Culture

A team of scientists has shown that the healing of skin blisters is driven by hair follicle stem cells, which delay their own development in the process.

The healing process of the tissues in the human body is particularly well-studied in skin, especially as skin serves as a layer of protection from the environment. However, there remain some specific types of skin injuries where the healing process is not well understood.

A team of scientists from Japan and Italy, including Associate Professor Ken Natsuga from the Graduate School of Medicine at Hokkaido University, have used models of skin blisters to explore the effects of injury on developing skin tissue. Their discoveries were published in the journal EMBO Reports.

The scientists performed their tests on mice which had artificially generated epidermal detachment, or skin blisters. They investigated the healing process by monitoring gene expressions and cell proliferation, tracing cell lineages, and employing mathematical models.

The team found that a type of stem cells (SCs), hair follicle stem cells (HFSCs), play an outsize role in blister healing. The HFSCs are mainly responsible for the healing of subepidermal blisters, from the base of the wound. The wound-healing activity of HFSCs is accompanied by delayed growth of hair follicles in the regenerated skin tissue. When HFSCs are reduced, another group of SCs, the interfollicular epidermal stem cells (IFESCs), can also contribute to healing, but only from the blister margins. They also confirmed that blister healing was affected by the shapes of keratinocytes, the primary skin cells, although the mechanism by which the shapes affect healing is still unclear.

The findings have revealed the balance between wound healing and development in skin, indicating many possibilities for the treatment of skin blistering in humans. The models used in this study may themselves be used for the development of new therapies for blister healing. The role of sweat glands could not be investigated, as mice lack sweat glands, and the role of mesenchymal cells, which have previously been shown to be involved in healing of skin wounds, was not examined. Future work will focus on these aspects.

"Our findings of the healing processes pave the way for tailored therapeutic interventions for epidermolysis bullosa, pemphigoid diseases and other blistering diseases," says Ken Natsuga.

Nearly 12,000 people in Sweden received sickness benefit from the Swedish Social Insurance Agency for COVID-19 during the first wave of the pandemic. The median duration of sick leave in this group was 35 days, but for many it was considerably more long-drawn-out, according to a University of Gothenburg study.

A research group in rehabilitation medicine at the University of Gothenburg has studied sick-leave patterns. The study now presented in the scientific journal BMC Public Health.

The study included all recipients of sickness benefit from the Social Insurance Agency for COVID-19 diagnoses in Sweden during the first pandemic wave, from 1 March to 31 August 2020, and monitored them for 4 months from the start of the sick-leave period.

Sickness benefit from the Swedish Social Insurance Agency is normally paid from day 15 of a sick-leave period. People whose sick leave lasted two weeks or less, with sick pay from the employer, were not included in the study.

Data from the Social Insurance Agency, the National Board of Health and Welfare, and Statistics Sweden were used. Describing sick leaves is a way to investigate the impact of diseases on society and individuals, but few other studies have specifically looked at this repercussion of the pandemic.

The results show that 11,955 people received sickness benefit for COVID-19 during the first wave. For a sizable proportion, sick leave was lengthy. The median time was 35 days, and for 9% sick leave was still underway at the end of the follow-up period, i.e., after 4 months.

The proportion of participants who were on sick leave for more than 12 weeks, i.e., those who may have been affected by what is known as "long-term COVID-19," was 13.3%.

Inpatient hospital care for COVID-19 was the strongest predictor of prolonged sick leave. Another major factor was sick leave in the previous year, 2019. Age, too, appears to have a bearing on the duration of sick leave.

However, the study showed no socioeconomic factors that clearly and consistently predicted long-drawn-out sick leave.

The research group behind the study belongs to the Department of Clinical Neuroscience at the Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, and Sahlgrenska University Hospital. Hanna C Persson is the study's corresponding author.

"The results indicate that the category of people who had been on long-term sick leave due to COVID-19 is heterogeneous, and that the disease is complex. For us to understand the whole picture, more studies are needed in this subject, and with a longer follow-up period," Persson says.

High running capacity is associated with health and longevity. However, whether high genetic running capacity promotes more efficient metabolism with aging is not known. A new study conducted in collaboration between the universities of Shanghai Jiao Tong University (China) and Jyväskylä (Finland) investigated the effects of genetic running capacity and aging on tissue metabolism. The study reveals that adipose tissue may have a key role in healthy aging.

Running capacity, expressed as aerobic capacity, refers to an individual's capacity to utilize oxygen and is known to decrease with age, thereby affecting the whole body metabolism and health.

"We currently lack the information whether high genetic aerobic capacity promotes healthier metabolism in different tissues as we age," explains Academy of Finland postdoctoral researcher Sira Karvinen from the Faculty of Sport and Health Sciences, University of Jyväskylä, Finland.

To study the question, animal models of high-capacity runners (HCR) and low-capacity runners (LCR) were utilized. These rodent lines differ in their aerobic capacity genetically. Samples of serum, muscle and adipose tissue were harvested from young and aged animals to explore the tissue metabolites.

"According to our results, high genetic running capacity was associated with more efficient amino acid metabolism in skeletal muscle. Inefficient amino acid metabolism is linked to increased adiposity and risk of metabolic diseases," says Karvinen.

High genetic running capacity and aging interactively affected lipid metabolism in muscle and adipose tissue, possibly contributing to healthier metabolism with aging.

The results suggest that adipose tissue may have a more significant role in promoting healthy aging than previously thought. According to the current literature, around 50% of an individual's aerobic capacity is genetically inherited and the other 50% can be gained via physical activity.

"Regular exercise promotes health whether you have genetically high or low aerobic capacity. Hence, it is highly recommended to promote one's metabolism with exercise especially at older age, when aerobic capacity as well as other health parameters decline," says the principal investigator, Professor Heikki Kainulainen from the Faculty of Sport and Health Sciences, University of Jyväskylä, Finland.

Universal school lunch programs make students healthier, and increase their lifetime income by 3%, according to a unique study from Lund University in Sweden published in The Review of Economic Studies.

Health disparities arise early in life and play a major role in economic outcomes among adults. Yet there are few studies on the long-term effects of school-based nutrition policies aimed at counteracting them. Researchers from Lund University and Stockholm University can now show that universal school lunch programs have significant long-term benefits for students' education, general health and income.

"Today, we take school lunches for granted in Sweden. But the fact is, it was a very conscious investment when Sweden introduced free lunches in the 1940s. These cooked meals were meticulously planned in terms of nutrition. This begs the question: did it affect students' well-being in the long-term? We wanted to find out", says Petter Lundborg, professor of economics at Lund University.

Sweden, Finland and Estonia have been serving free school meals for a long time, unlike the neighboring countries Norway and Denmark, where pupils bring their own lunch. In other countries, such as the US and the UK, poorer students are offered school meals, while others pay.

In the new study, the researchers examine the Swedish school lunch program that was introduced gradually in different municipalities from the mid-1940s. The program offered nutritious school lunches to all Swedish primary school students, free of charge.. The researchers focused on the introduction of school lunches between 1959 and 1969. They discovered that the initiative had a positive impact on the height of the students, their health as young adults, the level of education they attained, and their lifetime income.

"Our study shows that universal efforts that provide children with nutritious meals can be seen as a long-term investment. In other words: ensuring that children eat well, also pays off later in life in terms of health, education and income", says Dan-Olof Rooth, professor of economics at the Institute for Social Research (SOFI) at Stockholm University.

The study shows, among other things, that both boys and girls who took part in the school meal program throughout their schooling grew taller than those who did not have access to the program. Pupils who received school meals during the entire nine years of compulsory school became almost 1 cm taller and went to university more often compared with pupils without access to the program. However, most importantly, the students had a three percent higher lifetime income.

"We also noted some interesting differences in the effects, where children from poor households benefited the most, even if children from all households benefit to a certain extent. Students from poor families had a six percent higher lifetime income, and students from other households had about a two percent higher lifetime income. The reform thus benefited all students, from both poor and rich families", says Petter Lundborg.

The results are related: the students ate nutritious food at school, they became taller and more educated, which to a large extent can explain why they had a better income through life. However, the researchers found no long-term effects on mortality, morbidity or sick leave.

The effects of school meal programs can also be caused by factors that have nothing to do with nutrition. Therefore, the researchers also collected data on school absenteeism from municipal archives in Sweden. The researchers' analysis shows that the introduction of the school lunch program did not lead to any changes in school attendance, which was high even before school meals were introduced.

"A reasonable interpretation of our results is that the students became more receptive to what they were being taught when they ate a nutritious lunch. This is in line with a previous study, which found that test results among eleven-year-olds increased during the first year after the introduction of nutritious school meals in connection with the Jamie Oliver campaign in the UK", says Dan-Olof Rooth.

Petter Lundborg and Dan-Olof Rooth - who conducted the study together with Dr. Jesper Alex-Petersen - believe that their results are relevant to many western countries today, even though the Swedish school lunch program was introduced during the 1950s and 1960s. Sweden was a rich country, where school children did not lack food, but where parents lacked knowledge about healthy eating habits. The reform made school food nutritious and the same for everyone.

"It is important for many countries even today, because school meals and their nutritional content is a recurring issue. Our results show significant long-term economic benefits of school meals. You get a lot of 'bang for your buck' - it is extremely well-invested money", concludes Petter Lundborg.

About the study:

The researchers used newly collected historical data on the gradual implementation of the program across municipalities in Sweden between the years 1959 and 1969. During this period, 265 municipalities introduced the program, with a roughly equal number of municipalities each year.

These historical data were linked to administrative records that cover the population of primary school pupils, i.e., about 1.5 million pupils born 1942-1965. Using a difference-in-differences design, they estimated the impact of the school lunch reform on a broad range of outcomes taken from income and education registers, the military enlistment register, the medical birth register, and hospitalization and mortality registers.

Announcing a new article publication for BIO Integration journal. In this article the authors Yuhao Chen, Yue Li, Meng Du, Jinsui Yu, Fei Gao, Zhen Yuan and Zhiyi Chen from The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China, University of South China, Hunan, China and University of Macau, China discuss ultrasound neuromodulation: integrating medicine and engineering for neurological disease treatment.

Neurological diseases associated with dysfunctions of neural circuits, including Alzheimer's disease (AD), depression and epilepsy, have become increasingly prevalent. To tackle these issues, artificial stimulation or regulation of specific neural circuits and nuclei are employed to alleviate or cure certain neurological diseases.

Ultrasound neuromodulation is an emerging interdisciplinary approach, which integrates medicine and engineering methodologies in the treatment. With the development of medicine and engineering, ultrasound neuromodulation has gradually been applied in the treatment of central nervous system diseases. In this review, the authors summarize the mechanism of ultrasound neuromodulation and the advances of focused ultrasound (FUS) in neuromodulation in recent years, with a special emphasis on its application in central nervous system disease treatment.

FUS shows great potential for the treatment of epilepsy, tremor, AD, depression, and brain trauma. The authors also suggest future directions of ultrasound neuromodulation in clinical settings, with a focus on fusion with genetic engineering or nanotechnology

Various platforms which offer food home delivery services through courier services, such as riders or other types of distributors, have proliferated very quickly in recent years, especially in big cities. Due to this boom in last-mile delivery or logistics, UOC experts have studied the operation of the main food home delivery platforms, such as Just Eat, Glovo and Deliveroo, which work in the city of Barcelona, to analyse the profitability of these business models and estimate the number of orders needed to achieve this profitability.

"It's very difficult for these business models to be profitable by themselves", said Eduard J. Álvarez Palau, a researcher from the SUMA research group of the UOC's Faculty of Economics and Business, the main author of this work together with Ángel A. Juan, principal investigator of the ICSO research group of the UOC's IN3.

During the course of the research, the authors analysed public data from the different companies to ascertain how the profit is generated on this type of platform. As well as studying the revenues, both those which come directly from the restaurants and those which come from the clients, they also assessed the fixed costs and the variable costs involved in each delivery.

Profitability of the service

After analysing the context and the situation, the experts estimate that at least 8,000 orders a day are needed for this type of platform to begin to be profitable from its operation. "This would be the most benevolent scenario. With the alternative scenario, in which we add all those costs related to the expansion of this type of company in other markets, we find that these 8,000 services have to be increased to 19,000 for the operating system to profitable, which is a little surprising", explained Álvarez.

Despite this situation, these companies do not base their income on just their activity. They are founded on two pillars: the investors and venture capital funds which allow them to remain in the business and participate in other business models. "Although their main business is food home delivery, it's difficult for them to be economically profitable and, therefore, they have to begin to choose other complementary business models, such as the delivery of other types of products or complementary services for restaurants, such as ghost kitchens", he stressed.

Thanks to these participations, this type of platform thus obtains a higher percentage of profit. "Their ultimate goal tends to be to attract as many users as possible in order to offer them additional services, although it's true that in the course of the research we didn't focus on the internal algorithms of each platform".

For years now, this group of experts has been studying the different dynamics of urban logistics, especially the so-called "last mile", the final delivery of the product to the client. This has been a booming market in recent years and has been driven to a large extent by the circumstances arising from the pandemic. "This growth demonstrates a transformation that's taking place and continuing to grow".

Indeed, unlike other types of companies such as Amazon, the delivery people from home delivery platforms tend to be distributors who use bicycles or motorbikes, known as 'riders', because the origin of the product is restaurants from the city and greater flexibility is needed. "The cost of riders is another factor that we analysed and we considered alternative scenarios to the current ones", Álvarez added.

Future scenarios

Moreover, based on the data obtained, the authors observe future lines for this type of company in which the application of this type of services to other sectors, not just food delivery, is envisaged.

For example, one of the scenarios that the experts consider is the direct recruitment of the riders by these companies. In this case, the delivery costs would increase by 30%. However, the trend in this sector tends to be toward the mass outsourcing of riders with temporary employment agencies, which will slightly reduce this extra cost and maintain flexibility.

Indeed, the experts depict a future in which these companies also pursue several business lines in order to obtain greater economic profitability than that achieved from food home delivery operations.

This UOC research contributes to sustainable development goals (SDG) 8, decent work and economic growth, and 11, sustainable cities and communities.

Near-field light is invisible light at the subwavelength scale. Harnessed for a variety of practical applications, such as wireless power transfer, near-field light has an increasingly significant role in the development of miniature on-chip photonic devices. Controlling the direction of near-field light propagation has been an ongoing challenge that is of fundamental interest in photonics physics and can significantly advance a variety of applications.

So far, propagation of near-field light in a single direction is achieved by specific interactions between the electric dipole and the magnetic dipole in a system, which has led to inevitable complexities in device design. Hyperbolic metamaterials (HMMs), an important class of artificial anisotropic material with hyperbolic isofrequency contours, have attracted attention due to their unique ability to control near-field light by enabling subwavelength confinement of electromagnetic waves. Large wave-vector modes in HMMs are of particular interest because those modes are easier to integrate and have a smaller loss of energy at transfer.

As reported in Advanced Photonics, researchers from Tongji University in China recently demonstrated an all-electric scheme able to flexibly control the propagation direction of near-field light. They reported anomalous unidirectional excitation of hyperbolic modes with large wave-vector at subwavelength scales. According to their research, selective near-field coupling in HMMs is enabled by discrete electric dipoles with different phases, which serve as a metasource composed of all-electric components and with a symmetry-associated inner freedom.

Their research not only addresses the need for an all-electric experimental design scheme for near-field photonics, but also contributes fundamentally valuable symmetry-based excitation principles. Using a Huygens metasource, the researchers were able to observe the unidirectional excitation of hyperbolic bulk modes in a planar HMM. They found that unidirectional excitation in free space is the same as in the vertical direction, but opposite to that in the horizontal direction. These different propagation characteristics in horizontal and vertical directions are unique to the hyperbolic modes. In addition, the researchers used spin metasources to study the directional propagation of light in a planar hyperbolic waveguide. They found that, for the clockwise-rotating spin metasource, only the guided mode propagating from right to left is excited. And for the counterclockwise-rotating source, only the guided mode propagating from left to right is excited.

Overall, the research advances the fields of optical science and information communication, as the results provide the necessary conditions for highly efficient and experimentally verified photonics routing. For emerging applications in integrated optical devices, as well as wireless power transfer, switching, and filtering, this work promises unprecedented flexible control of near-field light.

The human gut microbiome is a complex community of trillions of microbes that are constantly interacting with each other and our bodies. It supports our wellbeing, immune system and mental health - but how is it sustained?

Researchers in the UK and Germany, alongside other international collaborators, have investigated the evolution of bacteria in the human gut microbiome - asking how these microbes persist throughout their lifetimes - taking into account internal and external influencing factors.

The results of the study will help inform tailored probiotics, live bacteria found in particular foods or supplements, as well as dietary or medical interventions, to treat gut disease and maintain a healthy gut microbiome.

Keeping a stable, healthy gut microbial population is mutually beneficial to us and the bacteria. In exchange for nutrition and a comfortable habitat, the microbe community returns the favour by providing us with health benefits, which we are now starting to understand.

Lead author and Group Leader Dr Falk Hildebrand from the Quadram Institute and Earlham Institute, explains: "We know that certain microbes colonise us at birth, and some can live with us for decades. Yet, although studies have looked at individual microbe species, the mechanisms and scale of persistence in the microbiome as a whole haven't been explored."

To examine this, a team of scientists at the Earlham Institute and Quadram Institute on the Norwich Research Park, along with the European Molecular Biology Laboratory (EMBL) in Germany, used metagenomics to analyse the evolutionary strategies and persistence of different bacteria in the human gut microbiome.

Metagenomics is the study of all of the genes from many different organisms in a population. In terms of the human gut microbiome, this process not only provides detailed information about the bacteria strains present but also indicates the enhancing capabilities of those different strains, based on their genetics, to keep the gut in good working order.

From analysing stool samples, the team re-examined metagenomes from over 2,000 adult and infant samples, including several from the same families and found three major dispersal strategies underlying human gut bacterial persistence. The data came from previously published studies looking at microbiome changes over time, with each individual providing on average 2-3 samples several months apart.

Last author and Director EMBL Heidelberg (Scientific Activities) Prof Peer Bork, said: "By looking into time series from individuals and family members and overlaying this with geographic information, ranging from household via city to country, we identified groups of bacterial strains that show different dispersal strategies. This presented very different persistence patterns in the host, regional spreading and the geographical distributions of hundreds of bacterial species."

The data was built into a diverse dataset of 5,278 metagenomes, which were probed to analyse patterns of persistence in the different types of bacteria and how these were influenced by the common factors: age, family members, geographic region, and antibiotic usage.

"Our analysis shows that most strains of bacteria present in the microbiome are very persistent - with the chances of a strain persisting for at least a year being over 90%," said Dr Hildebrand.

"Some microbe species did show consistent differences being either highly persistent taxonomic groups, or being low-persistent, relying more on exchanges between family members. In babies, however, the average persistence of bacterial strains dropped to 80%. This isn't unexpected; we know that especially in newborn babies there is an ongoing exchange of gut microbes."

Prof Bork, added: "What the study shows is that the intrinsic persistence levels of bacteria seen in adults are also reflected in children, and gradually we start to acquire those persistent bacteria up to about ten-years-old at which point the microbiome reaches a steady state. "

"Antibiotics had different effects of different types of bacteria, with the overall effect depending on how resilient different bacteria are, their intrinsic persistence, and to what extent they were replaceable within the microbiome."

To delve deeper into what drives persistence, the researchers compared microbiome communities beyond an individual level, but also across families, countries and regions. This allowed them to group bacteria based on their persistence characteristics and, through genomic analysis, look for clues to the evolution of these groups' strategies in dispersing among new human hosts.

Tenacious persistence

The first group, termed 'tenacious' bacteria, were the most persistent and well adapted for survival in the human gut. For example, these bacteria were able to survive by switching to different nutrition sources as the host moved through infancy and into adulthood.

Tenacious bacteria, however, are the ones most likely to be lost from the microbiome following antibiotic use. If we have been carrying these bacteria in us since childhood, their loss may be permanent. This is a particular concern in relation to over- and misuse of antibiotics.

Another group was termed the 'heredipersistent' bacteria, which are strains that are 'inherited' and cluster within families. These have a lower persistence in childhood and a higher turnover rate, suggesting cycles of reinfection is key to their persistence in an individual.

Genomic analysis showed that these bacteria tend to have genes allowing them to spread by spores, which would help transmission from, say, a parent to child, but also across a family unit.

A third group, named 'spatiopersistent', appear to cluster to their own geographic areas, but not associated with families.

With much current interest in maintaining or manipulating the microbiome for health, the research team hopes their holistic exploration of the evolution of different persistence in gut microbes will lead to better, more well-informed clinical strategies.

For example, one-off interventions like Faecal Microbiota Transplantation (FMT) may be suitable to introduce or even replace tenacious bacteria but not bacteria that rely on reinfection. These might benefit more from probiotic-based therapies or dietary changes that, over time, alter the gut environment to favour their colonisation and persistence.
The new insights into the wide-ranging and potentially permanent damage antibiotics can do to the microbiome could also point to new strategies to mitigate these differing effects.

"Our study gave us a much better idea of which gut bacteria are closely associated with their host, and which are more prone to switch between hosts. This is important information to inform pro-prebiotics and most medical applications targeting the human gut microbiome," added Dr Hildebrand.

The structure of a biomolecule can reveal much about its functioning and interaction with the surrounding environment. The double-helical structure of DNA and its implications for the processes of transmission of genetic information form an obvious example. In a new study by SISSA - Scuola Internazionale Superiore di Studi Avanzati, published in Nucleic Acids Research, experimental data were combined with computer simulations of molecular dynamics to examine the conformation of an RNA fragment involved in protein synthesis and its dependence on the salts present in the solution. The research has led to a new method for high-resolution definition of the structures of biomolecules in their physiological environments.

"X-ray crystallography, as used to discover the double-helical conformation of DNA, remains one of the most common techniques for studying biomolecule structures", explains SISSA physicist Giovanni Bussi. "This technique allows us to reconstruct the image of the molecule in solid state crystalline form. However, this yields a static view of the structure that may not correspond to that assumed in the aqueous natural environment in which biomolecules are normally found."

This is why researchers began to use the small-angle X-ray scattering (SAXS) technique in the last decade to study RNA molecules, which can have highly dynamic structures. This method can be used directly in aqueous solutions that reproduce the physiological environment. Furthermore, the composition of the solutions can be modified to study how the molecules adapt to different conditions. Unfortunately, however, SAXS has limited resolution, in the order of a nanometer. Giovanni Bussi and Mattia Bernetti, a research fellow at SISSA, therefore decided to enhance SAXS via a 'computational microscope', combining it with molecular dynamics simulations that allow computerised reconstruction of molecular structures at the atomic level.

"We studied a fragment of ribosomal RNA involved in protein synthesis," explain the researchers. "We used SAXS data, derived from aqueous solutions containing different mixtures of salts, that was provided by Kathleen B. Hall of the Washington University School of Medicine in St Louis, and combined them with molecular dynamics simulations. By this means we discovered the existence of two distinct conformations: one more compact and functional to the protein synthesis process, the other more extended, confirming the dynamic nature of RNA. In particular, we noticed how the prevalence of one structure over the other varies with the salts dissolved in solution, further underlining the importance of studying these molecules in an environment as similar as possible to that of the cell."

Bernetti and Bussi conclude that the results of the study, published in Nucleic Acids Research, have significance beyond the specific case and indicate an innovative method offering two advantages: "In this work, we combined molecular dynamics simulations and SAXS experimental data to obtain high-resolution structures of RNA biomolecules. This is a useful approach in two senses: on one hand, it allows detail to be added to SAXS experimental data, which in fact give a very approximate view; on the other hand, it allows results of molecular dynamics to be corrected if the models used in the simulations are insufficiently accurate."

Coronavirus disruption to weddings has highlighted the complexity and antiquity of marriage law and reinforced the need for reform, a new study shows.

During the pandemic the ease and speed with which couples were able to marry has depended on their chosen route into marriage - religious or civil - experts have found.

Rules to prevent the spread of the pandemic attempted to strike a balance between getting married as a legal event and a wedding as a social event, and this has failed to please anyone, according to the research.

As lockdown loomed, couples marrying in the Anglican church were able to apply for a common or special licence rather than waiting to have their banns read. During the first lockdown alone, the Church of England's Faculty Office issued 104 special licences in order to enable the marriages of those who were terminally ill, or who had a close family member who was terminally ill, whereas it would normally issue only 40 for this purpose in a whole year. By contrast, the Registrar-General - who is responsible for civil weddings - issued fewer licences than usual for this purpose.

The research was carried out by Professor Rebecca Probert, from the University of Exeter, and Dr Stephanie Pywell, from The Open University. They surveyed 1,449 people whose plans to marry in England and Wales had been affected by COVID-19 during the first lockdown in summer 2020.

Of these, 625 had been unable to marry on their intended wedding date as it fell during the period of lockdown. Just 10 managed to bring the date forward and marry before the start of lockdown, while 615 had to postpone their plans. A further 793 couples had been planning to marry between the end of lockdown and the end of 2020 and had had to change their plans in some way.

The remainder had either been prompted to marry in England and Wales on account of COVID-19, or had decided to postpone their wedding indefinitely, were no longer planning to marry, or were unable to marry.

Dr Pywell said: "The limited number of venues in which couples can marry made it impossible for most couples to marry during the pandemic, although they were able to do so in some other countries. We argue that the laws governing marriage in England and Wales must be fit for purpose in the twenty-first century, so that couples can marry with relative ease if there is a similar nationwide crisis in the future."

The survey asked couples whether they would have wanted to marry in a virtual ceremony. One in 11 said they would have considered a wedding via video-link had this been available. Couples were also asked if they would have been willing to marry in a socially-distanced ceremony with the minimum number of persons present required by law for a valid marriage. One in nine would have been happy to do so outdoors, and one in seven would have considered doing so indoors if different households were separated by screens. Overall, one in five would have considered at least one of these options.

The researchers say all these options deserve serious consideration, and that legislation should be amended to make this option available during any future emergency.

Dr Pywell said: "For those couples who simply wanted to be married, having to wait until weddings were permitted to go ahead with 30 guests was particularly frustrating, especially since pubs, restaurants, and gyms had been able to open earlier. Allowing marriages to go ahead earlier, with the minimum number of persons required by law, would have mitigated some of their anger and upset."

Professor Probert said: "Reform is clearly needed, but any such reform has to be holistic rather than piecemeal, and we hope that our findings will strengthen the case for making weddings law simpler and more flexible for the future. The fact that for much of 2020 and for 2021 so far couples were either unable to marry, or unsure as to whether their planned wedding would go ahead, led many to reflect on just how important it was to them. A wedding should be available to couples at the best and worst of times."

LOUISVILLE, Ky. - A clinical trial conducted at the University of Louisville has shown for the first time that heart failure treatments using cells derived from the patient's own bone marrow and heart resulted in improved quality of life and reduced major adverse cardiac events for patients after one year.

"This is a very important advance in the field of cell therapy and in the management of heart failure. It suggests that a treatment, given only once, can produce long-term beneficial effects on the quality of life and prognosis of these patients," said Roberto Bolli, M.D., director of the UofL Institute of Molecular Cardiology, who led the study at UofL. "The results pave the way for a larger, Phase 3 trial of cell therapy in heart failure."

UofL led enrollment among seven institutions participating in CONCERT-HF, a Phase 2 clinical trial testing the safety, feasibility and efficacy of two types of adult cells, used alone and in combination, in patients with heart failure.

CONCERT-HF evaluated the use of two types of cells - autologous mesenchymal stromal cells (MSCs) and c-kit positive cardiac cells (CPCs) - alone or in combination, in patients with heart failure caused by chronic ischemic cardiomyopathy, a decrease in heart pumping effectiveness due to heart attacks and a lack of blood getting to the heart. Autologous MSCs are derived from the patient's bone marrow and CPCs are from the patient's heart tissue. Both are known as "autologous" cells because they come from the same patient in whom they are returned for the treatment.

In the study, patients treated with CPC cells alone had a significant reduction in major adverse cardiac events, particularly hospitalization. Patients treated with MSC cells alone and with a combination of both types of cells experienced significantly improved quality of life compared with patients who received no treatment. Quality of life was assessed using patient responses to the Minnesota Living with Heart Failure Questionnaire, which gauges the degree to which physical, emotional and socioeconomic effects of heart failure adversely affect the patient's life and the extent to which they prevented the patient from living as they wanted to live.

"The results of this trial show for the first time that cell therapy reduces hospitalization for heart failure and improves clinical outcome, providing a cogent rationale for undertaking a pivotal Phase 3 trial" that could be the next step on the pathway to FDA approval, Bolli said.

The results of the CCTRN CONCERT-HF Trial were published in the European Journal of Heart Failure. The Phase 2, randomized, placebo-controlled trial, funded by NIH National Heart, Lung and Blood Institute, was conducted by the Cardiovascular Cell Therapy Research Network (CCTRN), a network of clinical trial researchers involved in cell therapy for heart disease that includes UofL. UofL led enrollment in the study, accounting for 25% of the 125 trial participants.

Bolli's expertise and long career in successful cardiac research led to the establishment of the CCTRN center at UofL in 2011. This consortium of leading cardiovascular research organizations includes Stanford University, the University of Miami, Indiana University, the Texas Heart Institute, the University of Florida and the Minneapolis Heart Institute Foundation in addition to UofL. The School of Public Health at the University of Texas Health Science Center at Houston serves as the data coordinating center.

Bolli is a pioneer in research using adult stem cells for cardiac disease. Over the past two decades, he has shown that CPCs are beneficial in many preclinical models of heart failure, thus paving the way for the CONCERT-HF trial. He also led the recent CCTRN SENECA Trial - the first study to show safety and potential efficacy of cell therapy in cancer survivors with heart failure caused by anticancer therapy.

Does evolution explain why we can't resist a salty chip? Researchers at NC State University found that differences between the elemental composition of foods and the elemental needs of animals can explain the development of pleasing tastes like salty, umami and sweet.

Taste tells us a lot about foods before they are swallowed and digested, and some tastes correspond with the elemental composition of foods. For example, an aged steak lights up the umami taste receptors, because it has a high concentration of the element nitrogen, which occurs in amino acid molecules. Nitrogen is essential for survival, but often occurs in low concentrations relative to the demand by animals. Likewise, sodium is limited in many foods in nature - think of life before supermarkets. So if you need sodium to survive - and all animals do - you are more likely to have adapted a taste for, and seek out, salty foods.

"Nutritional imbalances, even at the elemental level, can limit the growth and metabolism of animals," says Lee Demi, a co-author of the study and postdoctoral researcher in NC State's Department of Applied Ecology. "We posited that animals should have evolved the ability to taste, and enjoy, certain elements and nutrients that are most likely to be limiting for growth, due to their low concentrations in typical foods."

To investigate this hypothesis, Demi and colleagues compared the body elemental composition of three animal groups (mammals, fish, and insects) to the elemental composition of plants, the base of most food webs. They predicted that animals who eat foods composed of particular elements that are rare or unpredictable are more likely to have taste receptors that reward them for finding those same elements.

"Because animals have very limited ability to change their elemental composition, the old adage that 'You are what you eat' doesn't really apply," says Demi. "Rather, animals are rewarded with pleasing tastes for 'eating what they are', at least from an elemental composition perspective, which helps reduce the prospect of dietary nutrient limitation."

This is particularly important for omnivorous and herbivorous animals that eat a variety of different foods which vary in nutritional quality. Within this framework, taste becomes a tool that helps consumers prioritize which foods they should search for and consume, so they don't waste time on foods that have less of these necessary elements. Equally, taste can also inform consumers to avoid foods that contain too much of an element they need. This is why eating a handful of chips is more attractive than eating a handful of table salt.

Where you are on the food chain can predict the complexity of your taste systems. Some top predators, like orcas, have lost many taste receptors over evolutionary time. This study suggests that predators are less likely to experience strong elemental imbalances in their diet than herbivores or omnivores. Because their prey already match their elemental needs, predators experience less selective pressure to maintain elaborate taste systems. However, these top predators have kept their taste for salt, which can be harmful if overconsumed.

"Affinity for certain foods must have strong evolutionary drivers, because without taste, animals would be forced to overconsume everything in the hopes of hitting the magic ratio of elements needed for growth and development," says Benjamin Reading, co-author of the study and a professor in NC State's Department of Applied Ecology. "They would need to eat way too much and end up excreting huge quantities of those things they need less of, which is not efficient."

The research team also found strong evidence of convergent taste evolution in mammals, fish, and insects. Each group, although far apart on the phylogenetic tree, all have adapted tastes that prioritize the same infrequent elements, including sodium, nitrogen and phosphorus.

"Phosphorus is particularly intriguing because this recently discovered taste is most strongly linked to phosphate, which is also the primary form of phosphorus in many nucleic acids, ATP, phospholipids, etc.," says Brad Taylor, a co-author of the study and professor in NC State's Department of Applied Ecology. "Phosphate is the most readily available form of phosphorus for uptake by plants, and often the primary growth limiting element in organisms and ecosystems. So, links between the elemental form, taste receptors, organismal needs, and ecosystem are really direct."

While the neurobiological process of taste has been extensively researched, this study is the first to explore taste as an evolutionary tool for optimal foraging. The researchers suggest that this may open a new area of thought on how taste can indicate how animals impact their environments through foraging, nutrient-cycling, and other core principles of ecology.

Syracuse, N.Y. - A study of nearly 550 adults with intellectual and developmental disabilities receiving residential services in New York City found that age, larger residential settings, Down syndrome and chronic kidney disease were the most common risk factors for COVID-19 diagnosis, and heart disease was most associated with COVID-19 deaths.

The study, "Risk Factors Associated With COVID-19 Outcomes Among People With Intellectual and Developmental Disabilities Receiving Residential Services," was published June 8 by JAMA Network Open and provided the first evidence of the risk factors leading to COVID-19 diagnosis and death among people with IDD who receive residential services.

The study's findings suggest that the risk factors for COVID-19 diagnosis and mortality for people with IDD who receive residential services are similar to the general population. It also provided more evidence of increased risk for severe COVID-19 outcomes for people with Down syndrome.

"The results from this study reinforce early findings from the U.K. of increased risk for people with Down syndrome during the pandemic," said researcher Scott Landes. "While it will take time for scientists to fully discern the reasons for this increased risk, it is imperative that people with Down syndrome, their families, care providers and medical providers are fully aware of this trend and take all necessary precautions during this time."

The researchers also found that, similar to the nursing home population, an increased number of residents with IDD living in a group home was associated with more severe COVID-19 outcomes.

"We are to a place in the U.S. where access to COVID-19 vaccines is universal," Landes said. "While this will help alleviate some of the spread of the virus, it is necessary to continue monitoring and testing, especially in congregate settings such as group homes.

"However, unlike nursing homes, group homes for people with IDD have not always been afforded the resources necessary to perform routine COVID-19 testing for residents and staff," Landes added. "This is unacceptable. The results from this study indicate that all U.S. states should ensure that group homes are provided the same level of protection as nursing homes or other congregate care settings."

The research team for the study includes Landes, an associate professor of sociology and a faculty associate for the Aging Studies Institute at Syracuse University's Maxwell School of Citizenship and Public Affairs; Dr. Margaret Turk, Distinguished Service Professor of Physical Medicine and Rehabilitation at SUNY Upstate Medical Center in Syracuse, N.Y.; Marco Damiani, Chief Executive Officer, AHRC New York City; Philip Proctor, Enterprise Technology Strategy, AHRC New York City; and Sarah Baier, Licensed Clinical Social Worker, AHRC New York City.

The researchers set out by asking which individual and residential characteristics were associated with COVID-19 outcomes for people with IDD who receive residential services. They tracked COVID-19 outcomes for 543 people with IDD who were receiving support services and residential services from AHRC New York City in the city's five boroughs from March 1 through Oct. 1, 2020.

The researchers found that, like the general population, people with IDD who were older and/or had pre-existing health conditions were more likely to be diagnosed with, and die from, COVID-19. Chronic kidney disease and COPD were associated with an increased risk of being diagnosed; heart disease and cancer were associated with increased risk of death.

The researchers say that all of these risk factors point to the long-term need for to provide sufficient funding for IDD services.

"If we want to ensure the best health and quality of life outcomes for people with IDD, it's imperative that states do not cut funding for IDD services," Landes said. "In fact, the pandemic has underscored the critical need to increase our commitment to IDD services, including guaranteeing public health prioritization for people with IDD, providing medical care staff training on how to provide quality care for people with IDD, and increasing the pay for care staff."

A discovery from researchers at the University of Illinois Chicago may lead to new treatments for individuals who suffer from alcohol use disorder and depression.

The study, "Transcriptomics identifies STAT3 as a key regulator of hippocampal gene expression and anhedonia during withdrawal from chronic alcohol exposure," is published in the journal Translational Psychiatry by researchers at UIC's Center for Alcohol Research in Epigenetics.

"During withdrawal from long-term alcohol use, people often suffer from depression, which may cause them to start drinking again as a way to self-medicate. If we can treat that aspect, we hope we can prevent people from relapsing," said Amy Lasek, UIC associate professor of psychiatry and anatomy and cell biology at the College of Medicine, and an author of the study.

Withdrawal from chronic alcohol drinking can often result in depression. For this study, researchers removed postmortem hippocampus samples of rats in alcohol withdrawal. The hippocampus is a brain region that plays a role in depression and cognitive function. Researchers conducted RNA sequencing of all the RNA transcripts in the hippocampus and looked for those that were changed during withdrawal from alcohol.

One of the RNA transcripts that was changed makes a protein called STAT3. STAT3 is a transcription factor that controls the expression of many different genes, including immune response genes. Notably, several known STAT3-regulated genes were also increased in the hippocampus during withdrawal from alcohol, indicating that STAT3 might be a "master regulator" of several genes in the hippocampus during withdrawal.

The rats were treated during withdrawal with a compound that blocks STAT3 activity. The rats' withdrawal-induced anhedonia, or inability to feel pleasure, was alleviated.

Additionally, researchers looked at the same genes in human postmortem hippocampus samples of individuals who had a medical diagnosis of alcohol use disorder, alcoholism. They found that STAT3 and its target genes were elevated in the postmortem hippocampus of human subjects who died without alcohol in their systems -- in withdrawal or abstinent from alcohol -- when compared to samples from control subjects who did not have alcohol use disorder. These results were strikingly similar to the results found in the rat study.

"The human and rat studies are similar, which might mean that our rat results can potentially be applied to humans. We haven't done any treatments of people with alcohol use disorder, but we can see from the rat data that if we block STAT3 during withdrawal we can alleviate depression," Lasek said.

Some genes regulated by STAT3 are involved in the innate immune response in the brain. There is a known connection between hyperactive immune response and major depressive disorder, Lasek said.

"We know that chronic alcohol use can induce an immune response in the brain. By inhibiting STAT3, we think that we are dampening that hyperactive immune response by blocking the ability of STAT3 to increase the expression of these immune-response genes during withdrawal, Lasek said.

Lasek said inflammation in the brain is currently a hot research topic and further research may determine if dampening the brain's inflammatory response could treat psychiatric disorders.

Antidepressants currently available are not effective in reducing alcohol drinking. And other drugs available to treat alcohol use disorder are not universally effective. Further study for a better understanding of how STAT3 works could hopefully lead to more effective interventions for alcohol use disorder and related depression, Lasek said.

The spin of the Milky Way's galactic bar, which is made up of billions of clustered stars, has slowed by about a quarter since its formation, according to a new study by researchers at University College London (UCL) and the University of Oxford.

For 30 years, astrophysicists have predicted such a slowdown, but this is the first time it has been measured.

The researchers say it gives a new type of insight into the nature of dark matter, which acts like a counterweight slowing the spin.

In the study, published in the Monthly Notices of the Royal Astronomical Society, researchers analysed Gaia space telescope observations of a large group of stars, the Hercules stream, which are in resonance with the bar - that is, they revolve around the galaxy at the same rate as the bar's spin.

These stars are gravitationally trapped by the spinning bar. The same phenomenon occurs with Jupiter's Trojan and Greek asteroids, which orbit Jupiter's Lagrange points (ahead and behind Jupiter). If the bar's spin slows down, these stars would be expected to move further out in the galaxy, keeping their orbital period matched to that of the bar's spin.

The researchers found that the stars in the stream carry a chemical fingerprint - they are richer in heavier elements (called metals in astronomy), proving that they have travelled away from the galactic centre, where stars and star-forming gas are about 10 times as rich in metals compared to the outer galaxy.

Using this data, the team inferred that the bar - made up of billions of stars and trillions of solar masses - had slowed down its spin by at least 24% since it first formed.

Co-author Dr Ralph Schoenrich (UCL Physics & Astronomy) said: "Astrophysicists have long suspected that the spinning bar at the centre of our galaxy is slowing down, but we have found the first evidence of this happening.

"The counterweight slowing this spin must be dark matter. Until now, we have only been able to infer dark matter by mapping the gravitational potential of galaxies and subtracting the contribution from visible matter.

"Our research provides a new type of measurement of dark matter - not of its gravitational energy, but of its inertial mass (the dynamical response), which slows the bar's spin."

Co-author and PhD student Rimpei Chiba, of the University of Oxford, said: "Our finding offers a fascinating perspective for constraining the nature of dark matter, as different models will change this inertial pull on the galactic bar.

"Our finding also poses a major problem for alternative gravity theories - as they lack dark matter in the halo, they predict no, or significantly too little slowing of the bar."

The Milky Way, like other galaxies, is thought to be embedded in a 'halo' of dark matter that extends well beyond its visible edge.

Dark matter is invisible and its nature is unknown, but its existence is inferred from galaxies behaving as if they were shrouded in significantly more mass than we can see. There is thought to be about five times as much dark matter in the Universe as ordinary, visible matter.

Alternative gravity theories such as modified Newtonian dynamics reject the idea of dark matter, instead seeking to explain discrepancies by tweaking Einstein's theory of general relativity.

The Milky Way is a barred spiral galaxy, with a thick bar of stars in the middle and spiral arms extending through the disc outside the bar. The bar rotates in the same direction as the galaxy.