Culture

As many have recently discovered, social connections are vital to a person’s wellbeing. While social isolation is a core challenge associated with autism, researchers from Drexel University’s A.J. Drexel Autism Institute have laid the groundwork to show how interpersonal relationships, and the resources they provide, could impact autistic youth’s adult outcomes.

“Many autistic young adults are disconnected from people, communities and organizations that could provide them with valuable social resources to support their transition to adulthood,” said Elizabeth McGhee Hassrick, PhD, assistant professor in the Autism Institute and lead author of the study.

The study demonstrated how social network analysis can be adapted for the field of autism, by measuring the social networks of autistic adults and the resources gained from the social connections.

Researchers had 17 autistic adults during post-high school transition (ages 19 to 27) complete an online survey about their social connections and the different types of support they gain from those connections. Parents of three of the autistic adults were also surveyed to provide information about the social connections they rely on to help their autistic young adults transition successfully.

“Interpersonal relationships and the resources and support embedded in the social networks of autistic young adults could impact key adult outcomes, including quality of life, mental health, employment and independence,” said McGhee Hassrick.

According to the researchers, there is currently very little known about the social networks of young adults on the autism spectrum and no studies measuring the social capital of youth and their parents together.

This project produced new and useful ways of collecting social network data from young autistic adults that will produce knowledge about how to help young adults on the autism spectrum build networks that will produce social resources needed to support positive outcomes in adulthood.

The study does have limitations, as it was only designed to test the feasibility of the social network measure and does not provide information about how networks might impact outcomes. There is also the possibility of under-reporting the actual size and makeup of autistic young adult networks, due to the social network measure only allowing participants to identify five people.

“Future studies using our social network measure might provide valuable information about possible interventions that could help autistic youth acquire the social resources needed for successful adult outcomes,” said McGhee Hassrick.

From the four-foot-tall emperor penguin to the aptly named foot-long little penguin, these unique flightless birds have invaded habitats from Antarctica to the equator, not to mention the hearts of the public.

A comparison of the full genomes of 18 recognized species of penguins provides clues to how they achieved this success -- though not their adorability -- over tens of millions of years, through warm and cold climate swings. It also cautions that today's rapidly changing climate may be too much for them.

"We are able to show how penguins have been able to diversify to occupy the incredibly different thermal environments they live in today, going from 9 degrees Celsius (48 F) in the waters around Australia and New Zealand, down to negative temperatures in Antarctica and up to 26 degrees (79 F) in the Galápagos Islands," said Rauri Bowie, professor of integrative biology at the University of California, Berkeley, and curator in the Museum of Vertebrate Zoology (MVZ) at Berkeley. "But we want to make the point that it has taken millions of years for penguins to be able to occupy such diverse habitats, and at the rate that oceans are warming, penguins are not going to be able to adapt fast enough to keep up with changing climate."

The researchers established conclusively that penguins arose in the cool coastal regions of Australia and New Zealand, not frigid Antarctica, as many scientists thought, and they pinpoint the origin of penguins at about 22 million years ago.

Despite their success in spreading widely throughout the Southern Hemisphere, many penguin populations are now threatened. Breeding colonies of emperor penguins in Antarctica have had to relocate because of receding sea ice, while last year saw mass mortality of Adélie penguin chicks on the continent. Galápagos penguin populations are declining as warm El Niño events become more common. In New Zealand, populations of little and yellow-eyed penguins must be fenced off to protect them from the depredations of feral cats, while African penguin populations are declining drastically as the waters off southern Africa warm.

"We saw, over millions of years, that the diversification of penguins decreased with increasing temperature, but that was over a longtime scale," said Juliana Vianna, associate professor of ecosystems and environment at the Pontifical Catholic University of Chile in Santiago. "Right now, changes in the climate and environment are going too fast for some species to respond to the climate change."

Vianna is first author of a paper with Bowie and other colleagues describing their findings that will be published online this week in the journal Proceedings of the National Academy of Sciences.

Where did penguins come from?

For the study, Vianna, Bowie and colleagues at museums and universities around the world gathered blood and tissue samples from 22 penguins representing 18 species and then sequenced and analyzed their whole genomes to chart penguin movement and diversification over the millennia.

Their conclusions resolve several long-standing questions: in particular, where penguins originated -- along the coasts of Australia, New Zealand and nearby islands of the South Pacific -- and when -- 22 million years ago. The genetic evidence indicates that the ancestors of the king and emperor penguins, the two largest species, soon split off from the other penguins and moved to sub-Antarctic and Antarctic waters, respectively, presumably to take advantage of abundant food resources. This scenario is consistent with the contested hypothesis that the emperor and king penguins -- the only two species in the genus Aptenodytes -- are the sister group to all other penguin lineages.

"It was very satisfying to be able to resolve the phylogeny, which has been debated for a long time," Bowie said. "The debate hinged on where, exactly, the emperor and king penguins were placed in the family tree, whether they are nested inside the tree closer to other lineages of penguins or whether they are sisters to all the other penguins, which is what our phylogeny showed and some other previous studies had suggested. And it fits with the rich fossil history of penguins."

The other penguins diversified and spread widely across the southern oceans, after the Drake's Passage between Antarctica and the southern tip of South America fully opened about 12 million years ago. The opening revved up the clockwise-moving Antarctic Circumpolar Current allowed these flightless birds to swim with the ocean currents throughout the southern ocean, populating both the cold sub-Antarctic islands and the warmer coastal areas of South America and Africa, where they populated to coastlines and remote islands with cold, upwelling, nutrient-rich water.

Today, penguins are found in Australia and New Zealand (yellow-eyed, little and other crested penguins), Antarctica (emperor, Adélie, gentoo and chinstrap), the tropical west coast of South America (Galápagos and Humboldt), the southern coasts of South America (Magellanic and southern rockhopper), the South Atlantic (Magellanic and Macaroni), southern Africa (African) and some in the sub-Antarctic (king, gentoo and Macaroni), Indian Ocean islands (eastern rockhopper) and sub-tropical regions (northern rockhopper).

Using powerful analysis techniques, some developed recently to analyze historical interactions among humans and our Neanderthal and Denisovan relatives, the researchers were able to determine that several groups of penguins have interbred over the course of their evolutionary history. Through exchange of genetic material, penguins may have shared genetic traits that facilitated the diversification of penguins across the steep thermal and salinity gradients encountered in the southern oceans. The most hybridized are the rockhopper penguins and their close relatives, which experienced at least four introgressions, or transfers of genetic information, over the course of millions of years.

The team also pinpointed genetic adaptions that allowed penguins to thrive in new and challenging environments, including changes in genes responsible for regulating body temperature, which allowed them to adapt to subzero Antarctic temperatures, as well as tropical temperatures near the equator; oxygen consumption that permitted deeper dives; and osmoregulation, so they could survive on seawater without the need to find fresh water.

New analytical tools helped the researchers to infer the sizes of ancient penguin populations going back about 1 million years. Most penguin species, they found, increased to their greatest numbers as the world cooled 40,000 to 70,000 years ago during the last glaciation -- many species prefer to breed on snow and ice -- and some had a bump in population during the previous glaciation period 140,000 years ago.

Two species -- the gentoo and the Galápagos -- seem to have been declining in populations for at least the past 1 million years.

DNA from the most isolated birds on Earth

Vianna has long-running research projects on penguins in Chile and Antarctica and, for this study, obtained blood samples from many species in those areas. Colleagues in France, Norway, Brazil, Australia, the United States and South Africa supplied blood from some remote species -- Norwegian colleagues provided blood from the chinstrap penguin of the Bouvet islands, for example -- while Vianna and Bowie obtained blood samples from an African penguin in a colony at the California Academy of Sciences in San Francisco.

But some species were harder to locate. The researchers were forced to rely on tissue from a preserved specimen of the yellow-eyed penguin in UC Berkeley's MVZ, while the American Museum of Natural History in New York supplied tissue from preserved erect-crested and Fiordland penguins.

Each genome was sequenced 30 times by Illumina shotgun sequencing, which produced tiny pieces -- about 150 base pairs long -- of the entire genome. Vianna, who at the time was working with Bowie at UC Berkeley on a sabbatical, painstakingly aligned each piece along a reference genome that had previously been sequenced -- that of the emperor penguin -- as a scaffold.

"Having a reference genome is like using the cover of a puzzle box to assemble a jigsaw puzzle: You can take all your super little pieces and align them to that reference genome," Bowie said. "We did that with each of these penguin genomes."

The genome comparisons told them that penguins arose between 21 million and 22 million years ago, narrowing down the 10-to-40-million-year window determined previously from fossil penguins.

They also disproved a paper published last year that suggested that the closely related king and emperor penguins were a sister group to the gentoo and Adélie penguins. Instead, they found that the king and emperor penguins are the sister group to all other penguins.

Vianna and Bowie now have genome sequences of 300 individual penguins and are diving more deeply into the genetic variations within and among disparate penguin populations. They recently discovered a new lineage of penguin that awaits scientific description.

"Penguins are very charismatic, certainly," Vianna said. "But I hope these studies also lead to better conservation."

Today's DNA testing is highly accurate, but errors still occur due to the limited genetic information accessible with current technologies. These errors can have serious impact on people's lives.

New technology has been shown to reduce the chances of false associations and should be more widely used, said Jianye Ge, PhD., Associate Professor and Associate Director of the Center for Human Identification at The University of North Texas Health Science Center at Fort Worth. In a study titled "How Many Familial Relationship Testing Results Could Be Wrong?" Dr. Ge reviewed worldwide practices to assess the potential of errors. Co-author of the study is Dr. Bruce Budowle, Director and Professor for the Center for Human Identification.

"Millions of cases have been tested globally," Dr. Ge said. "Of those, tens of thousands of cases could have been falsely interpreted."

The paper published in PLOS Genetics points out that existing problems of paternity testing have occurred over many years. Those errors are namely unrelated individuals being falsely concluded as biological relatives and biological relatives being falsely concluded as not related, such as a biological father concluded as unrelated to a child in paternity testing cases.

"We used a realistic model to estimate that tens of thousands of cases could be wrongly interpreted over the past two decades," Dr. Ge said. "The problem is the current technology has limitations and thus improvements are needed."

Testing via short tandem repeat or STR-based technology has long been the gold standard of familial relationship testing, such as civil and criminal paternity tests, missing persons identification, and kinship verification with international migration. It is the same tool used in forensics worldwide to distinguish who may or may not have been the donor of biological evidence found at the crime scenes.

Since the STR markers for DNA typing was introduced in the late 1990s, there has not been dramatic improvements in testing.

"In the beginning, only a few STRs were used," Dr. Ge said. "That improved to 20 to 23, which is what is used now."

"The chance of a mistake with that technology is small, but because of the sheer magnitude of testing - millions of cases - errors are not uncommon." he said.

Advances in technology over the last decade allow typing of hundreds of thousands or millions of single nucleotide polymorphisms, or SNPs.

"With the high density SNP-based technology, the chance of making a mistake is substantially less likely," Dr. Ge said.

Although UNTHSC stopped providing civil paternity testing services years ago, it still uses the STR technology and information in the context of missing person cases and criminal paternity cases. Nationwide the center does about 1,000 missing persons cases a year.

"We do lots of relationship testing to determine if a missing person belongs to a family," Dr. Ge said. "We need to continue to reduce the chance of making a false conclusion."

The purpose of the study was to encourage the community to move forward to this new generation of testing. "We need to move forward so that mistakes in kinship relationship testing are less of a possibility," he said.

DURHAM, N.C. --If you're reluctant to identify as a Democrat or Republican even though you are staunchly liberal or conservative, you're probably also less prone to bias in other ways.

In a time where political affiliations can feel like they're leading to tribal warfare, a research team from Duke University's Trinity College of Arts & Sciences has found that the desire to be part of a group is what makes some of us more likely to discriminate against people outside our groups, even in non-political settings.

"It's not the political group that matters, it's whether an individual just generally seems to like being in a group," said Rachel Kranton. She is an economist who conducted the research with Scott Huettel, a psychologist and neuroscientist.

"Some people are 'groupy' - they join a political party, for example," Kranton said. "And if you put those people in any arbitrary setting, they'll act in a more biased way than somebody who has the same political opinions, but doesn't join a political party."

The research appears this week in the Proceedings of the National Academy of Sciences. Kranton and Huettel worked with Seth Sanders, formerly of Duke and now at Cornell, and Matthew Pease, a 2010 Duke graduate now at the University of Pittsburgh Medical Center.

The team tested what they call "groupiness" with 141 participants, using in-person research.

Participants were asked to allocate money to themselves and someone in their group, or to themselves and someone outside their group. They did this in different settings.

For one test, the participants were divided into groups according to their self-declared political leanings. In another setting, the groups were organized more neutrally, based on their preferences among similar poems and paintings. In a third test, the other recipients of the money were chosen at random.

The researchers expected to find the stronger people's opinions were within their group, the more they would discriminate against people outside the group.

But that wasn't the case.

What they found instead was that being more attached to the group itself made participants more biased against people outside their groups, regardless of the context, compared to people with similar political beliefs but who didn't identify as Democrat or Republican.

"There is this very specific distinction between the self-declared partisans and politically similar independents," Huettel said. "They don't differ in their political positions, but they do behave differently toward people who are outside their groups."

A third of the participants were not swayed at all by group membership when allocating their money. Those participants were more likely to be politically independent, the researchers found.

"People who say they're politically independent are much less likely to show bias in a non-political setting," Kranton said.

They also found less group-minded people made decisions faster.

"We don't know if non-groupy people are faster generally," Kranton said. "It could be they're making decisions faster because they're not paying attention to whether somebody is in their group or not each time they have to make a decision."

What makes people groupy? The researchers don't know, but they did rule out some possibilities. It doesn't relate to gender or ethnicity, for example.

"There's some feature of a person that causes them to be sensitive to these group divisions and use them in their behavior across at least two very different contexts," Huettel said. "We didn't test every possible way in which people differentiate themselves; we can't show you that all group-minded identities behave this way. But this is a compelling first step."

WASHINGTON, Aug. 17, 2020 -- In addition to possibly developing opioid use disorder, those who take opioids long term, including patients who have been prescribed the drugs for pain relief, can develop chronic inflammation and heightened pain sensitivity. Scientists now report in a pilot study that some of those side effects might be influenced by the body's own immune system, which can make antibodies against the drugs.

The researchers will present their results today at the American Chemical Society (ACS) Fall 2020 Virtual Meeting & Expo. ACS is holding the meeting through Thursday. It features more than 6,000 presentations on a wide range of science topics.

A brand-new video on the research is available at http://www.acs.org/fall2020-opioids.

"Extrapolating from previous work on opioid vaccines, we started thinking that the patient's own immune system could be responsible for some of the negative effects of long-term opioid use," says Cody J. Wenthur, Pharm.D., Ph.D., who led the study. "We thought the body could be mounting an immune response and making antibodies against the drugs."

The researchers, who are at the University of Wisconsin-Madison School of Pharmacy, Scripps Research and Scripps Clinic, realized that one issue with this hypothesis is that commonly prescribed opioids for back pain, such as hydrocodone or oxycodone, are not large enough molecules for the immune system to recognize as antigens. From their past studies, however, they knew that an immune response could be triggered if something larger were bound to the drugs. This could happen in the body when a protein in the bloodstream reacts with the opioid to create a larger molecule in a process called haptenization.

To find out whether long-term opioid users produced antibodies against the drugs, the team performed an enzyme-linked immunosorbent assay (ELISA). Blood samples were obtained from 19 patients who used either hydrocodone or oxycodone for chronic back pain and from three control patients who used over-the-counter remedies (OTCs) or non-pharmacologic approaches. Jillian Kyzer, Ph.D., a postdoc in Wenthur's lab, along with Hyeri Park, Ph.D., a postdoc in the laboratory of Kim Janda, Ph.D., developed new techniques to synthesize hydrocodone and oxycodone haptens, linking them with a common blood protein to form bioconjugates. These bioconjugates were then coated on the surface of ELISA plates, and the patients' blood samples were added. If antibodies against the haptens were present in the patients' blood, they would stick to the surface of the plate and would be detected by another antibody that binds and creates a colorful dye through an enzyme-linked reaction.

Anti-opioid antibodies were found in the plasma of 10 people who regularly took prescription opioids for chronic lower back pain and almost none were found in those who used OTCs. The larger the dose of opioid, the larger the antibody response. "This was surprising," Kyzer says. "We saw antibody responses in people who were taking large doses for as little as 6 months."

The scientists are now working on isolating the key opioid antigenic intermediates in the body that prompt the generation of antibodies. One possibility is that the intermediates are modified proteins known as advanced glycation end products (AGEs), which could form when hydrocodone or oxycodone metabolites react with a carbohydrate. AGEs have been implicated in diseases such as atherosclerosis, cancer and Alzheimer's disease, and they might help explain chronic inflammation in long-term opioid users. The researchers have observed preliminary signals of hydrocodone-associated AGE formation under conditions relevant to those found in the human body, and they are planning to validate these results soon.

Wenthur says the findings support undertaking a broader study to determine the prevalence of antibodies in people based on race, age and sex. "The research could also be helpful in identifying efficacy biomarkers for opioid vaccines that are entering clinical trials," Kyzer says. "If our findings hold up in subsequent research, you would expect individuals with higher levels of these antibodies to be poor candidates for anti-opioid vaccine therapy."

WASHINGTON, Aug. 17, 2020 -- Immunotherapies for cancer -- treatments that prime the immune system to attack tumors -- are valuable weapons in the anti-cancer arsenal. But some cancers are more difficult to target with this strategy than others. Today, scientists report a new type of immunotherapy that dramatically extends the survival of mice that have triple negative breast tumors, a difficult-to-treat form of cancer.

The researchers will present their results at the American Chemical Society (ACS) Fall 2020 Virtual Meeting & Expo. ACS is holding the meeting through Thursday. It features more than 6,000 presentations on a wide range of science topics.

A brand-new video on the research is available at http://www.acs.org/fall2020-breast-cancer.

"From an immunotherapy standpoint, one of the biggest problems with triple negative breast cancer is that it doesn't produce any known antigens, or molecules recognized by the immune system, that are unique to the tumor," says Cassandra Callmann, Ph.D., who is presenting the work. "If you don't have a known tumor-specific antigen, it's hard to train your immune system to go after the tumor while ignoring healthy cells."

According to the Triple Negative Breast Cancer Foundation, this disease accounts for 15-20% of all breast cancers. The tumor gets its name from the fact that it tests negative for the estrogen receptor, the progesterone receptor and excess HER2 protein -- three proteins commonly produced in large amounts by other types of breast cancer. Because triple negative breast cancer lacks these markers, many commonly used breast cancer drugs aren't effective. This is one reason triple negative breast cancer has a poorer prognosis than other forms of the disease, according to the American Cancer Society.

To develop a new type of treatment, Callmann, a postdoctoral fellow in the lab of Chad Mirkin, Ph.D., at Northwestern University, needed to take a different approach from conventional immunotherapies that target a tumor-specific antigen. "The idea was to take tumor cells, chop them up, feed them to the immune system and let it figure out what to go after on its own," Callmann says. Other researchers have tried this approach for different cancers, but they typically administer both the chopped-up tumor cells (called a lysate) and a molecule that stimulates the immune system, known as an adjuvant, as a mixture. Instead, the team packaged the lysate and the adjuvant together in a single nanoparticle. The nanoparticle, called a spherical nucleic acid (SNA), contained the lysate inside its core and many copies of a DNA adjuvant radiating from its lipid membrane shell.

When the team injected SNAs under the skin of mice, the SNAs traveled to the lymph nodes. There, SNAs entered the cells, released their cargo and stimulated the cells to mount an immune response against antigens in the lysate. Interestingly, a stronger immune response occurred when the researchers incorporated oxidized tumor cell lysates from stressed tumor cells into SNAs.

The researchers tested the treatment on mice in which mouse triple negative breast cancer tumors were implanted. Two-thirds of mice receiving SNAs with oxidized lysates experienced complete tumor remission for at least 90 days, whereas all untreated animals died by day 30. None of the treated mice had obvious side effects or autoimmune responses.

The therapy is not yet ready for clinical trials, Callmann says. One of the next steps will be to investigate why the oxidized lysates work better than regular lysates. The team has begun to identify subsets of the lysates that are more immunogenic than others. She notes that a stressed cell could be producing different proteins, or perhaps the oxidizing agent is changing chemical groups on proteins. To get a clearer picture, Callmann plans to conduct a proteomic analysis to identify proteins that differ between oxidized and non-oxidized lysates.

The oxidized lysate/SNA approach might prove useful for treating other tumors, as well. "We have demonstrated that the overall structural presentation of a cancer vaccine or immunotherapeutic, as opposed to simply the identity of the active chemical components, dictates its potency, and this finding is opening doors in the field," Mirkin says.

Clarification: The researchers involved with the work highlighted in this release analyzed 47 human tissue samples by mass spectrometry, and these samples were found to have monomers, or plastic constituents, in them. These samples were not spiked with plastics. In separate experiments, the researchers spiked tissue samples with polymers (plastic beads), and found they could use flow cytometry to detect the polymer plastics that they introduced in tissues. In future work, these methods will be used to see if nanoplastics can be detected in human tissues. Edits have been made in the press release to clarify this information.

Updated on Oct. 21, 2020

WASHINGTON, Aug. 17, 2020 — Plastic pollution of land, water and air is a global problem. Even when plastic bags or water bottles break down to the point at which they are no longer an eyesore, tiny fragments can still contaminate the environment. Animals and humans can ingest the particles, with uncertain health consequences. Now, scientists report that they are among the first to develop analytical methods and reporting strategies for examining plastic monomers, micro- and nanoplastics in mammalian tissues, including human organs and tissues.

The researchers will present their results today at the American Chemical Society (ACS) Fall 2020 Virtual Meeting & Expo. ACS is holding the meeting through Thursday. It features more than 6,000 presentations on a wide range of science topics.

“You can find plastics contaminating the environment at virtually every location on the globe, and in a few short decades, we’ve gone from seeing plastic as a wonderful benefit to considering it a threat,” says Charles Rolsky, Ph.D., who is presenting the work at the meeting. “There’s evidence that plastic is making its way into our bodies, but very few studies have looked for it there. And at this point, we don’t know whether this plastic is just a nuisance or whether it represents a human health hazard.”

Scientists define microplastics as plastic fragments less than 5 mm, or about 0.2 inches, in diameter. Nanoplastics are even smaller, with diameters less than 0.050 mm. Research in wildlife and animal models has linked micro- and nanoplastic exposure to infertility, inflammation and cancer, but health outcomes in people are currently unknown. Previous studies have shown that plastics can pass through the human gastrointestinal tract, but Rolsky and Varun Kelkar, who is also presenting the research at the meeting, are studying if the tiny particles accumulate in mammalian and human organs and how to detect them. Rolsky is a postdoctoral scholar and Kelkar is a graduate student in the lab of Rolf Halden, Ph.D., at Arizona State University.

To find out, the researchers collaborated with Diego Mastroeni, Ph.D., to obtain samples from a large repository of brain and body tissues that was established to study neurodegenerative diseases, such as Alzheimer’s. Samples were taken from human and animal lungs, liver, adipose tissue, spleen and kidneys –– mammalian organs likely to be exposed to, filter or collect plastic monomers and microplastics. To develop a method and test it, the team spiked nano/microplastic beads into a sample set mammalian tissues. Then, they analyzed the sample with flow cytometry. With this procedure, the researchers showed that they could detect the beads that they introduced into these samples. The researchers also created a computer program that converted information on plastic particle count into units of mass and surface area. They plan to share the tool online so that other researchers can report their results in a standardized manner. “This shared resource will help build a plastic exposure database so that we can compare exposures in organs and groups of people over time and geographic space,” Halden says. The flow cytometry method allowed the researchers to show that they can detect nano/microplastics in mammalian tissues to which these had been added. The researchers also demonstrated the use of μ-Raman spectrometry to study environmental contamination with microplastics, including polycarbonate (PC), polyethylene terephthalate (PET) and polyethylene (PE).

In addition, the researchers used another method called mass spectrometry to analyze 47 human liver and fat tissue samples. No materials were spiked into these samples. The team found plastic contamination in the form of monomers, or plastic building blocks, in every sample. Bisphenol A (BPA), still used in many food containers despite health concerns, was found in all 47 human samples.

Taken together, to the researchers’ knowledge, their study is the first to provide an array of methods for examining monomer, nano- and microplastic occurrence in human organs from individuals with a known history of environmental exposure. “The tissue donors provided detailed information on their lifestyle, diet and occupational exposures,” Halden says. “Because these donors have such well-defined histories, our study provides the first clues on potential plastic exposure sources and routes.”

Should people be concerned about the high detection frequency of plastic components (i.e., monomers) in human tissues? “We never want to be alarmist, but it is concerning that these non-biodegradable materials that are present everywhere can enter and accumulate in human tissues, and we don’t know the possible health effects,” Kelkar says. “Once we get a better idea of what’s in the tissues, we can conduct epidemiological studies to assess human health outcomes. That way, we can start to understand the potential health risks, if any.”

WASHINGTON, Aug. 17, 2020 -- Although true "cyborgs" -- part human, part robotic beings -- are science fiction, researchers are taking steps toward integrating electronics with the body. Such devices could monitor for tumor development or stand in for damaged tissues. But connecting electronics directly to human tissues in the body is a huge challenge. Now, a team is reporting new coatings for components that could help them more easily fit into this environment.

The researchers will present their results today at the American Chemical Society (ACS) Fall 2020 Virtual Meeting & Expo. ACS is holding the meeting through Thursday. It features more than 6,000 presentations on a wide range of science topics.

"We got the idea for this project because we were trying to interface rigid, inorganic microelectrodes with the brain, but brains are made out of organic, salty, live materials," says David Martin, Ph.D., who led the study. "It wasn't working well, so we thought there must be a better way."

Traditional microelectronic materials, such as silicon, gold, stainless steel and iridium, cause scarring when implanted. For applications in muscle or brain tissue, electrical signals need to flow for them to operate properly, but scars interrupt this activity. The researchers reasoned that a coating could help.

"We started looking at organic electronic materials like conjugated polymers that were being used in non-biological devices," says Martin, who is at the University of Delaware. "We found a chemically stable example that was sold commercially as an antistatic coating for electronic displays." After testing, the researchers found that the polymer had the properties necessary for interfacing hardware and human tissue.

"These conjugated polymers are electrically active, but they are also ionically active," Martin says. "Counter ions give them the charge they need so when they are in operation, both electrons and ions are moving around." The polymer, known as poly(3,4-ethylenedioxythiophene) or PEDOT, dramatically improved the performance of medical implants by lowering their impedance two to three orders of magnitude, thus increasing signal quality and battery lifetime in patients.

Martin has since determined how to specialize the polymer, putting different functional groups on PEDOT. Adding a carboxylic acid, aldehyde or maleimide substituent to the ethylenedioxythiophene (EDOT) monomer gives the researchers the versatility to create polymers with a variety of functions.

"The maleimide is particularly powerful because we can do click chemistry substitutions to make functionalized polymers and biopolymers," Martin says. Mixing unsubstituted monomer with the maleimide-substituted version results in a material with many locations where the team can attach peptides, antibodies or DNA. "Name your favorite biomolecule, and you can in principle make a PEDOT film that has whatever biofunctional group you might be interested in," he says.

Most recently, Martin's group created a PEDOT film with an antibody for vascular endothelial growth factor (VEGF) attached. VEGF stimulates blood vessel growth after injury, and tumors hijack this protein to increase their blood supply. The polymer that the team developed could act as a sensor to detect overexpression of VEGF and thus early stages of disease, among other potential applications.

Other functionalized polymers have neurotransmitters on them, and these films could help sense or treat brain or nervous system disorders. So far, the team has made a polymer with dopamine, which plays a role in addictive behaviors, as well as dopamine-functionalized variants of the EDOT monomer. Martin says these biological-synthetic hybrid materials might someday be useful in merging artificial intelligence with the human brain.

Ultimately, Martin says, his dream is to be able to tailor how these materials deposit on a surface and then to put them in tissue in a living organism. "The ability to do the polymerization in a controlled way inside a living organism would be fascinating."

WASHINGTON, Aug. 17, 2020 -- Uniforms of U.S. Army soldiers must meet a long list of challenging requirements. They need to feel comfortable in all climates, be durable through multiple washings, resist fires and ward off insects, among other things. Existing fabrics don't check all of these boxes, so scientists have come up with a novel way of creating a flame-retardant, insect-repellent fabric that uses nontoxic substances.

The researchers will present their results today at the American Chemical Society (ACS) Fall 2020 Virtual Meeting & Expo. ACS is holding the meeting through Thursday. It features more than 6,000 presentations on a wide range of science topics.

"The Army presented to us this interesting and challenging requirement for multifunctionality," says study leader Ramaswamy Nagarajan, Ph.D. "There are flame-resistant Army combat uniforms made of various materials that meet flame retardant requirements. But they are expensive, and there are problems with dyeing the fabrics. Also, some of the raw materials are not produced in the U.S. So, our goal was to find an existing material that we could modify to make it flame retardant and insect repellent, yet still have a fabric that a soldier would want to wear."

Because Nagarajan's research group focuses on sustainable green chemistry, the team sought nontoxic chemicals and processes for this study. They chose to modify a commercially available 50-50 nylon-cotton blend, a relatively inexpensive, durable and comfortable fabric produced in the U.S. The material is used in a wide range of civilian and military applications because the nylon is strong and resistant to abrasion, whereas the cotton is comfortable to wear. But this type of textile doesn't inherently repel bugs and is associated with a high fire risk.

"We started with making the fabric fire retardant, focusing on the cotton part of the blend," explains Sourabh Kulkarni, a Ph.D. student who works with Nagarajan at the University of Massachusetts Lowell Center for Advanced Materials. "Cotton has a lot of hydroxyl groups (oxygen and hydrogen bonded together) on its surface, which can be activated by readily available chemicals to link with phosphorus-containing compounds that impart flame retardancy." For their phosphorus-containing compound, they chose phytic acid, an abundant, nontoxic substance found in seeds, nuts and grains.

Next, the researchers tackled the issue of making the material repel insects so that soldiers wouldn't have to spray themselves repeatedly or carry an additional item in their packs. The team took permethrin, an everyday nontoxic insect repellent, and attached it to the fabric using plasma-assisted deposition in collaboration with a local company, LaunchBay. Through trial and error, the researchers eventually got both the phytic acid and permethrin to link to the fabric's surface molecules.

Using methods to measure heat release capacity and total heat release, as well as a vertical flame test, they found that the modified material performed at least 20% better than the untreated material. They also used a standard insect repellency test with live mosquitoes and found that the efficacy was greater than 98%. Finally, the fabric remained "breathable" after treatment as determined by air permeability studies.

"We are very excited," Nagarajan says, "because we've shown we can modify this fabric to be flame retardant and insect repellent -- and still be fairly durable and comfortable. We'd like to use a substance other than phytic acid that would contain more phosphorous and therefore impart a greater level of flame retardancy, better durability and still be nontoxic to a soldier's skin. Having shown that we can modify the fabric, we would also like to see if we can attach antimicrobials to prevent infections from bacteria, as well as dyes that remain durable."

WASHINGTON, Aug. 17, 2020 -- Spun by spiders and silkworms, silk has mystified human engineers who have yet to figure out how to artificially recreate this tough, fine fiber. But by combining silk, which is safe for use in the human body, with synthetic compounds, one research team is getting closer to developing new implantable composite materials with the best properties of both. Potential applications, which are still years away, could include structures that hold bone in place after surgery or replacements for the cartilage cushions in the knee.

The researchers will present their results today at the American Chemical Society (ACS) Fall 2020 Virtual Meeting & Expo. ACS is holding the meeting through Thursday. It features more than 6,000 presentations on a wide range of science topics.

"Silk has great potential for use in biomedical applications," says Juan Guan, Ph.D., the project's principal investigator. "Silk is versatile, and the human body tolerates it quite well, and can even degrade and absorb it."

Silk has a long history in medicine. Records of ancient doctors stitching up patients with fibers spun by silkworms date back nearly 2,000 years. And today, surgeons finish certain surgeries, such as those on the eye, with silk sutures.

By combining silk and synthetic polymers, Guan and her colleagues at Beihang University are seeking to develop versatile new materials for use in medicine and, potentially, other fields as well. While other researchers have already developed composite materials with silk, they have typically worked with short fibers or the primary protein in silk. Guan, however, focuses on silk fabric woven from a long, single thread. Silkworms' cocoons can contain fibers nearly 5,000 feet long, and when used whole in fabric, such a fiber can more effectively distribute mechanical stress than a series of shorter, discrete ones, she says. In their studies, Guan's team uses silk from the common, domesticated silkworm Bombyx mori, as well as tougher, more stretchy fibers from the wild species Antheraea pernyi.

The researchers combine this fabric with a polymer matrix, often an epoxy, which is used in adhesives. Together, the fabric and the polymer form a laminate -- similar to the durable surface covering found on some furniture -- which can then be cut into the shapes the researchers need.

Guan and her colleagues say that the properties of these new materials could make them a better match for the tissues within the human body than what is being used today. For instance, they are collaborating with orthopedic doctors to devise structures resembling cages that temporarily hold vertebrae in place as they fuse after surgery, a task currently accomplished mostly using metal. The silk composites' hardness and stiffness is more compatible with bone, making them potentially more resilient yet more comfortable than metal structures, she says.

There are challenges, however. The inside of the human body is moist, a potential problem because water can soften and weaken silk. In new experiments, Guan and her colleagues tested how silk-epoxy composite materials hold up when exposed to humidity or immersed in water. For use alongside bone, they must maintain a certain stiffness. The experiments showed that while this attribute decreased under wetter conditions, the composites remained stiff enough to function as implants, she says.

While the epoxy attaches firmly to the silk fiber, it has a major drawback: The body can't break down the epoxy and absorb it, meaning it would not be suitable for implants intended to dissolve. So, Guan recently began working with biopolymers that, like silk, the body can break down and absorb. However, these composites have less internal cohesion than those that contain an epoxy. "The key question is how to make the interface between the biopolymer and the silk fabric more robust," she says.

The scientists are also looking to supplement silk with other types of fibers. In a recent study, they added carbon fibers into the mix. "The notion of hybridizing silk with other fibers makes it possible to produce a rather nice spectrum of properties that you can optimize for a given application," says Robert O. Ritchie, Ph.D, an author of the carbon fiber study. Potential uses for these new structural materials, he says, could be anywhere: in the human body, or even in tennis rackets or on airplane engines.

WASHINGTON, Aug. 17, 2020 -- Global economic growth comes with increasing demand for energy, but stepping up energy production can be challenging. Recently, scientists have achieved record efficiency for solar-to-fuel conversion, and now they want to incorporate the machinery of photosynthesis to push it further.

The researchers will present their results today at the American Chemical Society (ACS) Fall 2020 Virtual Meeting & Expo. ACS is holding the meeting through Thursday. It features more than 6,000 presentations on a wide range of science topics.

"We want to fabricate a photocatalytic system that uses sunlight to drive chemical reactions of environmental importance," says Lilac Amirav, Ph.D., the project's principal investigator.

Specifically, her group at the Israel Institute of Technology is designing a photocatalyst that can break down water into hydrogen fuel. "When we place our rod-shaped nanoparticles in water and shine light on them, they generate positive and negative electric charges," Amirav says. "The water molecules break; the negative charges produce hydrogen (reduction), and the positive charges produce oxygen (oxidation). The two reactions, involving the positive and negative charges, must take place simultaneously. Without taking advantage of the positive charges, the negative charges cannot be routed to produce the desired hydrogen."

If the positive and negative charges, which are attracted to one another, manage to recombine, they cancel each other, and the energy is lost. So, to make sure the charges are far enough apart, the team has built unique heterostructures comprised of a combination of different semiconductors, together with metal and metal oxide catalysts. Using a model system, they studied the reduction and oxidation reactions separately and altered the heterostructure to optimize fuel production.

In 2016, the team designed a heterostructure with a spherical cadmium-selenide quantum dot embedded within a rod-shaped piece of cadmium sulfide. A platinum metallic particle was located at the tip. The cadmium-selenide particle attracted positive charges, while negative charges accumulated on the tip. "By adjusting the size of the quantum dot and the length of the rod, as well as other parameters, we achieved 100% conversion of sunlight to hydrogen from water reduction," Amirav says. A single photocatalyst nanoparticle can produce 360,000 molecules of hydrogen per hour, she notes.

The group published their results in the ACS journal Nano Letters. But in these experiments, they studied only half of the reaction (the reduction). For proper function, the photocatalytic system must support both reduction and oxidation reactions. "We were not converting solar energy into fuel yet," Amirav says. "We still needed an oxidation reaction that would continually provide electrons to the quantum dot." The water oxidation reaction occurs in a multi-step process, and as a result remains a significant challenge. In addition, its byproducts seem to compromise the stability of the semiconductor.

Together with collaborators, the group explored a new approach -- looking for different compounds that could be oxidized in lieu of water -- which led them to benzylamine. The researchers found that they could produce hydrogen from water, while simultaneously transforming benzylamine to benzaldehyde. "With this research, we have transformed the process from photocatalysis to photosynthesis, that is, genuine conversion of solar energy into fuel," Amirav says. The photocatalytic system performs true conversion of solar power into storable chemical bonds, with a maximum of 4.2% solar-to-chemical energy conversion efficiency. "This figure establishes a new world record in the field of photocatalysis, and doubles the previous record," she notes. "The U.S. Department of Energy defined 5-10% as the 'practical feasibility threshold' for generating hydrogen through photocatalysis. Hence, we are on the doorstep of economically viable solar-to-hydrogen conversion."

These impressive results have motivated the researchers to see if there are other compounds with high solar-to-chemical conversions. To do so, the team is using artificial intelligence. Through a collaboration, the researchers are developing an algorithm to search chemical structures for an ideal fuel-producing compound. In addition, they are investigating ways to improve their photosystem, and one way might be to draw inspiration from nature. A protein complex in plant cell membranes that comprises the electrical circuitry of photosynthesis was successfully combined with nanoparticles. Amirav says that this artificial system so far has proven fruitful, supporting water oxidation while providing photocurrent than is 100 times larger than that produced by other similar systems.

August 17, 2020 -- A subcommittee of the American Thoracic Society Assembly in Sleep and Respiratory Neurobiology has released new clinical practice guidelinesto help advise clinicians on the optimal management of patients with chronic obstructive pulmonary disease (COPD) and chronic hypercapnia. Hypercapnia is the buildup of carbon dioxide in the bloodstream. The guidelines, published online in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine, is titled "Long-Term Non-Invasive Ventilation in Chronic Stable Hypercapnic Chronic Obstructive Pulmonary Disease: An Official American Thoracic Society Guideline."

The committee, comprised of leading clinicians working in pulmonary and critical care medicine, as well as patient representatives, developed a consensus approach and summarized evidence for addressing five PICO (patients, intervention, comparator, outcome) questions related to non-invasive ventilation (NIV) for chronic hypercapnic COPD. Recommendations were formulated by the panel of pulmonary and sleep physicians, respiratory therapists and methodologists using the Evidence-to-Decision framework, a systematic and transparent approach to groups making well-informed health care recommendations.

While NIV is used for patients with COPD and chronic hypercapnia, up to this point, evidence for clinical efficacy and optimal management of therapy have been limited.

"This guideline is needed because patients with severe COPD are very sick and have few therapies that have been shown to improve outcomes," said guideline Chair Robert L. Owens, MD, associate professor, Division of Pulmonary, Critical Care and Sleep Medicine, University of California, San Diego. "Clinicians who care for these patients need information about whether to consider non-invasive ventilation and some practical advice on how to set up patients with NIV."

The group's main recommendations are to:

use nocturnal NIV in addition to usual care of patients with chronic stable hypercapnic COPD;

have patients with chronic stable hypercapnic COPD undergo screening for obstructive sleep apnea (OSA) before initiation of long-term NIV;

avoid initiating long-term NIV during admission for acute-on-chronic hypercapnic respiratory failure, favoring instead reassessment for NIV at 2-4 weeks after resolution;

avoid the use of in-laboratory overnight polysomnography (PSG) to titrate NIV in patients with chronic stable hypercapnic COPD who are initiating NIV, and

use NIV with targeted normalization of PaCO2 in hypercapnic COPD patients on long-term NIV.

To develop each of the recommendations, the panel reviewed results from numerous randomized clinical trials, and looked at such factors as health equity and availability of pulmonary and critical care specialists in medically underserved areas, as well as the likelihood of patient compliance. Because some or all of these issues may impact each of the recommendations, all recommendations were considered conditional. The group outlined unanswered questions for each recommendation, as well as future research directions. They also examined what other specialty organizations were saying on these issues.

"It is exciting to consider NIV as additional therapy for those with hypercapnic COPD," the authors stated. "However, there are many issues to consider."

Among these issues are: appropriate patient selection; implementation barriers; the need for more data to guide the goals of therapy, especially on how clinicians should target PaCO2; addressing regulatory/payor considerations on the ability to obtain home NIV for COPD, and the potential for worsening health care disparities due to the cost and expertise needed to provide NIV for patients with stable hypercapnic COPD.

Dr. Owens concluded, "This guideline is needed now because studies in the last few years have shown improved outcomes with non-invasive ventilation for patients with severe COPD. The guideline incorporates recent studies, while also highlighting priority areas for research."

When clinicians resort to phage therapy for patients who don't respond to antibiotics, the patients are usually very ill and time is of the essence. But the average time for labs to produce therapeutic phages is more than a month.

The main reason for this is the lack of a standardized phage purification process for research labs, despite the fact that phage therapy -- which uses viruses to destroy disease causing bacteria -- has been around for over a century.

Now, a San Diego State University lab that produces phage therapeutics for clinicians across the country for compassionate use has developed standardized guidelines intended to not only streamline the process using existing lab equipment, but also shorten it to two to three weeks, cutting the typical processing time by half.

"Many of our patients have so little time, so speed is of the essence and this protocol would really make a difference, since one run can produce enough doses to treat a patient for months," said Dwayne Roach, the Conrad Prebys chair of virology and assistant professor at SDSU.

The protocol, he said, combines traditional techniques with modern filtration technology to produce higher phage yields and reduce endotoxin levels compared to previously developed methods.

The open source guidelines were published in a paper in Nature Protocols in July.

Bacteriophages and phage therapy

Typical candidates for phage therapy are patients who have multi-drug resistant bacteria, a more and more common fallout of overusing antibiotics. Phage is short for bacteriophage, which literally means "bacteria eater." They are viruses that only attack bacteria, not people, and are found in soil, water and sewage, requiring them to be purified before use.

Phage therapy is not approved yet in the United States and Europe, except on a case-by-case basis under compassionate use. The military is also interested in phage therapy for the battlefield, where it could be used as a sterilizing wash to remove bacteria from wounds.

Since this is still an emerging field, labs take varying approaches to phage purification. The protocols developed by the SDSU researchers are straightforward, and use simple, standard microbiology lab equipment to remain affordable. They are suitable even for labs in countries with limited resources that wish to ramp up phage production.

Lack of protocols a key bottleneck

Since Roach's lab has a library of phages on hand, much of the back-end work of collecting and cultivating them has already been completed. The protocols allow his team to supply clinicians with the best-fit phages in as little as a week.

"Our protocol provides a standard of production for medicinal phages that consistently provides potentially thousands of phage treatment doses," said Tiffany Luong, first author and a doctoral student in Roach's lab. "We provide instruction and rationale for each step in our process which allows the user to tailor the procedure to their specific equipment and bacterial species."

Identifying groups of phages that are effective against multi-drug resistant bacteria has become easier over the years.

But Dr. Robert 'Chip' Schooley, director of the Center for Innovative Phage Applications and Therapeutics at the University of California San Diego, said however that the absence of rigorous, scalable approaches for producing therapeutic phages in academic laboratories and delivering them to the patient's bedside is a major bottleneck.

"Dr. Roach's protocol guidelines are an outstanding example of the rigor required to safely take phages into the clinic," Schooley said. "These guidelines will be of great interest to other academic laboratories and to regulatory agencies as we move into the next phases of phage therapeutics."

Reducing endotoxins

When Roach's team began working with physicians in spring 2019, they had to figure out how to streamline the process. By scrutinizing each step and comparing different methods, the team identified cross-flow filtration -- when the flow travels across the surface of the filter instead of into it -- as the most efficient and effective purification method, and Roach presented the results and accelerated timeline at a conference later in the year.

While Roach and Luong looked at process optimization, Ann-Charlott Salabarria, a postdoctoral researcher, worked on setting parameters for ensuring safety of the end product with multiple tests, including confirming that endotoxin levels met U.S. Food and Drug Administration (FDA) guidelines.

One of the FDA's major concerns with phage products is its endotoxin levels, which can harm patients and need to be removed as part of the purification process. The published protocol will help ensure the phage products are safe above and beyond the FDA minimum requirements, Roach explained.

"Our tests do validate that this process removes almost all endotoxins and exotoxins," Roach said. "We wanted to publish our protocol as a resource for other labs because purification has been very time consuming, taking away time from research."

Phage strain selection is another important aspect to developing phage therapeutics. To screen out unwanted genes in phage genomes, Roach enlisted the help of SDSU microbial geneticist and bioinformatics expert Robert Edwards.

"Phage genomes contain so many different components and may mobilize other toxins or antibiotic resistance genes," Edwards said. "It is absolutely imperative that we understand these viruses at the molecular level to ensure that we are not introducing anything potentially harmful into already ill patients."

The researchers will continue to focus on improving safety in phage therapy, by testing it on tissue and mice cell cultures.

"We hope this protocol will allow more research labs to participate in re-introducing phages to Western medicine," Luong said.

PHILADELPHIA-- While about a quarter of physicians and researchers working in advanced heart failure (HF) and transplant cardiology are women, representation of women leading HF research remains limited, according to new research led by Penn Medicine. The authors say the findings point to a need to support great gender diversity among researchers to drive diversity among clinical trial participants and even improve patient outcomes. The analysis, published this month in Circulation: Heart Failure, showed that that less than 20 percent of first authors on manuscripts cited to support the highest recommendations in HF treatment guidelines were women, and less than 15 percent of the senior authors were women. Furthermore, only 16 percent of contemporary clinical trials in HF had a woman as a first or senior author. The research is the first of its kind to explore gender disparities in authorship of HF guideline citations and clinical trials.

Despite this lack of representation in authorship, researchers found that clinical trials with higher proportions of women authors had a higher number of female participants--aligning with a longstanding priority from federal organizations to increase the enrollment of women in clinical trials.

"Diversity in authorship can have a snowball effect across the field--not only in improving gender equity in cardiovascular medicine, but also perhaps in reducing the underrepresentation of women in clinical trials," said Nosheen Reza, MD, the study's lead author, an instructor of Cardiovascular Medicine, and advanced HF and transplant cardiologist in the Perelman School of Medicine at the University of Pennsylvania. "For many reasons, institutions are now taking a hard look at improving diversity, inclusion, and equity, and our findings represent benchmarking data that organizations can utilize and build from."

The researchers identified authors of publications referenced in so-called class I recommendations--representing the strongest clinical guidelines and recommendations--in the United States (173) and European HF guidelines (100), and of publications of HF trials with more than 400 participants published between 2001 and 2016 (118). After authors' genders were determined by using a multinational database and name matching algorithm, the researchers evaluated the authorship patterns--with a focus on those who led the research for each paper--over time.

On average, the overall proportions of women as first authors of referenced publications in the United States HF guidelines was 18 percent and 16 percent for European HF guidelines, and as last authors 13 percent and 12 percent, respectively. From 1986 to 2016, the percentage of women authorship modestly increased overall in guideline citations.

The proportions of women as first or last authors in HF clinical trials did not change significantly over time, and only 16 percent of the HF clinical trials examined had a woman as a first or senior author. However, HF trials with a woman first or senior author were associated with a higher proportion of enrolled female clinical trial participants (39 percent versus 26 percent).

"While the reasoning behind this interesting phenomenon is still unknown, it's clear representation is an important element for improving care for women," Reza said. "One hypothesis we have for this finding is that women may be more likely to enroll as participants in clinical trials that they know are being conducted by women investigators. Another possibility could be that women investigators are more likely to refer women patients for enrollment in clinical trials. This is certainly an area in which future research is needed."

The authors call for efforts to rectify these disparities, especially since women authorship of HF clinical trials is an important predictor of the enrollment of female participants, which may help to reduce the underrepresentation of women in HF clinical trials.

"Institutions must come together to make a committed effort to improve diversity, inclusion, and equity on promotions committees, editorial boards, steering committees, and other leadership bodies in the HF research enterprise. Women will not overcome these hurdles if these metrics and efforts don't change. By advocating for broad scale efforts in these domains, such as including more women in leadership positions and increasing the mentorship of women across career stages in medicine, we'll be able to develop future generations of experienced and accomplished women investigators and mentors in HF, and advance science together without leaving anyone behind," Reza said.

Co-authors include Ayman Samman Tahhan, Penn's Nadim Mahmud, Ersilia M. DeFilippis, Alaaeddin Alrohaibani, Muthiah Vaduganathan, Stephen J. Greene, Annie Hang Ho, Gregg C. Fonarow, Javed Butler, Christopher O'Connor, Mona Fiuzat, Orly Vardeny, Ileana L. Piña, JoAnn Lindenfeld, Mariell Jessup.

New research published today in
The Journal of Physiology shows that nitrate improves function in the diaphragm, the muscle involved in coughing and breathing, by improving power. The study done in old mice, if replicated in humans, could provide a strategy for helping elderly people clear the lungs more effectively and avoid infection.

Previous studies showed nitrate was helping muscles by improving use of calcium in the muscle. This finding that it's additionally affecting power is significant, especially in the context of COVID-19, because the diaphragm is the primary inspiratory muscle used for breathing and coughing, the latter being relevant for clearing the lungs.

The research team at the University of Florida found that dietary nitrate supplementation elicited a pronounced increase in contractile function (power) of the diaphragm, a respiratory muscle, of old mice.

They made their measurements during maximal activation, so the effects observed seem to be caused by an improvement in the function of contractile proteins rather than calcium handling.

Few short-term interventions have such a profound impact on muscle contractile function, as was observed in this study.

Dietary nitrate is readily available for humans and could be used, under proper supervision, to improve respiratory muscle dysfunction that contributes to shortness of breath and morbidity in the elderly.

The researchers gave sodium nitrate to old mice in their drinking water daily for 14 days. The control group received regular water. Diaphragm muscle contractile function cannot be assessed directly in live animals or humans. Thus, they tested diaphragm function in muscle tissues under controlled conditions for muscle stimulation and oxygenation.

The main limitations are that mouse and human diaphragm have different percentages of fast and slow muscle cells. Mouse diaphragm consists of 90% fast muscle cells; the human diaphragm consists of 25-50% fast muscle cells depending on several factors that include and age and sex.

Dietary nitrate seems to exert a greater impact on the contractile function of fast muscle cells. Thus, the benefits to the human diaphragm may not as pronounced as was observed in mice. They also only tested male mice, and the benefits for females is unknown.

Leonardo Ferreira, senior author on the study said:

"Our findings are especially important in light of the current COVID-19 pandemic as they suggest that, if replicated in humans, dietary nitrate is useful to improve respiratory muscle dysfunction that contributes to difficulty in weaning patients from mechanical ventilation."