Culture

USC researchers have achieved a better way to identify elusive DNA variants responsible for genetic changes affecting cell functions and diseases.

Using computational biology tools, scientists at the university's Dornsife College of Letters, Arts and Sciences studied "variable-number tandem repeats" (VNTR) in DNA. VNTRs are stretches of DNA made of a short pattern of nucleotides repeated over and over, like a plaid pattern shirt. Though they comprise but 3% of the human genome, the repetitive DNA governs how some genes are encoded and levels of proteins are produced in a cell, and account for most of the structural variation.

Current methods do not accurately detect the variations in genes in some repetitive sequences. The new method by the USC scientists can detect variants among different populations of people and how it they affect gene expression, which helps to discover links between VNTR variation and traits or disease.

"This type of repetitive DNA has been called 'dark matter' of the human genome because it has been difficult to sequence and analyze how it varies," said Mark Chaisson, assistant professor of quantitative and computational biology and corresponding author of the study. "We showed that variation in dark matter can have a substantial effect on cellular processes, so future studies may use this approach to understand the genetic basis of disease and ways to improve our health."

The study was published in Nature Communications on July 12

The study also says:

Variants in genetic codes are responsible for Huntington's disease, Lou Gehrig's disease (ALS), schizophrenia, diabetes and attention-deficit disorder, as previous research has shown.

While other tools, based on algorithms, have been developed to detect genetic variants, they provide incomplete information, especially for the VNTRs.

The new software tool the USC scientists developed derives from a repeat-pangenome graph, a data structure that encodes population diversity and repetitions of VNTR locations on a chromosome to identify more gene sequences with better accuracy.

Scientists have produced the first fine-detail molecular blueprints of a bacterial enzyme known as Lit, which is suspected to play a "stealthy" role in the progression of infection by reducing the immune response.

Blueprints such as these allow drug designers to uncover potential weaknesses in bacterial arsenals as they seek to develop new therapeutics that may help us win the war against antibiotic resistance.

The study, led by scientists from the School of Biochemistry and Immunology and the Trinity Biomedical Sciences Institute (TBSI) at Trinity College Dublin, has just been published by leading international journal Nature Communications.

Lipoproteins and their role in bacterial infection

Lipoproteins serve diverse functions in the bacterial cell. Some are essential for survival while some play an important role by engaging with the innate immune response of the host.

The growing list of enzymes responsible for building lipoproteins includes the recently discovered Lit (lipoprotein intramolecular transacylase), which creates a specific lipoprotein that "cools the immune response" - raising the likelihood that Lit enables the bacteria to gain a foothold in the host by stealth.

With a view to understanding how Lit functions at the molecular level, the Trinity-led team has just produced Lit's all-important, high-resolution crystal structure from Bacillus cereus - a common bacteria found in soil and food.

Combined with other analytical techniques, molecular dynamics simulations and quantum mechanics approaches, the team now has a detailed understanding of how it functions.

Professor Martin Caffrey, Fellow Emeritus (Trinity and TBSI), is the senior author of the research. Underlining its significance and potential societal impact, he said:

"We believe Lit is very likely a virulence factor, negatively impacting host immune response to infection. As such, it could well turn out to be an important target for the development of critically needed antibiotics against which resistance is much less likely to evolve. And it is no exaggeration to say that antibiotic resistance poses a genuine, growing threat to our society.

"With a high-resolution crystal structure and a strong foundation for understanding how it functions in bacterial cells, we are in a similar position to where we were four years ago when we published similar work concerning a related lipoprotein processing enzyme, known as lipoprotein signal peptidase II (or LspA). LspA is currently under intense scrutiny as an antibiotic target by several research groups - including ours in TBSI - and by a number of pharmaceutical companies."

Oncotarget published "A novel E2F1-regulated lncRNA, LAPAS1, is required for S phase progression and cell proliferation" which reported that long non-coding RNAs are major regulators of many cellular processes, including cell cycle progression and cell proliferation.

Inhibition of LAPAS1 expression increases the percentage of S phase cells, and its silencing in synchronized cells delays their progression through S phase.

In agreement with its suggested role in cell cycle progression, prolonged inhibition of LAPAS1 attenuates proliferation of human cancer cells.

Importantly, knockdown of SPNS2 rescues the effect of LAPAS1 silencing on cell cycle and cell proliferation.

Summarily, they identify LAPAS1 as a novel E2F-regulated lncRNA that has a potential role in human cancer and regulates cell-cycle progression and cell proliferation, at least in part, via regulation of SPNS2.

They identify LAPAS1 as a novel E2F-regulated lncRNA that has a potential role in human cancer and regulates cell-cycle progression and cell proliferation

Dr. Doron Ginsberg from The Bar-Ilan University said, "The human genome expresses many thousands of long non-coding RNAs (lncRNAs), which are transcripts longer than 200 bases that lack a significant open reading frame."

Increasing evidence indicates that lncRNAs are key regulators of important biological processes including cell cycle progression, cell proliferation and apoptosis.

Specifically, some lncRNAs function in regulation of cell cycle progression via modulation of critical cell cycle players, such as the cyclins, CDKs, CDK inhibitors, pRB, and p53.

Transcription factors that regulate mRNA transcription were shown to also regulate lncRNAs expression.

Inhibition of LAPAS1 expression delays progression of cells through S phase and inhibits proliferation of human cancer cells.

Thus, the authors identify LAPAS1 as a new E2F-regulated lncRNA that has a potential role in human cancer and regulates cell proliferation and cell-cycle progression, at least in part, via regulation of SPNS2.

The Ginsberg Research Team concluded in their Oncotarget Research Output, "this study reports the identification of a novel lncRNA that affects cell cycle progression and cell proliferation and may affect cancer progression. Its initial characterization shows that it is transcriptionally regulated by E2F and it exerts its activity, at least in part, by regulating SPNS2."

Imagine sitting out in the sun, reading a digital screen as thin as paper, but seeing the same image quality as if you were indoors. Thanks to research from Chalmers University of Technology, Sweden, it could soon be a reality. A new type of reflective screen - sometimes described as 'electronic paper' - offers optimal colour display, while using ambient light to keep energy consumption to a minimum.

Traditional digital screens use a backlight to illuminate the text or images displayed upon them. This is fine indoors, but we've all experienced the difficulties of viewing such screens in bright sunshine. Reflective screens, however, attempt to use the ambient light, mimicking the way our eyes respond to natural paper.

"For reflective screens to compete with the energy-intensive digital screens that we use today, images and colours must be reproduced with the same high quality. That will be the real breakthrough. Our research now shows how the technology can be optimised, making it attractive for commercial use," says Marika Gugole, Doctoral Student at the Department of Chemistry and Chemical Engineering at Chalmers University of Technology.

The researchers had already previously succeeded in developing an ultra-thin, flexible material that reproduces all the colours an LED screen can display, while requiring only a tenth of the energy that a standard tablet consumes.

But in the earlier design the colours on the reflective screen did not display with optimal quality. Now the new study, published in the journal Nano Letters takes the material one step further. Using a previously researched, porous and nanostructured material, containing tungsten trioxide, gold and platinum, they tried a new tactic - inverting the design in such a way as to allow the colours to appear much more accurately on the screen.

Inverting the design for top quality colour

The inversion of the design represents a great step forward. They placed the component which makes the material electrically conductive underneath the pixelated nanostructure that reproduces the colours - instead of above it, as was previously the case. This new design means you look directly at the pixelated surface, therefore seeing the colours much more clearly.

In addition to the minimal energy consumption, reflective screens have other advantages. For example, they are much less tiring for the eyes compared to looking at a regular screen.

To make these reflective screens, certain rare metals are required - such as the gold and platinum - but because the final product is so thin, the amounts needed are very small. The researchers have high hopes that eventually, it will be possible to significantly reduce the quantities needed for production.

"Our main goal when developing these reflective screens, or 'electronic paper' as it is sometimes termed, is to find sustainable, energy-saving solutions. And in this case, energy consumption is almost zero because we simply use the ambient light of the surroundings," explains research leader Andreas Dahlin, Professor at the Department of Chemistry and Chemical Engineering at Chalmers.

Flexible with a wide range of uses

Reflective screens are already available in some tablets today, but they only display the colours black and white well, which limits their use.

"A large industrial player with the right technical competence could, in principle, start developing a product with the new technology within a couple of months," says Andreas Dahlin, who envisions a number of further applications. In addition to smart phones and tablets, it could also be useful for outdoor advertising, offering energy and resource savings compared with both printed posters or moving digital screens.

More about the research

Research on the nano-thin electronic paper has been ongoing for several years at Chalmers, and the work has been rewarded with both international attention and major strategic research grants.

The technology in Chalmers researchers' reflective screens is based on the material's ability to regulate how light is absorbed and reflected. In the current study, tungsten trioxide is the core material, but in previous studies, researchers also used polymers. The material that covers the surface conducts electronic signals throughout the screen and can be patterned to create high-resolution images.

The scientific article Electrochromic Inorganic Nanostructures with High Chromaticity and Superior Brightness has been published in Nano Letters and is written by Marika Gugole, Oliver Olsson, Stefano Rossi, Magnus P. Jonsson and Andreas Dahlin. The researchers are active at Chalmers University of Technology and Linköping University.

Researchers have identified a specialized protein that appears to help prevent tumor cells from entering the bloodstream and spreading to other parts of the body.

"We have discovered that this protein, TRPM7, senses the pressure of fluid flowing in the circulation and stops the cells from spreading through the vascular system," said Kaustav Bera, a Johns Hopkins University PhD candidate in chemical and biomolecular engineering and a lead author of the study, which was done with colleagues at the University of Alberta and Universitat Pompeu Fabra.

"We found that metastatic tumor cells have markedly reduced levels of this sensor protein, and that is why they efficiently enter into the circulation rather than turning away from fluid flow," said Bera.

The findings, published in Science Advances, help shed light on a little-understood part of metastasis called intravasation, when cancer cells that have separated from a primary tumor enter the circulation in order to travel to other parts of the body and establish colonies.

The researchers further show that artificially increasing the expression of TRPM7 in tumor cells may help stop intravasation--and ultimately metastasis--in its tracks.

TRPM7 has long been known to regulate calcium in cells, but this new insight into its role in cell migration is exciting, according to the researchers. "The process is akin to what happens when you touch a hot kettle, feel it's hot, and remove your hand," said senior study author Konstantinos Konstantopoulos, a professor of chemical and biomolecular engineering and member of the Johns Hopkins Kimmel Cancer Center.

The protein senses the flow of the fluid in the circulatory system and instructs the cell to reverse direction, thereby inhibiting intravasation, he said.

Typically, the cells in the human body--for example, muscle cells, fat cells, and epithelial cells--stay contained in their respective regions. The major exception are blood cells, which patrol the body fighting pathogens. And then there are cancer cells, which have mutations that allow them to travel and spread.

It is at this point of spreading that cancer becomes much more dangerous. "Many people will be diagnosed with a primary tumor, but as long as this tumor is contained, a surgical procedure can save the person," said Christopher Yankaskas, a lead author and former member of Konstantopoulos's lab who is now a scientist at Thermo Fisher Scientific.

For their initial experiment, the researchers observed healthy fibroblast cells moving through microchannels arranged perpendicularly in a ladder-like configuration in which the fluid could be controlled. When these cells encountered channels where fluid was moving, they reversed their direction in response to the shear stress exerted from the flow. However, when the cells encountered channels where fluid wasn't moving, they proceeded into them.

The researchers then used a process known as RNA interference to block the cells from expressing TRPM7. What they observed was striking, they say. When this sensor protein was disabled, the healthy cells no longer reversed direction in response to the flow. "Imagine you then pick up the kettle with an oven mitt, which reduces your sensitivity to the heat," said Konstantopoulos.

In subsequent experiments the researchers found that normal cells had higher levels of TRPM7 than sarcoma cells (a type of cancerous tumor cells), and that artificially expressing the protein in the tumor cells increased their sensitivity to the fluid flow.

When the normal cells reverse their direction of migration, they avoid exposure to shear stress, but this is not the case for tumor cells, explained Konstantopoulos. "The tumor cells are less sensitive, and that's why they continue entering the circulatory system."

"The goal was to see if we could take these cancerous cells and make them behave like normal cells," said Bera. "And we managed to do that."

A separate analysis of human patient data showed that those with osteosarcoma, breast, gastric, and liver cancer who expressed high levels of TRPM7 were more likely to live longer than those with lower levels of the protein.

More research is needed, but the team hopes that the findings could eventually lead to new cancer therapies using CRISPR activation, an exciting emerging DNA editing tool.

"We'll need further developments before we can take this to the clinical setting, but we believe we provide, for the first time, a definitive picture of the role of TRPM7 in a crucial step of tumor metastasis," said Konstantopoulos.

Athletes may have more than twice the risk of irregular heart rhythm

Younger athletes are at greater risk of atrial fibrillation than older athletes, say researchers

Athletes appear to be almost two and half times more likely than non-athletes to experience irregular heart rhythms (atrial fibrillation), suggests new research published in the British Journal of Sports Medicine.

In addition, those athletes involved in mixed sports such as football, rugby or netball appear to have the highest risk when compared with athletes taking part in endurance sports such as Nordic skiing, orienteering or rowing.

Previous studies have shown that physical activity can improve cardiovascular health and is associated with reduced illness and deaths, but they have suggested there is a threshold beyond which exposure to increasing levels of exercise is linked to heart issues including atrial fibrillation - a condition that can raise the risk of stroke, heart failure and other heart-related problems.

UK researchers led by Canterbury Christ Church University in Canterbury set out to review existing studies on the subject and explore what impact the type of sport in which athletes took part had on their risk of atrial fibrillation to reach a more conclusive picture of overall prevalence among athletes.

They reviewed and analysed 13 suitable studies that were published between 1990 and December 2020 which had looked at athletes who took part in sports including cycling, running, swimming, Nordic skiing, orienteering, rowing, football, rugby, and netball.

The 13 studies included data on 70,478 participants, collectively, which included 63,662 controls and 6,816 athletes.

The authors found that the risk of atrial fibrillation was 2.46 times higher among athletes than non-athletes.

When the authors split the studies into those that involved participants with and without cardiovascular disease risk factors (such as type 2 diabetes and high blood pressure), they found there was no significant difference in the relative risk of atrial fibrillation in athletes and non-athletes with these risk factors.

However, in athletes and non-athletes without cardiovascular disease risk factors athletes had a significantly higher relative risk (3.7 times higher) of atrial fibrillation than non-athletes.

In addition, younger athletes (aged under 55) had a much higher risk (3.6 times) of atrial fibrillation than older athletes (aged 55 and older) who were 76% more likely to have the condition than non-athletes.

Analysis also showed that athletes taking part in mixed sports rather than endurance sports had a higher risk of atrial fibrillation.

Their study had some limitations such as the fact that it analysed research with different approaches such as case control and cohort design, and there was limited data on female athletes, making it difficult to look at the relative risk of atrial fibrillation by gender.

Nevertheless, the researchers conclude: "Athletes have a significantly greater likelihood of developing atrial fibrillation compared with non-athlete controls.

"Younger aged athletes have a greater relative risk of atrial fibrillation compared with older athletes; however, exercise dose parameters, including training and competition history, as well as potential gender differences for the risk of atrial fibrillation requires future research."

BOSTON - By implementing a long-term, prospective approach to the development of celiac disease, a collaborative group of researchers has identified substantial microbial changes in the intestines of at-risk infants before disease onset. Using advanced genomic sequencing techniques, MassGeneral Hospital for Children (MGHfC) researchers, along with colleagues from institutions in Italy and the University of Maryland, College Park, uncovered distinct preclinical alterations in several species, pathways and metabolites in children who developed celiac disease compared to at-risk children who did not develop celiac disease.

As part of the MGHfC Celiac Disease, Genomic, Microbiome and Metabolomic (CDGEMM) Study, researchers identified changes in the gut microbiomes (collection of microorganisms) and metabolomes (molecular components of cells and tissues) of infants that occurred months before celiac disease onset. Changes include an "increased abundance of pro-inflammatory species and decreased abundances of protective and anti-inflammatory species at various time points preceding the onset of the disease," according to the group's article published in the Proceedings of the National Academy of Sciences.

"In this proof-of-concept study, we compared the gut microbiome of 10 infants who went on to develop celiac disease to the gut microbiome of 10 infants who did not develop the autoimmune condition," says Maureen Leonard, MD, lead author and clinical director of the Center for Celiac Research and Treatment at MGHfC. "We found significant changes in the intestinal microbes, pathways and metabolites as early as 18 months before disease onset. This was much earlier than we expected," adds Leonard.

In CDGEMM, researchers in Italy, Spain and the U.S. are studying 500 genetically at-risk infants from birth through age ten, allowing them to track changes in gut microbiota before celiac disease develops. CDGEMM researchers have been collecting extensive blood and fecal samples and voluminous environmental data on each participant since 2014. In this study, researchers used metagenomic analysis that enabled them to link microbial composition with function, highlighting changes in pathways associated with either increased inflammatory processes or reduced inflammation. "This study demonstrates the power of next-generation sequencing coupled with bioinformatics to detect these important changes," says co-author Rita Colwell, PhD, from the Institute of Advanced Computer Studies, University of Maryland, College Park.

"We needed a longitudinal, birth-cohort study of these at-risk infants to move microbiome research from associative observations to more causative studies," says senior author Alessio Fasano, MD, director of the Center for Celiac Research and Treatment at MGHfC. "This approach will help us to develop novel strategies for the diagnosis and treatment of a variety of conditions in which the microbiome could play a pathogenic role," adds Fasano.

He suggests that these findings, if confirmed by larger datasets, may represent specific therapeutic targets for disease interception and possible prevention of celiac disease onset through microbiome manipulation during the preclinical phase. "With these findings, we anticipate that we will be able to distinguish who will remain healthy and who will develop celiac disease months before the onset of the disease," adds Fasano.

Better treatments of HER2-positive breast cancer are closer at hand, thanks to new research by a team led by Université de Montréal professor Jean-François Côté at the cytoskeleton organization and cell-migration research unit of the UdeM-affiliated Montreal Clinical Research Institute.

Published in PNAS, the journal of the U.S. National Academy of Sciences, the new research by Marie-Anne Goyette, a doctoral student in Côté's laboratory, reveals a highly promising therapeutic target to counter the HER2-positive breast cancer.

In HER2-positive breast cancer, a gene called HER2 is expressed that promotes an aggressive form of the disease. Affecting 20 per cent of women suffering from breast cancer in Canada, the HER2-positive subtype is associated with a poor prognosis.

What threatens the life of the majority of cancer patients is the power of tumour cells to spread and thus metastasize to other organs, which can interfere with vital body functions. Increasingly, personalized medicine has generated a lot of hope for patients expressing the HER2 gene, but relapses are frequent in many.

Immunotherapy is an important avenue for treating these drug-resistant patients, but so far with little apparent benefit. As a result, researchers are trying to deepen their understanding of the tumours' immune environment and thereby better target the treatments and those most likely to respond to them.

It is with this in mind that Côté's team studied an important phenomenon in solid tumours called hypoxia. Hypoxia is manifested by a lack of oxygen caused by the rapid growth of the tumour, and leads to the production of metastases, a weakened immune system and resistance to treatment. In short, by making tumours more aggressive while reducing the body's ability to defend itself, hypoxia promotes cancer progression, which can be fatal to those affected.

In a preclinical model, the IRCM team identified a protein called AXL whose action is crucial for hypoxia to take place. By blocking the action of this protein in the tumour, using various novel techniques, the team observed a recovery of blood vessels and a revitalization of the tumour's immune environment. Blocking the action of the tumour also reduced its ability to metastasize in other organs.

"It's as if we had succeeded, on the one hand, in breaking down the protective walls of the tumour against the immune system, thus making it more vulnerable to immunological treatments, and, on the other hand, in preventing the tumour from moving elsewhere," said Goyette, the new study's first author.

The potential of this study is all the more important as it opens the way for further research on the subject from the perspective of various fields of biomedical research, the researchers believe. The sharing of expertise has once again proved its worth, they say.

"Cutting-edge personalized medicine in immunology has faced significant resistance from this type of cancer and we had the expertise in molecular research to help overcome these obstacles," said Côté. "We have not only shed light on a central mechanism of the functioning of some of the most aggressive tumours, but in doing so we have also unveiled a way to create an environment conducive to more effective treatments."

Astronomers have made the rare sighting of two stars spiralling to their doom by spotting the tell-tale signs of a teardrop-shaped star.

The tragic shape is caused by a massive nearby white dwarf distorting the star with its intense gravity, which will also be the catalyst for an eventual supernova that will consume both. Found by an international team of astronomers and astrophysicists led by the University of Warwick, it is one of only very small number of star systems that has been discovered that will one day see a white dwarf star reignite its core.

New research published by the team today (12 July) in Nature Astronomy confirms that the two stars are in the early stages of a spiral that will likely end in a Type Ia supernova, a type that helps astronomers determine how fast the universe is expanding.

This research received funding from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) and the Science and Technology Facilities Council, part of UK Research and Innovation.

HD265435 is located roughly 1,500 light years away and comprises a hot subdwarf star and a white dwarf star orbiting each other closely at a rate of around 100 minutes. White dwarfs are 'dead' stars that have burnt out all their fuel and collapsed in on themselves, making them small but extremely dense.

A type Ia supernova is generally thought to occur when a white dwarf star's core reignites, leading to a thermonuclear explosion. There are two scenarios where this can happen. In the first, the white dwarf gains enough mass to reach 1.4 times the mass of our Sun, known as the Chandrasekhar limit. HD265435 fits in the second scenario, in which the total mass of a close stellar system of multiple stars is near or above this limit. Only a handful of other star systems have been discovered that will reach this threshold and result in a Type Ia supernova.

Lead author Dr Ingrid Pelisoli from the University of Warwick Department of Physics, and formerly affiliated with the University of Potsdam, explains: "We don't know exactly how these supernovae explode, but we know it has to happen because we see it happening elsewhere in the universe.

"One way is if the white dwarf accretes enough mass from the hot subdwarf, so as the two of them are orbiting each other and getting closer, matter will start to escape the hot subdwarf and fall onto the white dwarf. Another way is that because they are losing energy to gravitational wave emissions, they will get closer until they merge. Once the white dwarf gains enough mass from either method, it will go supernova."

Using data from NASA's Transiting Exoplanet Survey Satellite (TESS), the team were able to observe the hot subdwarf, but not the white dwarf as the hot subdwarf is much brighter. However, that brightness varies over time which suggested the star was being distorted into a teardrop shape by a nearby massive object. Using radial velocity and rotational velocity measurements from the Palomar Observatory and the W. M. Keck Observatory, and by modelling the massive object's effect on the hot subdwarf, the astronomers could confirm that the hidden white dwarf is as heavy as our Sun, but just slightly smaller than the Earth's radius.

Combined with the mass of the hot subdwarf, which is a little over 0.6 times the mass of our Sun, both stars have the mass needed to cause a Type Ia supernova. As the two stars are already close enough to begin spiralling closer together, the white dwarf will inevitably go supernova in around 70 million years. Theoretical models produced specifically for this study predict that the hot subdwarf will contract to become a white dwarf star as well before merging with its companion.

Type Ia supernovae are important for cosmology as 'standard candles'. Their brightness is constant and of a specific type of light, which means astronomers can compare what luminosity they should be with what we observe on Earth, and from that work out how distant they are with a good degree of accuracy. By observing supernovae in distant galaxies, astronomers combine what they know of how fast this galaxy is moving with our distance from the supernova and calculate the expansion of the universe.

Dr Pelisoli adds: "The more we understand how supernovae work, the better we can calibrate our standard candles. This is very important at the moment because there's a discrepancy between what we get from this kind of standard candle, and what we get through other methods.

"The more we understand about how supernovae form, the better we can understand whether this discrepancy we are seeing is because of new physics that we're unaware of and not taking into account, or simply because we're underestimating the uncertainties in those distances.

"There is another discrepancy between the estimated and observed galactic supernovae rate, and the number of progenitors we see. We can estimate how many supernovae are going to be in our galaxy through observing many galaxies, or through what we know from stellar evolution, and this number is consistent. But if we look for objects that can become supernovae, we don't have enough. This discovery was very useful to put an estimate of what a hot subdwarf and white dwarf binaries can contribute. It still doesn't seem to be a lot, none of the channels we observed seems to be enough."

The findings of the study, funded by the National Institute for Health Research (NIHR) and led by Professor Kristian Pollock from the University of Nottingham, are published in Palliative Medicine.

When somebody is seriously ill and dying at home, managing their medications can be a difficult and complex task. This is made more difficult given that the care often needs to be given when patients and their families are tired and emotional. Family members are often assumed to be willing and able to support patients with their medication. However, little is known about what these tasks involve or how families cope with them.

In this study, a team of experts explored the views of patients and families managing medications in their homes. The study reports the outcomes of 21 interviews with bereaved family caregivers and 43 interviews with patients and current family caregivers.

The research found:

More awareness is needed to understand the ways that managing medications add to the considerable burden of care and work that must be undertaken when someone is seriously ill and dying at home;

Family caregivers are increasingly expected to undertake complex and technical medication tasks formerly carried out by professionals, but with little if any training, supervision or support; this trend has been exacerbated by Covid-19

The work of managing medications is critical to enabling patients to remain at home at the end of life.

The findings of the research have implications for practice and policy:

Health care professionals will benefit from a greater understanding of the complexities of medications management undertaken by patients and families in order to identify and tailor the support they can provide.

Substantial reduction in the complexity and bureaucracy of Health and Social Care services is needed for them to can be navigable for patients and families managing medications at the end of life.

The lack of presence of Community Pharmacists in this research suggests there may be a greater role for them in supporting patients and families to manage medications at home.

Dr Eleanor Wilson, from the Nottingham Centre for the Advancement of Palliative and End of Life Care (NCARE) in the School of Health Sciences at the University of Nottingham, worked on the study. She said: "Our findings show that managing medications at the end of life can be considerable 'work'. Including practical and physical work of organising, ordering and collecting medications, the emotional work of supporting someone to take their medication and the knowledge-based work of understanding what medications are for, when they should be taken and what side effects they may cause.

"This medicines 'work' often needs to be done when patients and families are tired, upset and under pressure, so health professionals need to be alert to how much they are asking families to do at this time."

ITHACA, N.Y. - Traces of the gas phosphine point to volcanic activity on Venus, according to new research from Cornell University.

Last autumn, scientists revealed that phosphine was found in trace amounts in the planet's upper atmosphere. That discovery promised the slim possibility that phosphine serves as a biological signature for the hot, toxic planet.

Now Cornell scientists say the chemical fingerprint support a different and important scientific find: a geological signature, showing evidence of explosive volcanoes on the mysterious planet.

"The phosphine is not telling us about the biology of Venus," said Jonathan Lunine, professor of physical sciences and chair of the astronomy department at Cornell. "It's telling us about the geology. Science is pointing to a planet that has active explosive volcanism today or in the very recent past."

Lunine and Ngoc Truong, a doctoral candidate in geology, authored the study, "Volcanically Extruded Phosphides as an Abiotic Source of Venusian Phosphine," published July 12 in the Proceedings of the National Academy of Sciences.

Truong and Lunine argue that volcanism is the means for phosphine to get into Venus' upper atmosphere, after examining observations from the ground-based, submillimeter-wavelength James Clerk Maxwell Telescope atop Mauna Kea in Hawaii, and the Atacama Large Millimeter/submillimeter Array (ALMA) in northern Chile.

If Venus has phosphide - a form of phosphorous present in the planet's deep mantle - and, if it is brought to the surface in an explosive, volcanic way and then injected into the atmosphere, those phosphides react with the Venusian atmosphere's sulfuric acid to form phosphine, Truong said.

Lunine said their phosphine model "suggests explosive volcanism occurring," while "radar images from the Magellan spacecraft in the 1990s show some geologic features could support this."

In 1978, on NASA's Pioneer Venus orbiter mission, scientists uncovered variations of sulfur dioxide in Venus' upper atmosphere, hinting at the prospect of explosive volcanism, Truong said, similar to the scale of Earth's Krakatoa volcanic eruption in Indonesia in 1883.

But, Truong said, "confirming explosive volcanism on Venus through the gas phosphine was totally unexpected."

Many exoplanets have opaque atmospheres, obscured by clouds or hazes that make it hard for astronomers to characterize their chemical compositions. A new study shows that haze particles produced under different conditions have a wide range of properties that can determine how clear or hazy a planet's atmosphere is likely to be.

Photochemical reactions in the atmospheres of temperate exoplanets lead to the formation of small organic haze particles. Large amounts of these photochemical hazes form in Earth's atmosphere every day, yet our planet has relatively clear skies. The reason has to do with how easily haze particles are removed from the atmosphere by deposition processes.

"It's not just haze production but also haze removal that determines how clear the atmosphere is," said Xinting Yu, a postdoctoral fellow at UC Santa Cruz and lead author of the study, published July 12 in Nature Astronomy.

Yu and her colleagues measured the properties of haze particles produced in the laboratory under conditions representative of exoplanet atmospheres, including a range of gas compositions, temperatures, and energy sources. Coauthor Xi Zhang, assistant professor of Earth and planetary sciences at UC Santa Cruz, said laboratory experiments like this are essential for understanding haze formation and its impact on observations.

"We can't bring haze samples back from exoplanets, so we have to try to mimic the atmospheric conditions in the laboratory," he said.

According to Yu, haze removal depends on a critical material property of the particles called surface energy. "Surface energy describes how cohesive or 'sticky' the material is," she said.

Sticky haze particles readily bond with each other when they collide, growing into larger particles that fall out of the atmosphere onto the surface of the planet (a process called dry deposition). They also make good condensation nuclei for cloud droplets and are easily removed by wet deposition. Hazes produced on Earth typically have high surface energy and are therefore 'sticky' and efficiently removed from the atmosphere.

Yu's laboratory experiments show that the hazes produced in exoplanet atmospheres are highly diverse, with properties that depend on the conditions in which they are produced.

"Some of them are similar to the Earth haze, have high surface energy, and are easy to remove, leading to clear skies," she said. "But some of them have very low surface energy, like a non-stick pan; they do not bond with other particles very well and remain as small particles hanging in the atmosphere for a long time."

The study found that a critical factor is the temperature at which the haze particles are created. Hazes produced at around 400 Kelvin (260°F) tended to have the lowest surface energies, leading to less efficient removal and hazier atmospheres. This finding actually corresponds with observed trends, Yu said, noting that exoplanets at temperatures of 400 to 500 K tend to be the haziest.

Cooler planets located in the habitable zones of their host stars are more likely to have clear atmospheres, she said. "We may not have to worry about habitable exoplanets being too hazy for future observations, as hazes tend to have higher surface energies at lower temperatures," Yu said. "So it is easy to remove these hazes, leaving relatively clear atmospheres."

Astronomers are looking forward to having a powerful tool for characterizing exoplanet atmospheres with the upcoming James Webb Space Telescope (JWST). When an exoplanet transits across the face of its star, its atmosphere filters the light from the star, giving astronomers with a sensitive enough telescope (like JWST) an opportunity to identify the chemical components of the atmosphere using transmission spectroscopy.

A hazy atmosphere would interfere with transmission spectroscopy, but the hazes themselves may still yield valuable information, according to Zhang.

"Hazes are not featureless," he said. "With better telescopes, we may be able to characterize the composition of exoplanet hazes and understand their chemistry. But the observations will be very hard to explain without data from laboratory experiments. This study has revealed the huge diversity of haze particles, and understanding their optical properties will be a high priority for future studies."

A diet rich in fermented foods enhances the diversity of gut microbes and decreases molecular signs of inflammation, according to researchers at the Stanford School of Medicine.

In a clinical trial, 36 healthy adults were randomly assigned to a 10-week diet that included either fermented or high-fiber foods. The two diets resulted in different effects on the gut microbiome and the immune system.

Eating foods such as yogurt, kefir, fermented cottage cheese, kimchi and other fermented vegetables, vegetable brine drinks, and kombucha tea led to an increase in overall microbial diversity, with stronger effects from larger servings. "This is a stunning finding," said Justin Sonnenburg, PhD, an associate professor of microbiology and immunology. "It provides one of the first examples of how a simple change in diet can reproducibly remodel the microbiota across a cohort of healthy adults."

In addition, four types of immune cells showed less activation in the fermented-food group. The levels of 19 inflammatory proteins measured in blood samples also decreased. One of these proteins, interleukin 6, has been linked to conditions such as rheumatoid arthritis, Type 2 diabetes and chronic stress.

"Microbiota-targeted diets can change immune status, providing a promising avenue for decreasing inflammation in healthy adults," said Christopher Gardner, PhD, the Rehnborg Farquhar Professor and director of nutrition studies at the Stanford Prevention Research Center. "This finding was consistent across all participants in the study who were assigned to the higher fermented food group."

Microbe diversity stable in fiber-rich diet

By contrast, none of these 19 inflammatory proteins decreased in participants assigned to a high-fiber diet rich in legumes, seeds, whole grains, nuts, vegetables and fruits. On average, the diversity of their gut microbes also remained stable. "We expected high fiber to have a more universally beneficial effect and increase microbiota diversity," said Erica Sonnenburg, PhD, a senior research scientist in basic life sciences, microbiology and immunology. "The data suggest that increased fiber intake alone over a short time period is insufficient to increase microbiota diversity."

The study will be published online July 12 in Cell. Justin and Erica Sonnenburg and Christopher Gardner are co-senior authors. The lead authors are Hannah Wastyk, a PhD student in bioengineering, and former postdoctoral scholar Gabriela Fragiadakis, PhD, who is now an assistant professor of medicine at UC-San Francisco.

A wide body of evidence has demonstrated that diet shapes the gut microbiome, which can affect the immune system and overall health. According to Gardner, low microbiome diversity has been linked to obesity and diabetes.

"We wanted to conduct a proof-of-concept study that could test whether microbiota-targeted food could be an avenue for combatting the overwhelming rise in chronic inflammatory diseases," Gardner said.

The researchers focused on fiber and fermented foods due to previous reports of their potential health benefits. While high-fiber diets have been associated with lower rates of mortality, the consumption of fermented foods can help with weight maintenance and may decrease the risk of diabetes, cancer and cardiovascular disease.

The researchers analyzed blood and stool samples collected during a three-week pre-trial period, the 10 weeks of the diet, and a four-week period after the diet when the participants ate as they chose.

The findings paint a nuanced picture of the influence of diet on gut microbes and immune status. On one hand, those who increased their consumption of fermented foods showed similar effects on their microbiome diversity and inflammatory markers, consistent with prior research showing that short-term changes in diet can rapidly alter the gut microbiome. On the other hand, the limited change in the microbiome within the high-fiber group dovetails with the researchers' previous reports of a general resilience of the human microbiome over short time periods.

Designing a suite of dietary and microbial strategies

The results also showed that greater fiber intake led to more carbohydrates in stool samples, pointing to incomplete fiber degradation by gut microbes. These findings are consistent with other research suggesting that the microbiome of people living in the industrialized world is depleted of fiber-degrading microbes.

"It is possible that a longer intervention would have allowed for the microbiota to adequately adapt to the increase in fiber consumption," Erica Sonnenburg said. "Alternatively, the deliberate introduction of fiber-consuming microbes may be required to increase the microbiota's capacity to break down the carbohydrates."

In addition to exploring these possibilities, the researchers plan to conduct studies in mice to investigate the molecular mechanisms by which diets alter the microbiome and reduce inflammatory proteins. They also aim to test whether high-fiber and fermented foods synergize to influence the microbiome and immune system of humans. Another goal is to examine whether the consumption of fermented food decreases inflammation or improves other health markers in patients with immunological and metabolic diseases, and in pregnant women and older individuals.

"There are many more ways to target the microbiome with food and supplements, and we hope to continue to investigate how different diets, probiotics and prebiotics impact the microbiome and health in different groups," Justin Sonnenburg said.

Electroconvulsive therapy (ECT) is a medically safe mental health intervention, according to a new study led by CAMH researcher Dr. Tyler Kaster as part of his doctoral studies at ICES and the University of Toronto. The study was published today in the journal The Lancet Psychiatry, and is among the largest and most comprehensive to compare the safety of ECT with standard treatment amongst individuals with depression.

Multiple studies over a period of decades have confirmed the effectiveness of ECT as a mental health intervention for people with treatment-resistant depression. Up to 80 per cent of people with severe depression who receive ECT achieve remission. However, despite this success rate, only one per cent of people with severe depression ever receive ECT, likely due to concerns about side effects of ECT such as cognitive and medical complications.

This study, entitled Risk of serious medical events in patients with depression treated with electroconvulsive therapy: a propensity score-matched, retrospective cohort study, looked at the psychiatric records of over 10,000 patients in Ontario whose depression was serious enough to require at least three days of hospitalization, and compared the risk of medical hospitalization or death within 30 days for patients who had ECT compared to patients who did not. It concludes that, "among individuals hospitalized with depression, there is not a clinically significant increased risk for serious medical events with exposure to ECT while the risk of suicide appears to be significantly reduced. The benefits of ECT on depression outcomes may outweigh its risks in this population."

"ECT is the single most effective treatment we have in psychiatry for depression," said lead author CAMH Psychiatrist Dr. Tyler Kaster, who treats ECT patients at the CAMH Temerty Centre for Therapeutic Brain Stimulation. "But prejudice and discrimination around the treatment is enormous in terms of preventing people from accessing it."

In Canada, over 1 in 9 adults (3.2 million Canadians or 11.3 per cent) will experience a major depression in their lifetime, at which time they will most likely be prescribed antidepressants and/or psychotherapy. However, about a third of these individuals will fail to respond to these first-line treatments, and then will be diagnosed with treatment-resistant depression. There are a number of interventions for this condition including medication combinations, new drugs like ketamine and a neurostimulation treatment called repetitive transcranial magnetic stimulation (rTMS). However, when these treatments don't lead to improvement or when a depression becomes very severe leading to hospitalization, ECT is often considered as the next step, as it is highly effective at rapidly reducing symptoms of depression and suicidal thinking. Learn more about ECT on the CAMH website.

Dr. Simone Vigod, study corresponding author, senior adjunct scientist at ICES and Chief of Psychiatry at Women's College Hospital, said the study illustrates the importance of emphasizing the safety and efficacy of ECT as an effective mental health intervention for people for whom nothing else has worked. "At Women's College Hospital, we believe that supporting people living with mental health conditions has never been more important," added Dr. Vigod. "Doing so requires providing patients with a full spectrum of evidence-based treatments founded on rigorous research evidence. This investigation adds to the existing body of research on the safety and efficacy of ECT, which can serve as a valuable option for those with severe depression."

Dr. Kaster believes that the persistent fear associated with ECT is a reflection of the overall level of prejudice and discrimination that continues to persist in regards to mental illness itself.

CAMH continues to be Canada's leader in neurostimulation treatment delivery, and treats approximately 250 patients per year with ECT. CAMH's Temerty Centre for Therapeutic Brain Intervention is one of the world's leading centres in brain stimulation treatment, research and training. Through clinical research projects, the Temerty Centre is driving treatment advances using repetitive transcranial magnetic stimulation (rTMS), magnetic seizure therapy (MST), and ECT.

The ubiquitous overuse injuries that nag runners may stem from an unlikely culprit: how far you lean forward.

Trunk flexion, the angle at which a runner bends forward from the hip, can range wildly--runners have self-reported angles of approximately -2 degrees to upward of 25. A new study from the University of Colorado Denver (CU Denver) found that greater trunk flexion has significant impact on stride length, joint movements, and ground reaction forces. How you lean may be one of the contributors to your knee pain, medial tibial stress syndrome, or back pain.

"This was a pet peeve turned into a study," said Anna Warrener, PhD, lead author and assistant professor of anthropology at CU Denver. Warrener worked on the initial research during her postdoc fellowship with Daniel Liberman, PhD, in the Department of Human Evolutionary Biology at Harvard University. "When [Lieberman] was out preparing for his marathons, he noticed other people leaning too far forward as they ran, which had so many implications for their lower limbs. Our study was built to find out what they were."

The study was published in Human Movement Science.

A New Angle on Overuse Injuries

The head, arms and trunk constitute roughly 68% of total body mass. Small changes in trunk flexion have the potential to substantially alter lower-limb kinematics and ground reaction forces (GRF) during running.

To study the downstream effects, Warrener and her team recruited 23 injury-free, recreational runners between the ages of 18 and 23. They recorded each participant running 15-second trials at their self-selected trunk position and three others: a 10-, 20-, and a 30-degree angle of flexion. But to make the study work, they had to first figure out how to get each runner to bend at the right slant.

"We had to create a way in which we could reasonably force someone into a forward lean that didn't make them so uncomfortable that they changed everything about their gait," said Warrener. The team hung a lightweight, plastic dowel from the ceiling just above the runners' heads, moving it up or down, depending on the angle needed.

Contrary to the team's original hypothesis, the average stride length decreased 13 cm and stride frequency increased from 86.3 strides/min to 92.8 strides/min. Overstride relative to the hip increased 28%.

"The relationship between strike frequency and stride length surprised us," said Warrener. "We thought that the more you lean forward, your leg would need to extend further to keep your body mass from falling outside the support aera. As a result, overstride and stride frequency would go up. The inverse was true. Stride length got shorter and stride rate increased."

Warrener believes this may be due to a decrease in the aerial phase (if they're not getting as much air time, runners will take shorter steps), which means leg swings quickened as a result of reduced forward movement.

"The act of swinging your leg is really expensive as you're running," said Warrener. "Swinging it faster as you lean forward may mean a higher locomotor cost."

Compared to the participants' natural trunk flexion, increased angles led to a more flexed hip and bent knee joint. A bigger lean also changed the runners' foot and lower limb position, leading to an increased impact of GRF on the body (rate of loading by 29%; vertical ground reaction force impact transients by 20%).

The combination of trunk flexion angle, foot and leg placement, and GRF variables, shows that excessive trunk flexion could be one cause of injurious running form and, according to Warrener, is key for understanding how diverse running forms optimize economy and performance.

"The big picture takeaway is that running is not all about what is happening from the trunk down--it's a whole-body experience," said Warrener. "Researchers should think about the downstream effects of trunk flexion when studying running biomechanics."