during this crisis are viewing higher-priced products as having better quality. A paper published in the Journal of Consumer Research finds that scarcity actually decreases consumers' tendency to use price to judge a product's quality.

"Scarcity is aversive and triggers the desire to compensate for the shortage, and to seek abundance," said paper co-author Ashok Lalwani, associate professor of marketing at Kelley. "People who face scarcity are less likely to view less vs. more expensive options as belonging to different categories, and thus are open to differences at either or both ends of the price continuum."

This is the first paper to directly show the impact of scarcity on price-quality judgments. The findings are applicable amid times of economic crisis, natural disasters and social disturbances.

"We suggest that people may not only differ in terms of how they categorize purchases, but also in terms of the extent to which they categorize, and scarcity reduces the tendency," Lalwani said.

While consumers frequently judge the quality of a product based on its price, during times of scarcity consumers change their thinking and are less likely to categorize objects and are less likely to use the price of a product to infer its quality, Lalwani and his co-authors found.

The business implications for managers at high-end stores or those who want to increase sales of high-priced items are numerous. Lalwani suggested that one way such managers can activate the belief that higher prices indicate higher quality is by varying context or environmental factors. This could include encouraging consumers -- such as through contests or sweepstakes -- to categorize assorted items by price to facilitate the use of price-tiers as a basis for judging a product's quality.

"The same objective could also be attained by reducing consumers' desire for abundance," Lalwani said. "For example, inside the store, managers could have portraits, displays or ads highlighting the harmful effects of gluttony or hoarding behavior. Doing so may increase customers' price-quality inferences and shift them from purchasing lower-priced to higher-priced goods.

"Our findings also suggest that when stronger price-quality inferences are desired, retailers are advised to avoid utilizing scarcity messages, such as 'sale ends this week' or 'while supplies last,' especially for product categories in which the proportion of high-priced items is high, as priming scarcity among consumers may decrease their price-quality inferences."

Other authors of the paper, "The Impact of Resource Scarcity on Price-Quality Judgments," were Hanyong Park, assistant professor of marketing at the Eli Brand College of Business at Michigan State, and David Silvera, retired associate professor of marketing at the University of Texas at San Antonio.

For much of the 20th century, summer was considered "polio season," and people were accustomed to seeing swimming pools and movie theaters closed to stave off the latest epidemic. Shaking hands was off limits, and even touching money was perilous. The ever-present threat of death or permanent paralysis from polio was part of life, as were regular social-distancing efforts to limit the terrible disease's spread.

For many younger people in America, the idea of living under threat from a serious infectious disease has been hard to imagine, at least until COVID-19. But now the story of the victory over polio is even more resonant. In a new editorial in the journal Science, UVA Health's William A. Petri, MD, PhD, and graduate student Alexandra N. Donlan highlight medicine's great triumph over polio, at least in the West, and hold out hope we can do the same for COVID-19.

"Nearly four decades ago the United States was faced with a similar challenge, the race to develop a vaccine against an infectious disease," said Petri, an infectious disease expert who is developing a COVID vaccine. "Jonas Salk's demonstration of the ability of vaccination to prevent paralysis due to polio in 1955 led to a nationwide celebration and Salk's invitation to the White House."

Preventing Polio

The editorial authors call the prevention of polio epidemics a "signature success of science in the 20th century." But it was no easy task, they note, and the worldwide eradication of polio remains elusive.

Salk first developed an injectable vaccine in the mid-1950s. It was then tested in 2 million children in what Petri and Donlan call a "herculean" effort. "Today," they write, "the faith in, and support of, scientific research by the American public is, arguably, founded on the polio vaccine."

The Oral Vaccine

An oral vaccine soon followed, developed by Albert Sabin, and the two vaccines have served as the armament for vanquishing polio around the world. There is a drawback to the oral vaccine, however: Because it is manufactured using live, but weakened, virus, recipients excrete live virus in their stool. This can lead to disease transmission in communities with low vaccination rates, especially in areas with limited sanitation infrastructure. There are also, rarely, cases of the weakened virus taking sufficient hold in a vaccine recipient to allow person-to-person transmission. This has resulted in polio outbreaks in recent years in Africa and parts of Asia. To overcome this, with the support of the Bill & Melinda Gates Foundation there is fast-tracking of clinical trials of a new version of the oral vaccine, much as scientists are fast-tracking potential vaccines for COVID-19.

While more work remains to be done to eradicate polio around the world, the disease's conquest in the West speaks to the tremendous power of vaccine research. Polio, in America, stands alongside measles, mumps, tetanus, smallpox and more as serious diseases that are no longer a serious threat. Hopefully, in the not-too-distant future, COVID-19 will join that list.

"As the world faces COVID-19," the scientists conclude, "it is heartening to see the same application of science to public health for [COVID] as the one used for the last 70 years of polio-virus research."

More than 65,000 Americans are diagnosed annually with head
and neck cancer, which most often occurs inside the mouth and throat. For
patients who undergo surgery to treat this cancer, guidelines recommend that prompt
initiation of radiotherapy — within six weeks — is critical for best outcomes.

Unfortunately, delays in initiating post-operative radiotherapy
(PORT) are far too common. Patients do not always understand the importance of
prompt initiation of radiotherapy and may have to overcome other barriers, such
as lack of social support and insurance. In addition, health care providers do
not always communicate with one another or coordinate care. These avoidable
delays have a negative impact on outcomes in a disease that claims almost
15,000 lives in the U.S. each year.

To ameliorate this crisis, a research team at the Medical
University of South Carolina has developed and validated tools known as
nomograms to help predict treatment delays in high-risk patients based on
individualized risk factors. The team was led by Evan Graboyes, M.D., an
assistant professor in the Department of Otolaryngology-Head & Neck Surgery
at MUSC and a member of the Cancer Control Program at Hollings Cancer Center. The
results of the nomogram study were reported in JAMA Otolaryngology–Head & Neck Surgery.

“A nomogram is a
graphical representation of a mathematical model that we are using to predict
how likely it is that a patient with head and neck cancer may have a treatment
delay,” explained Graboyes. “We hope that these nomograms can be used to
identify patients at highest risk for treatment delays so that we can target
interventions to them to decrease the risk of delay.”

Standard-of-care treatment for patients with head and neck
cancer combines surgery, radiation and chemotherapy. However, treatment outcomes
remain very poor, and only about 50% of head and neck cancer patients with advanced
disease will survive after 5 years.

With the goal of improving the survival rate of patients
with head and neck cancer, Graboyes and his team developed and validated two
types of nomograms for predicting delays in PORT. The study examined pre- and
post-surgical data from 60,766 adult patients with head and neck cancer,
grouped into different cohorts.

The first nomogram is based on information available to both
the clinician and patient during the surgical consultation. At this point, the
patient will know whether he or she is likely going to have surgery followed by
radiation therapy.

“This type of nomogram will provide a personalized estimate
of the risk of delay commencing PORT and can be used to enhance counseling and guide
interventions for patients with higher risks of delay,” explained Graboyes.

The findings of Graboyes’ study suggest that stage 4 cancer
and oral cavity sites are two of the main variables associated with delayed
PORT initiation. Knowing this type of information beforehand will enable
patients to obtain pre-surgical dental oncologic treatment referrals and may
greatly improve timely PORT introduction.

The second nomogram incorporates information from before and
after surgery. According to Graboyes, this nomogram can be used by health care
systems to compare their rates of PORT delay in a risk-adjusted fashion that
acknowledges differences in the types of patients being treated.

In addition, the nomogram may guide quality improvement
initiatives. For example, one of the key factors associated with delayed PORT
was prolonged length of stay after surgery. This information may help physicians
to reduce the length of time patients stay in the hospital after surgery, eliminating one hurdle to prompt initiation of radiation treatment.

Although the two nomograms were developed in one cohort of
patients and validated in a second cohort of patients with head and neck cancer
from across the U.S., the study still had some key limitations. The nomogram
didn’t account for individual patient education, income, social support, dental
disease, smoking or alcohol consumption. Therefore, more research will be
needed to understand the degree to which these factors lead to delays in PORT
initiation. A future study will help to address some of these limitations.

Graboyes believes that the current study will help head and
neck cancer patients get the treatment they need and improve their chance of survival.

“I would love it if patients and clinicians would be able to
use the nomogram website to get more precise, quantitative information about
the risk of PORT delay and use it to educate patients, counsel them before
treatment and communicate risk precisely,” said Graboyes. “We know that getting
patients timely head and neck cancer care that follows guidelines is a
promising strategy to improve survival among these patients. I hope these
nomograms will be a practical and useful tool as we work toward the goal of
decreasing treatment delays.”

About the Medical University of South Carolina

Founded in 1824 in Charleston, MUSC is the oldest medical school in the South as well as the state's only integrated academic health sciences center with a unique charge to serve the state through education, research and patient care. Each year, MUSC educates and trains more than 3,000 students and 800 residents in six colleges: Dental Medicine, Graduate Studies, Health Professions, Medicine, Nursing and Pharmacy. The state's leader in obtaining biomedical research funds, in fiscal year 2019, MUSC set a new high, bringing in more than $284 million. For information on academic programs, visit http://musc.edu.

As the clinical health system of the Medical University of South Carolina, MUSC Health is dedicated to delivering the highest quality patient care available while training generations of competent, compassionate health care providers to serve the people of South Carolina and beyond. Comprising some 1,600 beds, more than 100 outreach sites, the MUSC College of Medicine, the physicians' practice plan and nearly 275 telehealth locations, MUSC Health owns and operates eight hospitals situated in Charleston, Chester, Florence, Lancaster and Marion counties. In 2019, for the fifth consecutive year, U.S. News & World Report named MUSC Health the No. 1 hospital in South Carolina. To learn more about clinical patient services, visit http://muschealth.org.

MUSC and its affiliates have collective annual budgets of $3.2 billion. The more than 17,000 MUSC team members include world-class faculty, physicians, specialty providers and scientists who deliver groundbreaking education, research, technology and patient care.

About Hollings Cancer Center

The Hollings Cancer Center at the Medical University of South Carolina is a National Cancer Institute-designated cancer center and the largest academic-based cancer research program in South Carolina. The cancer center comprises more than 100 faculty cancer scientists and 20 academic departments. It has an annual research funding portfolio of more than $44 million and a dedication to reducing the cancer burden in South Carolina. Hollings offers state-of-the-art diagnostic capabilities, therapies and surgical techniques within multidisciplinary clinics that include surgeons, medical oncologists, radiation therapists, radiologists, pathologists, psychologists and other specialists equipped for the full range of cancer care, including more than 200 clinical trials. For more information, visit http://www.hollingscancercenter.org.

Journal

JAMA Otolaryngology–Head & Neck Surgery

DOI

10.1001/jamaoto.2020.0222

For most adolescents, playing video games is an enjoyable and often social form of entertainment. While playing video games is a fun pastime, there is a growing concern that spending too much time playing video games is related to negative developmental outcomes and can become an addiction.

A recent six-year study, the longest study ever done on video game addiction, found that about 90% of gamers do not play in a way that is harmful or causes negative long-term consequences. A significant minority, though, can become truly addicted to video games and as a result can suffer mentally, socially and behaviorally.

"The aim of this particular study is to look at the longer-term impact of having a particular relationship with video games and what it does to a person over time," said Sarah Coyne, a professor of family life at BYU and lead author of the research. "To see the impact, we examined the trajectories of pathological video gameplay across six years, from early adolescence to emerging adulthood."

In addition to finding long-term consequences for addicted gamers, this study, published in Developmental Psychology, also breaks down gamer stereotypes and found that pathological gaming is not a one size fits all disorder.

Pathological video gameplay is characterized by excessive time spent playing video games, difficulty disengaging from them and disruption to healthy functioning due to gaming.

Only about 10% of gamers fall into the pathological video gameplay category. When compared to the non-pathological group, those in the study displayed higher levels of depression, aggression, shyness, problematic cell phone use and anxiety by emerging adulthood. This was despite the groups being the same in all these variables at the initial time point, suggesting that video games may have been important in developing these negative outcomes.

To measure predictors and outcomes to video game addiction, Coyne studied 385 adolescents as they transitioned into adulthood. Each individual completed multiple questionnaires once a year over a six-year period. These questionnaires measured depression, anxiety, aggression, delinquency, empathy, prosocial behavior, shyness, sensory reactivity, financial stress and problematic cell phone use.

Two main predictors for video game addiction were found: being male and having low levels of prosocial behavior. Having higher levels of prosocial behavior, or voluntary behavior meant to benefit another person, tended to be a protective factor against the addiction symptoms.

Aside from the predictors, Coyne also found three distinct trajectories of video game use. Seventy-two percent of adolescents were relatively low in addiction symptoms across the six years of data collection. Another 18% of adolescents started with moderate symptoms that did not change over time, and only 10% of adolescents showed increasing levels of pathological gaming symptoms throughout the study.

The results suggest that while about 90% of gamers are not playing in a way that is dysfunctional or detrimental to the individual's life, there is still a sizable minority who are truly addicted to video games and suffer addiction symptoms over time.

These findings also go against the stereotype of gamers living in their parent's basement, unable to support themselves financially or get a job because of their fixation on video games. At least in their early twenties, pathological users of video games appear to be just as financially stable and forward-moving as gamers who are not addicted.

"I really do think that there are some wonderful things about video games," Coyne said. "The important thing is to use them in healthy ways and to not get sucked into the pathological levels."

Ann Arbor, May 13, 2020 -- New research and guidance in the American Journal of Preventive Medicine, published by Elsevier, focus on critical topics pertaining to community and individual health during the COVID-19 epidemic.

RESEARCHERS OUTLINE GUIDELINES TO HELP ADDRESS THE UNIQUE AND OFTEN OVERLOOKED RISKS POSED BY COVID-19 TO BOTH PRISON INMATES AND CORRECTIONAL OFFICERS

The correctional environment is often considered distinct or isolated from the wider society and health system, but the wellbeing of correctional workers and prisoners is inexorably linked to the health of the country as a whole. Almost 3 million people are incarcerated, or work in, state and federal prisons, local jails, and other detention facilities. Their safety is inherently a matter of public health. Researchers highlight some of the inherent risks within correctional systems that may increase COVID-19 transmission among and between inmates and staff. They outline recommendations from the Centers for Disease Control and Prevention, WHO, and other organizations to help correctional professionals mitigate these risks and protect and treat anyone who lives and works in their institution. This includes collaboration between correctional systems and their local public health authorities, adherence to the principles of infectious disease control, and early release or furlough of prisoners whose release would pose fewer public safety risks than their continued incarceration.

"Both correctional employees and inmates have long been overlooked by our society, community leaders, and legislators," said lead author Andre Montoya-Barthelemy, MD, MPH, HealthPartners Occupational and Environmental Medicine, St. Paul, MN; and American College of Occupational and Environmental Medicine, Elk Grove Village, IL. "As we researched this article, we were immediately struck by how abruptly COVID-19 has exposed our neglect of those who live and work within the prison system, and how the health of our neighbors in the correctional environment is so tightly bound to our own."

"COVID-19 and the Correctional Environment: The American Prison as a Focal Point for Public Health," by Andre Montoya-Barthelemy, MD, MPH, Charles D. Lee, MD, JD, MBA, CCHP-P, Dave Cundiff, MD, MPH, and Eric Smith, DO, MPH, CTWH (https://doi.org/10.1016/j.amepre.2020.04.001). Journalists wishing to speak with the authors should contact monto88@umn.edu.

VULNERABLE POPULATIONS MAY PAY THE HIGHEST PRICE IN THE COVID-19 EPIDEMIC, RESEARCHERS WARN

Marginalized in the best of times, people who are homeless, incarcerated, or using drugs are likely to experience a higher risk of exposure to SARS-CoV-2 because of their social circumstances. A response to these forgotten populations must be central to the COVID-19 response. Planning should incorporate dedicated efforts, funding, and guidelines specific to these populations, both because they deserve care and services and not doing so poses greater risk to the broader community.

Researchers note that homeless shelters are ideal for viral transmission. They caution that healthcare resources may be prioritized for those at least risk of death, and vulnerable populations may be further marginalized. "People who are homeless, incarcerated or living with opioid use disorder already experience significant stigma and health inequities. It is critical that public health responses to SARS-CoV-2 account for these populations so as not to exacerbate existing disparities and to hamper community transmission," explains lead author Elizabeth M. Salisbury-Afshar, MD, MPH, of the Center for Addiction Research and Effective Solutions, American Institutes for Research, Chicago IL.

"Vulnerable Populations: Weathering the Pandemic Storm," by Elizabeth M. Salisbury-Afshar, MD, MPH, Josiah D. Rich, MD, MPH, and Eli Y. Adashi, MD, MS (https://doi.org/10.1016/j.amepre.2020.04.002). Journalists wishing to speak with the authors should contact esalisbury@air.org.

RESEARCHERS FIND CLEAR RACIAL AND INCOME DISPARITIES IN RISK FACTORS FOR SEVERE COVID-19, WHICH SHOULD BE CONSIDERED IN PHYSICAL DISTANCING AND OTHER PROTECTIVE MEASURES

Identifying those at heightened risk of several illness from COVID-19 is essential for modeling disease, designing return to work criteria, allocating economic assistance, advancing health equity, and limiting morbidity and mortality. To date there has been limited analysis of the population at risk based on income, and racial and ethnic factors, but preliminary national data suggest that disparities in hospitalization are already developing. Using data from the 2018 Behavioral Risk Factor Surveillance System, a nationally representative study of more than 400,000 adults, Matthew Raifman MPP, of the Department of Environmental Health, and Julia Raifman, ScD, of the Department of Health Law, Policy and Management, both at the Boston University School of Public Health, Boston, MA, found clear disparities in the prevalence of risk factors for severe COVID-19. In particular, Non-Hispanic Black Americans and American Indians are disproportionately at higher risk of severe illness relative to non-Hispanic White Americans. People with lower incomes are more likely to be at risk; 25 million Americans living in households receiving less than $25,000 a year have at least one risk factor for severe COVID-19 illness.

"COVID-19 is the most recent example in the long history of structural inequalities shaping the burden of disease in America," the authors note. "Decades of inequitable policies have created conditions in which there are disparities by race and income in access to healthcare, wealth, education, and employment, each of which are associated with chronic diseases that elevate the risk of severe illness due to COVID-19. By focusing testing, case detection and treatment programs in communities most at risk of severe illness due to COVID-19, we may be able to reduce the overall toll of the disease."

"Disparities in the Population at Risk of Severe Illness from COVID-19 by Race/Ethnicity and Income," by Matthew Raifman, MPP and Julia Raifman, ScD (https://doi.org/10.1016/j.amepre.2020.04.003) Journalists wishing to speak with the authors should contact mraifman@bu.edu.

MANDATORY SOCIAL DISTANCING MEASURES IN CLARKE COUNTY, GA SLOWED THE SPREAD OF COVID-19, COMPARED TO SURROUNDING COUNTIES AND THE REST OF THE STATE

In the state of Georgia, Clarke County was among the first to adopt a mandatory policy of sheltering in place (SIP) in response to the COVID-19 epidemic, effective March 20, 2020. Except for one neighboring county, the counties surrounding Clarke County did not implement similar measures, and statewide measures were not put into effect until April 3, 2020. Mark H. Ebell, MD and Grace Bagwell-Adams, PhD, MPA, of the College of Public Health, University of Georgia, Athens, GA, explain that this variation in policies at a "hyperlocal" level created a natural experiment prior to the statewide policy change and allowed them to examine the relationship between SIP policy implementation and the doubling rates of COVID-19 cases for Clarke County versus surrounding counties. Doubling time is a key metric used to evaluate whether progress is being made in containing a virus: the faster it takes the number of cases to double in an area, the faster the disease is spreading.

Dr. Ebell and Dr. Bagwell-Adams observed that doubling time in Clarke County was 11.3 days longer compared to surrounding counties and increased by an average of eight days compared with the entire state. Looking at percentage daily increases, they found a 30 percent decrease in percent increases in Clarke County compared with other counties. "Our report reinforces the fact that mandatory implementation of distancing measures is the most important way to slow the spread of the COVID-19 pandemic," say Dr. Ebell and Dr. Bagwell-Adams. "Our mayor and commission were two weeks ahead of the rest of Georgia in mandating isolation measures, and we think the community has benefited as a result."

"Mandatory Social Distancing Associated with Increased Doubling Time: An Example Using Hyperlocal Data," by Mark H. Ebell, MD, MS, and Grace Bagwell-Adams, PhD, MPA (https://doi.org/10.1016/j.amepre.2020.04.006). Journalists wishing to speak with the authors should contact ebell@uga.edu