Culture

Ozone disinfectants can be used to sterilize cloth and n95 masks against COVID-19

COVID-19 pandemic is proving to be havoc for the whole world and an unending challenge for the healthcare systems, hospitals, medics and paramedics. The most vivid example is the shortage of equipment and preventive kits, including the n95 masks. Indeed, there has been high demand of the n95 masks in the hospitals but the shortage of it has forced many local hospitals to use the ordinary masks also. The bigger problem for the healthcare professionals and others in the hospitals is, how best to sterilize (clean) the masks for use and, if need arises, reuse.

Dr. Craig G Burkhart, from the Department of Medicine, University of Toledo College of Medicine, Toledo, Ohio, USA, in his Editorial published in the journal, The Open Dermatology Journal, defines a suitable way for sterilizing the protective masks. According to him, the best cleansing solution for protective masks is treating them with chemical sterilizing agents. The sterilizing agents following the chemistry that the oxidative processes with low molecular weight molecules, used with tested methodologies, can kill all bacteria, mold, and viruses. Ozone sterilization is one very effective method.

Ozone or activated oxygen (O3) is a sterilizing agent that has proved successful in destroying bacteria, fungi, viruses, and protozoa. Combatting viruses, ozone diffuses into their protein coat, all the way to the nucleic acid, damaging and killing the organism. The activated oxygen destroys the unsaturated lipid envelope of the virus by breaking the existing multiple bond configuration. As the nuclear content of the virus cannot live without an intact lipid envelope, thus the virus gets killed. COVID-19 virus is one such virus that has an unsaturated lipid envelope enclosing the nuclear content. Other viruses that cannot withstand the activated oxygen include poliovirus 1 and 2, human rotavirus, Norwalk virus, Parvoviruses, and Hepatitis A, B, and non-A non-B.1.

SoClean is one of the sanitizers that use this very method for sterilizing cloths, masks and such items. It comes with the Continuous Positive Airway Pressure (CPAP) machines and, both can be used to sterilize the n95 and other masks for reusing in the hospitals and elsewhere.

This editorial is open access and can be read from the following link: https://benthamopen.com/ABSTRACT/TODJ-14-14

Credit: 
Bentham Science Publishers

What do ants and light rays have in common when they pass through lenses?

image: Figure 1. Similarities between dispersion of light and dispersion of ant trails across convex and concave lenses between light sources and target, or nest and food patch.
Light rays that originate from the light source and pass through a lens (a) to reach the target can travel through the wider area of the convex lens (b) compared to the concave lens (c). Ants (d) travelling between their nest and food source behave in a generally similar manner: they disperse more across the convex (e) than that across the concave "lens" (f) made of Velcro that slows ants down. The underlying hypothetical reason for this similarity is the tendency to reduce travel time by the both, the light and the ants.

Image: 
Choi J, Lim H, Song W., Cho H., Kim HY, Lee SI, Jablonski PG.[(b, c, e, f are adapted and modified from Choi et al. <Scientific Reports> (2020)) (https://www.nature.com/articles/s41598-020-65245-0)

Light and foraging ants seem totally unrelated, but they have one thing in common: they travel along time-reducing paths. According to Fermat's principle about the refraction of a ray of light, the light bends when it meets a matter with different refractive indices and travels through time-minimizing paths. Recently, similar behavior was reported in foraging ants in a lab setting: ants 'bend' their travel paths when they enter a substrate that slows them down. But would the ants behave similarly as the light passing through convex or concave lenses when they travel through impediments with lens-like shapes? A multidisciplinary team of researchers from Seoul National University (SNU) and DGIST in Korea, composed of ecologists and an engineer conducted experiments in the field to find out if the ants indeed behave similarly to the light.

The study has started with the following reasoning. Laws of optics predict that light rays reach the target on the other side of a convex lens by crossing the convex lens nearly everywhere; the crossing points can be quite far from the center of the lens (Fig. 1b). On the other hand, light rays cross the concave lens can reach the target only when it pass through the points near the center of the lens (Fig. 1e)

The researchers asked whether ants also show similar trends when they cross lens-shaped impediments, made of Velcro tape, during their foraging trips. On the Velcro "lens", the ants cannot walk as fast as they can on normal, flat surface. The researchers put these "lenses" between the nest entrance and the food source near several colonies of the Japanese carpenter ants and observed what happened. It turned out that the trails of ants crossing the "convex lens" diverged away from the center more than they did on the "concave lens". This means that more ants avoided the central thick part of convex impediment, and more ants walked through the central narrow part of concave impediment. This suggests that ants tend to avoid the parts of impediments that considerably slow them down.

This general similarity to the behavior of light crossing through convex and concave lenses is consistent with the idea that foraging ants, like light rays, use time-reducing paths. "I studied math and physics as an undergraduate, and this has helped me to come up with this research idea after I was exposed to the wonders of the behavior of ants by my Lab mate, Dr. Woncheol Song" says Ph.D. candidate Jibeom Choi, who conducted the experiments and created a mathematical model of ant behavior. Collaboration between a behavioral ecologist, Prof. Piotr Jablonski (Laboratory of Behavioral Ecology and Evolution, SNU) and a theoretical engineer, Prof. Hoyoung Kim (Microfluids & Soft Matter Laboratory, SNU), additionally highlights the multidisciplinary merit of this study. "This is an example of synergistic effect of multidisciplinary collaboration; by crossing the boundaries between disciplines, we have a fuller understanding of the natural world.", remarks the integrative ecologist in the study, Prof. Sang-im Lee (Laboratory of Integrative Animal Ecology, DGIST), who has been actively pursuing multidisciplinary research at SNU and DGIST, and has been involved in research on ants for years.

There are, however, remaining questions to be solved. As pointed out by authors themselves, the behavior of individual ants on the Velcro impediment and its borders has not been thoroughly investigated and it may contribute to the observed pattern. Therefore, further studies should focus on the behavior of individual ants at the edges between different substrates.

Credit: 
Laboratory of Behavioral Ecology and Evolution at Seoul National University

Can copying your friends help you achieve your goals?

Consumers often struggle to achieve self-set life improvement goals, but what if deliberately emulating the successful strategies used by their friends could help them?

A new paper published in the Journal of the Association for Consumer Research shows that encouraging people to find and mimic exercise strategies used by their friends increases the amount of time people spent exercising relative to receiving an exercise strategy passively. In the study, Katie S. Mehr, Amanda E. Geiser, Katherine L. Milkman, and Angela L. Duckworth introduce the "copy-paste prompt," a nudge that encourages consumers to seek out and mimic a goal-achievement strategy used by an acquaintance.

Copy-paste prompts "are easy to implement, virtually costless, and widely applicable with the potential to improve outcomes ranging from healthy eating to academic success," the authors write in "Copy-Paste-Prompts: A New Nudge to Promote Goal Achievement."

Copy-paste prompts may be more effective than other methods for bolstering goal achievement for several reasons: behaviors are more appealing when learned from observation, plus learning from models increases both a person's expectations of their own abilities and their likelihood of using information. However, consumers may not take full advantage of opportunities to observe and emulate others in their social network. In this case, copy-paste prompts may add value by helping consumers better take advantage of this resource. Plus, the information is more customized and goal relevant, since consumers select peers whose behavior they want to emulate.

In the authors' longitudinal study, over 1,000 participants were asked how many hours they spent exercising in the last week and were randomly assigned to one of three conditions: the copy-paste prompt condition, a quasi-yoked control condition, or a simple control condition.

In the copy-paste prompt condition, participants read the following:

"In this study, we want to help you learn about an effective hack or strategy that someone you know uses as motivation to exercise. Over the next two days, we'd like you to pay attention to how people you know get themselves to work out. If you want, you can ask them directly for their motivational tips and strategies."

In the quasi-yoked control condition, participants read the following:

"In this study, we're hoping to help you learn about an effective hack or strategy that motivates people to exercise. Over the next two days, we'd like you to get ready to learn a new strategy to motivate you to exercise."

The participants who received the copy-paste prompt spent more time exercising the following week than participants assigned to either a quasi-yoked or simple control condition. "The benefits of copy-paste prompts are mediated by the usefulness of the adopted exercise strategy, commitment to using it, effort put into finding it, and the frequency of social interaction with people who exercise regularly," the authors write.

Looking ahead, the authors write, "It may be that once a consumer learns to copy-paste in one domain (e.g., exercise), she will be able to apply this technique in a way that improves many other outcomes (e.g., retirement savings)."

Credit: 
University of Chicago Press Journals

How exposure to negative feedback in influences goal-directed consumer behaviors

Threats to self-esteem and negative feedback are pervasive in today's society. Social media researchers, for example, have shown a link between frequent usage of social media websites and upward social comparison and negative affect.

How does this influence consumer behavior? A new paper published in the Journal of the Association for Consumer Research examines how single and repeated exposure to negative feedback in one domain influences goal-directed consumer behaviors.

In "The Motivating And Demotivating Effects Of Negative Feedback On Cross-Domain Goal Pursuit Behaviors," authors Alison Jing Xu, Shirley Y. Y. Cheng, and Tiffany Barnett White hypothesize that receiving negative feedback induces a general motive to boost one's self-view, which motivates people to pursue proving goals (i.e., those that allow them to demonstrate their competence), even in areas that are unrelated to the feedback. The authors propose that negative feedback also demotivates the pursuit of enjoyment goals (i.e., those that focus on the pursuit of pleasure and therefore have no self-restorative characteristics).

These motivational consequences not only influence consumers' goal pursuit behaviors when a single goal (either a proving goal ["Playing this game can prove my intellectual abilities"] or an enjoyment goal ["I would have a lot of fun playing this game"] is activated, but also affect consumers' choice between a proving goal and an enjoyment goal.

Although receiving negative feedback may give rise to negative affect, the motivational consequences of negative feedback on goal pursuit behaviors were not driven by negative affect, per se. Instead, the motivation to boost one's self-view mediates the motivational influence of negative feedback on goal pursuit behaviors in other unrelated domains.

The authors conducted four experiments to support their hypothesis: manipulating negative feedback by providing performance feedback on a creativity test or an emotional intelligence test, and demonstrating its influence on consumers' motivation to pursue either a proving or an enjoyment goal, as well as on consumers' choice between a proving goal and an enjoyment goal.

"We showed that receiving negative feedback in an unrelated domain motivated consumers to spend more effort searching for product information if their search behavior was driven by the goal to identify the best option and prove their ability to make wise decisions (i.e., a proving goal)," the authors write. However, when consumers' search behavior was driven by the goal of having fun (i.e., an enjoyment goal), receiving negative feedback reduced search efforts.

Study participants who received negative performance feedback on a creativity task in one study responded by searching for information about options in an ostensibly unrelated study when this search behavior was framed as a proving goal. Similarly, receiving negative feedback on an emotional intelligence quiz increased participants' later likelihood of choosing to play a game that could demonstrate and improve their intellectual abilities (Clash of Clans) versus one they would enjoy more and have more fun playing (Fruit Ninja).

The findings also suggest that while consumers may be eager to self-improve when they receive initial negative feedback, repeated negative feedback exposure may undermine their confidence in their ability to self-repair, resulting in their being less motivated to pursue proving goals. This finding has important implications not only for the dynamic effects of self-repair motives on consumer behavior, but also for how to give negative feedback. "Specifically, it suggests that although people generally strive to self-improve after negative feedback, too much negative feedback can lead them to seek enjoyment rather than self-improvement, even in areas that have nothing to do with what they failed on previously," the authors write.

The findings may offer a path through which firms can have a positive impact on consumers' well-being. The findings suggest that, independent of potential effects of mood, receiving feedback that causes consumers to experience a threat to their self-concept (e.g., unflattering social comparison on a social media website) can influence not only their preferences for a given brand, but also the depth of their engagement with that brand. For example, the consumers in the first experiment were not only interested in trying the items in the assortment following negative (versus positive) feedback, they also literally searched more options for a longer period of time.

The drop of self-esteem as a result of upward social comparison may facilitate the marketing of goods, services, and activities that are associated with proving (but not enjoyment) goals (e.g., via Facebook ads) in the short run but not in the long run.

Credit: 
University of Chicago Press Journals

Renewable energy advance

image: New characterization techniques developed at the Catalysis Center for Energy Innovation may help improve electrochemical storage technologies, such as fuels cells used in UD's hydrogen fuel cell buses.

Image: 
Photo by Jon Cox and courtesy of Josh Lansford

Renewable technologies are a promising solution for addressing global energy needs in a sustainable way.

However, widespread adoption of renewable energy resources from solar, wind, biomass and more have lagged, in part because they are difficult to store and transport.

As the search for materials to efficiently address these storage and transport needs continues, University of Delaware researchers from the Catalysis Center for Energy Innovation (CCEI) report new techniques for characterizing complex materials with the potential to overcome these challenges.

The researchers recently reported their technique in Nature Communications.

Seeing the parts, as well as the whole

Currently technologies exist for characterizing highly ordered surfaces with specific repeating patterns, such as crystals. Describing surfaces with no repeating pattern is a harder problem.

UD doctoral candidate and 2019-2020 Blue Waters Graduate Fellow Josh Lansford and Dion Vlachos, who directs both CCEI and the Delaware Energy Institute and is the Allan and Myra Ferguson Professor of Chemical and Biomolecular Engineering, have developed a method to observe the local surface structure of atomic-scale particles in detail while simultaneously keeping the entire system in view.

The approach, which leverages machine learning, data science techniques and models grounded in physics, enables the researchers to visualize the actual three-dimensional structure of a material they are interested in up close, but also in context. This means they can study specific particles on the material's surface, but also watch how the particle's structure evolves -- over time -- in the presence of other molecules and under different conditions, such as temperature and pressure.

Put to use, the research team's technique will help engineers and scientists identify materials that can improve storage technologies, such as fuel cells and batteries, which power our lives. Such improvements are necessary to help these important technologies reach their full potential and become more widespread.

"In order to optimize electrochemical storage technologies, such as fuel cells and batteries, we must understand how they work and what they look like," said Lansford, the paper's lead author, who is advised at UD by Vlachos, the project's principal investigator.

"We need to understand the structure of the materials we are generating, in detail, so that we can recreate them efficiently at a large scale or modify them to alter their stability."

Computational modeling

Lansford concedes that it is too costly and time-consuming to model complex structures directly. Instead, they take data, generated from a single spot on the surface of a material, and scale it to be representative for a variety of catalysts on many surfaces of many different materials.

Imagine a cube made up of many atoms. The atoms located on the corners of the cube will have different properties than, say, the atoms located on one side of the cube. This is because on the corners, fewer atoms will be connected to each other and atoms may be spaced closer together. While on the side of the cube, more atoms will be connected even though they may be spaced farther apart from each other.

The same is true for catalyst materials. Even if we can't see them with the naked eye, the particles that make up a catalyst are adsorbed onto many different sites on the material -- and these sites have different edges, bumps and other variations that affect how materials located there will behave. Because of these differences, scientists can't just use a single number to try to quantify what's happening across a material's entire surface, so they have to estimate what these surfaces look like.

According to Lansford, this is where computational modeling can help.

The research team used experimental measurements of different wavelengths of infrared light and machine learning to predict and describe the chemical and physical properties of different surfaces of materials. The models were trained entirely on mathematically generated data, allowing them to visualize many different options under many different conditions.

They developed special open-source software to apply the technique on different metals, materials and adsorbates. The methodology is flexible enough to be used with other spectroscopic techniques beyond infrared light, so that other scientists and engineers can modify the software to advance their own work.

"This work introduces an entirely new way of thinking on how to bridge the gap between real-world materials and well-defined model systems, with contributions to surface science and machine learning that stand on their own," said Lansford.

Credit: 
University of Delaware

Beware of false negatives in diagnostic testing of COVID-19

image: Maribel Jose and Zhellann Aguilar test Covid-19 samples in the lab.

Image: 
Keith Weller/Johns Hopkins Medicine

One of the most commonly used diagnostic tools, particularly during this pandemic, is the reverse transcriptase polymerase chain reaction test (RT-PCR), which uses a person's respiratory sample to detect viral particles and determine if the person may have been exposed to a virus. Laboratory professionals across the U.S. and the globe have used RT-PCR to find out if a person has been infected with SARS-CoV-2, the virus that causes COVID-19. These tests have played a critical role in our nation's response to the pandemic. But, while they are important, researchers at Johns Hopkins have found that the chance of a false negative result -- when a virus is not detected in a person who actually is, or recently has been, infected -- is greater than 1 in 5 and, at times, far higher. The researchers caution that the predictive value of these tests may not always yield accurate results, and timing of the test seems to matter greatly in the accuracy.

In the report on the findings published May 13 in the journal Annals of Internal Medicine, the researchers found that the probability of a false negative result decreases from 100% on Day 1 of being infected to 67% on Day 4. The false negative rate decreased to 20% on Day 8 (three days after a person begins experiencing symptoms). They also found that on the day a person started experiencing actual symptoms of illness, the average false negative rate was 38%. In addition, the false negative rate began to increase again from 21% on Day 9 to 66% on Day 21.

The study, which analyzed seven previously published studies on RT-PCR performance, adds to evidence that caution should be used in the interpretation of negative test results, particularly for individuals likely to have been exposed or who have symptoms consistent with COVID-19.

Credit: 
Johns Hopkins Medicine

New testing system predicts septic shock outcomes

More than 1.7 million Americans develop sepsis each year, and more than 270,000 die from it. The condition--which happens when the body has an extreme response to a bacterial or viral infection, causing a chain reaction that can lead to organ failure and death--has few strategies for treatment.

That's what Savas Tay found a few years ago, when his mother died from sepsis. "I learned that there is very little they can do to really monitor and diagnose these patients," said Tay, associate professor of molecular engineering at the Pritzker School of Molecular Engineering (PME) at the University of Chicago. "A good percentage of them will ultimately die, which is unacceptable, considering the high-quality facilities, physicians, and therapies we have available. I was kind of enraged with the situation."

So Tay set out to do something about it. Now, he and his collaborators have developed a new, extremely sensitive method that can quantify bacteria, an antibiotic resistant gene, and immune molecule levels within sepsis patients, far more rapidly than current protocols.

By deploying these tests at intervals, the researchers also found that it wasn't the absolute levels of these markers that mattered--it was the change in the levels. Using machine learning, they accurately predicted which patients with sepsis would recover quickly, recover later, or ultimately succumb to the condition. That information could ultimately help physicians diagnose and treat patients in a more personalized way.

"Our findings provide a new approach to the diagnosis of sepsis with the potential to identify the causal pathogen early," said Gokhan Mutlu, professor of medicine and chief of pulmonary and critical care medicine at UChicago and co-author of the research. "This will allow us to use the appropriate antibiotics earlier before the culture results are available and minimize the use of antibiotics that are needed to treat the infection. By combining the pathogen-related and host response data, we are able to predict outcomes in patients with sepsis."

The results were published May 25 in the journal Nature Communications.

Understanding how to treat sepsis

Because sepsis is often caused by microbial infections, the condition is usually initially treated with antibiotics. Treatment must happen quickly--any delay in the administration of correct antibiotics increases the chances of the patient dying. But doctors often aren't sure which bacteria is causing the infection, and growing cultures to pinpoint the bacteria can take days.

Even if doctors can treat the infection directly, the condition can cause the body's immune response to become exaggerated. By attacking the pathogens, the immune system can release too many immune system proteins called cytokines, which can ultimately overwhelm the body and kill the patient. Anti-inflammatory drugs can help treat this, but often physicians do not know when this "cytokine storm" is taking place until it's too late.

"The immune system has a gas and a brake," Tay said. "You need the gas to kill the pathogens, but you need the brake so you don't overshoot inflammation and harm the patient. In all of this, timing is critical. We wanted to know if we could monitor bacterial load and cytokines at the same time, and monitor their changes, to provide better guidance about who should get certain treatments."

Creating an extremely sensitive test

Tay, an expert in single-cell analysis and microfluidics, and his team developed a digital polymerase chain reaction (PCR) test that uses digital proximity litigation assays to quantify the levels of certain genes and proteins in the blood.

Specifically, the test uses a blood sample to test for gram-negative (GN) and gram-positive (GP) bacterial DNA, which is abundant in many septic patients. It also tests for levels of the IL-6 and TNF proteins, the cytokines that the immune system releases to attack pathogens. In addition, it tests for the blaTEM gene, which signifies antibiotic resistance.

The test is extremely sensitive--able to quantify very small changes in the concentrations of these molecules--and provides results within a few hours. Tay worked with pulmonologists at University of Chicago Medicine to try out the test on samples from septic patients.

The researchers took samples once a day for two days from 32 patients and tested their bacterial and protein levels. They found that the bacterial levels of the patients who lived decreased as time went on.

However, in almost every patient that died, IL-6 levels increased throughout their time at the hospital. Even patients who had low bacterial levels to begin with still died if their IL-6 levels increased, showing that the immune system potentially overshot and attacked their own body.

Though IL-6 has been considered a major biomarker in sepsis before, previous researchers did not realize that it was the change in the levels--not the levels themselves--that predicted this outcome.

In addition, the researchers found several patients with the gene that indicates antibiotic resistance, which would be helpful information for the physicians treating them.

"Sepsis manifests itself differently in each person, therefore having a test like this to shed light on that variation could one day be used by providers to identify which patients may respond better to certain treatments or interventions," said Krysta Wolfe, a pulmonologist and assistant professor of medicine at UChicago, and co-author of the research.

Using machine learning algorithms, the researchers could ultimately use these biomarkers to predict who would recover early, recover late, or die, with nearly 100% accuracy.

"All of the sudden we have this method that allows us to really understand how these patients are going to fare," Tay said. "If there are patients that are going to do badly, then you can start treating these patients in different ways, perhaps with drugs that will help block the immune system from overshooting."

Extending the test to other diseases

Right now, the test happens in a lab, but Tay and his group are developing a machine that can quickly test samples on site at ICUs. They are proceeding with a clinical trial and hope to extend the test to include more groups of bacteria beyond just the GN and GP levels, to help physicians better understand which antibiotics are needed in order to help reduce antibiotic resistance.

This test could also be extended to other infections where cytokines can overtake the body, including viral infections like COVID-19.

"A rapid test like this is needed in many situations and could really change the game for treatment of sepsis," Tay said. "This is a disease that can kill everybody, regardless of your situation."

Credit: 
University of Chicago

High rates of COVID-19 on American Indian reservations - water and language barriers affect risk

May 26, 2020 - Early in the pandemic, American Indian Reservations have experienced a disproportionately high incidence of COVID-19 infections: four times higher than in the US population, reports a study in the July/August issue of the Journal of Public Health Management and Practice. The special issue of JPHMP focuses on COVID-19, with commentaries and scientific articles describing the pandemic in the United States and globally. The journal is published in the Lippincott portfolio by Wolters Kluwer.

Lack of indoor plumbing is a strong risk factor for COVID-19 in tribal communities, while the incidence appears lower in households that speak English only, according to the new research led by Desi Rodriguez-Lonebear, PhD, of UCLA. "These key findings have implications for communication, implementation, and success of recommendations such as hand washing and state/tribal stay-at-home orders in American Indian Reservation communities," the researchers write.

Insights on Factors Affecting COVID-19 Incidence on American Indian Reservations

Using publicly reported information on COVID-19 cases, along with reservation-level data from a previous national survey, Dr. Rodriguez-Lonebear and colleagues analyzed household and community characteristics associated with rates of COVID-19 in tribal communities. The study focused on 287 American Indian Reservations and tribal homelands (in Oklahoma) with an average population of about 12,500.

As of April 20, 2020, these communities had a total of 861 COVID-19 cases. About 60 percent of cases were in the Navajo Nation. At that time, the incidence of COVID-19 was more than four times higher for people living on a reservation, compared to the United States as a whole: 0.24 versus 0.057 cases per 1,000 people.

On analysis of household and community factors, the number of COVID-19 cases was substantially higher on American Indian Reservations where a higher percentage of homes lacked complete indoor plumbing. The researchers write, "While some reservation communities have elected not to pursue full plumbing facilities for historical, cultural and environmental reasons, there are certainly solutions, like providing potable water and hand sanitizer, that could improve critical sanitation needs."

The number of COVID-19 cases was lower on reservations with a high percentage of English-only households - highlighting the need for public health campaigns in Indigenous languages. "This is of particular concern given there are 150 different Indigenous languages spoken by more than 350,000 people in the US today," according to the authors.

Along with household plumbing and language, overcrowding has been identified as a potential infection risk factor. However, at least early in the pandemic, overcrowding - defined as more than one person per room - was not related to COVID-19 incidence on American Indian reservations.

Due to its timing, the study could not address how reservation-level conditions affect the risk of death from COVID-19. Any such analysis would have to consider the unique circumstances surrounding healthcare access and infrastructure in tribal communities. "With inadequate public health infrastructure, limited medical resources, and high rates of poverty, communities on Indian reservations are poorly equipped to manage a pandemic like COVID-19," Dr. Rodriguez-Lonebear and coauthors write.

The researchers outline the implications for policy and practice addressing the impact of COVID-19 on American Indian reservations - including the need for access to potable water and communication of critical health information in Indigenous languages. Dr. Rodriguez-Lonebear and colleagues conclude: "In the long-term, increase direct public health funding to tribes for infrastructure development and secure American Indian household access to environmental health infrastructure such as indoor plumbing, where desired."

Credit: 
Wolters Kluwer Health

Researchers discover key player in hepatitis A virus infection

image: Hepatitus A virus particles (pink) trapped in lysosomes (yellow intracellular organelles), unable to initiate replication in the cytoplasm of cells due to UCGC enzyme being knocked out.

Image: 
Maryna Kapustina, PhD, UNC School of Medicine

CHAPEL HILL, NC - May 26, 2020 - How hepatitis A virus (HAV) manages to enter liver cells called hepatocytes and initiate infection had remained a mystery for fifty years until now. University of North Carolina School of Medicine researchers designed experiments using gene-editing tools to discover how molecules called gangliosides serve as de facto gatekeepers to allow the virus entry into liver cells.

The research, published in Nature Microbiology, has revealed gangliosides as a key player in HAV and has led to several other questions, such as how exactly viral RNA transitions between different compartments in human liver cells to replicate and cause disease.

"Discovering that gangliosides are essential receptors for HAV infection adds an interesting plot twist to the hepatitis A story," said senior author Stanley Lemon, MD, professor of medicine and microbiology at the UNC School of Medicine and member of the UNC Institute for Global Health and Infectious Diseases. "Gangliosides are structurally similar across mammalian species, unlike proteins, which helps explain cross-species transmission of ancient hepatoviruses. Understanding what helps a virus jump from one animal species to another is incredibly important, as evidenced so plainly by the current Covid-19 pandemic."

HAV was discovered nearly 50 years ago, and although there is a vaccine, there is no treatment. The virus still infects more than 1.4 million people globally each year, and in recent years has been causing increasing numbers of hepatitis cases in the United States, some fatal. Many people experience very mild or no symptoms, especially children. Patients with symptoms, which can last eight weeks and sometimes longer, often experience nausea, vomiting, diarrhea, jaundice, fever, and abdominal pain. After initial infection, 10 to 15 percent of infected individuals experience a recurrence of symptoms during the first six months. Acute liver failure is rare, but more common in elderly people.

HAV infects people through mechanisms similar to other viruses; it interacts with receptor molecules on the surface of human cells to gain entry. Knowing the receptor for a virus not only helps researchers understand how the virus enters cells, but also creates opportunities to design antivirals to block the interaction to prevent or treat disease.

Among the five known hepatitis viruses that cause acute or chronic liver disease in humans, receptors have been identified for hepatitis C virus and hepatitis B virus. For hepatitis A, the identity of the receptor remained elusive. The black sheep of the picornavirus family, it uniquely exists in two modes: as nonenveloped (naked) viruses (nHAV), comprised of a protein shell called a capsid surrounding an RNA genome; or as 'quasi-enveloped' viruses (eHAV), in which capsids containing the viral genome are cloaked inside host cell membranes.

Once inside the liver, eHAV is released from infected hepatocytes to circulate in the blood, whereas naked nHAV particles are shed in feces. Both virus types are infectious. Being cloaked with host-derived membranes gives eHAV an advantage in evading antibody responses, while the naked virion is extraordinarily stable and spreads readily in the environment. But how did each virus get into liver cells and the blood in the first place?

Years ago, the human protein TIM1 was reported to be a receptor for HAV. The gene that encodes this protein even bears the official name HAV cellular receptor 1 (HAVCR1). But recent studies in Lemon's laboratory showed that cells lacking TIM1 still allow HAV infection.

To find a more likely culprit for the receptor, Anshuman Das, PhD, a postdoc in the Lemon lab at the time of this research and now at Duke University., used CRISPR-Cas9 gene editing to knock out approximately 20,000 genes in cultured cells to find which human genes are essential for the virus to invade. They identified five particular genes, all of which were required by the virus. Turns out, these genes encode enzymes or transporters that make possible the synthesis of gangliosides. (Transporters are molecules that traffic chemicals across channels inside cells.)

Gangliosides are sugary fatty acid molecules. The enzyme ceramide glucosyltransferase creates gangliosides. And the gene UGCG encodes for that enzyme.

"UGCG was the lead culprit of the five genes that lit up our screen using CRISPR-Cas9," Lemon said.

The researchers then knocked out UGCG, which prevented HAV infection. They also treated liver-derived cells with a chemical inhibitor of ceramide glucosyltransferase to prevent both eHAV and nHAV infection.

The researchers then injected synthetic HAV RNA directly into cells to discover that the viral RNA replicated well, suggesting that gangliosides were required for entry of the virus into cells, but not needed for it to make copies of its genome, or new virus particles, once it gets into cells.

Subsequent experiments revealed that - in the absence of gangliosides - both naked and quasi-enveloped HAV particles do in fact get part way into the cell, but they end up getting stuck in a compartment called the lysosome. Viral replication does not occur. When the researchers added back gangliosides, the accumulated viruses used the gangliosides to exit the lysosome and continue their invasion of the cell, ending up releasing their genomes into the cell cytoplasm where the virus then began to replicate.

"This means gangliosides are essential for a late-step entry of HAV into cells," said Anshuman Das, PhD, a postdoc in the Lemon lab at the time of this research and now at Duke University. "They function as true receptors."

Although questions remain, the researchers say that understanding the role of gangliosides may open up new avenues for prevention and possibly even treatment of hepatitis A.

Credit: 
University of North Carolina Health Care

Countering COVID-19 impacts on children from low-income households

image: COVID-19's impact on children from low-income households.

Image: 
M.E. Newman, Johns Hopkins Medicine, using public domain images

The COVID-19 pandemic has magnified the social, educational and health care disparities already plaguing the nearly 40 million Americans the U.S. Census Bureau estimates are living in poverty. Perhaps the hardest hit members of that population, say three pediatricians at Johns Hopkins Children's Center and Children's National Hospital, are children from low-income households who are experiencing major disruptions in already inconsistent routines and less-than-adequate resources critical to learning, nutrition and social development because of restrictions in place to curb the spread of the disease.

In a viewpoint article published in the May 13 issue of JAMA Pediatrics, the physicians provide examples of how efforts to keep COVID-19 in check have disproportionally impacted the nearly 1 in 5 U.S. children whose family incomes are below the poverty level.

"For example, many school districts are engaging in distance learning during the pandemic, but there is wide variability in the ability to access quality educational instruction, digital technology and internet service, especially by rural and urban students," says Megan Tschudy, M.D., M.P.H., assistant medical director at the Harriet Lane Clinic of Johns Hopkins Children's Center and assistant professor of pediatrics at the Johns Hopkins University School of Medicine. "In some urban areas, as many as one-third of students are not participating in online classes because of challenges accessing the internet."

The authors cite other difficulties that COVID-19 policies and regulations have placed on children from low-income households, including missing months of school by a student population commonly burdened by chronic absenteeism, the inability to get nutritious meals previously provided before and during school hours, and removal of key resources available at schools such as "consistent and caring adults who can help build resiliency and offer holistic support."

To counter the increased disparities brought about by the pandemic and help prevent children from low-income households "experiencing consequences for a lifetime," the authors recommend that future COVID-19 legislation target child health and well-being. They say that this effort should include expanding services and increasing funding for health and nutrition assistance programs, improving child tax credits, and expanding access to high-speed internet and versatile electronic devices so that all children can participate in distance learning.

Credit: 
Johns Hopkins Medicine

Humans have beneficial bacteria uniquely adapted for life in our noses

image: This scanning electron microscopy image of the Lacticaseibacillus casei AMBR2 strain from the nose shows long, spike-like fimbriae that allow the bacteria to adhere to the cell surface of our nose.

Image: 
De Boeck et al. / Cell Reports

Beneficial strains of bacteria residing in our guts, genital tracts, and skin have been shown to play a role in human health, and now, researchers publishing May 26 in the journal Cell Reports suggest that some of these "good" bacteria also have a niche in our noses. They found that people with chronic nasal and sinus inflammation had fewer lactobacilli in their upper respiratory tract than healthy controls and were able to identify a specific strain of the bacteria that has evolved to better survive the oxygen-rich environment of the nose. As a part of their study, the researchers developed a proof-of-concept nasal spray that could deliver lactobacilli to the nose, where the bacteria were able to colonize the upper respiratory tract of healthy volunteers.

Senior author Sarah Lebeer of the University of Antwerp became interested in the microbiota of the nose when her mother underwent a surgery for lifelong problems with headaches and chronic rhinosinusitis. "My mother had tried many different treatments, but none worked. I was thinking it's a pity that I could not advise her some good bacteria or probiotics for the nose," recalled Lebeer, who was previously studying gut and vaginal probiotics. "No one had ever really studied it."

To see whether the bacteria we associate with gut health also play a role in the health of the upper respiratory tract, Lebeer and her Procure team (http://www.procureproject.be/) compared nose bacteria between 100 healthy individuals and 225 chronic rhinosinusitis patients. They looked at the prevalence of 30 different families of bacteria in the upper respiratory tract of their participants and found that the healthy people had a greater abundance of lactobacilli than the patients--up to 10 times more in some parts of the nose. Lactobacilli are well-known beneficial, rod-shaped bacteria that have pathogen-inhibiting properties because they produce lactic acid through sugar fermentation, but these bacteria had never been studied in detail in the nose.

The researchers took a closer look and discovered a specific strain of the Lacticaseibacillus that not only showed some anti-inflammatory and antimicrobial effects against pathogens but also unique features that enables the strain to better adapt to the environment of the nose. Although most lactobacilli prefer to grow in the absence of oxygen, the identified strain showed unique genes making it able to cope with the higher oxidative stress levels in the nose. Moreover, the researchers observed the bacteria covered with flexible, hair-like tubes called fimbriae, which allow them to adhere to the surface cells in the nose, indicating an interaction between the bacteria and host.

The researchers then sought to verify their findings in vivo. However, "one limitation is that there are actually no real good animal models or mechanistic models to study the interaction of nose bacteria and human host," says Lebeer. "The microbiome of the nose of mice compared with humans, it's certainly different. Also, mice are nose breathers and they don't get chronic rhinosinusitis; they have fewer allergies and inflammations."

But the results from the lab, and the long history of safe use of lactobacilli, allowed the researchers to study the bacteria in humans instead of animal models. The team created a kind of "probiotic nasal spray" with a selected lactobacillus strain in a special formulation for 20 healthy volunteers. Introducing bacteria to the nose can be challenging, because it's so good at filtering out foreign substances; any substance introduced to the nose usually disappears within 15 minutes. However, after two weeks of administering the spray twice daily, the bacteria stayed in the nose longer than 15 minutes--they colonized the nose for up to two weeks without adverse effects. The study of the spray was not set up to look at beneficial effects, although anecdotally some participants mentioned having fewer nasal problems and said they could breathe better.

The next step for the researchers is to understand whether the fimbriae and the ability to endure oxidative stress are key to beneficial anti-inflammatory properties of the strain, as well as to identify which antimicrobial molecules the strain produces in addition to lactic acid. Ultimately, the team's goal is to develop therapeutics based on nasal probiotics to improve the symptoms of sinusitis patients.

"Sinusitis patients don't have a lot of treatment options," says Lebeer, and with the treatments that are available, problems such as antibiotic resistance and side effects often arise. "We think that certain patients would benefit from remodeling their microbiome and introducing beneficial bacteria in their nose to reduce certain symptoms. But we still have a long way to go with clinical and further mechanistic studies."

Credit: 
Cell Press

Fit test, filtration efficiency of disposable N95 masks after irradiation

What The Study Did: The fit and filtration efficiency of disposable N95 masks after sterilization by cobalt-60 gamma irradiation are examined in this quality improvement study.

Authors: Avilash Cramer, M.S., of the Harvard-MIT Division of Health Sciences and Technology in Charlestown, Massachusetts, is the corresponding author.

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

(doi:10.1001/jamanetworkopen.2020.9961)

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

Credit: 
JAMA Network

Evidence insufficient regarding interventions to prevent illicit drug use in children, teens and young adults

Bottom Line: The U.S. Preventive Services Task Force (USPSTF) has concluded that current evidence is insufficient to make a recommendation regarding primary care-based behavioral counseling interventions to prevent illicit drug use (including nonmedical use of prescription drugs) in children, adolescents and young adults. The USPSTF routinely makes recommendations about the effectiveness of preventive care services and this recommendation is consistent with its 2014 statement, although it now includes young adults ages 18-25. Illicit drug use, defined as the use of substances (not including alcohol or tobacco products) that are illegally obtained or involve nonmedical use of prescription medications, contributes to the leading causes of death among young people ages 10-24.

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

(doi:10.1001/jama.2020.6774)

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

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

Credit: 
JAMA Network

Effect of workplace wellness program on employee health, medical use

What The Study Did: This randomized clinical trial evaluated the effect of a workplace wellness program that included health screenings, wellness activities and financial incentives on employee health, health beliefs and medical use after 12 and 24 months among 4,800 employees at a large U.S. university.

Authors: David Molitor, Ph.D., of the University of Illinois at Urbana-Champaign, is the corresponding author.

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

(doi:10.1001/jamainternmed.2020.1321)

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

Credit: 
JAMA Network

Warwick scientists discover how cells respond to fasting

image: Cells expressing GFP-Sequoia-LIR mutant (green nuclei) activate autophagy (shown by red puncta).

Image: 
University of Warwick

The UK has the highest level of obesity in Europe, in fact it's estimated half the population could be obese by 2050. Obesity is a significant risk factor for increased morbidity and mortality

Fasting, has been a trend in recent years to maintain a healthy weight, the body responds to fasting using autophagy, a cellular self-recycling process

The proteins required for autophagy to work during fasting have been identified by researchers from the School of Life Sciences at the University of Warwick

Understanding how the proteins work means researchers can activate autophagic pathways to help people maintain a normal body weight

As modern life-styles and high calorie diets drive the UK's obesity levels up, researchers from the University of Warwick have found how cells respond to fasting and activate the process called autophagy, which means a healthier lifestyle can be promoted to help people maintain a healthy body weight.

The UK has the highest level of obesity in Western Europe, with its levels having more than trebled in the last 30 years, it is estimated that more than half of the population could be obese by 2050 in UK. Obesity is a significant risk factor for increased morbidity and mortality. The cause of the rapid rise in obesity has been blamed on modern lifestyles, including high-calorie diet.

Intermittent fasting, alternate-day fasting, and other forms of periodic caloric restriction are beneficial to maintain a healthy body weight and have gained popularity during the last few years. To respond to fasting, cells use autophagy, a cellular self-recycling process.

A team of researchers led by Professor Ioannis Nezis from the School of Life Sciences, University of Warwick, discovered how cells activate autophagy genes during fasting. In the paper titled 'Regulation of expression of autophagy genes by Atg8a-interacting partners Sequoia, YL-1 and Sir2 in Drosophila', published in the journal Cell Reports on the 26th May, Dr Anne-Claire Jacomin, Dr Stavroula Petridi, PhD student Marisa Di Monaco and Professor Ioannis Nezis have discovered proteins which are required for the transcription of autophagy genes.

The proteins are called Sequoia, YL-1 and Sir2, these proteins interact with the cytoplasmic autophagy-related protein Atg8a. These interactions recruit Atg8a in the nucleus to control the transcription of autophagy genes. This is the first study that uncovers a nuclear role of the cytoplasmic protein Atg8a.

Lead author of the research Professor Ioannis Nezis, from the School of Life Sciences at the University of Warwick, comments:

"Understanding the molecular mechanisms of activation of autophagy genes during fasting will help us to use interventions to activate the autophagic pathways to maintain a normal body weight and promote healthy well-being."

Credit: 
University of Warwick