Culture

In general, surgeons who perform numerous cataract operations every year encounter relatively few severe cases, and this probably contributes to their lower complication rate, as shown by a study led from the University of Gothenburg. These results provide new knowledge in the endeavor to further improve healthcare for a large group of patients.

Cataract surgery is the most frequent surgical intervention in Sweden, carried out some 130,000 times annually. During the surgery, which takes about ten minutes, the cloudy lens in the patient's own eye is replaced by an implanted artificial one made of plastic ("intraocular lens").

Data from the Swedish National Cataract Register, where these operations are recorded, enabled the researchers to analyze surgical outcomes in the years 2007-2016 at an individual level -- that is, for each surgeon. Although the surgeons' identities were coded, the results provide new knowledge and understanding.

A previous study showed that surgeons who performed 500 or more cataract operations a year had the best outcomes, in terms of an established quality measure: the proportion of patients suffering the complication known as "posterior capsule rupture." This means that a hole forms in the capsule that surrounds the old lens and is used as support for the new one.

In the current study, now published in the journal Ophthalmology, the researchers have proceeded to investigate how much case mix -- that is, how many cases of a more severe nature are treated by individual surgeons -- affects the outcome.

Madeleine Zetterberg, Professor of Ophthalmology at Sahlgrenska Academy, University of Gothenburg, and senior consultant at the University Hospital, is the lead and corresponding author.

"We saw that although the high-volume surgeons, too, had severe surgical cases, that proportion was lower than for the other surgeons. So an overwhelming proportion of the high-volume surgeons' operations were simple cases, which may contribute to their lower incidence of complications," she says.

Zetterberg and her fellow authors belong to the steering group for the Swedish National Cataract Register. Since data on operations and complications for each individual surgeon began to be registered in 2007, the proportion of high-volume surgeons has risen successively.

"Surgeons need to be aware of how operation volumes affect outcomes. A cataract operation is mostly a routine intervention, and the complication rate is generally low. But it's important to remember that complications do occur and they may be serious."

Since 2015, a majority of cataract procedures in Sweden are being performed at private clinics, to which the work is outsourced by the regional authorities to meet the high level of needs. In the next study, Zetterberg will look more closely at the role of the type of clinical unit -- whether under private or public management -- in terms of operation volume, incidence of complications and degree of severity among the cases dealt with.

"This is vital information for us to learn how best to shape healthcare so as to ensure both high accessibility and good patient safety," she concludes.

Speech and singing spread saliva droplets, a phenomenon that has attracted much attention in the current context of the Covid-19 pandemic. Scientists from the CNRS, l'université de Montpellier, and Princeton University* sought to shed light on what takes place during conversations. A first study published in PNAS revealed that the direction and distance of airflow generated when speaking depend on the sounds produced. For example, the accumulation of plosive consonants, such as the "P" in "PaPa," produces a conical airflow that can travel up to 2 metres in 30 seconds. These results also emphasize that the time of exposure during a conversation influences the risk of contamination as much as distance does. A second study published on 2 October in the journal Physical Review Fluids describes the mechanism that produces microscopic droplets during speech: saliva filaments form on the lips for the consonants P and B, for example, and are then extended and fragmented in the form of droplets. This research is being continued with the Metropolitan Opera Orchestra ("MET Orchestra") in New York, as part of a project to identify the safest conditions for continuing this prestigious orchestra's activity.

CORVALLIS, Ore. - Conservation projects aimed at protecting land-dwelling species could net major gains in helping species living in streams, lakes and wetlands with relatively minor adjustments, an international research collaboration that included Oregon State University has discovered.

Published today in Science, the findings are important because freshwater ecosystems host roughly 10% of all known species and one-third of all vertebrates despite comprising less than 1% of the Earth's surface.

Streams, ponds, lakes, rivers and swamps also play a key role in climate regulation and in providing food and fuel for communities around the globe.

Thanks to human-caused pressures over the last half-century - including habitat loss, overexploitation of resources, dam building and introduction of non-native species - freshwater vertebrates have seen their populations fall by about 80%, more than double the decline for marine and terrestrial vertebrate populations.

Climate change and pollution are exacerbating the problem, and scientists say new conservation approaches are needed to save freshwater ecosystems and the species that live in them. But typically, conservation efforts have focused much more heavily on land than water.

Bob Hughes, senior research professor of fisheries and wildlife in OSU's College of Agricultural Sciences, was part of a collaboration led by scientists at Brazil's University of São Paulo and University of Lavras and Britain's Lancaster University that analyzed more than 1,500 species in the Amazon.

The scientists looked at both terrestrial and aquatic species - including fish, dragonflies, caddisflies, birds and beetles - and ran simulations of various conservation strategies.

"When the strategies prioritized only terrestrial species, the benefit to freshwater species was on average 22% of what it was for strategies that prioritized freshwater species," Hughes said. "But when we used a joint focus, it was possible to increase freshwater benefits by as much as 600% at the expense of just a 1% drop in terrestrial benefits."

Conservation projects have generally focused on protecting species that live on land, said co-lead author Cecilia Gontijo Leal from the University of São Paulo and University of Lavras, and if freshwater species are considered at all, it is assumed that they will be protected incidentally - as a by-product of efforts to conserve land species.

"But we found that to address the freshwater biodiversity crisis, freshwater species need to be explicitly incorporated into conservation planning," she said.

Co-lead author Gareth Lennox of Lancaster University said the findings illustrate "a great opportunity for conservation, where protection for one species group does not require either loss of protection for others or significant funding increases."

Because conservation energy has more often been directed at land species, information is somewhat lacking on the distribution of freshwater species, the scientists say. That means one challenge in protecting those species is not necessarily knowing where they are, particularly in tropical regions.

But because a critical factor for freshwater conservation is the concept of connectivity - the surface links between lakes, wetlands and streams - the researchers developed a new method for protecting freshwater species.

"Freshwater species crucially depend on the connectivity of river systems," said Silvio Ferraz of the University of São Paulo. "By designing conservation reserve networks that take such connectivity into consideration, we found that freshwater protection could still be doubled in the absence of species distribution data. This shows that there are few impediments to vastly improving freshwater conservation in data-poor regions of the world."

Jos Barlow from Lancaster University stressed that the urgency of the biodiversity crisis facing humanity means that the many important and endangered freshwater species can no longer be overlooked.

"Our findings show that conservation that thinks across ecosystems and habitats can provide substantially improved outcomes compared to more narrowly focused efforts," Barlow said.

EVANSTON, Ill. -- Northwestern University researchers have developed the first quantitative model that captures how politicized environments affect U.S. political opinion formation and evolution.

Using the model, the researchers seek to understand how populations change their opinions when exposed to political content, such as news media, campaign ads and ordinary personal exchanges. The math-based framework is flexible, allowing future data to be incorporated as it becomes available.

"It's really powerful to understand how people are influenced by the content that they see," said David Sabin-Miller, a Northwestern graduate student who led the study. "It could help us understand how populations become polarized, which would be hugely beneficial."

"Quantitative models like this allow us to run computational experiments," added Northwestern's Daniel Abrams, the study's senior author. "We could simulate how various interventions might help fix extreme polarization to promote consensus."

The paper will be published on Thursday (Oct. 1) in the journal Physical Review Research.

Abrams is an associate professor of engineering sciences and applied mathematics in Northwestern's McCormick School of Engineering. Sabin-Miller is a graduate student in Abrams' laboratory.

Researchers have been modeling social behavior for hundreds of years. But most modern quantitative models rely on network science, which simulates person-to-person human interactions.

The Northwestern team takes a different, but complementary, approach. They break down all interactions into perceptions and reactions. A perception takes into account how people perceive a politicized experience based on their current ideology. A far-right Republican, for example, likely will perceive the same experience differently than a far-left Democrat.

After perceiving new ideas or information, people might change their opinions based on three established psychological effects: attraction/repulsion, tribalism and perceptual filtering. Northwestern's quantitative model incorporates all three of these and examines their impact.

"Typically, ideas that are similar to your beliefs can be convincing or attractive," Sabin-Miller said. "But once ideas go past a discomfort point, people start rejecting what they see or hear. We call this the 'repulsion distance,' and we are trying to define that limit through modeling."

People also react differently depending on whether or not the new idea or information comes from a trusted source. Known as tribalism, people tend to give the benefit of the doubt to a perceived ally. In perceptual filtering, people -- either knowingly through direct decisions or unknowingly through algorithms that curate content -- determine what content they see.

"Perceptual filtering is the 'media bubble' that people talk about," Abrams explained. "You're more likely to see things that are consistent with your existing beliefs."

Abrams and Sabin-Miller liken their new model to thermodynamics in physics -- treating individual people like gas molecules that distribute around a room.

"Thermodynamics does not focus on individual particles but the average of a whole system, which includes many, many particles," Abrams said. "We hope to do the same thing with political opinions. Even though we can't say how or when one individual's opinion might change, we can look at how the whole population changes, on average."

An antiviral medication which effectively inhibits replication of the coronavirus causing the COVID-19 and, at the same time, fights the immune reaction that is killing COVID-19 patients around the world.

This is the hope of a group of researchers headed by Christian Kanstrup Holm and David Olagnier who are behind a newly-published new study in the journal Nature Communications. The study shows that a drug called dimethyl fumarate (DMF), which is approved for the treatment of multiple sclerosis patients, inhibits the growth of a range of viruses in the body's cells and that this includes the coronavirus (SARS-CoV2) - at least when the researchers test it in a test tube.

"As we're doing basic research, we obviously don't know whether the drug works on infections in humans, and it's up to the infectious disease experts to test for this. However, I have to say that I'm very optimistic," says Christian Kanstrup Holm, who, like his colleague David Olagnier, is associate professor at the Department of Biomedicine at Aarhus University, Denmark.

The current research results have been underway for a while now. When the pandemic struck, Christian Kanstrup Holm and his colleagues were in the process of testing the effects of a drug which was virtually identical with a particular sclerosis medicine, namely a substance called 4-octyl-itaconate, which is used on e.g. the herpes virus, smallpox virus (vaccinia virus) and zika virus, and which is also known to lead to foetal defects - all as part of the hunt for a broad spectrum antiviral medication. And their testing succeeded beyond expectations.

"Then the coronavirus suddenly appeared, which we therefore also tested, and saw an enormous effect. The number of duplications that the coronavirus makes of itself in the body's cells were simply drastically reduced," explains Christian Kanstrup Holm.

"At the same time, the drug inhibited the immune reaction or inflammatory condition that constitutes a large portion of the actual threat for coronavirus patients. People don't just die of the virus in itself, but also of the inflammation that occurs in the lungs," he says.

When the research group saw the encouraging results with 4-octyl-itaconate, they repeated the tests with a corresponding approved product, dimethyl fumarate (DMF), which showed virtually the same inhibitory effect.

This means that the effect of dimethyl fumarate (DMF) can be tested on corona patients 'here and now', if clinicians in Denmark or abroad - and the company that holds the patent - are prepared to test it in human trials.

"You can really save a lot of time when you're testing a medication that has already been approved and tested in another context," says Christian Kanstrup Holm with reference to the statutory phases involved in getting a medication approved from scratch.

"I'd really likely to be attached to this type of clinical trial if there are infectious disease researchers who assess that the result is worth proceeding with. As a basic researcher, I have neither access to patients, nor am I qualified to conduct clinical testing," he adds.

Researchers at Uppsala University have found that an effective way of treating the coronavirus behind the 2003 SARS epidemic also works on the closely related SARS-CoV-2 virus, the culprit in the ongoing COVID-19 pandemic. The substance concerned is nitric oxide (NO), a compound with antiviral properties that is produced by the body itself. The study is published in the journal Redox Biology.

"To our knowledge, nitric oxide is the only substance shown so far to have a direct effect on SARS-CoV-2," says Åke Lundkvist, a professor at Uppsala University, who led the study.

Since there is still no effective cure for COVID-19, the main emphasis in the treatments tested has been on relieving symptoms. This can shorten hospital stays and reduce mortality. To date, however, it has not been possible to prove that any of these treatments has affected the actual virus behind the infection.

Nitric oxide (NO) is a compound produced naturally in the body. Its functions include acting like a hormone in controlling various organs. It regulates, for example, tension in the blood vessels and blood flow between and within organs. In acute lung failure, NO can be administered as inhaled gas, in low concentrations, to boost the blood-oxygen saturation level. During the SARS (severe acute respiratory syndrome) coronavirus epidemic of 2003, this therapy was tried out with success. One key reason for the successful results was that inflammation in the patients' lungs decreased. This property of nitric oxide - the protection it affords against infections, by being both antibacterial and antiviral - is the very one that now interests the researchers.

Their study builds further on a discovery about the coronavirus that caused the first SARS epidemic. In 2003, NO released from S-Nitroso-N-acetylpenicillamine (SNAP) proved to have a distinct antiviral effect. The researchers from Uppsala University and Karolinska Institute have now investigated how the novel coronavirus involved in the current pandemic, SARS CoV-2, reacts to the compound. And SNAP was shown to a clear antiviral effect on this virus, too - and an effect that grew stronger as the dose was raised.

"Until we get a vaccine that works, our hope is that inhalation of NO might be an effective form of treatment. The dosage and timing of starting treatment probably play an important part in the outcome, and now need to be explored as soon as possible," Åke Lundkvist says.

The research group are now planning to proceed by investigating the antiviral effects of NO emitted in gas form. To do so, they will construct a model in the laboratory in order to safely simulate a conceivable form of therapy for patients.

Cell lines injected with free nucleic acid are widely used for drug discovery and disease modeling. To avoid genetically mixed cell populations, investigators use dilution techniques to select single cells that will then generate identical lines. However, the route of limiting dilutions is tedious and time consuming.

A new study by Northwestern researchers shows how Nanofountain Probe Electroporation (NFP-E), a tool that delivers molecules into single-cells, could solve that issue, and could lead to new applications for drug screening and designing patient-specific courses of treatment.

The team, led by Northwestern Engineering's Horacio Espinosa and including Joshua Leonard, demonstrates the versatility of NFP-E -- which introduces DNA or RNA into cells using electricity. It can also deliver both proteins and plasmids in a variety of animal and human cell types with dosage control. The team included John Kessler, the Ken and Ruth Davee Professor of Stem Cell Biology and professor of neurology and pharmacology at the Northwestern University Feinberg School of Medicine.

The new method can be used to study disease or for cell therapy. In the former, the genome is manipulated. In the latter, gene-editing occurs in cells such as T-cells to treat cancer with immunotherapies.

By employing single-cell electroporation, the process of introducing DNA or RNA into single cells using a pulse of electricity, which briefly open pores in the cell membrane, their work shows how NFP-E achieves fine control over the relative expression of two co-transfected plasmids. Moreover, by pairing single-cell electroporation with time-lapse fluorescent imaging, their investigation reveals characteristic times for electro-pore closure.

"We demonstrated the potential of the NFP-E technology in manipulating a variety of cell types with stoichiometric control of molecular cargo that can be used for conducting a wide range of studies in drug screening, cell therapies, and synthetic biology," said Espinosa, James N. and Nancy J. Farley Professor in Manufacturing and Entrepreneurship and professor of mechanical engineering and (by courtesy) biomedical engineering and civil and environmental engineering.

Currently, biomolecules can be delivered into cells in numerous ways: viral vectors; chemical carriers, such as cell-penetrating peptides and polymer nano-capsules; lipofectamine, and bulk electroporation.

"There exist a number of strategies for delivering biomolecules into cells, but each has its limitations," said Leonard, associate professor of chemical and biological engineering and Charles Deering McCormick Professor of Teaching Excellence. "For instance, chemical carriers confer relatively slow delivery and can be toxic to the cell; viral vectors are often efficient but can induce adverse immune responses and insertional genotoxicity. Use of any traditional method often requires substantial effort to optimize the protocol depending on the cell type and molecule to be delivered, and, therefore, a readily generalizable biomolecule delivery strategy would offer some meaningful advantages."

The new NFP-E system enables single-cell delivery of DNA, RNA, and proteins into different immortalized cell lines as well as primary cells with more than 95 percent efficiency and more than 90 percent cell viability.

"The results indicate that the cell membrane resealing time scales non-linearly with the pulse voltage and the number of electroporation pulses, reaching a maximum at intermediate values," Espinosa said. "That means long pulsing times or high voltages appear not to be necessary for efficient molecular transport across cell membranes. That feature is important in obtaining high transport efficiency while keeping cell toxicity to a minimum."

Using single-cell electroporation technology, the researchers were able to understand transport mechanisms involved in localized electroporation-based cell sampling. One obstacle to nondestructive temporal single-cell sampling is the small amounts of cytosol -- the fluid inside cells -- that are extracted, which makes it challenging to test or detect RNA sequences or proteins.

Research showed that the scaling of membrane resealing time is a function of various electroporation parameters, providing insight into post-pulse electro-pore dynamics.

"The work addresses the need to understand ways to increase the cytosol-sampled amount, without adversely affecting cells," Espinosa said. "That can guide the research community in designing experiments aimed at electroporation-based sampling of intracellular molecules for temporal cell analysis."

This research is related to previous work that developed a minimally invasive method to sample cells that can be repeated multiple times. That earlier investigation, which used electric pulses to extract enzymes from the cytosol, assisted understanding of the kinetics of pore formation and closure.

Animal acoustic signals are amazingly diverse. Researchers from the University of Zurich and the University of Saint-Etienne, together with French, American and Dutch collaborators, explored the function and diversification of animal acoustic signals and the mechanisms underlying the evolution of animal communication systems.

To this end, they used Shannon & Weaver's 'Mathematical Theory of Communication' originally ap-plied to telecommunications in 1949, which has transformed the scientific understanding of animal communication. This theory allows the amount of information in a signal to be quantified. The researchers were the first to use this framework within an evolutionary perspective to explore the bio-logical information encoded in an animal signal.

How drumming structure evolves over time

In deciding which biological model to choose, the researchers selected the woodpeckers' drumming as their ideal candidate. This bird family is known for rapidly striking their beaks on tree trunks to communicate. The team combined acoustic analyses of drumming from 92 species of woodpeckers, together with theoretic calculations, evolutionary reconstructions, investigations at the level of ecolog-ical communities as well as playback experiments in the field.

"We wanted to test whether drumming has evolved to enhance species-specific biological information, thereby promoting species recognition", says lead author Maxime Garcia of the UZH Department of Evolutionary Biology and Environmental Studies.

Constant amount of information for 22 million years

Results demonstrate the emergence of new drumming types during woodpeckers evolution. Yet, despite these changes in drumming structure, the amount of biological information about species identity has remained relatively constant for 22 million years. Selection towards increased biological infor-mation thus does not seem to represent a major evolutionary driver in this animal communication system. How then can biological information be concretely maintained in nature? Analyses of existing communities around the globe show that ecological arrangements facilitate the efficiency of drumming signals: Communities are composed of only a few species, which distribute their drumming strategies to avoid acoustic overlap. "The responses to different drumming structures seen in our experimental approach show the ability of individuals to recognize their own species based on acoustic cues about species identity found in drumming signals", says Garcia. This way, biological information about spe-cies identity can be maintained without necessarily inducing a strong evolutionary pressure on drum-ming signals.

The present study shows that random and unpredictable changes in the structure of communication signals over time can occur while maintaining the signals overall informative potential within and across species. This work leads the way to further investigate the evolution of meaning associated with communicating through multiple communication channels.

In the search for the chemical origins of life, researchers have found a possible alternative path for the emergence of the characteristic DNA pattern: According to the experiments, the characteristic DNA base pairs can form by dry heating, without water or other solvents. The team led by Ivan Halasz from the Rudjer Boskovic Institute and Ernest Mestrovic from the pharmaceutical company Xellia presents its observations from DESY's X-ray source PETRA III in the journal Chemical Communications.

"One of the most intriguing questions in the search for the origin of life is how the chemical selection occurred and how the first biomolecules formed," says Tomislav Stolar from the Rudjer Boskovic Institute in Zagreb, the first author on the paper. While living cells control the production of biomolecules with their sophisticated machinery, the first molecular and supramolecular building blocks of life were likely created by pure chemistry and without enzyme catalysis. For their study, the scientists investigated the formation of nucleobase pairs that act as molecular recognition units in the Deoxyribonucleic Acid (DNA).

Our genetic code is stored in the DNA as a specific sequence spelled by the nucleobases adenine (A), cytosine (C), guanine (G) and thymine (T). The code is arranged in two long, complementary strands wound in a double-helix structure. In the strands, each nucleobase pairs with a complementary partner in the other strand: adenine with thymine and cytosine with guanine.

"Only specific pairing combinations occur in the DNA, but when nucleobases are isolated they do not like to bind to each other at all. So why did nature choose these base pairs?" says Stolar. Investigations of pairing of nucleobases surged after the discovery of the DNA double helix structure by James Watson and Francis Crick in 1953. However, it was quite surprising that there has been little success in achieving specific nucleobase pairing in conditions that could be considered as prebiotically plausible.

"We have explored a different path," reports co-author Martin Etter from DESY. "We have tried to find out whether the base pairs can be generated by mechanical energy or simply by heating." To this end, the team studied methylated nucleobases. Having a methyl group (-CH3) attached to the respective nucleobases in principle allows them to form hydrogen bonds at the Watson-Crick side of the molecule. Methylated nucleobases occur naturally in many living organisms where they fulfil a variety of biological functions.

In the lab, the scientists tried to produce nucleobase pairs by grinding. Powders of two nucleobases were loaded into a milling jar along with steel balls, which served as the grinding media, while the jars were shaken in a controlled manner. The experiment produced A:T pairs which had also been observed by other scientists before. Grinding however, could not achieve formation of G:C pairs.

In a second step, the researchers heated the ground cytosine and guanine powders. "At about 200 degrees Celsius, we could indeed observe the formation of cytosine-guanine pairs," reports Stolar. In order to test whether the bases only form the known pairs under thermal conditions, the team repeated the experiments with mixtures of three and four nucleobases at the P02.1 measuring station of DESY's X-ray source PETRA III. Here, the detailed crystal structure of the mixtures could be monitored during heating and formation of new phases could be observed.

"At about 100 degrees Celsius, we were able to observe the formation of the adenine-thymine pairs, and at about 200 degrees Celsius the formation of Watson-Crick pairs of guanine and cytosine," says Etter, head of the measuring station. "Any other base pair did not form even when heated further until melting." This proves that the thermal reaction of nucleobase pairing has the same selectivity as in the DNA.

"Our results show a possible alternative route as to how the molecular recognition patterns that we observe in the DNA could have been formed," adds Stolar. "The conditions of the experiment are plausible for the young Earth that was a hot, seething cauldron with volcanoes, earthquakes, meteorite impacts and all sorts of other events. Our results open up many new paths in the search for the chemical origins of life." The team plans to investigate this route further with follow-up experiments at P02.1.

DESY is one of the world's leading particle accelerator centres and investigates the structure and function of matter - from the interaction of tiny elementary particles and the behaviour of novel nanomaterials and vital biomolecules to the great mysteries of the universe. The particle accelerators and detectors that DESY develops and builds at its locations in Hamburg and Zeuthen are unique research tools. They generate the most intense X-ray radiation in the world, accelerate particles to record energies and open up new windows onto the universe. DESY is a member of the Helmholtz Association, Germany's largest scientific association, and receives its funding from the German Federal Ministry of Education and Research (BMBF) (90 per cent) and the German federal states of Hamburg and Brandenburg (10 per cent).

Could a poo transplant one day be the secret of eternal youth?

Faecal transplants could one day be used as a therapy to restore cognitive function in the elderly - according to new research from the University of East Anglia, the University of Florence and the Quadram Institute.

A new study published today shows how faecal transplants from older to younger mice altered their gut microbiome, which in turn impacted their spatial learning and memory.

The research team hope that reversing the procedure could one day see faecal transplantation used to combat cognitive decline among the elderly.

Dr David Vauzour, from UEA's Norwich Medical School, said: "Ageing is an inevitable process that starts immediately after birth and ultimately leads to physical health problems as well as a decline in psychological well-being and cognitive function.

"Research has shown that the aging process may be linked with age-related changes in our gut microbiota.

"Recently, the existence of two-way communication between the gut and the brain - known as the 'gut-brain axis' - has emerged as an important player in shaping aspects of behaviour and cognitive function.

"We wanted to see whether transferring gut microbes from older to younger mice could affect parts of the central nervous system associated with ageing."

The research team performed faecal transplants from older adult mice to younger adult mice and then assessed the young adults for markers such as anxiety, exploratory behaviour and memory.

After the transplantation, the team found significant differences in the young mice's microbial profiles.

While the young adults showed no significant changes in markers of anxiety, explorative behaviour or locomotor activity, they did show impaired spatial learning and memory as measured in a maze test.

These changes were paralleled by alterations in the expression of proteins associated with synaptic plasticity and neuro transmission, and changes to cells in the hippocampus part of their brains - responsible for learning and memory.

Dr Vauzour said: "Our research shows that a faecal transplantation from an old donor to a young recipient causes an age-associated shift in the composition of gut microbiota.

"The procedure had an impact on the expression of proteins involved in key functions of the hippocampus - an important part of the brain that has a vital role in a variety of functions including memory, learning but also in spatial navigation and emotional behaviour and mood.

"In short, the young mice began to behave like older mice, in terms of their cognitive function."

Prof Claudio Nicoletti, from the University of Florence, Italy, said: "While it remains to be seen whether transplantation from very young donors can restore cognitive function in aged recipients, the findings demonstrate that age-related shifts in the gut microbiome can alter components of the central nervous system.

"This work highlights the importance of the gut-brain axis in ageing and provides a strong rationale to devise therapies aiming to restore a young-like microbiota to improve cognitive functions and quality of life in the elderly," he added.

"Manipulating the microbiome is increasingly being seen as a way of improving or maintaining human health, and these results are an exciting indication of its potential for helping us age healthily" said Prof Arjan Narbad from the Quadram Institute.

"We have established an FMT service on the Norwich Research Park to treat serious gut infections and now want to explore in humans its effectiveness in combating a number of age-related conditions, including cognitive decline."

The research was led by a team at UEA and the University of Florence, in collaboration with colleagues at the University of Milan, the Earlham Institute, University of Siena, the Quadram Institute, and Nottingham Trent University.

The study was based on the authors' original hypothesis that a specific novel mechanism responsible for linking distinct symptoms into a single disease may exist in the brain. 'A disease is more complex than a collection of symptoms. For example, while decreased appetite or blues can occur in many people, only together these symptoms form a disease - depression. We suggested that there must be some kind of molecular "link", likely mediated by specific brain genes, that "bring together" diseases by combining their symptoms, but not causing symptoms per se,' explained Professor Alan Kaluev, study's Principal Investigator and head of the Laboratory of Biological Psychiatry at the Institute of Translational Biomedicine at St Petersburg University.

When studying mental disorders, researchers try to understand which gene in the brain is responsible for a particular symptom. The C57BL/6?J mice in a chronic social stress model are often used as an experimental model. This animal model, created in the 1980s in Novosibirsk, is generated by placing two male mice in the same cage, where they begin to fight, after which they are separated by a transparent partition with holes through which they can feel each other, but cannot contact. They are left separated in the same cage for the whole day, and then the manipulations are repeated daily for 3 weeks. As a result, the 'winners' and the 'losers' reveal themselves clearly, and the state of 'losers' is of particular interest for studying anxiety and depression.

'In the classical model of chronic social stress, if the defeated losers are stressed for about 10 days, they develop anxiety-like state, but do not show 'depression' yet. However, if you continue to stress them, then after 20 days these animals develop a pronounced depressive-like state, but no longer have anxiety. Simply put - it takes 10 days of fights to cause "mouse" anxiety - one brain pathology. And by 20 days they already have depression. Thus, the question we asked in the present study concerned what happens in the middle of this interval - for example, on day 15? Hypothetically, this is the point where one pathology (anxiety) begins to turn into another (depression). If you imagine a train at a junction: it can go left or right - then the track switches, and the switch (relay) is the 15th day. This "relay" itself does not cause anxiety or depression. However, this switch in the brain may involve its own set of unique genes,' explained Professor Kaluev.

As he noted, these 'switch' genes cannot be detected by classical methods of genetics, because they are not responsible for any symptom: neither for anxiety, nor for depression. They only hypothetically 'switch' from one pathology to another. To experimentally prove their hypothesis, the researchers performed a genome-wide screening of mice brain gene activity in two key areas - the prefrontal cortex (responsible for long-term planning and social behaviour) and the hippocampus (responsible for memory).

'Our present discovery can be briefly summarized as follows: we found that on Day 15 during the transition from experimental anxiety- to depression-like state in mice, neither genes associated with neurotransmitters (as during the anxiety-like state) nor with the inflammation (as with depression-like state) are involved. Rather, these 'transitional' mechanisms are associated with the cytoskeleton and astrocytes - the glial cells in the brain that are increasingly associated with mental illness. Overall, we showed that when in mice one brain pathology progresses into another, unique cellular mechanisms are activated. In fact, they may act as a unique molecular "switch" that can send the vector of pathogenesis either in one direction (anxiety) or in another (depression),' explained Dr. Kaluev.

The scientist also noted that with continued stress, in about 70% of people with chronic anxiety it can turn into depression. At the same time, traditional antidepressants do not always work effectively. According to study director, only about 30-40% of people respond to therapy, and the majority either does not respond at all, or reacts in a weak form. He stressed that, at the same time, the number of detected cases is growing every year, and fundamentally new drugs for depression have not appeared over the past half century.

'It therefore seems that stopping depression is a key unmet biomedical task. And since existing antidepressants are not always effective, the question arises: how can we stop this 'rushing train' of brain affective pathology? If it is already on the path to depression, can we slow it down? Or, alternatively, we can target the "switch" of the track instead, to present depression progression? As such, the putative mechanisms we have discovered can become a new target for creating fundamentally new classes of psychotropic drugs,' added the professor.

He also emphasised that our mouse data are highly consistent with recent clinical evidence where astrocytes and cytoskeletal mechanisms are increasingly implicated in human affective pathogenesis. The research team plans to test their hypothesis in humans, in the long term aiming to understand how exactly to influence the 'switch' and stop depressive disorder at its very beginning.

We need to know about these psychological and social profiles so we can understand how protective actions against contagious diseases are adopted, and then define the correct preventive approaches. At the very start of the coronavirus crisis - before restrictive measures were taken - a team of health behaviour specialists from the University of Geneva (UNIGE) managed to collect a large amount of data about the adoption of protective measures. Through a study published in the journal Applied Psychology: Health and Well-Being, the Geneva psychologists analysed how people in Britain followed the precautions recommended in their country. The study focuses on how the behaviour of others influences individual decision-making, known as the social dilemma. It notes that beliefs about COVID-19, such as thinking that the disease is dangerous or feelings of vulnerability, have little impact on whether or not an individual takes up protective measures. The people least likely to adopt these measures are those who believe that the precautions taken by others mean that they do not need to take their own. These psychosocial profiles (among others identified in the study) point to possible solutions for creating prevention messages that are more effective.

A better understanding of human behaviour when it comes to making a positive contribution to a community can be used to develop more appropriate prevention measures and messaging. This is a form of behaviour analysis that is very useful for ecological issues and blood donation. Lisa Moussaoui is first author of the study as well as being a lecturer and research fellow in the health psychology research group in UNIGE's Faculty of Psychology and Educational Sciences (FPSE). She explains the approach thus: &laquoWe are trying to understand how people make decisions and act so that preventive interventions can be made.» This is why, when the Swiss Federal Office of Public Health announced it would be introducing a semi-lockdown on March 13, 2020, the researcher and her colleagues decided to bring their expertise to bear regarding the COVID-19 health crisis.

Using the United Kingdom as a model

The Geneva psychologists turned to the United Kingdom, which - unlike Switzerland - had not yet entered lockdown: this meant the researchers could analyse behaviours before the official measures came into force, enabling them to concentrate on the initial decisive phases. A representative sample of 1,006 UK citizens served as the basis for the study, which included a series of questions relating to monitoring the adoption of the preventive measures recommended by the British health authorities. &laquoWe measured variables such as perceived vulnerability to COVID-19, the perceived severity of the disease and a number of other beliefs,» says Nana Ofosu, a doctoral student at UNIGE and co-author of the study.

Few socio-demographic differences

The psychologists observed that preventive measures were spontaneously adopted by a large section of the population. &laquoIt's a known phenomenon. Informing people about the presence of a danger is enough to bring about a massive and rapid change in behaviour. We've seen the same thing in other tragic situations, such as the AIDS pandemic. But, in spite of everything, pockets of resistance do exist,» explains Olivier Desrichard, FPSE professor and co-author of the study.

Level of education, family environment, age and the number of cases declared in the region do not influence behaviour. &laquoIt's an outcome that contradicts rumours claiming that certain categories of the population, such as young people, followed instructions less than others,» adds Moussaoui.

How other people behave: a source of social dilemma

&laquoIf no one else is doing it, why should I be the only one making the effort? &laquo The more the study participants agreed with this question, the less they adopted preventive measures. Another factor negatively influences their adoption: the &laquodrop-in-the-bucket» phenomenon - the feeling that your own contribution is pointless compared to the size of the danger. Finally, the study emphasises the fact that the more social contacts the participants had, such as professional relationships, the more they felt vulnerable, even though this did not inspire them to adopt the correct actions.

Preventive approach that needs refining

The study confirms the fact that social dilemmas influence behaviour. This psychosocial approach offers an interesting counterpoint to the way information is communicated about COVID-19, one that focuses on the dangerous nature of the virus and the importance of observing instructions. &laquoIt's important to know the real determinants of behaviour before embarking on a preventive action so as not to miss the intended goal. Most of the people interviewed were already convinced about the importance of respecting the recommendations. It follows,» concludes Moussaoui,» that this kind of message is not really useful to influence their behaviour».

What The Study Did: The U.S. Army Public Health COVID-19 Task Force describes the results of an independent investigation of the shore-based USS Theodore Roosevelt outbreak response and 736 sailors in isolation status.

Authors: Gadiel R. Alvarado, D.O., of the Brooke Army Medical Center in Fort Sam Houston, Texas, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.20981)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

DUARTE, Calif. -- A City of Hope-led study revealed little effort has been made to improve older adult representation in clinical trials of new cancer drugs, even when the treatment is aimed at a disease that disproportionately affects this age group.

"There is currently no incentive to establish real-world effectiveness among older adults. Older adults need a seat at the table," said Mina Sedrak, M.D., M.S., lead author of the study and deputy director of the Center for Cancer and Aging at City of Hope, a world-renowned independent research and treatment center for cancer, diabetes and other life-threatening diseases.

Two in 5 Americans with cancer are age 70 or older, yet fewer than 25% of patients in cancer clinical trials registered with the Food and Drug Administration are in this age group, Sedrak said.

The study was published in the journal CA: A Cancer Journal for Clinicians on Oct. 1. Researchers reviewed 8,691 studies that evaluated barriers which hindered older adults from participating in cancer trials. Twelve articles defined complex, interrelated problems as root causes, including stringent eligibility criteria, physician concern for toxicity, ageism, transportation and caregiver burden.

Only one study implemented an intervention meant to increase enrollment of older adults in trials - and it was not successful. This finding starkly amplifies the lack of effective strategies to improve participation of this underrepresented group in cancer research.

The researchers report that cancer trials must ask appropriate questions tailored or driven by the needs of older adults with cancer and should measure relevant outcomes. Their call to action applies to all oncologists and primary care providers, not just geriatric oncologists, Sedrak said, adding that patients should advocate for themselves.

"Ask your doctor about clinical trial opportunities when you're diagnosed with cancer and do your own research because there may be an option that you haven't heard about. It may benefit you, but perhaps your doctor may not have considered you for the investigational trial," he said.

What The Study Did: This observational study looked at the association between Medicaid expansion under the Patient Protection and Affordable Care Act (ACA) and long-term home health care and nursing home use among newly eligible low-income adults and older adults whose eligibility did not change.

Authors: Courtney Harold Van Houtven, Ph.D., of the Durham Veterans Affairs Health Care System in Durham, North Carolina, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.18728)

Editor's Note: The article includes conflicts of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.