PFAS compounds were engineered to resist friction and heat, and are in many products that we use daily, from furniture to meat packaging. However, it is this “slippery” characteristic that makes them persist in ecosystems and poses a risk to our health.

“These compounds are engineered to be persistent on purpose; this is how they keep stains off your couch and eggs from sticking to your frying pan,” says Tom Kwak, unit leader of NC Cooperative Fish and Wildlife Research Unit, professor of applied ecology at NC State, and a co-author of the study. “We pay the price for these compounds when they enter the aquatic ecosystem.”

In a study measuring real-time PFAS contamination levels along the entire food chain of this major Atlantic river — from water and sediment to insects and fish — the researchers identified two PFAS hot spots along the Pee Dee and were able to establish strong links of PFAS transmission up the aquatic food chain.

The research team collected water, sediment, algae, plant, insect, fish, crayfish, and mollusk samples at five study sites along the length of the Yadkin-Pee Dee River, which begins in Blowing Rock, N.C., and runs 230 miles to empty into the Atlantic Ocean at Winyah Bay, South Carolina. They analyzed the samples for 14 different PFAS compounds.

While nearly every sample contained PFAS compounds, the site with the greatest PFAS concentrations was just downstream of the Rocky River input, which drains part of the watershed from Charlotte, N.C. and the surrounding area. The site with the second greatest PFAS concentrations was downstream in South Carolina, but there is no known or plausible input of PFAS for that region.

In aquatic food chains, biofilm — the soupy mixture of algae and bacteria that sticks to your boat — is the base resource for all life further up the chain. In this study, the largest concentrations of 10 of the 14 PFAS compounds measured were in biofilm samples. Unsurprisingly, aquatic insects, which primarily eat biofilm, had the greatest accumulation of PFAS compounds of all the living taxa the researchers sampled. This confirms a strong trophic link, or step in the food chain, showing how PFAS transfers from biofilm to insects, which are then eaten by freshwater fish.

When PFAS is in every step of the food chain, the compounds accumulate at each step. For example, a fish caught in an area with PFAS may have eaten hundreds of insects, each of which has consumed contaminated biofilm and other plants.

“We are part of the food chain and when we ingest these foods, we accumulate their PFAS loads, too,” says Greg Cope, William Neal Reynolds Distinguished Professor of Applied Ecology, coordinator of the NC State Agromedicine Institute, and corresponding author of the study. “This gives new meaning to the phrase, ‘You are what you eat.'”

“Even if you are not concerned about chemical exposure and effects to the native aquatic taxa, would you want to drink water or eat a fish with known PFAS contamination?” asks Tiffany Penland, former NC State graduate student and first author of the study. “We need to educate ourselves and each other so that we are cognizant of the contamination to the natural resources that we depend on every day.”

“Studying only one species or link in the food chain could not tell the whole story, and might even yield erroneous conclusions on the amounts of PFAS in river ecosystems,” says Cope. “Studies like this that show how widely prevalent PFAS are within entire ecosystems, even when they do not have a direct industrial input, highlight our need to understand how these compounds impact the health of ecosystems, and ultimately, our health.”

Fungi cause diverse, serious societal and economic problems in the UK and globally. As well as causing fatal diseases in humans, fungi devastate food crops and spoil valuable products and materials. This has led to an antifungals/fungicide industry worth around $30bn globally.

There are tight regulations around the use of fungicides and antifungals and there is also growing resistance of fungi to these agents.

In a paper published today in Science Advances, experts from the University’s Schools of Life Sciences, Pharmacy, and Engineering, show how they have developed an innovative solution to tackle fungi, by passively blocking fungal attachment to surfaces using a coating of (meth)acrylate polymers, and so negating the need to use potentially harmful anti-fungals or other bioactive chemicals.

Through previous work, the team found different combinations of fungicides which worked against fungi and also produced new understanding of preservative action against spoilage fungi.

Although these advances meant less use of certain fungicides and chemicals, frequent tightening of regulations around usage are restricting the take up of technologies that still rely on bioactive agents, while spread of resistance worsens the problem. Consequently, potential bioactive-free technologies for combatting fungi are highly attractive to the industry.

In this latest study, scientists show an alternative fungal control strategy, which doesn’t have the ‘killing affect’ of fungicides.

The team identified polymers that resist the attachment of different kinds of fungi, including pathogens. They screened hundreds of (meth)acrylate polymers in high throughput, identifying several that reduce attachment of the human pathogen Candida albicans, the crop pathogen Botrytis cinerea, and other fungi.

Specific chemical features of the polymers were associated with weak fungal attachment. The materials were not toxic, supporting their passive utility. The team developed a formulation with the materials for inkjet-based 3D printing. Printed voice-prosthesis components showed up to 100% reduction in C. albicans biofilm versus commercial materials. Furthermore, spray-coated leaf surfaces resisted fungal infection, with no plant toxicity.

A similar approach against bacterial pathogens is also now being developed for a catheter coating to prevent infections in patients.

Professor Simon Avery, from the School of Life Sciences at the University is a lead investigator on the paper, he said: “This is the first high-throughput study of polymer chemistries resisting fungal attachment.

“Our engagement to date with industry has highlighted a clear need for a new approach to control fungi and the major socioeconomic problems that they cause, as the value of existing strategies using bioactives (antifungals, fungicides) is eroded by growing resistance and regulations.

“This passive, anti-attachment technology that we have been developing addresses this need. We have been able to show that different polymers are effective in resisting diverse fungi that have broad socio-economic impacts.”

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The findings were published June 5, 2020, in Science Immunology. The study was led by researchers in the Center for Cancer Research at the National Cancer Institute (NCI), in collaboration with researchers from the National Institute of Allergy and Infectious Diseases (NIAID), both part of the National Institutes of Health (NIH), as well as the U.S. Department of Defense’s Walter Reed National Military Medical Center, and four other hospitals nationally.

These findings should not be considered clinical advice but are being shared to assist the public health response to COVID-19. While BTK inhibitors are approved to treat certain cancers, they are not approved as a treatment for COVID-19. This strategy must be tested in a randomized, controlled clinical trial in order to understand the best and safest treatment options for patients with severe COVID-19.

The BTK protein plays an important role in the normal immune system, including in macrophages, a type of innate immune cell that can cause inflammation by producing proteins known as cytokines. Cytokines act as chemical messengers that help to stimulate and direct the immune response. In some patients with severe COVID-19, a large amount of cytokines are released in the body all at once, causing the immune system to damage the function of organs such as the lungs, in addition to attacking the infection. This dangerous hyperinflammatory state is known as a “cytokine storm.” At present, there are no proven treatment strategies for this phase of the illness. The study was developed to test whether blocking the BTK protein with acalabrutinib would reduce inflammation and improve the clinical outcome for hospitalized patients with severe COVID-19.

This prospective off-label clinical study included 19 patients with a confirmed COVID-19 diagnosis that required hospitalization, as well as with low blood-oxygen levels and evidence of inflammation. Of these patients, 11 had been receiving supplemental oxygen for a median of two days, and eight others had been on ventilators for a median of 1.5 (range 1-22) days.

Within one to three days after they began receiving acalabrutinib, the majority of patients in the supplemental oxygen group experienced a substantial drop in inflammation, and their breathing improved. Eight of these 11 patients were able to come off supplemental oxygen and were discharged from the hospital. Although the benefit of acalabrutinib was less dramatic in patients on ventilators, four of the eight patients were able to come off the ventilator, two of whom were eventually discharged. The authors note that the ventilator patient group was extremely clinically diverse and included patients who had been on a ventilator for prolonged periods of time and had major organ dysfunction. Two of the patients in this group died.

Blood samples from patients in the study showed that levels of interleukin-6 (IL-6), a major cytokine associated with hyperinflammation in severe COVID-19, decreased after treatment with acalabrutinib. Counts of lymphocytes, a type of white blood cell, also rapidly improved in most patients. A low lymphocyte count has been associated with worse outcome for patients with severe COVID-19. The researchers also tested blood cells from patients with severe COVID-19 who were not in the study. In comparison with samples from healthy volunteers, they found that these patients with severe COVID-19 had higher activity of the BTK protein and greater production of IL-6. These findings suggest that acalabrutinib may have been effective because its target, BTK, is hyperactive in severe COVID-19 immune cells.

The results of this study were used to inform the trial design of the CALAVI (acalabrutinib) randomized, controlled clinical trial, sponsored by AstraZeneca, which will examine the safety and efficacy of acalabrutinib in patients with severe COVID-19.

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But according to a new Dartmouth-led paper published in the New England Journal of Medicine, more emphasis should be placed on addressing the inaccuracy of diagnostic tests, which play a key role in containing the pandemic.

“Diagnostic tests, typically involving a nasopharyngeal swab, can be inaccurate in two ways,” explains lead author Steven Woloshin, MD, MS, a professor of medicine and community and family medicine at Dartmouth’s Geisel School of Medicine, and of The Dartmouth Institute for Health Policy and Clinical Practice. “A false-positive result mistakenly labels a person infected, with consequences including unnecessary quarantine and contact tracing. False-negative results are far more consequential because infected persons who might be asymptomatic may not be isolated and can infect others.”

In their paper, Woloshin and his colleagues discuss factors contributing to the current limitations of diagnostic tests — including variability in test sensitivity and the lack of a standard process for validating test accuracy — and also cite several large studies whose frequent false-negative results are cause for concern.

The researchers draw several conclusions from their work. “Diagnostic testing will help to safely open the country, but only if the tests are highly sensitive and validated against a clinically meaningful reference standard — otherwise we cannot confidently declare people uninfected,” says Woloshin.

The FDA should also ensure that test manufacturers provide details of their tests’ clinical sensitivity and specificity at the time of market authorization. Tests without such information will have less relevance to patient care.

“Measuring the sensitivity of tests in asymptomatic people is an urgent priority,” says Woloshin. “A negative result on even a highly sensitive test cannot rule out infection if the pretest probability — an estimate before testing of a person’s chance of being infected — is high, so clinicians shouldn’t trust unexpected negative results.”

This estimate might depend on how common COVID-19 is where a person lives, their exposure history, and symptoms, he says.

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The cause of cystic fibrosis are mutations in the cystic fibrosis transmembrane conductor regulator gene (CFTR). This gene contains the blueprint for a chloride channel on the surface of cells in the body. Normally, this channel mediates the accumulation of salt and fluids on the surface of the airways thereby leading to a continuous cleaning of the airways. Defects in the CFTR channel prevent the transport of chloride ions and thus the humidification of the respiratory tract. As a result, the airways of affected individuals literally get plugged by a thickened, viscous mucus that leads to airway obstruction — patients are at the risk of suffocating.

At the University of Münster, the lab of Prof. Thorsten Marquardt has now discovered a new disease that is caused by defects in another chloride channel, TMEM16A. This channel is also present on the surface of airway cells. In cooperation with the lab of Prof. Karl Kunzelmann of the University of Regensburg, the researchers evaluated the cellular effects of the disorder that is caused by a total loss of TMEM16A function. Surprisingly, they discovered that not only TMEM16A but also CFTR is not functional in these patients. Excitingly, this has the potential to improve the treatment of patients suffering from cystic fibrosis.

“We were astonished that children with TMEM16A deficiency don’t have any respiratory symptoms at all. A loss of CFTR function due to lack of TMEM16A does not lead to clinincal symptoms of cystic fibrosis in these kids,” states Dr. Julien Park, first author and researcher at the Marquardt lab at the Department of General Pediatrics at the University Hospital Münster. Similarly, the group of Prof. Karl Kunzelmann found in a mouse model that a double knock out of CFTR and TMEM16A does not develop lung disease.

Taken together, these results raise an intriguing question: Could the pharmacological inhibition of TMEM16A improve the respiratory symptoms of patients with cystic fibrosis? A significant reduction of mucus production and secretion as a consequence of TMEM16A inhibition has previously been shown under laboratory conditions. The researchers want to study this approach further in the future: “As a next step, we are planning clinical trials to evaluate a treatment of cystic fibrosis with TMEM16A inhibitors,” states Karl Kunzelmann.

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Archaeological remains have shown that in the middle part the Stone Age, there were at least three different but partially contemporary cultural groups in Sweden. The groups are often called: Funnel Beaker culture, which is associated with Scandinavia’s first farmers; Pitted Ware culture, which is mainly linked to fishing and hunting; and Battle Axe culture, which represents a blended culture of herding and farming.

In addition to sustaining themselves in different ways, the three groups had different burial rituals and different kinds of objects. The research team behind the new study has previously been able to show that people in the three cultural groups also differed genetically.

The genetic mapping the researchers did at that time was invaluable as they investigated why some Pitted Ware graves seemed to be influenced by the Battle Axe culture, even though the two cultures lived relatively differently during their centuries of co-existence.

Gotland has several large, well-preserved cemeteries with typical Pitted Ware culture graves. The dead were usually buried lying on their backs and with gifts, such as hunting tools and bones from seals, among other things. Neither large stone blocks nor mounds were placed on the graves.

“In addition to the typical Pitted Ware graves, there were also several atypical graves with apparent influences from Battle Axe culture. For example, some individuals were buried lying on their sides with their legs pulled up, and some had battle axes as burial gifts, which is usually associated with Battle Axe culture,” says Professor Jan Storå, archaeologist at Stockholm University and one of the authors of the study.

The researchers have analysed DNA from 25 Stone Age individuals from four Pitted Ware culture burial grounds on Gotland. About half of the individuals were buried in typical Pitted Ware culture graves and the other half of the graves showed influences from Battle Axe culture.

To their surprise, the researchers found that none of the individuals were genetically related to people from Battle Axe culture. On the contrary, everyone appeared to belong to a very homogeneous group that demonstrated the most genetic similarity to the hunter-gatherer groups of earlier periods.

“This is a unique study that contributes to our understanding of the interactions between the cultural groups of the Stone Age. We can conclude that people in Pitted Ware culture were influenced by, among others, Battle Axe culture, but because we found no genetic connection between the groups, contact was likely in the form of trade and other means, rather than through migration,” says Helena Malmström, archaeogeneticist at Uppsala University and one of the authors of the study.

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