Culture

Below please find a summary and link(s) of new coronavirus-related content published today in Annals of Internal Medicine. The summary below is not intended to substitute for the full article as a source of information. A collection of coronavirus-related content is free to the public at http://go.annals.org/coronavirus.

A Dangerous Myth: Does Speaking Imply Breathing?
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The belief that a person's ability to speak precludes the possibility of suffocation is false and can have fatal consequences. A commentary from Beth Israel Deaconess Medical Center reviews basic respiratory physiology and highlights the clinician's role in educating the public against relying on speech as a sign of adequate respiration, especially when this misconception is used to propagate injustice or violence. The authors explain that air hunger is the most uncomfortable and emotionally distressing quality of dyspnea. Data from studies of war and torture victims show that the sensation of suffocation is the single strongest predictor of posttraumatic stress disorder and can cause more persistent psychological damage than mock execution with a pistol. This finding suggests that clinicians have a fundamental responsibility to serve as advocates for persons who report respiratory distress. Read the full text: https://www.acpjournals.org/doi/10.7326/M20-4186.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. The lead author, Anica C. Law, MD, MS, can be reached through Jackie Mitchel at jsmitche@bidmc.harvard.edu.

Researchers at Johns Hopkins Bloomberg School of Public Health have identified the sequence of molecular events by which tiny, tick-like creatures called house dust mites trigger asthma and allergic rhinitis.

The researchers, whose study was published online June 22 in Nature Immunology, found that allergy-triggering molecules from dust mites can interact with an immune protein called SAA1, which is better known as a sentinel against bacteria and other infectious agents. The researchers showed step-by-step how this interaction between mite-molecules and SAA1 triggers an allergic-type immune response in mice.

The findings reveal what may be a significant new pathway by which allergic and inflammatory disorders arise. They also suggest that blocking the pathway could potentially work as a preventive or treatment strategy against asthma and other allergic reactions.

"We think that the signaling interactions that occur immediately downstream of the mite-proteins' activation of SAA1 may be good targets for future drugs," says study senior author Marsha Wills-Karp, PhD, the Anna M. Baetjer Professor of Environmental Health and Chair of the Department of Environmental Health and Engineering at the Bloomberg School.

Asthma affects between 8 to 15 percent of people in the U.S., and is typically triggered by dust mites, tree and grass pollens, and other allergens. Researchers suspect that this inappropriate immune triggering happens when the immune system mistakes allergens--which are otherwise harmless--for pieces of bacteria or other infectious agents. However, the molecular mechanisms underlying this misidentification haven't been well understood.

In their study, Wills-Karp and her colleagues zeroed in on SAA1, an immune protein that is found, among other places, in the fluid that lines the airways and other mucosal surfaces. A member of the evolutionarily ancient "innate immune system" of mammals, SAA1 is thought to have evolved as a sentinel or early-responder molecule that, for example, recognizes and helps clear away certain types of bacteria and other infectious agents.

The researchers found that exposure to dust-mite proteins causes an asthma-like sensitization of the airways of the control group mice. In contrast, exposure to dust-mite proteins hardly had any effect in mice in which SAA1 was neutralized by antibodies, or in mice whose genes for SAA1 were knocked out. Further experiments confirmed that SAA1, when it is present, directly binds certain dust-mite allergens called fatty-acid binding proteins, which have structural similarities with proteins found in some bacteria and parasites. This allergen-SAA1 interaction releases SAA1 into its active form, wherein it activates a receptor called FPR2 on airway-lining cells. The airway cells then produce and secrete large quantities of interleukin-33, a protein known for its ability to stimulate allergic-type immune responses.

Confirming the likely relevance to humans, the researchers found evidence of increased production of SAA1 and FPR2 in nasal airway-lining cells from patients with chronic sinusitis--which is often linked to dust-mite allergens--compared to healthy controls.

"We think that different allergens take different routes to the activation of interleukin-33 and related allergic responses, and this SAA1-FPR2 route seems to be one that is taken by some dust-mite allergens," Wills-Karp says.

She and her colleagues now plan to investigate why some people develop allergic disorders in which this pathway is hyperactive, while most don't. They also plan to explore the possibility of blocking this pathway, perhaps at the SAA1-FPR2 interaction, as a way of treating asthma and other allergic disorders.

The researchers suspect that the newly described SAA1-FPR2 allergic pathway may be relevant not only in asthma and hay fever-type disorders but also in atopic dermatitis (eczema) and food allergies--possibly even in chronic inflammatory disorders such as rheumatoid arthritis and atherosclerosis.

The more interactions and connections firm's social media marketing strategy generates, the more customer engagement value it brings.

In the new study, Fang Fang Li and Jorma Larimo from the University of Vaasa and Leonidas Leonidou from the University of Cyprus look at the strategic use of social media from firm perspective, and systematically consolidate and extend present knowledge on social media marketing strategies.

The study was recently published in one of the world's leading journals in marketing field - Journal of the Academy of Marketing Science (ABS 4*).

- Despite widespread understanding among marketers of the need to integrate social media into firms' marketing strategies, relatively few firms have strategized their social media appearance and involvement. For most companies, the ongoing challenge is not to initiate social media campaigns, but to effectively and strategically use social media in order to engage customers and build valuable relationships with them, say professor Jorma Larimo and doctoral student Fang Fang Li from the University of Vaasa.

To gain insights from both academics and practitioners, the authors interviewed 15 decision makers from China, Finland and Sweden and conducted two separate surveys, first participated by 52 marketing managers from USA and the second one received inputs from 43 social media marketing international scholars.

The study shows that the mere use of social media alone does not generate customer value, but rather, the connections and interactions between the firm and its customers - as well as among customers themselves - can be used strategically for resource transformation and exchanges between the interacting parties.

- Interacting with customers via social media provides tremendous opportunities for firms to learn more about their customers and opens up new possibilities for product or service co-creation, says Fang Fang Li.

Another key result is that the in the study four distinctive social media marketing strategies were identified, namely social commerce strategy, social content strategy, social monitoring strategy, and social CRM strategy, representing progressing levels of strategic maturity in social media use. Their adoption does not follow a sequential pattern, but is highly depended on the firm´s ability to identify and leverage customer-owned resources, as well as firm´s willingness to allocate resources in order to foster collaborative conversations, develop appropriate responses, and enhance customer relationships.

- Actively interacting with customers using social media should be a never-ending process, which, with proper monitoring and right incentives, can help favorably influence customer behavior, says professor Jorma Larimo.

The results offer fresh insights into the nature, conceptualization, and types of social media marketing strategies. Furthermore, the findings have important implications for social media marketing scholars and practitioners in identifying social media resources and capabilities. Authors also present several fruitful future research directions.

WEST LAFAYETTE, Ind. -- Drones and other aircraft effectively spray pesticides over miles of crops, but the method also can pollute the environment if wind carries the mist off-target.

One of the problems is that tiny droplets are hard for aerial crop sprayers, inkjet printers and a wide range of other machines to control. Purdue University engineers are the first to come up with the math formula that was missing to measure a key property of these droplets.

"There are many properties that affect how a droplet forms. One of those important properties is surface viscosity, which people have had a heck of a time trying to measure because they just didn't have the tools to do it," said Osman Basaran, Purdue's Burton and Kathryn Gedge Professor of Chemical Engineering.

Pesticides and other chemicals contain additives called surfactants. These surfactant molecules resist each other at a liquid's surface, giving rise to a sticky force called surface viscosity that can make the droplet smaller. The higher the surface viscosity, the more compact a droplet's shape.

Basaran and his students have figured out a way to calculate surface viscosity just by looking at how a droplet stretches. A picture taken of the stretched droplet as it starts to break gives the values to put into a simple math formula that provides the surface viscosity measurement.

The formula is described in a paper published in the journal Physical Review Letters. The discovery ends a decades-long race by researchers around the world to make surface viscosity measurable. Other co-authors on this paper include Hansol Wee, Brayden Wagoner and Pritish Kamat.

Not being able to measure exactly how much surface viscosity affects drop formation has put limits on making machines safer and more precise, said Basaran, who directs a center that works to resolve the science behind problems in manufacturing machinery.

Solutions provided by the center, called the Purdue Process Safety and Assurance Center, directly help partners in industries such as agriculture, health care and energy.

A better understanding of droplets and how to control them affects all those industries. Like crop spraying, inkjet printing in a factory produces tiny droplets that can get into the air and cause breathing problems.

More precise control of a liquid-like substance also could enhance a machine's performance, such as giving a 3D printer the ability to produce more reliable or detailed objects.

"A material with too high or too low surface viscosity can lead to bad outcomes in the manufacturing process. Knowing those measurements allows you to use different chemistries to make a material that doesn't lead to a surface viscosity that's going to result in a bad outcome," Basaran said.

Next, Basaran's team plans to incorporate this math formula into experiments for recommending new machine designs. The formula could also become a commercial instrument in the future, such as a smartphone app.

"This discovery opens up a lot of avenues for basic research that just weren't possible before," Basaran said.

WASHINGTON -- The U.S. Naval Research Laboratory's Large Angle Spectrometric Coronagraph (LASCO) instrument identified the 4000th comet discovered by the Solar and Heliospheric Observatory (SOHO), a joint mission between the European Space Agency and NASA on June 15.

LASCO, which is aboard SOHO, was developed in 1995 to see the extremely faint emission from the region around the Sun called the corona. Operating in space for nearly 25 years, the telescope has seen much more space action than researchers originally anticipated -- discovering well over half of all known comets.

"In less than 25 years SOHO has added this huge volume to the archives of our comet knowledge, and it comes from a telescope not designed to see comets," said Karl Battams, NRL computational scientist. "This is exciting for many reasons, but perhaps mostly because LASCO is discovering comets that are otherwise completely unobservable from Earth due to their proximity to the Sun."

The majority of the comet discoveries were made by amateur astronomers who participated in the NASA-funded and NRL-managed Sungrazer project, which encourages citizen scientists to peruse imagery from SOHO and the Sun-Earth Connection Coronal and Heliospheric Investigation (SECCHI) instrument suite on the NASA Solar Terrestrial Relations Observatory (STEREO) and search for previously unknown comets. New comet findings are reported through the website, and subsequently verified and measured by Battams, who has led this Project since 2003.

"The people who discovered these comets were not necessarily professional astronomers, they were people at home," Battams said. "People of all ages, backgrounds, and countries have volunteered their time to be a part of this citizen science project. The 4000th comet is a testament to the invaluable input from so many volunteers all around the world over the past two decades."

The Navy has a unique interest in the Sun and near -Sun environment. Much of the Navy's equipment, and equipment we use every day, such as GPS, is impacted by the Sun. Studying comets traveling near the Sun helps researchers gain a greater understanding of Earth's closest star, as they observe the comets reacting to its extreme environment.

Battams is a computational scientist and astrophysicist within the Solar and Heliospheric Physics Branch under the Space Sciences division at NRL. The mission of this Branch is to develop improved heliospace environment understanding, awareness, sensors, forecast capabilities, and monitoring tools that predict operational impacts and enable real-time threat warning; and transition these developments to support the Navy/Marine Corps and other agencies.

In many countries, sharing a bed with a partner is common practice. Yet, research investigating the relationship between bed sharing and sleep quality is both scarce and contradictory. Most studies have compared co-sleep to individual sleep in couples by only measuring body movements. However, Dr. Henning Johannes Drews of the Center for Integrative Psychiatry (ZIP), Germany and colleagues overcame these limitations by also assessing sleep architecture in couples that shared a bed.

Researchers conducted the study among 12 young, healthy, heterosexual couples who spent four nights in the sleep laboratory. They measured sleep parameters both in the presence and absence of the partner using dual simultaneous polysomnography, which is a "very exact, detailed and comprehensive method to capture sleep on many levels -- from brain waves to movements, respiration, muscle tension, movements, heart activity" says Dr. Drews. Additionally, the participants completed questionnaires designed to measure relationship characteristics (e.g., relationship duration, degree of passionate love, relationship depth, etc.)

The results showed that rapid-eye movement (REM) sleep is both increased and less disrupted in couples sleeping together compared to when they slept individually. This finding is particularly relevant because REM sleep, which is associated with vivid dreams, has been linked to emotion regulation, memory consolidation, social interactions and creative problem solving.

The team also found that couples synchronize their sleep patterns when sleeping together. This synchronization, which is not linked to the fact that partners disturb each other during the night, is positively associated with relationship depth. In order words, the higher participants rated the significance of their relationship to their life, the stronger the synchronization with their partner.

The researchers propose a positive feedback loop in which sleeping together enhances and stabilizes REM sleep, which in turns improves our social interactions and reduces emotional stress. Although researchers did not specifically measure these possible effects, Dr. Drews says that "since these are well known effects of REM sleep, it is very likely that they would be observed if testing for them."

Interestingly, researchers found an increased limb movement in couples who share the bed. However, these movements do not disrupt sleep architecture, which remains unaltered. Dr. Drew states that "one could say that while your body is a bit unrulier when sleeping with somebody, your brain is not."

Although results are promising, many questions remain to be answered. "The first thing that is important to be assessed in the future is whether the partner-effects we found (promoted REM sleep during co-sleep) are also present in a more diverse sample (e.g., elderly, or if one partner suffers from a disease)" says Dr. Drew.

Despite the small sample size and the explorative nature of some of the analyses, this research furthers our understanding of sleep in couples and its potential implication for mental health. Dr. Drews adds that "sleeping with a partner might actually give you an extra boost regarding your mental health, your memory, and creative problem-solving skills."

An article in CMAJ (Canadian Medical Association Journal) provides an overview on personal protective equipment (PPE) in health care settings, including evidence on effectiveness of N95 masks, as well as the importance of including health care worker perspectives on usage of this equipment. http://www.cmaj.ca/lookup/doi/10.1503/cmaj.200575

"Answering questions such as how aerosols are generated, how limited supply of PPE can be managed, how care can be organized to optimize PPE use, and how health care worker perspectives can be integrated into organizational decisions are central to protecting health care workers from COVID-19 and future pandemic pathogens," writes Dr. Jeanna Parsons Leigh, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, with coauthors.

The authors analyze the use of N95 masks compared with medical masks in preventing viral respiratory infections and suggest ways to manage the limited supply of N95 masks and other PPE. They hope the article will help organizations with decision-making around how to protect health care workers and patients while managing often scarce resources.

Real-world effectiveness of PPE may vary, especially during the early stages of an outbreak. As well, complex PPE regimens may not be better at protecting against transmission.

"More is not necessarily better: for Ebola, critical errors remained more common in enhanced versus basic PPE regimens despite training," write the authors. Meticulous attention to training health care workers in the correct methods of donning and doffing PPE is crucial.

Involving health care workers in developing strategies for PPE use as well as clear communication is important for ensuring front-line workers have confidence and use PPE effectively.

"Critical to choosing PPE regimens, but rarely explored, is how safe health care workers feel with the PPE regimen designated by their local hospital," write the authors. "Individuals and organizations may interpret the literature differently, and may arrive at different conclusions as to which PPE is appropriate for a given context for a novel virus. A breakdown in trust and communication can lead to conflict, anxiety and worker absences."

"Perspectives on personal protective equipment in acute-care facilities during the COVID-19 pandemic" is published June 25, 2020.

To manage Canada's emergency stockpile of medical supplies and personal protective equipement (PPE), the government could consider several approaches, including a "prime-vendor" model selling directly to health care organizations to minimize financial and equipment waste, according to an article in CMAJ (Canadian Medical Association Journal)

"Stock expiration is an important challenge with national stockpiles. Accordingly, a new long-term PPE supply-chain solution is urgently needed,"write Dr. Scott Laing, Department of Family Medicine, University of Ottawa, with Ellen Westervelt, Queensway Carleton Hospital, Ottawa, Ontario.

The National Emergency Stockpile System (NESS), established in 1952 as a result of the Cold War, had an estimated $300 million in assets in 2010, with an operating budget of $4 million and $7.7 million in warehouse leases. Many supplies have expired, leaving inadequate supplies during the current pandemic, and the NESS lacks an electronic inventory management system, which hampers its effectiveness.

"The Government of Canada is currently struggling to coordinate timely procurement of new PPE owing to long wait times for order fulfillment, which was also identified in the 2010 audit," write the authors. "The resulting PPE shortages have hindered provision of some health services, particularly in the community, where many family doctors have had limited access to essential PPE."

The United States and Australia face similar challenges with high costs due to equipment expiration and disposal expenses.

A long-term strategy for stockpiling critical supplies could include integrating the NESS with the commercial supply as a "prime vendor," perhaps modelled after shared services organizations.

The authors note that there are logistical challenges with a prime-vendor approach and, if pursued, the prime vendor should start on a small scale and expand only when ready.

Lecce, 25th June 2020 - Gold nanoparticles have been developed in the laboratory in order to reduce the cell death of neurons exposed to overexcitement. The study, is the result of an international collaboration coordinated by Roberto Fiammengo, researcher at the Center of Biomolecular Nanotechnologies of the IIT-Istituto Italiano di Tecnologia (Italian Institute of Technology) in Lecce (Italy). The international team also involves colleagues at the University of Genoa, Imperial College London, King's College London, the Center for Synaptic Neuroscience and Technology of the Istituto Italiano di Tecnologia in Genoa and the Max Planck Institute for Medical Research in Heidelberg.

Excessive stimulation of neurons by the neurotransmitter glutamate, which is usually involved in the excitatory communication among neurons, can damage nerve cells and cause their degeneration. This phenomenon, known with the term excitotoxicity, is common in many neuroinflammatory and neurodegenerative diseases, such as Alzheimer's and Huntington's disease, but also in case of epilepsy, brain trauma and stroke.

In particular, these nanoparticles were designed and prepared by the IIT team in Lecce (Italy), and are functionalized with peptides that allow selective inhibition of extrasynaptic glutamate receptors involved in the excitotoxicity. In fact, the size of the nanoparticles is 20 - 50 times larger than that of classic drugs resulting in the blockade of only the receptors located outside the synapses. In this way, correct neurotransmission is preserved while the excessive activation that leads to cell death is avoided.

The molecular mechanism underlying the neuroprotective effect of the nanoparticles has been clarified by the experimental work carried out by Pierluigi Valente at the University of Genoa, in collaboration with Fabio Benfenati's group of the Center for Synaptic Neuroscience and Technology of the IIT in Genoa (Italy).

The results of this research sets the basis for treatment of neurological diseases in which the excessive release of glutamate is at the basis of the pathology. The possibility of specifically blocking extrasynaptic receptors, mainly responsible for cell death, without interfering with synaptic transmission, opens up promising perspectives for targeted therapy without major side effects.

"We have developed nanoparticles with unique and necessary properties to answer to the indications of neurobiologists and physiologists - declares Roberto Fiammengo - Coordinating such a multidisciplinary group of researchers was an extremely stimulating task and the results obtained show that this is the winning approach."

"Even if, at the moment, the nanoparticles developed cannot be used in therapy, - concludes Pierluigi Valente of the University of Genoa, first author of the paper - this study shows how nanotechnology can provide important indications for treatment of many neuroinflammatory and neurodegenerative diseases."

The Ik, a small ethnic group in Uganda, are not incredibly selfish and mean as portrayed in a 1972 book by a prominent anthropologist, according to a Rutgers-led study.

Instead, the Ik are quite cooperative and generous with one another, and their culture features many traits that encourage generosity, according to the study in the journal Evolutionary Human Sciences.

"The Mountain People," an ethnography by anthropologist Colin M. Turnbull, made a big splash for an academic work. The New York Times and Time magazine reviewed the book, which inspired a stage play, and physician Lewis Thomas included an essay about the Ik in his bestselling book "The Lives of a Cell: Notes of a Biology Watcher."

The Ik live in the far northeast corner of Uganda, near its borders with Kenya and South Sudan. A Rutgers-led team of scientists studied them as part of The Human Generosity Project, a transdisciplinary effort to better understand generosity and other forms of cooperation among people around the world.

The scientists included the Ik in their project because of Turnbull's claim that, far from being generous, the Ik were extraordinarily selfish and mean. He attributed the selfish behaviors he witnessed to a culture of selfishness.

Lead author Cathryn Townsend, a former Rutgers post-doctoral scientist and faculty member now at Baylor University, spent 2016 with the Ik and returned briefly in 2017 and 2018.
She discovered that their culture includes many traits that encourage generosity. For example, a favorite Ik saying is tomora marang, which means "it's good to share," and many Ik believe that Earth spirits called kijawika monitor people's behavior, punish those who fail to share and reward the very generous.

Townsend also documented Ik generosity quantitatively using an experimental game, finding they're no less generous, on average, than any of the hundreds of other groups of people in the world who have played the same game.

Why, then, did Turnbull observe so much selfishness among the Ik? Although Turnbull was aware that they experienced a severe famine while he was there, he failed to appreciate the impact starvation has on human behavior. Instead, he followed a common tendency among cultural anthropologists to attribute all human behavior to culture.

"One implication of Townsend's work is that we must always consider the possibility that factors other than culture, including but not limited to starvation, can also shape human behavior," said senior author Lee Cronk, a professor in the Department of Anthropology in the School of Arts and Sciences at Rutgers University-New Brunswick. "Another implication is that we can no longer use the Ik as an example of a society that has embraced selfishness. Far from being an exception, the Ik are just as cooperative and generous as other people around the world. They do not deserve the reputation they have been given by Turnbull's book."

Townsend plans to return to the Ik to continue her studies of how they cooperate. She will be looking in particular at how they are interdependent with one another.

In recent years, the number of women who entered U.S. medical school surpassed the number of men. But gender inequities still exist in many areas of medicine. Of academic hospital medicine programs, 79% are run by men, Johns Hopkins researchers report in a new paper published March 3 in the Journal of General Internal Medicine, and male hospitalist leaders are more likely to have attained the rank of full professor than women leaders.

"Despite making a number of strides in medicine when it comes to gender bias, this is an area where we still haven't reached full equality," says Carrie Herzke, M.D., assistant professor of medicine and associate vice chair for clinical affairs in the Department of Medicine at the Johns Hopkins University School of Medicine.

Previous studies found that, in academic medicine, women comprise only 39% of full-time faculty and 22% of full-time professors. They are also significantly underrepresented in hospital leadership positions, and there are gender disparities regarding career advancement and compensation.

Hospital medicine as a dedicated medical specialty is a relatively young field. "Hospitalists" who are trained in internal medicine and focus their work on hospitalized patients rather than outpatient settings have only existed for about two decades. Due to how new the field is, some speculate it may have fewer gender imbalances than more established fields of medicine.

In collaboration with the Society of Hospital Medicine, Herzke and her colleagues conducted a survey of all U.S. academic hospital programs associated with the Association of American Medical Colleges. After identifying 135 programs, surveys were sent electronically to academic hospitalist leaders of each program. Participants were asked about the gender of the hospitalist program leader, the program's size and organization, faculty characteristics, and perceptions about promotion and faculty development.

"We had a sense that there were some gender issues when people had looked at these areas before," says Herzke. "Obviously, our hope was that we would see fewer inequities in our data."

Of the 135 programs, 80 responded to the survey, and responding programs did not differ significantly from nonresponding programs in terms of funding, region, age or type of institution. While programs reported approximately equal numbers of male and female faculty members, 79% of program directors were male. Moreover, 37% of male hospitalist leaders were full professors while no female hospitalist leaders held that rank.

"Even in this new specialty, we don't have gender parity," says Herzke. "There have been numerous studies suggesting that programs, and society in general, do better when we have more diverse teams and diverse leadership."

The ability to sequence the genome of a tumor has revolutionized cancer treatment over the last 15 years by identifying drivers of cancer at the molecular level. But understanding the genetic diversity of individual cells within a tumor and how that might impact the disease progression has remained a challenge, due to the current limitations of genomic sequencing.

Using a microfluidic droplet based single cell sequencing method, USC researchers have simultaneously sequenced the genomes of close to 1,500 single cells, revealing genetic diversity previously hidden in a well-studied melanoma cell line.

The study, just published in Nature Communications Biology, demonstrates the ability of single-cell sequencing to reveal possible evolutionary trajectories of cancer cells.

"We used this approach to examine a standard cancer cell-line, examined thousands of times by many different labs," said David Craig, PhD, co- director of the Institute of Translational Genomics at Keck School of Medicine of USC and study author. "What was really surprising here, was with this technology we uncovered complexity we did not expect. This line actually consistently became a mixture of different types of cells. Reexamining decades of prior work on this line - now with this new information - we have new insights into tumor evolution."

Getting a high-resolution view of cancer's complexity

Currently, the genetic information of a tumor is typically obtained by sequencing millions of tumor cells together, rather than individually. While this method offers a broad view of the genetic makeup of the tissue it can miss small populations of cancer cells within a tumor that are different from the majority of cells.

With other approaches that analyze the DNA of individual cells, the process is laborious, taking weeks to process just a few cells and requiring resources that most laboratories do not have.

For this study, researchers used an emerging technique called "single-cell copy number profiling." developed by 10X Genomics with novel analysis methods that integrated these results with those of historical methods.

"Instead of analyzing tissue DNA that is the average of thousands of cells, we analyzed the individual DNA of close to 1500 cells within a single experiment," said Dr. Enrique Velazquez-Villarreal, lead author and assistant professor of translational genomics at Keck School of Medicine at USC. "Studying cancer at this higher resolution, we can discover information that lower-resolution bulk sequencing misses."

Their analysis revealed at least four major sub-populations of cells, also known as clones, that are expected to have, at some point during the cancer cell line's evolution, mutated from the original cancer cell.

The ability to identify sub-clones in cancer tissue could provide important biological insights into how cancer progresses, how it spreads and why it can become resistant to treatment.

"What if there's a small population of cells in a tumor that has acquired a change that makes them resistant to therapy? If you were to take that tumor and just grind it up and sequence it, you may not see that change," said John Carpten, PhD, study author and Co-Leader of the Translational and Clinical Sciences Program at the USC Norris Comprehensive Cancer Center, Chair of the Department of Translational Genomics, Keck School of Medicine, and Co-Director of the USC Institute for Translational Genomics. "If you go to the single cell level, you not only see it, but you can see the specific population of cells that has actually acquired that change. That could provide earlier access to the molecular information that could help define treatment approaches."

The researchers plan to share their data in the hope that more cancer researchers will focus on single-cell sequencing. They are also using their technique to study genetic diversity in clinical cancer specimens as a way to better understand the early molecular changes that lead to aggressive and tough-to-treat advanced cancers.

As far as humans are concerned, bacteria can be classified as either harmful, pathogenic bacteria and harmless or beneficial non-pathogenic bacteria. To develop better treatments for diseases caused by pathogenic bacteria, we need to have a good grasp on the mechanisms that cause some bacteria to be virulent. Scientists have identified genes that cause virulence, or capability to cause disease, but they do not fully know how bacteria evolve to become pathogenic.

To find out, Professor Chikara Kaito and his team of scientists from Okayama University, Japan, used a process called experimental evolution to identify molecular mechanisms that cells develop to gain useful traits, and published their findings in PLoS Pathogens. "We're excited by this research because no one has ever looked at virulence evolution of bacteria in an animal; studies before us looked at the evolution in cells," said Prof Kaito.

The scientists decided to start with a non-pathogenic Escherichia coli (or E. coli for short) and repeatedly mutate it and use it to infect silkworms, an insect that is often used as a model for infectious diseases, and then test whether it will cause death in silkworms.

Through this experiment, the scientists created E. coli strains with a 500-fold increased virulence compared to the original bacterial strain and found that mutations in the gene that code for one specific protein, the "lipopolysaccharide transporter (LPS) transporter," was one of the reasons for the increased virulence. This protein forms a part of the bacterial cell membrane and protects the bacteria from harm. Because of this, the LPS transporter is necessary for E. coli to grow.

The mutations that increased bacterial deadliness appeared to give E. coli resistance against some antibiotics, as well as some antibacterial substances from the silkworms. The reason for this is likely a corresponding increase in the concentration of structures called outer membrane vesicles, which the bacteria release to absorb harmful compounds to prevent them from entering the bacteria and harming them.

Researchers also identified the characteristics of substances that pathogenic strains were resistant to, showing that they were "hydrophobic" (or water-repelling) and positively charged. This fit with the increased amount of outer membrane vesicles, which are hydrophobic and negatively charged, allowing them to hold onto those substances (because, of course, opposite forces attract). The scientists also showed that the mutations occurred in parts of LPS transporter that are directly on the outside of the bacterial membrane. The scientists suspect that this is because these areas are more exposed to the environment, thereby experience more natural selection, and are thereby more susceptible to mutation.

"What we've done here is identify several things about pathogenic bacteria," explains Prof Kaito. "We showed for the first time that mutations to LPS transporter can increase virulence, and we provided evidence for how that virulence actually happens--the mutant bacteria make more outer membrane vesicles." And that's not all, the team also pinpointed specific structural changes to mutated LPS transporter that could explain why virulence is different across bacteria--because each species might have a different structure.

When asked about how his work contributes to scientific understanding and to medicine, Prof Kaito elaborates, "Before our study, it wasn't very clear how bacteria actually evolved properties that made them more harmful, so our study helps clarify this. An understanding of this process means the possibility of creating drugs or other therapy that can keep bacteria from becoming pathogenic, especially if we find more proteins like LPS transporter, where mutations can have such a big effect."

Of course, further studies are needed to explore whether the mutations observed in this study will also increase virulence when the bacteria infect animals bigger than silkworms, like mammals. But this study is definitely the first step toward unraveling the mystery of differences between dangerous and harmless bacteria.

How do environmental exposures during pregnancy and childhood influence the risk of obesity in children? The Barcelona Institute for Global Health (ISGlobal), a centre supported by the "la Caixa" Foundation, and the University of Southern California led the first major study to investigate the associations between many pollutants and environmental factors --77 prenatal and 96 childhood exposures-- and the risk of childhood obesity. The findings show that air pollution, smoking and certain characteristics of the built environment--such as high population density-- may play a role in the development of obesity in children.

To date, several studies have addressed the effect of environmental pollutants, lifestyle factors, and urban environment factors on childhood obesity, but they studied each single exposure separately. The exposome concept has changed the way we investigate how environmental risks affect health. Instead of analysing the possible health consequences of, exposome studies consider many different exposures a person faces altogether. This approach takes into account many elements we are exposed to through our diet, lifestyle and the environment where we live.

The new study, which forms a part of the HELIX project and was published in Environmental Health Perspectives, used data on more than 1,300 children aged 6 to 11 years from birth cohort studies in six European countries: France, Greece, Lithuania, Norway, Spain and the United Kingdom.

The authors used data on body mass index (BMI), waist circumference, skinfold thickness and body fat mass to determine the children's overweight and obesity status. Blood and urine samples from the children and their mothers during pregnancy were also analysed. In total, 77 pregnancy and 96 childhood exposures were assessed, including air pollutants, built environment, green spaces, smoking and chemical pollutants (persistent organic pollutants, heavy metals, phthalates, phenols and pesticides).

ISGlobal researcher Martine Vrijheid, who coordinates the HELIX project and was the first author of the study, commented: "The prevalence of childhood obesity is increasing at alarming rates across the globe and may have increased even more than usual during the COVID-19 lockdown period." The findings of the study, which used data collected before anti-COVID-19 measures were introduced, were in line with global trends: the combined prevalence of overweight and obesity was 29% for the study population as a whole, with higher percentages for the cohorts from Spain (43%) and Greece (37%).

The results showed that exposure to smoking (both maternal smoking during pregnancy and second-hand smoking during childhood), air pollution (PM2.5 and PM10 particulate matter and nitrogen dioxide, indoor and outdoor) as well as certain characteristics of the built environment were associated with a higher childhood BMI. Differences in socio-economic status did not explain these findings.

Associations with chemical pollutants were less consistent, with some chemicals measured in child blood (heavy metals copper and cesium) showing higher BMI, and others (persistent organic pollutants such as PCBs and DDE pesticides) showing lower BMI. This may be explained by the fact that chemicals were measured at the same time as obesity in the children, and obesity status may have influenced chemical blood levels. Longitudinal follow-up of the cohort is needed to establish this.

Obesity and Unwalkable Cities

"The children who live in densely populated areas and go to schools in areas with few services and facilities were more likely to be obese," commented Leda Chatzi, Professor of Preventive Medicine at the University of Southern California and last author of the study. The relationship between obesity and the characteristics of the built environment "is in line with the findings of previous research and could be explained by a lack of opportunities for children to walk or engage in other outdoor physical activities," she adds.

"These findings provide further evidence that modifying environmental exposures early in life can limit the risk of obesity and associated complications," commented Martine Vrijheid. "The implications for public health are important since these results may help to identify obesity-related exposures that could be targeted for prevention and intervention early in life." 

Funding: The study received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no 308333 - the HELIX Project and the National Institute of Environmental Health Sciences NIEHS R21ES029681.

What The Study Did: This randomized clinical trial evaluates the effect of treatment with colchicine on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with COVID-19.

Authors: Spyridon G. Deftereos, M.D., Ph.D., of the National and Kapodistrian University of Athens in Greece, 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.2020.13136)

Editor's Note: The article includes conflicts 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.