Culture

Sugarcane bagasse and other kinds of agricultural waste biomass can be used as raw materials for the manufacturing of fine chemicals. To this end, however, it is necessary to develop technologies that are competitive with the processes currently used by the petrochemical industry to obtain these high-value compounds for specialized applications.

A group of researchers affiliated with institutions in Brazil and the United Kingdom has succeeded in advancing in this direction by developing a novel simplified biotechnological route to convert sugarcane bagasse and wheat straw into fine chemicals with applications in the food, cosmetics and pharmaceutical industries, among others. The researchers are now looking for partners to commercialize the technology.

The new process was developed during a project supported by FAPESP under the aegis of its Bioenergy Research Program (BIOEN) and is described in an article published in the journal Green Chemistry.

The researchers work at the University of Sorocaba (UNISO) and the University of Campinas (UNICAMP) in São Paulo State, Brazil, and at the University of Manchester and the University of Warwick in the UK.

"We managed to develop a biocatalytic route to produce coniferol and other aldehydes and aromatic acids directly from agricultural waste biomass," Fábio Márcio Squina, a professor at UNISO and principal investigator for the project, told FAPESP Innovative R&D.

Coniferol is so valuable that a gram can cost as much as €300. It is used to synthesize various chemicals that are equally costly, such as pinoresinol, a hypoglycemic agent, and sesamin, which has anti-hypertensive properties and helps lower cholesterol levels. Coniferol is also a floral scent precursor and has the potential to be used by the perfume and cosmetics industries in developing fragrances.

In the petrochemical industry, coniferol is obtained by processes of chemical synthesis involving complex routes or the use of hazardous reagents. These include sodium borohydride, as well as other toxic products, transition metals and complex catalysts that accelerate chemical reactions.

To develop a simpler process that eliminates the use of hazardous substances and mitigates the environmental impact, the researchers produced biocatalysts and applied them directly to agricultural waste. In this manner, they succeeded in releasing ferulic acid from lignocellulosic biomass and converting it directly into coniferol.

"By means of a cascade of three catalytic enzymes developed in recent years, also with applications in biofuel production, we produced coniferol in a simplified process with a conversion yield as high as 97%," Squina said.

Combination of enzymes

One of the catalytic enzymes used in the new process is a feruloyl esterase (XynZ). Produced by a bacterium in the genus Clostridium, the enzyme characterized by the Brazilian researchers is capable of removing ferulic acid from plant biomass. Ferulic acid is an aromatic compound accounting for approximately 2% of lignocellulosic biomass.

Another of these enzymes is aldo-keto reductase (AKR). Produced by the Asian subterranean termite Coptotermes gestroi and discovered by the Brazilian scientists, AKR can catalyze coniferol production. However, another class of enzymes called carboxylic acid reductase (CAR) is needed to produce the compound from lignocellulose-derived ferulic acid.

Different combinations of AKRs and CARs were tested while PhD candidate Robson Tramontina was at the University of Manchester with a Research Internship Abroad scholarship from FAPESP (São Paulo Research Foundation).

The results of the tests showed that the best combination used a CAR derived from Nocardia iowensis, a species of bacterium found in soil and described by the British scientists.

Once the ideal combination was found, a strain of the bacterium Escherichia coli was developed to produce recombinant genes from C. gestroi and N. iowensis.

In contact with lignocellulosic material such as sugarcane bagasse and wheat straw, the combination of the bacterium with the enzyme feruloyl esterase triggered a cascade of chemical reactions that led to the production of coniferol.

"This new route enables us to obtain not just coniferol but also other high-value aldehydes and aromatic alcohols that have applications in a range of industries," Squina said.

Search for partners

The researchers are now working on ways to intensify the process and on economic feasibility studies.

Preliminary calculations show that the new biotechnological route can increase the value of sugarcane bagasse and wheat straw up to 5,000-fold and multiply the price of ferulic acid by a factor of up to 75 when these residues are converted into coniferol.

"We're currently engaged in a search for partners interested in developing the technology for industrial use and possibly adapting it to other raw materials or to produce other commercially worthwhile compounds," Squina said.

Scientists have a pretty good handle on how the birds and the bees work, but it comes to mating, almost all millipedes have been a mystery--until now. For the first time, researchers have puzzled out how these tiny creatures' complex genitalia work, thanks to new imaging techniques and blacklights that make the different tissues glow. The findings are published in a new paper in the journal Arthropod Structure and Development.

"This is the first time we've been able to understand these millipedes' mechanism of insertion, how the male and female organs interact with each other. Before this, we had no idea how he would actually get the sperm into her," says Petra Sierwald, an associate curator at the Field Museum in Chicago and one of the paper's authors.

Millipedes are centipedes' chill vegetarian cousins. They're in a different animal group from insects and spiders, but they're part of the same big umbrella of arthropods. They have dozens of legs, but they're slow movers--they eat decaying plants, so they don't need to be speedy to catch a meal.

"Millipedes are mulch munchers," says Sierwald. "They are in waste management, and they're very good at it."

There are over 13,000 different species of millipedes known to science (with many more discovered every year), and they each have their own unique way of mating. The genus that Sierwald and her colleagues focused on in this study, Pseudopolydesmus, is made up of half-inch-long brown millipedes from North America. They're not too exciting to look at, but their behavior makes them stand out to scientists: they're unusually eager to mate, even in laboratory conditions.

"One of the problems with millipedes is that they do a lot of things while they are dug into the ground, and if you take them out, you will disturb them and they'll stop what they're doing," says Sierwald. Not Pseudopolydesmus, though. "They will even mate in the lab in the Petri dish under the light."

But while Pseudopolydesmus are the exhibitionists of the millipede world, it's still hard to see exactly what's going on down there--there are a lot of legs in the way.

"This paper has been a long time in the making. It started out when I found a pair of this genus, a male and female, in copula, sort of attached. Their legs were obscuring everything," says Sierwald.

To solve this problem, Sierwald and her colleague, Field Museum co-author Stephanie Ware, experimented with different lighting and imaging techniques. Ware took dozens of photographs of the tiny subjects at slightly varying distances, and then used a computer program to stack the images together and combine them so that all the miniscule details were in focus. so She took photos in both natural and ultraviolet light conditions since the millipedes' genitals glow under UV light, making it easier to tell the different tissues apart. The resulting blacklight photos look like a rave, albeit one made up of microscopic millipede genitalia.

To get further information about the structure of the millipedes' genitals, Xavier Zahnle at the University of California Davis, the paper's first author, conducted micro-CT scanning. "You can put these tiny millipedes into test tubes and do CT scanning on them, and you don't have to dissect the specimen, so it remains intact," explains Sierwald. "That is the really cool thing. The CT scan takes images of slices, and Xavier worked out the entire complex software program to analyze the slices and put them back together."

All of these images of the millipedes' genitalia, both on their own and locked together in the act of mating, helped the researchers figure out how the process actually works for Pseudopolydesmus.

In most millipedes, including Pseudopolydesmus, the male's testes are located in the body starting behind his second pair of legs. But his gonopods, the specialized pair of legs used to insert sperm into the female, are way back on his legs of the seventh body ring. "He has to ejaculate and then dig his seventh-ring gonopods into that ejaculate," she explains. "It's a blue-ish liquid."

Once the male has gotten his gonopods covered in blue ejaculate, he's ready to insert them into a female's vulvae. "She has two openings, one on each side between her second pair of legs," says Sierwald. The microscopic images showed the tiny fleshy part of the male's gonopods that actually enter the vulvae. "We had no idea for this entire group, which part is inserted and where it is inserted in the female," says Sierwald. Tiny claws on the end part of the male gonopod hook behind ridges on the female vulva.

After mating, the female's vulvae get sealed up with a gooey secretion, trapping the sperm inside. Later, when she lays her eggs, they get coated with the stored sperm on their way out of her body. The new imaging in this study also helps show how that process works.

"Before this study, we had no idea really where the secretions came from. I always thought it came from the male, because I thought the male wanted to seal off the female so that she couldn't mate again," says Sierwald. "But now, having seen the glands inside the female's vulvae through the CT-scanning, I think most of that secretion comes from the female. I don't know whether that is her way of protecting her vulvae or preserving the sperm. Those are interesting fields for further study."

In addition to giving us a better understanding of the mechanics of millipede sex, Sierwald hopes the project will enable scientists to better understand the relationships between different millipede species, which could shed light on how they evolved.

"This study will be important for understanding how millipedes in this genus are related and how they're distributed," says Sierwald. "They can tell us about the geologic history of North America. As mountain ranges and rivers formed, groups of millipedes would get cut off from each other and develop into new species." And, she notes, Pseuopolydesmus is just the tip of the iceberg.

"There are 16 orders of millipedes in the world, and for most of them, we have only faint ideas what the vulvae look like."

There is a growing consensus that the gut microbiome is involved in many aspects of physical and mental health, including the onset of Parkinson's disease, multiple sclerosis, and even some behaviors. The microbiota of the small intestine in particular are likely to have important effects on human health because most nutrients and drugs are absorbed by the body in this location. To study the gut microbiome, researchers typically use mice and rats because these animals are easy to take care of, reproduce quickly, and have many biological similarities to humans. But there are significant differences between humans and these animals. One such difference--the propensity for laboratory rodents to eat their own feces--may have major implications for research related to the small-intestine microbiome.

In a study published in the journal Microbiome, researchers in the laboratory of Rustem Ismagilov, Caltech's Ethel Wilson Bowles and Robert Bowles Professor of Chemistry and Chemical Engineering and director of the Jacobs Institute for Molecular Engineering for Medicine, show that standard lab mice (that consume their feces) may have important differences in their small-intestine microbial communities as compared to humans.

The research community has been aware for many decades that lab rodents consume feces, a practice known as coprophagy, but what has not been understood is how this activity actually affects conditions inside the small intestine, says Said Bogatyrev, Caltech postdoctoral scholar in chemical engineering and lead author of the study.

"Most researchers also assume that coprophagy is solved by housing mice on wire floors that allow the feces to fall through. However, rats and mice are very good at eating poop right as it comes out," he says, "so we suspected the wire floors might not actually be that effective."

In the study, Bogatyrev and his fellow researchers investigated the microbiome in the small intestines of lab mice to see whether the microbiome and its function differ when these mice are prevented from consuming their own poop, and if doing so would make these lab mice more similar to humans.

To find out, the research team fitted mice with "tail cups"--basically little mouse diapers that capture the animals' feculence and prevent them from eating it. When the researchers analyzed the gut contents and microbial communities of these diapered mice, they found significant differences in their small intestines as compared with those of standard mice.

As might be expected, mice that consumed poop had much higher microbial loads (around 100 times higher), of large-intestine (and fecal) microbiota, and different profiles of bile acids in their small intestines, compared with the diapered mice. Their intestines were similar, however, to those of humans with microbial overgrowth disorders, such as small intestinal bacterial overgrowth (SIBO), which can cause diarrhea and weight loss. In contrast, the conditions inside the small intestines of the mice that did not eat their own feces more closely resembled the conditions inside the small intestine of a healthy human.

Bogatyrev calls the process of bringing fecal bacteria into the small intestine through coprophagy "self-reinoculation." By consuming their own poop, the mice reintroduce bacteria from the large intestine into the small intestine, and change the conditions and microbial communities in the upper gut.

Bogatyrev and his colleagues did not attempt to determine how self-reinoculation might generally affect research involving mice, but they suspect that there could be wide-ranging implications to numerous research areas if the digestive systems of the mouse models do not behave like those of humans.

"One area could be dietary research," he says. "If you have more microbes in the small intestine, that, in turn affects the bile-acid composition there and the nutrients in the diet may be absorbed differently. Fats, for example. Another area could involve probiotics and the microbial ecology of the gut. Self-reinoculation can cause inconsistent results in controlled-administration protocols because you don't know how the probiotics are being reintroduced to the gut by the animals themselves."

And another big area where coprophagy would matter could be drug research, Bogatyrev adds. Researchers use rodents in preclinical models, and the drugs administered are often absorbed in the small intestine, where they can potentially be affected by small-intestine microbiota.

"Although there's a recognition that self-reinoculation with fecal flora and metabolites may be an issue and it may affect some study outcomes, we just don't know yet how important it is. This work suggests that the effects of self-reinoculation need to be rigorously tested, which provides a plethora of opportunities for future research," Bogatyrev says.

In 2018, California wildfires burned more than 1.8 million acres and caused smoke to drift hundreds of miles. As the frequency and intensity of wildfires increases with climate change, California agricultural workers are at greater risk of smoke exposure as they often have no option but to work outdoors.

A new study from researchers at the University of California, Davis, finds that while wildfires and smoke exposure are recognized by farmworkers and employers as a growing threat and safety concern, the means to address these concerns differs between the two groups.

"What stood out in this study is the substantial disparities between agricultural employers and farmworkers," said Heather Riden with the Western Center for Agricultural Health and Safety at UC Davis.

Riden, who led the research in partnership with the California Institute for Rural Studies, said that while growers and employers expressed concern about poor air quality at the time of the study in 2018, many had no clear plans or protocols for measuring air quality or managing workers in such conditions. While the public is advised to stay indoors due to poor air quality during a wildfire, agricultural work often continues.

The study also found that when farmworkers were offered protective masks, many found them difficult to use while working due to heat-related discomfort and chafing. Others believed wearing two bandanas over the mouth and nose would provide just as much protection.

Farmworkers' experience is compounded by economic need.

"Many farmworkers will continue working, even in unsafe conditions, to support their families. They don't have many other options," said Riden.

NEW REGULATIONS

Last year, the state Division of Occupational Safety and Health, better known as Cal/OSHA, enacted an emergency regulation requiring employers to take measures to protect workers from wildfire smoke when the Air Quality Index reaches 151 or greater, which is considered unhealthy. Riden said as CAL/OSHA begins to craft permanent regulations, she hopes it takes the study's findings into consideration.

"This highlights the need for better awareness for both agricultural employers and farmworkers about the health risks associated with wildfire smoke," said Riden. "Employers also need training materials and concrete steps they can take to protect workers."

To assist agricultural employers with meeting the requirements outlined in the newly adopted regulation, the Western Center for Agricultural Health and Safety developed training materials and an employer checklist.

Within days of birth, a few drops of blood are collected from every newborn in California--and across the United States -- which are then stored on filter paper and screened for dozens of genetic and congenital disorders, such as phenylketonuria (PKU), an inherited metabolic disorder that can result in intellectual disability, seizures, heart and behavioral problems.

Researchers at University of California San Diego School of Medicine have launched a Phase II research study to look for signs of another similarly devastating disorder, one that typically does not appear in seemingly healthy children until years later: autism spectrum disorder or ASD.

The UC San Diego Newborn Screening-Autism Risk Study is designed to determine whether the dried and stored blood drops of children later diagnosed with ASD contain within them the tell-tale presence and combinations of biological molecules and environmental chemicals that might predict the risk of a future ASD diagnosis.

"We know from the history of certain genetic diseases, such as PKU, that if children can be identified before the first symptoms have appeared, then the disease can be prevented, even though the children have the DNA mutations," said Principal Investigator Robert Naviaux, MD, PhD, professor of medicine, pediatrics and pathology at UC San Diego School of Medicine. "I believe that over half of autism cases may be preventable if only we had a way to identify the children at risk before the first symptoms appear."

Naviaux said the new study is important for two reasons: the dramatic rise in diagnosed cases of ASD and increasing evidence that early intervention in children at risk of ASD can significantly improve outcomes.

The prevalence of ASD has risen from 20 in 100,000 births in the 1970s to 1,700 in 100,000 in 2014, according to the U.S. Centers for Disease Control and Prevention -- an 84-times increase. Approximately one in 59 children is diagnosed with ASD. Statistics from the U.S. Department of Education and other government agencies indicate autism diagnoses are increasing at the rate of 10 to 17 percent per year.

Changes in diagnostic criteria and reporting practices account for 60 percent of the rise, at most, according to previously published research. "This means that even by the most conservative estimates, the prevalence of ASD has increased at least 34 times," said Naviaux. The overarching question for Naviaux and others is why? Is it genetics? The environment?

"Our genes have not changed significantly in the past 50 years," said Naviaux. Single gene mutations play a causal role in approximately 10 percent of ASD cases. The vast majority of ASD cases are idiopathic or of unknown cause, most likely the result of a combination of genes, environmental factors or something yet to be identified.

"More than 1,000 genes can contribute to the risk and resistance a child has to ASD, but more than 95 percent of these genes are common variations also present in asymptomatic parents and children who don't have ASD," Naviaux said. "A clue to how the genetics of ASD is misinterpreted is the fact that many of the genes that contribute to ASD are the same genes that contribute to other disorders like schizophrenia and bipolar depression. In most cases, DNA only sets what is possible, not what is destined."

The new Phase II study will focus on exposure and possible roles of chemicals and compounds (detected in blood) and how they might interact with genes. Researchers will use a blood test developed in Naviaux's lab to analyze the presence of more than 600 metabolites --typically small molecules produced by metabolism, the life-sustaining chemical reactions in all organisms. Metabolites from amino acids and antioxidants to vitamins and lipids serve diverse, crucial functions, including as fuel, signal carriers, structure providers, defenders and regulators among them.

Earlier research by Naviaux and others has found that persons with ASD appear to have a shared "metabolic signature." That is, their biological chemistry is comparable, though their genetics are unique.

Testing will also look at more than 400 environmental chemicals in each dried blood drop. Exposure to these chemicals, such as commonly used pesticides, flame retardants, air pollutants, lead, mercury and polychlorinated biphenyls or PCBs, has been linked to several neurodevelopmental disorders, including ASD.

Naviaux and colleagues believe that the majority of ASD symptoms are the result of a treatable metabolic syndrome triggered by persistence activation of the cell danger response (CDR), a natural and universal cellular reaction to injury or stress. Chronic CDR, they suggest, results in disrupted and incomplete healing at the metabolic and cellular levels. In ASD, the consequence may be dysfunctional neural circuits and internal systems, producing autism's well-documented symptoms and behaviors.

"Metabolism is the real-time result of our genes interacting with the environment," said Naviaux. "Environmental chemical or biotoxin exposures --the 'exposome' -- at critical developmental windows can produce delayed effects that become apparent only after months or years. By measuring metabolism and the exposome, it may be possible to identify children at risk for developing autism before the first behavioral symptoms appear."

The study seeks 400 participants between the ages of three and 10 years old, meeting these requirements:

Born in California
Have a confirmed diagnosis of ASD from a licensed clinician or be a healthy child not taking any prescription medications (200 participants from each group)
Born after a normal term pregnancy of 37 to 42 weeks
Have not had a medical issue that required readmission to the hospital in the first month of life

The study requires parents of participating children to answer questionnaires covering pregnancy, labor and delivery, the child's health history and that of the family. Consented analyses will be conducted of dried blood drops recorded as part of California's Newborn Screening program, which began in 1966 and now screens for 80 different genetic and congenital disorders. Blood spots have been saved and stored by the California Department of Public Health since 1982. No new blood tests or behavioral testing will be required for the Phase II study.

Naviaux said he hopes to screen and enroll the full complement of participants by June 2020. Analyses of the identified and retrieved blood spots is expected to be complete by June 2021.

"We then hope to expand the testing program to states like New Jersey, New York, Pennsylvania and Washington by enlisting collaborators in each of those states who will be able to apply the new methods we have developed.

"Each new state has slightly different policies and regulations regarding the collection and storage of dried blood spots from universal newborn screening programs, so this medium-scale expansion study will teach us what will be needed to launch a national study."

Citation rates of scholarly journal articles are tracked in many medical specialties and can affect health care treatment and research. Until the publication of a recent Rutgers-led study in JAMA Network Open, there have been no comprehensive bibliometric studies of obstetrics and gynecology articles.

The researchers identified 3,767,874 articles in the journal Science's Science Citation Index Expanded and profiled the top-cited 100 ob-gyn articles that were published in non-specialty journals, which includes general medicine and surgery journals, and the top-cited 100 ob-gyn articles that were published in specialty journals to see how academic journals work together to disseminate knowledge in the ob-gyn field.

"Health professionals who take care of women must know how the medical journals they read shape the delivery of health care in the ob-gyn field," said Justin S. Brandt, an assistant professor in the Department of OB/GYN and Reproductive Sciences at the Rutgers Robert Wood Johnson Medical School.

The researchers found substantial differences between top-cited ob-gyn articles that were published in non-specialty journals compared to those published in ob-gyn journals. Compared to top-cited articles that were published in specialty journals, those published in general medicine and surgery journals were more frequently cited, covered topics with broader appeal to wider audience reach, and showed higher levels of evidence. According to Brandt, the lead researcher, these are the articles that have the highest impact in ob-gyn.

The New England Journal of Medicine led with the most cited articles among the 100 top-cited ob-gyn articles published in non-specialty journals. The researchers found that 65 of these articles originated from academic institutions within the United States. On the other hand, the researchers found that the American Journal of Obstetrics and Gynecology was the most influential specialty journal. Forty-three of the top-cited 100 articles published in specialty journals originated in the United States.

The researchers concluded that specialty and non-specialty journals work together to ensure the optimal distribution of impactful articles to all women's health care professionals. They said their findings provided an insight into how academic journals with different goals work together for this purpose.

"It is likely that this also occurs in other medical fields, so further bibliometric studies are needed to characterize this relationship among journals," Brandt said.

EAST LANSING, Mich. - A Michigan State University- and University of Maryland-led study featured on the cover of this week's Science magazine should sound alarm bells regarding the "biodiversity crisis" or the loss of wildlife around the world.

The loss of any species is devastating. However, the decline or extinction of one species can trigger an avalanche within an ecosystem, wiping out many species in the process. When biodiversity losses cause cascading effects within a region, they can eliminate many data-deficient species ¬- animals that have eluded scientific study or haven't been researched enough to understand how best to conserve them.

"Some species that are rare or hard to detect may be declining so quickly that we might not ever know that we're losing them," said Elise Zipkin, MSU integrative biologist and the study's lead author. "In fact, this study is less about snakes and more about the general loss of biodiversity and its consequences."

The snakes in question reside in a protected area near El Copé, Panama. The new study documents how the snake community plummeted after an invasive fungal pathogen wiped out most of the area's frogs, a primary food source. Thanks to the University of Maryland's long-term study tracking amphibians and reptiles, the team had seven years of data on the snake community before the loss of frogs and six years of data afterwards.

Yet even with that extensive dataset, many species were detected so infrequently that traditional analysis methods were impossible. To say that these snakes are highly elusive or rare would be an understatement. Of the 36 snake species observed during the study, 12 were detected only once and five species were detected twice.

"We need to reframe the question and accept that with data-deficient species, we won't often be able to assess population changes with high levels of certainty," Zipkin said. "Instead, we need to look at the probability that this snake community is worse off now than it used to be."

Using this approach, the team, which included former MSU integrative biologists Grace DiRenzo and Sam Rossman, built statistical models focused on estimating the probability that snake diversity metrics changed after the loss of amphibians, rather than trying to estimate the absolute number of species in the area, which is inherently difficult because snakes are so rare.

"We estimated an 85% probability that there are fewer snake species than there were before the amphibians declined," Zipkin said. "We also estimated high probabilities that the occurrence rates and body conditions of many of the individual snake species were lower after the loss of amphibians, despite no other systematic changes to the environment."

When animals die off en masse, such as what is happening with amphibians worldwide, researchers are dealing mainly with that discovery and are focused on determining the causes. But what happens to everything else that relies on those animals? Scientists don't often have accurate counts and observations of the other species in those ecosystems, leaving them guessing to the consequences of these changes. The challenge is exacerbated, of course, when it involves rare and data-deficient species.

"Because there will never be a ton of data, we can't pinpoint exactly why some snake species declined while others seemed to do okay or even prospered after the catastrophic loss of amphibians." Zipkin said. "But this phenomenon, in which a disturbance event indirectly produces a large number of 'losers' but also a few 'winners,' is increasingly common and leads to worldwide biotic homogenization, or the process of formally dissimilar ecosystems gradually becoming more similar."

The inability to put their finger on the exact cause, however, isn't the worst news to come from their results. The truly bad news is that the level of devastation portends to much greater worldwide loss than the scientific community has been estimating.

"The huge die-off of frogs is an even bigger problem than we thought," said Doug Levey, a program director in the National Science Foundation's Division of Environmental Biology. "Frogs' disappearance has had cascading effects in tropical food chains. This study reveals the importance of basic, long-term data. When these scientists started counting snakes in a rainforest, they had no idea what they'd eventually discover."

Zipkin agrees that long-term data is important to help stakeholders ascertain the extent of the issue.

"We have this unique dataset and we have found a clever way to estimate declines in rare species," she said. "It's sad, however, that the biodiversity crisis is probably worse than we thought because there are so many data-deficient species that we'll never be able to assess."

On a positive note, the scientists believe that improved forecasts and modeling could lead to bolstering conservation efforts. Making data-driven, proactive changes can prevent massive die offs and curb biodiversity loss.

BOSTON - E-cigarettes have been sold for more than a decade, seemingly without incident, but in the summer of 2019 serious lung injuries began appearing among some e-cigarette users -- especially adolescents and young adults. By last January of 2020, the Centers for Disease Control and Prevention reported more than 2,700 hospitalizations for EVALI, or e-cigarette or vaping product use-associated lung injury, and confirmed 60 deaths in 27 states with more under investigation. The cases have now been linked primarily vaping of marijuana and additives, but before this was discovered, many people using nicotine-containing e-cigarettes became concerned.

"We were curious whether this outbreak led vapers to consider stopping using e-cigarettes or increased people's desire to quit," said Sara Kalkhoran, MD, MAS, an investigator at MGH's Tobacco Research and Treatment Center, an assistant professor at Harvard Medical School and the lead author of the study, published in the Journal of General Internal Medicine. "We thought people might be going to the internet to look into ways to help them quit."

Using Google Trends, Kalkhoran and her colleagues found that searches on such terms as "quit vaping" increased as much as 3.7-fold during the EVALI outbreak. "Then these searches then died down, so the timing of the outbreak was strongly associated with searches on how to get off of these products," Kalkhoran said. She added that this suggests a stronger need for messaging, both from a public health perspective and at a clinical level, "before something like this happens."

It also means that healthcare providers need to be asking patients specifically about vaping, since "people who vape may not think of themselves as smoking. People are looking into quitting these products, so we need to be able to screen in a context where we can actually help them clinically and they don't have to go to the internet for information."

A new study led by researchers at the UCLA Jonsson Comprehensive Cancer Center found that treating soft tissue sarcoma with radiation over a significantly shorter period of time is safe, and likely just as effective, as a much longer conventional course of treatment.

Sarcoma, a rare type of cancer of the soft tissues (for example, muscle, nerves, fat, or fibrous tissue) or bone, affects about 13,000 people of all ages in the United States each year. Many people with a soft tissue sarcoma diagnosis receive a five-week course of radiation therapy (daily Monday through Friday). Four to five weeks after that, the tumor is removed in surgery. In this study at UCLA, a national leader in the care of patients with sarcoma, researchers used a condensed five-day radiation regimen that considerably cuts down the length of treatment and the time to surgery.

"Shortening the radiation therapy from five weeks to five days has been a very meaningful change for patients," said lead author Dr. Anusha Kalbasi, assistant professor of radiation oncology in the division of molecular and cellular oncology. "Five weeks of daily treatments is a burdensome commitment for patients. The daily back-and-forth can be expensive and time consuming, and it can really interfere with work, school or parenting. So finding a way to safely shorten the radiation treatment is a significant advancement in improving the quality of care for patients with hard-to-treat cancers like sarcoma."

Researchers enrolled 52 adults at UCLA diagnosed with a soft tissue sarcoma of the limbs or trunk -- where these tumors most commonly occur -- that was localized and had not spread to other parts of the body. The participants underwent a condensed form of radiation therapy for five days, followed by surgery. The team then analyzed and followed the cohort for an average of 2 1/2 years.

They found less than 6% of the patients with at least two years of follow-up on the clinical trial had a recurrence of their tumor, which is on par with studies using the conventional five-week regimen, Kalbasi said.

"The main reason we treat sarcoma patients with radiation before surgery is to prevent the tumor from recurring where it was removed," said Kalbasi, who is also a member of the Jonsson Cancer Center. "As an added benefit, in some cases it can cause the tumor to shrink. So far it appears that the five-day treatment is working just as well as the five-week treatment."

Along with studying tumor recurrence rates, researchers also closely examined the severity of wound complications. Sarcoma surgery often requires a large incision to remove the tumor and can by itself result in wound complications. Adding radiation before surgery can slow the healing process even more. The team wanted to make sure the condensed five-day treatment didn't make wound complications worse.

"In the long term, having radiation before surgery lowers the chance of side effects like swelling, joint stiffness and fibrosis, that are big contributors to quality of life," Kalbasi said. "But this comes at a trade-off with a higher rate of wound complications immediately after surgery. The good news is that our five-day treatment did not increase the chance for wound issues after surgery compared to the conventional five-week treatment."

Not only did the researchers find that wound complications were virtually the same for the two therapies, but they also identified a new set of biomarkers that could indicate how likely someone will be to encounter significant wound complications.

By using a DNA swab from each participant to test for mutations, the team found that they could identify microRNA-disrupting genetic biomarkers that are associated with the risk of wound complications.

"We know from experience that different patients respond to the same amount of radiation in different ways, and we have always believed that it is due to the patient's personal response to radiation," said study co-author Dr. Joanne Weidhaas, a professor of radiation oncology and director of translational research at the David Geffen School of Medicine at UCLA, who led the biomarker studies. "This type of biomarker lets us know up front who may or may not have a high risk of wound complications, and can potentially help us determine the best type of treatment to offer for patients. Having this information upfront is a big advantage, which can really advance personalized medicine."

In the two years since the study began, the team also noticed a rapid rise in the number of patients coming to UCLA, a high-volume sarcoma center, for radiation treatment before surgery. Nearly half of the study participants traveled more than 100 miles to UCLA for radiation treatment. Past studies have shown treating sarcomas at a high-volume center with the expertise of a multidisciplinary sarcoma team is associated with improved outcomes.

The five-day radiation therapy regimen may not only preferred by people undergoing the treatment, but it will also result in more people having access to care at high-volume centers that specialize in treating such a rare cancer, Kalbasi said.

To further validate the study's findings, the team plans to continue to follow the cohort for at least five years to see if, in terms of cancer control and longer-term side effects, the five-day radiation treatment continues to be just as safe and effective as the traditional five-week treatment. The team has also expanded the clinical trial to include patients who are also receiving chemotherapy before surgery.

The experimental antiviral remdesivir successfully prevented disease in rhesus macaques infected with Middle East respiratory syndrome coronavirus (MERS-CoV), according to a new study from National Institutes of Health scientists. Remdesivir prevented disease when administered before infection and improved the condition of macaques when given after the animals already were infected.

The new report from NIH's National Institute of Allergy and Infectious Diseases (NIAID) appears in the Proceedings of the National Academy of Sciences.

MERS-CoV is closely related to the 2019 novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV) that has grown to be a global public health emergency since cases were first detected in Wuhan, China, in December.

Remdesivir has previously protected animals against a variety of viruses in lab experiments. The drug has been shown experimentally to effectively treat monkeys infected with Ebola and Nipah viruses. Remdesivir also has been investigated as a treatment for Ebola virus disease in people.

The current study was conducted at NIAID's Rocky Mountain Laboratories in Hamilton, Montana. The work involved three groups of animals: those treated with remdesivir 24 hours before infection with MERS-CoV; those treated 12 hours after infection (close to the peak time for MERS-CoV replication in these animals); and untreated control animals.

The scientists observed the animals for six days. All control animals showed signs of respiratory disease. Animals treated before infection fared well: no signs of respiratory disease, significantly lower levels of virus replication in the lungs compared to control animals, and no lung damage. Animals treated after infection fared significantly better than the control animals: disease was less severe than in control animals, their lungs had lower levels of virus than the control animals, and the damage to the lungs was less severe.

The scientists indicate that the promising study results support additional clinical trials of remdesivir for MERS-CoV and COVID-19, the disease that SARS-CoV-2 causes. Several clinical trials of remdesivir for COVID-19 are under way in China, and other patients with COVID-19 have received the drug under a compassionate use protocol.

The Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services, also provided support for this study. Gilead Sciences, Inc., developed remdesivir, also known as GS-5734, and collaborated in the research.

MERS-CoV emerged in Saudi Arabia in 2012. Through December 2019, the World Health Organization had confirmed 2,499 MERS-CoV cases and 861 deaths (or about 1 in 3). Because about one-third of MERS-CoV cases spread from infected people being treated in healthcare settings, the scientists suggest that remdesivir could effectively prevent disease in other patients, contacts of patients, and healthcare workers. They also note the drug might help patients who are diagnosed with MERS or COVID-19 if given soon after symptoms start.

BROOKLYN, N.Y. (February 13, 2020) - Pregnant urban African American and immigrant Afro-Caribbean women are more likely to receive the prenatal health information they need if they are given access to mhealth apps like Text4baby. That is the finding of a new study from SUNY Downstate Health Sciences University School of Public Health.

The study, "Using Text Messaging to Improve Access to Prenatal Health Information in Urban African American and Afro-Caribbean Immigrant Pregnant Women: Mixed Methods Analysis of Text4baby Usage", was published online today in the journal JMIR mHealth and uHealth.

This study aimed to understand the real-life experiences of pregnant urban African American and Afro-Caribbean immigrant women with accessing quality prenatal health care and health information; to assess usage of mHealth for seeking prenatal health information; and to measure changes in participants' knowledge, perceptions, and behavioral intent to use the Text4baby mHealth educational intervention.

Beginning with a focus group of nine women, the investigators identified three barriers these women faced in getting quality prenatal health information including the quality of patient-provider engagement, a lack of social support, and acculturalization of immigrant women.

"We discovered that inadequate engagement with their provider left these women feeling indifferent about the prenatal care and information they received in the clinical setting," said Tenya M. Blackwell, BS, MS, DrPH, lead author of the study and Director of Community Engagement and Research at the Arthur Ashe Institute for Urban Health. "Based on these findings, we developed a survey of 49 women to gauge whether an app like Text4baby might bridge this indifference."

The results of this survey showed 63% believed an app like Text4baby would provide them with the extra support they wanted during pregnancy. Additionally, on a Likert scale of 1 to 5, their perception of the usefulness, compatibility and relative advantage of using the app ranked at 4.26, 4.41 and 4.15 respectively.

In a follow-up survey to measure changes in knowledge, perceptions and intent, these women showed a 14% increase from earlier testing in reporting their intent to use the app, and a 28% increase in their intent to speak more with their provider about the prenatal health information they learned about on Text4baby.

"In today's society, smart phones are ubiquitous and information delivered through them cuts across most social, cultural and economic barriers," said Laura Geer, PhD, MHS, principal investigator and Chair and Associate Professor, Department of Environmental and Occupational Health Sciences at SUNY Downstate Health Sciences University School of Public Health. "Even with a small sample size, these results clearly demonstrate how mhealth apps, focused on prenatal health, can go a long way in overcoming the economic, social and cultural barriers these women face in receiving the prenatal health information and care they need to have a healthy pregnancy."

Feb. 13, 2020 -- In an article published today in Science magazine, University of Houston Law Center Professors Jim Hawkins and Jessica L. Roberts call for stronger consumer safeguards to protect the privacy of personal information collected online by health-related companies.

The article, "When health tech companies change their terms of service, consumers may have limited control over their data," explains that because most health-related apps and websites are not operated by health care providers, they are largely unregulated in the tracking and use of intimate digital data. Consumers and companies enter into an agreement that outlines their rights and obligations in the use and protection of data. Many companies, however, reserve the right to unilaterally change terms of service agreements as to what they can do with user data, such as share it or sell it to other companies.

The authors write that most users of health-related apps and online sites do not read the fine print of the agreements and are unaware when the terms are changed. Consumers who assumed their data was confidential are vulnerable to loss of privacy as personal information, including genetic data, details about mental health, and medical history and even doctor appointments could be shared with other companies. Courts have generally sided with the companies, leaving consumers little recourse.

Hawkins and Roberts suggest several options Congress could take to protect consumers, including: require mandatory notice to users that changes are being made to the terms of service; allow users to opt out of any changes and revert to the original terms; and require user consent for significant changes as is the case with all other contracts.

"Health tech companies can change minor things that don't affect the consumers' experience with the product in substantial ways," Hawkins concluded. "They can fix small bugs in their terms of service, but for things that really matter to the consumer, we argue for the old fashioned way -- get the person to agree to them."

Hawkins, the Alumnae College Professor in Law, conducts research and teaches in the areas of commercial and business law, the fringe banking industry and the fertility business.

Roberts, the Leonard Childs Professor in Law Roberts and director of the Health Law & Policy Institute, specializes in genetics and the law, health law and disability law. Her research operates at the intersection of health law, ethics and social justice.

Because of the quick and deadly outbreak in late December of a novel coronavirus in Wuhan, China, now known as COVID-19 - infecting tens of thousands and killing hundreds within weeks, while spreading to at least 24 other countries - many governments, including the United States, have banned or significantly restricted travel to and from China.

And while travel bans are frequently used to stop the spread of an emerging infectious disease, a new University of Washington and Johns Hopkins University study of published research found that the effectiveness of travel bans is mostly unknown.

However, said lead author Nicole Errett, a lecturer in the UW Department of Environmental & Occupational Health Sciences in the School of Public Health, that's largely due to the fact that very little research into the effectiveness of travel bans exists.

"Some of the evidence suggests that a travel ban may delay the arrival of an infectious disease in a country by days or weeks. However, there is very little evidence to suggest that a travel ban eliminates the risk of the disease crossing borders in the long term," said Errett, co-director of the ColLABorative on Extreme Event Resilience, a research lab focused on addressing real-world issues relevant to community resilience.

The researchers combed through thousands of published articles in an effort to identify those that directly addressed travel bans used to reduce the geographic impact of the Ebola virus, SARS (Severe Acute Respiratory Syndrome), MERS (Middle East Respiratory Syndrome) and the Zika virus. They did not include studies of influenza viruses, for which travel bans have already been shown to be ineffective in the long term.

In the end, the researchers were able to identify just six studies that fit their criteria. Those six were based on models or simulations, not data from actual bans after they were implemented, to assess the effectiveness of travel bans in controlling outbreaks. Consequently, to improve research in this area, the study authors recommend that research questions, partnerships and study protocols be established ahead of the next outbreak so empirical data can be collected and assessed quickly.

"Travel bans are one of several legal options that governments have drawn on to mitigate a pandemic," said co-author Lainie Rutkow, a professor of health policy and management at Johns Hopkins Bloomberg School of Public Health. "As coronavirus spreads, our study raises the importance of understanding the effectiveness of legal and policy responses intended to protect and promote the public's health."

"When assessing the need for, and validity of, a travel ban, given the limited evidence, it's important to ask if it is the least restrictive measure that still protects the public's health, and even if it is, we should be asking that question repeatedly, and often," said co-author Lauren Sauer, an assistant professor of emergency medicine at Johns Hopkins University's School of Medicine and director of operations with the university's Office of Critical Event Preparedness and Response.

Consequently, the authors write, additional research is "urgently needed" to inform policy decisions, especially in light of the tremendous social, economic and political impacts of their implementation.

STONY BROOK, February 13, 2020 -- Governments must provide larger spatial protections in the Greater Caribbean for threatened, highly migratory species such as sharks, is the call from a diverse group of marine scientists including Stony Brook University School of Marine and Atmospheric Sciences (SoMAS) PhD Candidate, Oliver Shipley, and led by the conservation NGO Beneath the Waves in a letter to published in Science (Feb. 14).

With up to one-third of all open ocean shark species threatened extinction due to overfishing, conservation strategies that protect areas where sharks spent significant portions of their time are becoming increasingly important. In light of recent calls to protect 30 percent of our oceans by 2030, large marine protected areas, which can stretch from 100,000 sq. km to over 300,000 sq. km, have emerged as a popular management tool for their potential to enhance ecological processes and promote sustainable fisheries. One of the greatest benefits of these large conservation zones is their potential to conserve sharks, which travel long distances and can connect multiple jurisdictions over short time periods.

The letter in Science states that the Greater Caribbean, which boasts some of the highest rates of marine biodiversity and contains some of the most migratory shark species in the world, has been overlooked in these conversations.

"Through conducting years of scientific research on sharks in the Caribbean, I have witnessed first-hand, the benefits that marine protected areas can have for shark populations," said Shipley, a close collaborator of Dr. Austin Gallagher, Chief Scientist at Beneath the Waves. "We hope that currently protected nations, such as The Bahamas, can carry the torch and provide a foundation on which to base broader policy. For this to be a success, we will need to continue to build strong relationships and further understand the needs of key stakeholder groups throughout the wider Caribbean. We are extremely confident that this is going to happen."

"The diversity of countries sharing ocean space in the Greater Caribbean is remarkable, and we know that migratory shark species connect many of these countries along their migrations," said Gallagher. "Though there are many examples of establishing marine protected areas in the region, there are few that are big enough to encompass the space use of large sharks, such as tiger sharks which can move thousands of miles per year."

Recent research suggests that sharks are surprisingly rare in many Caribbean nations, likely due to decades of unregulated overharvest. However, certain areas such as the Bahamas, which have banned longline fishing and protected sharks in recent decades, have benefitted from the significant socioeconomic inputs generated from live sharks in the diving industry, estimated to be over US $140 million per year.

A new study of people who received medical assistance in dying (MAiD) in Ontario found that about three-quarters were cared for by palliative care practitioners at the time of their request for MAiD, and MAiD recipients were younger, wealthier and more likely to be married than the general population at time of death. These findings dispel concerns that MAiD requests are driven by lack of access to palliative care services or by socioeconomic vulnerabilities.
The article is published in CMAJ (Canadian Medical Association Journal) along with a related editorial. http://www.cmaj.ca/lookup/doi/10.1503/cmaj.200016

MAiD was legalized in Canada in June 2016, and as of October 2018, 6749 Canadians received MAiD.

The federal government and the government of Quebec are currently in consultation around drafting new eligibility criteria for MAiD, after a decision of the Quebec Superior Court that one provision of the previous laws violated the Canadian Charter of Rights and Freedoms.

"There has been and will be much discussion about socioeconomic vulnerability and access to palliative care, and how these factors influence requests for MAiD," says Dr. James Downar, lead author of the study and a specialist in critical care and palliative care at The Ottawa Hospital and University of Ottawa, Ottawa, Ontario. "Since this study represents the comparison of MAiD recipients to all deaths overall, and uses Canadian data, it could help inform this discussion and the upcoming legislation."

Researchers analyzed clinical and socioeconomic data from 2241 Ontarians who received MAiD, and compared this with data from all 186 814 people in the province who died between June 2016 to October 2018, from databases kept by the Office of the Chief Coroner for Ontario and ICES. Among those who received MAiD, the median age was 75 years and half were women; almost two-thirds of patients (64%) had cancer, 12% of patients had neurodegenerative disease, 8.5% had cardiovascular disease and 7.5% had respiratory disease.

Patients who received MAiD reported both physical (99.5%) and psychologic (96.4%) suffering.

"[W]e found that people who chose MAiD reported physical or psychologic suffering as the primary reason, despite engagement of palliative care in [77%] of patients, which suggests that for many patients the MAiD requests were not because of poor access to palliative care," write the authors.

Almost half of MAiD recipients were married and the majority (85%) lived in a private home before receiving MAiD. They were younger than people who did not receive MAiD and more likely to live in a higher income neighbourhood, which suggests that MAiD requests are unlikely to be driven by social or economic vulnerability, say the authors.

Requests for MAiD can be emotionally difficult for patients and families, and any delays can exacerbate distress. The study found that only 6.6% of families reported challenges with access to MAiD and these delays were not associated with socioeconomic status. The authors noted, however, that the MAiD data set included only people who actually received MAiD, so these findings would not reflect the experience of patients who requested MAiD but never received it.

"The data presented here do not address the moral question of whether any amount of suffering can justify the hastening of death. However, the growing trend toward legalization and use of MAiD in many parts of the world should prompt the health care and research community to improve our understanding and treatment of the type of distress that leads to a MAiD request," the authors conclude.

In a related editorial, Dr. Andreas Laupacis, CMAJ's editor-in-chief, writes, "Downar and colleagues' findings should allay fears that people living in Ontario are choosing MAiD because they have little social support or have poor access to health care. This study found the opposite, which suggests that more attention needs to be paid to ensure that those who are socially or economically vulnerable and eligible for MAiD are aware that MAiD is an option." http://www.cmaj.ca/lookup/doi/10.1503/cmaj.200213

He cautions that as we move into a new era in which the Canadian government is considering expanding eligibility to MAiD to minors, people with severe mental illness and to those who anticipate losing the capacity to request MAiD in future, Canada will need new safeguards.

"If access to MAiD is expanded, new safeguards, specifically tailored to each new indication for MAiD, should be put in place. Then, we must once more proceed with caution, measure carefully and reassess," concludes Dr. Laupacis.