The extraordinary work, just published in leading journal Cell Reports Medicine, has wide-ranging implications from improving our fundamental understanding of viral resistance to the potential design of therapies to treat infected people.

Between 1977-79 in Ireland, several thousand women were exposed to the hepatitis C virus through contaminated anti-D, which is a medication made using plasma from donated blood and given to Rhesus negative women who are pregnant with a Rhesus positive fetus. The medication prevents the development of antibodies that could be dangerous in subsequent pregnancies. Some of the anti-D used during the 1977-79 period was contaminated with hepatitis C.

From this outbreak, three groups of people were identifiable: those who were chronically infected; those who cleared the infection with an antibody response; and those who appeared protected against infection without making antibodies against hepatitis C.

Cliona O’Farrelly, Professor of Comparative Immunology in Trinity’s School of Biochemistry and Immunology, is the senior author of the research article. Cliona, who is based in the Trinity Biomedical Sciences Institute, said:

“We hypothesised that women who seemed to resist HCV infection must have an enhanced innate immune response, which is the ancient part of the immune system that acts as a first line of defence.

“To test this we needed to make contact with women exposed to the virus over forty years ago and ask them to help us by allowing us to study their immune systems to hunt for scientific clues that would explain their differing responses.

“After a nationwide campaign over 100 women came forward and we have gained some unique and important insights. That so many women — many of whom have lived with medical complications for a long time — were willing to help is testament to how much people want to engage with science and help pursue research with the potential to make genuine, positive impacts on society. We are deeply grateful to them.”

The scientists ultimately recruited almost 40 women from the resistant group, alongside 90 women who were previously infected.

In collaboration with the Institut Pasteur in Paris they then invited almost 20 women in each group to donate a blood sample that they stimulated with molecules that mimic viral infection and lead to activation of the innate immune system.

Jamie Sugrue, PhD Candidate in Trinity’s School of Biochemistry and Immunology, is first author of the research article. He said:

“By comparing the response of the resistant women to those who became infected, we found that resistant donors had an enhanced type I interferon response after stimulation. Type I interferons are a key family of antiviral immune mediators that play an important role in defence against viruses including hepatitis C and SARS-CoV-2, or COVID-19.

“We think that the increased type I interferon production by our resistant donors, seen now almost 40 years after the original exposure to hepatitis C, is what protected them against infection.

“These findings are important as resistance to infection is very much an overlooked outcome following viral outbreak, primarily because identifying resistant individuals is very difficult — since they do not become sick after viral exposure, they wouldn’t necessarily know that they were exposed. That’s why cohorts like this, though tragic in nature, are so valuable — they provide a unique opportunity to study the response to viral infections in an otherwise healthy population.”

The lab’s efforts are now focused on leveraging these biological findings to unpick the genetics of viral resistance in the HCV donors. Their work on HCV resistance has already helped ignite international interest in resistance to other viral infections, including SARS-CoV-2, the virus that causes COVID-19.

The O’Farrelly lab has expanded its search for virus-resistant individuals by joining in the COVID human genetic effort and by recruiting members of the public who have been heavily exposed to SARS-CoV-2 but never developed an infection.

Cellulose is a key structural component of plant cell walls and is the reason why trees can grow to such heights. But the secret of its material strength actually lies in its overlapping nanoscopic fibers. In recent years, many commercial products have used cellulose nanofiber (CNF) materials because their strength and durability make them a good replacement for polymer-based materials such as plastics that can be detrimental to the environment. But now and for the first time, a research team led by Professor Junichiro Shiomi from the University of Tokyo’s Graduate School of Engineering has investigated previously unknown thermal properties of CNF, and their findings show these materials could be even more useful still.

“If you see plant-derived materials such as cellulose or woody biomass used in applications, it’s typically mechanical or thermally insulating properties that are being employed,” said Shiomi. “When we explored the thermal properties of a yarn made from CNF, however, we found that they show a different kind of thermal behavior, thermal conduction, and it’s very significant, around 100 times higher than that of typical woody biomass or cellulose paper.”

The reason yarn made from CNF can conduct heat so well is due to the way it’s made. Cellulose fibers in nature are very disorganized, but a process called the flow-focusing method combines cellulose fibers, orientating them in the same way, to create CNF. It’s this tightly bound and aligned bundle of rod-shaped fibers that allows heat to transfer along the bundle, whereas in a more chaotic structure it would dissipate heat more readily.

“Our main challenge was how to measure the thermal conductivity of such small physical samples and with great accuracy,” said Shiomi. “For this, we turned to a technique called T-type thermal conductivity measurement. It allowed us to measure the thermal conductivity of the rod-shaped CNF yarn samples which are only micrometers (a micrometer equaling one-thousandth of a millimeter) in diameter. But the next step for us is to perform accurate thermal tests on two-dimensional textilelike samples.”

Shiomi and his team hope that their investigation and future explorations into the use of CNF as a thermally conductive material could give engineers an alternative to some environmentally damaging polymers. In applications where heat transfer is important, such as certain electronic or computational components, it could greatly reduce the consequences of discarded electronic equipment, or e-waste, thanks to the biodegradable nature of CNF and other plant-based materials.

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Materials provided by University of Tokyo. Note: Content may be edited for style and length.

Klebsiella pneumoniae causes many respiratory, intestinal and urinary tract infections. Due to its resistance to most common antibiotics and its high virulence, some of its strains can be fatal for 40% to 50% of infected people. There is an urgent need to develop new therapeutic molecules to counter it. “Since the 1930s, medicine has relied on antibiotics to get rid of pathogenic bacteria,” explains Pierre Cosson, professor in the Department of Cell Physiology and Metabolism at the UNIGE Faculty of Medicine, who led this research. “But other approaches are possible, among which trying to weaken the bacteria’s defence system so that they can no longer escape the immune system. This avenue seems all the more promising as the virulence of Klebsiella pneumoniae stems largely from its ability to evade attacks from immune cells.”

An amoeba as a model

To determine whether or not the bacteria were weakened, the UNIGE scientists used an experimental model with surprising characteristics: the amoeba Dictyostelium. This single-cell organism feeds on bacteria by capturing and ingesting them, using the same mechanisms that immune cells use to kill pathogens. “We genetically modified this amoeba so that it could tell us whether the bacteria it encountered were virulent or not. This very simple system then enabled us to test thousands of molecules and identify those that reduced bacterial virulence,” explains Pierre Cosson.

Weakening the bacteria without killing them

Developing a drug is a long and expensive process, with no guarantee of results. The UNIGE scientists therefore opted for a quicker and safer strategy: reviewing existing drugs to identify possible new therapeutic indications. The research team evaluated the effect on Klebsiella pneumoniae of hundreds of drugs already on the market, with a wide range of therapeutic indications. A drug developed to combat herpes, edoxudine, proved particularly promising.

“By altering the surface layer that protects the bacteria from their external environment, this pharmacological product makes it vulnerable. Unlike an antibiotic, edoxudine does not kill the bacteria, which limits the risk of developing resistance, a major advantage of such an anti-virulence strategy,” says the researcher.

Although the effectiveness of such a treatment in human beings has yet to be confirmed, the results of this study are encouraging: edoxudine acts even on the most virulent strains of Klebsiella pneumoniae, and at lower concentrations than those prescribed to treat herpes. “Sufficiently weakening the bacteria without killing them is a subtle strategy, but one that could prove to be a winner in the short and long terms,” concludes Pierre Cosson.

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Materials provided by Université de Genève. Note: Content may be edited for style and length.

First developed by the World Health Organisation, Psychological First Aid (PFA) is the globally recommended training for people, such as healthcare workers, who support others during emergencies.

It offers guidance on delivering psychosocial care in the immediate aftermath of an emergency event.

Although PFA training was originally created for people to support others, scientists from Northumbria University and the University of Highlands and Islands (UHI) have now also identified it as a suitable way of helping care workers look after their own mental health and wellbeing.

As part of the national response to the COVID-19 pandemic, in June 2020 the UK government introduced free to access online PFA training in an effort to support frontline staff, such the 1.8 million people working in care homes across the country.

Evaluating the effectiveness of this initiative, academics at Northumbria and UHI investigated the uptake of PFA training among healthcare workers in UK care homes and assessed its effects on their wellbeing.

Funded by the Royal College of Nursing Foundation, the study was the first of its kind and makes recommendations regarding further implementation of Psychological First Aid.

The researchers found that while the uptake of PFA training was low among healthcare workers — less than 10% of study participants had done the training — those who had undertaken PFA coped better.

The results suggest that PFA training helped in overcoming stress and coping via self-growth and improving relationships with others, but there was a concern around accessibility, which academics say could possibly explain the low uptake of training.

Some research participants described that it helped them cope better when thinking of giving up their job and promoted resilience, with one person commenting: “(PFA) has helped me cope better, it was a position I was thinking of giving up at one time and now I have the strength to carry on.”

Others described how it helped support them in their experiences of bereavement to overcome the trauma of the pandemic: “I found it (PFA) useful as it helped me cope with bereavement as well as the experience of seeing relatives affected by COVID-19.” Another participant went as far as to say that PFA training “should be made compulsory for all staff especially in nursing and care homes during the pandemic or not.”

Dr Mariyana Schoultz, the project lead and Associate Professor in Mental Health in Northumbria’s Department of Nursing, Midwifery and Health, said: “Findings suggest that PFA training has the potential to: strengthen resilience for staff in health and social care; promote anti-stigma messages and normalise help seeking behaviour; PFA holds the potential to minimise the risk of developing more serious psychological problems such as Post-Traumatic Stress Disorder (PTSD). But we need more research in this area.

“We therefore recommend that consideration be given to funding an integrated programme of research and development to further develop, implement, and evaluate a co-produced iteration of PFA for use in the UK care home sector and beyond.”

Deepa Korea, Director of the RCN Foundation, said “Staff working in social care during the pandemic faced significant pressures which inevitably had an impact on their own mental health and emotional wellbeing. That’s why I am delighted that the RCN Foundation was able to commission this important study which adds to the body of evidence about the practical ways in which we can support health and social care staff.”

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Materials provided by Northumbria University. Note: Content may be edited for style and length.