Publisher Health

New insight on the link between a gene called SORBS2 and congenital heart disease has been published today in eLife, with findings that may help explain the cause of the disease in some patients.
Some people with congenital heart disease are missing part of the long arm of chromosome 4, otherwise known as chromosome 4q. Chromosomes are thread-like structures made up of DNA. When part of the chromosome is missing, it means that some of the genes located on that section are also lost. Previous studies have linked heart defects related to chromosome 4q deletion syndrome to a missing copy of the HAND2 gene that is found in chromosome 4 and is important for heart development. But not every patient with a heart defect is missing HAND2, which suggests other genes are likely involved as well.
“A previous study of one patient with congenital heart disease suggested mutations in a gene called SORBS2 might be responsible, but this finding had yet to be confirmed,” explains first author Fei Liang, a physician at the Neonatal Intensive Care Unit, Shanghai Children’s Medical Center, China.
To explore the potential role of SORBS2 in congenital heart disease, Liang and colleagues suppressed the gene in developing human heart cells grown in the laboratory. This led to the development of abnormally shaped heart cells and interfered with the ability of cardiac muscle cells to undergo necessary changes in gene expression.
The team’s additional studies in genetically engineered mice showed that a lack of SORBS2 led to the absence or duplication of the wall between the two upper chambers of the heart in 40% of embryos. This duplication is a condition known as double atrial septum. However, the effect was much milder in comparison to human heart defects, suggesting that SORBS2 may be a ‘small effect size’ congenital heart disease gene — that is to say, it plays a minor role in the disease.
The team further examined how a lack of SORBS2 can affect gene expression in both mice and human cells. Their results highlighted how the levels of other genes and proteins are elevated or reduced in response to the lack of SORBS2, ultimately leading to heart defects and damage.
Finally, they found that rare, damaging variants of the SORBS2 gene were significantly enriched in 300 congenital heart disease cases where gross chromosomal aberrations did not occur. This provides additional genetic evidence that SORBS2 variants have a role in causing general congenital heart disease.
“Our combined studies help explain the cause of congenital heart disease in chromosome 4q deletion syndrome patients who still have the functional HAND2 gene,” concludes senior author Zhen Zhang, a professor at Shanghai Pediatric Congenital Heart Disease Institute and Pediatric Translational Medicine Institute, Shanghai Children’s Medical Center. “They provide an effective approach for identifying other genes that play a minor role in congenital heart disease and other multigenic diseases. Interestingly, we found that SORBS2 deficiency can cause double atrial septum, a very rare cardiac anomaly linked to a condition called paradoxical thromboembolism. The exact causes of this anomaly are currently unknown, and we hope our study paves the way for exploring this further.”
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Weakened electrical signals in the brain may be an early warning sign of age-related neurodegenerative diseases such as Alzheimer’s disease, suggests a study published today in eLife.
The findings hint at new ways to identify early on patients who may have an age-related brain disease. They also provide new insights on the changes that occur in the brain as these diseases develop.
“As tools for detecting Alzheimer’s disease early are limited, there is a need to develop a reliable, non-invasive test that would enable early diagnosis,” says first author Murty Dinavahi, who was a PhD Research Scholar at the Centre for Neuroscience, Indian Institute of Science (IISc), Bengaluru, India, at the time the study was carried out, and is now a Postdoctoral Associate at the University of Maryland, US.
Previous studies in mice with a condition similar to Alzheimer’s disease had suggested that weakened gamma brain waves may be an early sign of disease. Based on these findings, Murty and colleagues conducted a community-based study on around 250 elderly subjects. They compared gamma wave activity in 12 people diagnosed with mild cognitive impairment, and five with Alzheimer’s disease, with their healthy peers.
The researchers used a technique called electroencephalography to measure electrical activity in the participants’ brains while they viewed black and white patterns on a screen. These patterns are known to induce gamma oscillations in the part of the brain that processes visual information. The team also monitored the participants’ eye movements during the experiments.
Their results showed that people who had been diagnosed with mild cognitive impairment or Alzheimer’s disease had weaker gamma waves in their brain than healthy individuals of the same age.
“We observed reductions in the strength of gamma waves in early stages of age-related cognitive decline,” Murty says. “Changes in these electrical signals could provide an early warning sign of an impending disease.” He adds that an early diagnosis could help individuals put care plans in place or allow them to begin treatments sooner.
“Our work provides a low-cost and non-invasive way to detect early signs of Alzheimer’s disease,” concludes senior author Supratim Ray, Associate Professor at the Centre for Neuroscience, IISc. “This could be useful for clinicians and scientists studying early changes that take place in the brain during age-related neurodegenerative diseases, and potentially lead to new ways to diagnose and treat these conditions.”
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Men who suffer sensory loss, particularly hearing loss, are more likely to be physically inactive and obese than women, according to a new study published in the European Journal of Public Health.
Researchers analysed data from more than 23,000 Spanish adults, and examined associations with physical inactivity and obesity in people with vision and hearing loss, and explored differences between men and women.
Results suggest inactive people with hearing loss were 1.78 times more likely to be obese compared to those who did not have any hearing loss. In people who had difficulty seeing, the odds ratio is slightly smaller, with a likelihood of obesity being 1.375 times higher than those who did not report vision loss.
The association between physical activity and obesity was higher in men with hearing loss, who were 2.319 times more likely to be obese than women who reported difficulty hearing. Obesity in those with sight loss was 1.556 times higher in inactive men than women.
Those with combined seeing and hearing difficulties had the highest prevalence of physical inactivity (44.8%) and obesity (26.1%). Analysis showed a significant association between physical inactivity and obesity in men with vision or hearing loss, but not in women.
Around 62% of adults in Spain are overweight, with 26% reporting as obese. In the UK, the figures are broadly similar at around 64% and 28% respectively, suggesting strong similarities between the countries.
A total of 11.04% of the people surveyed self-reported vision loss, 6.96% reported hearing loss, and 3.93% reported suffering both vision and hearing loss.
Lead author Professor Shahina Pardhan, Director of the Vision and Eye Research Institute at Anglia Ruskin University, said: “It is clear from our study that there are significant differences between genders.
“Although women were overall less physically active than men, we found an association between physical inactivity and obesity in men, but not in women. This indicates that, especially in people with vision and hearing losses, exercise and being active has a very important role in preventing obesity for men.
“Adults, especially those with sensory losses, should be encouraged to be as physically active as possible but there are obviously challenges, strongly suggesting that intervention and encouragement would play a very important role.
“An effective strategy to increase the levels of physical activity in this population group would be through targeted intervention programmes based on health awareness on the importance of physical activity.”
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A study by RCSI indicates that exercise is probably the most effective short-term treatment for depression in people with coronary heart disease, when compared to antidepressants and psychotherapy or more complex care.
The study, led by researchers at RCSI University of Medicine and Health Sciences, is published in the June edition of Psychosomatic Medicine.
This is the first systematic review to compare treatments for depression in those with coronary disease and the findings provides valuable clinical information to help doctors determine the best treatment plan for patients.
The researchers reviewed treatment trials which investigated antidepressants, psychotherapy, exercise, combined psychotherapy and antidepressants, and collaborative care (i.e. treatments devised by a multidisciplinary team of clinicians with input from the patient).
To measure effectiveness, the researchers looked at factors including patient adherence to the treatment (dropout rate) and change in depressive symptoms eight weeks after commencing treatment.
The strongest treatment effects were found to be exercise and combination treatments (antidepressants and psychotherapy). However, as the combination study results have a high risk of bias, the findings of the review suggest that exercise is probably the most effective treatment. Antidepressants had the most research support, while psychotherapy and collaborative care did not perform very well.
“Depression is common in patients with coronary artery disease. Having both conditions can have a significant impact on the quality of life for patients so it is vital that they access to the most effective treatments,” commented Dr Frank Doyle, Senior Lecturer Division of Population Health Sciences, RCSI and the study’s first author.
“Our study indicates that exercise is likely to be the best treatment for depression following coronary artery disease. Our findings further highlight the clinical importance of exercise as a treatment as we see that it improves not only depression, but also other important aspects of heart disease, such as lowering blood pressure and cholesterol, in these patients.”
“We continue to see emerging evidence of the importance of lifestyle to treat disease — in comparison to other treatments — but further high-quality research is needed. People with coronary heart disease who have symptoms of depression should talk to their doctor about treatments that are most suitable for their personal needs, and clinicians can be confident of recommending exercise to their patients.”
Dr Frank Doyle and the study’s senior authors, Prof. Jan Sorensen (Health Outcomes Research Centre, RCSI) and Prof. Martin Dempster (School of Psychology, Queen’s University Belfast), conducted the study in collaboration with researchers in the USA, The Netherlands, the UK and Denmark.
This study was also the first of its kind to establish a new method to conduct systematic reviews known as a hybrid review, which is a combination of umbrella reviews and systematic reviews.
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In cases of severe varicose vein disease, dilated veins are usually removed or destroyed. However, when patients later need a bypass due to circulatory problems, the large blood vessels are then not available as a substitute. In a multicentre study led by Dr. Dominic Mühlberger from the Vascular Surgery Department at Ruhr-Universität Bochum’s St. Josef Hospital, researchers tested a vascular preservation therapy developed in-house: applying a thin sheath around the defective vein eliminated the varicose vein problem in over 95 per cent of cases. The research team published their findings in the Journal of International Medical Research on 6 April 2021.
When the blood pools in the leg
Varicose veins are more than just a cosmetic problem: the unsightly bulges might result in serious health problems such as leg ulcers, thromboses or even pulmonary embolisms. The cause of varicose vein disease is usually a weakness in the connective tissue, which causes the vein wall to give way and thus the vein diameter to grow. This process is accelerated by pregnancy or frequent standing and sitting.
The increase in vein diameter impairs the function of the vein valves. The valve leaflets are pulled apart and a leak develops, which is called valve insufficiency. The blood pools in the leg where it leads to an increase in venous blood pressure. This valve insufficiency most often affects the truncal vein, also called the great saphenous vein or great rose vein, which opens in the groin.
Like a second skin
The therapy concepts to date have been based on a radical approach: destruction by laser or by radio wave therapy, or removal of insufficient truncal veins by stripping surgery. “At the RUB Hospital, we have developed an alternative to the radical methods with the procedure of extraluminal valvuloplasty, which adopts an organ-preserving approach,” explains Professor Achim Mumme, Director of Vascular Surgery. Venous valves are repaired through a small incision in the groin. A sheath of wafer-thin polyurethane is placed around the dilated vein like a second skin. The sheath acts as a kind of internal compression stocking that returns the vein, which is weak in connective tissue, to its normal diameter.
Use primarily when risk factors for circulatory disorders are present
In a multicentre study, the team tested the effectiveness of the organ-preserving treatment method. “With a success rate of 95.24 per cent, vein repair with the novel polyurethane sheath proved to be an effective therapeutic alternative to radical treatment methods,” outlines study supervisor Dominic Mühlberger. “The great advantage of extraluminal valvuloplasty is that the truncal vein is preserved — unlike in radical therapy methods.”
This is especially important if circulatory problems occur at a later stage in life. In this case, the presence of suitable bypass material can be decisive for the treatment options. The truncal veins are needed as vascular graft in cardiovascular surgery. Whereas the lack of suitable autologous replacement material worsens the prognosis.
“Vein-preserving therapy for varicose veins should be used above all when risk factors for the development of circulatory disorders are present, such as smoking, high blood pressure, diabetes or lipometabolic disorders,” concludes Mühlberger.
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Materials provided by Ruhr-University Bochum. Original written by Meike Drießen; translated by Donata Zuber. Note: Content may be edited for style and length.

Coronavirus vaccines may be available for U.S. children as young as six months by the fall, drugmakers say. Pfizer and Moderna are testing their vaccines in children under 12, and are expected to have results in hand by the end of the summer.Compared with adults, children are much less likely to develop severe illness following infection with the coronavirus. But nearly four million children in the United States have tested positive for the virus since the start of the pandemic, according to the American Academy of Pediatrics.Doctors continue to see rare cases of multisystem inflammatory syndrome in children, a condition linked to Covid-19 that can affect multiple organs, including the heart. Vaccinating children should further contribute to containment of the virus by decreasing its spread in communities.Pfizer announced on Tuesday that it was moving to test its vaccine in children aged 5 through 12 years. It will begin testing the vaccine in infants as young as six months in the next few weeks.The company said last month that it expected to apply to the Food and Drug Administration in September for emergency authorization of the vaccine for children ages 2 to 11. The Pfizer-BioNTech vaccine was authorized last month for use in children 12 through 15.Based on data from an earlier study that assessed safety, Pfizer will give two doses of 10 micrograms each — a third of the dose given to adolescents and adults — to children ages 5 to 11 years, and two doses of three micrograms each to children six months to 5 years.“We take a deliberate and careful approach to help us understand the safety and how well the vaccine can be tolerated in younger children,” said Dr. Bill Gruber, a senior vice president at Pfizer.The study will enroll up to 4,500 children at more than 90 clinical sites in the United States Finland, Poland and Spain. Pfizer’s researchers plan to submit the full data from the trials this summer for publication in a peer reviewed journal.In March, Moderna began testing varying doses of its vaccine in younger children. That trial aimed to enroll 6,750 healthy children in the United States and Canada. Results are not expected till the end of the summer, and the vaccine’s authorization by the F.D.A. will take longer.“I think it’s going to be early fall, just because we have to go down in age very slowly and carefully,” Moderna’s chief executive, Stéphane Bancel, said on Monday.The company announced late last month that its vaccine was powerfully effective in 12- to 17-year-olds, and plans to apply to the F.D.A. for authorization in that age group. Last week, Moderna also asked the agency for full approval of its vaccine, rather than the emergency use for which it is currently authorized.The United States will not be the first country in the world to authorize a coronavirus vaccine for young children. China has approved Sinovac’s vaccine for children as young as 3-years-old, according to the company’s chairman. The approval has not been officially announced.

An essential tool. An inspiration for artists. A public nuisance. The humble shopping cart has been all of these in the decades since it was invented. But what does it reveal about our character?The next time you go to the grocery store, consider the ordinary shopping cart as something more than a rattling basket blocking your parking space.In the 1930s, an American grocer named Sylvan Goldman invented the precursor to the modern day shopping cart, using a folding frame that was fixed on a set of wheels. He hoped that people would buy more groceries if they did not have to carry heavy baskets as they browsed.And they did.But over the decades, the shopping cart has evolved from its mundane existence as the centerpiece of every grocery store run.Like the Campbell’s Soup can, it has become an unlikely icon in a subculture that celebrates the common object.Shopping carts have been the focus of books and films, and their use examined in magazine columns and classrooms as tools to explain how humans behave in public. They have found a dubious niche on the internet as the stars of a YouTube show, followed by half a million people. They have even inspired musicians: The steady clacking of a cart rolling down a street was the inspiration for both the sound and the words in Neil Young’s 1994 song “Safeway Cart.”They are also a nuisance. Legislators and store owners across the United States have struggled with how to prevent the carts from being stolen, left in handicapped parking spots, discarded on sidewalks, abandoned at bus stops or tipped into creeks.Shirley Yu for The New York TimesAn Enduring Cultural ArtifactIn 2005, a cart infiltrated the British Museum, when the artist Banksy paired one with a cave man on a piece of fake prehistoric rock art — and then secretly installed the rock in a gallery, unnoticed for days.Another Banksy creation, the painting “Show Me the Monet,” incorporated discarded carts in nature. It sold at auction for about $10 million in December.John H. Lienhard, a history of technology professor at the University of Houston, described shopping carts as a “flash of genius” that altered American life during an episode of his public radio show, “The Engines of Our Ingenuity.”Decades after that 1995 broadcast, Dr. Lienhard is still trying to explain how the utilitarian origins of shopping carts broadened into cultural appeal.“They mirror us,” he said in an interview. “We want to walk. We want to carry. And now we aid our walking and carrying. And then our walking and carrying becomes mentally associated with wheeling.”“That means the technology of the commonplace is terribly important,” he said.Far From the SupermarketThe 2009 film “Cart” illustrates what Dr. Lienhard called the “symbiotic relationship” of humans and shopping carts.In the film, a shopping cart is given a mind of its own, navigating the perils of city streets as it searches for a boy who has left his jacket in the basket. The cart then saves the boy’s life by blocking an oncoming car.Jesse Rosten, the director, said the idea arose when he and a friend spotted an overturned cart in a parking lot. A sad song was on the radio as they drove past it, adding to the potential for cinematic melancholy.“We laughed the whole way home, imagining back stories for this down-and-out cart who was struggling against the world,” he said. “We’ve all seen abandoned shopping carts out in the world, and the film is one take on how carts end up where they do.”Portraits of carts in the wild are also captured in the 2006 book “The Stray Shopping Carts of Eastern North America: A Guide to Field Identification.”The Buffalo artist behind the book, Julian Montague, spent seven years photographing carts in dumpsters, in alleys, on lawns, wherever they turned up. “It is a weird object,” he said.“Somebody can take it someplace and chop the wheels off, or take laundry to the basement,” he said. “Unlike a plastic bag, it has multiple lives.”Shirley Yu for The New York TimesCarts as a Test of CharacterSome people steal them. Others leave them wherever they like.Private companies have gotten creative. In California, stray carts are reported on hotlines to companies that specialize in repatriating them to their store lots.At the supermarket chain ALDI, shoppers unlock carts with a quarter, which is returned when the carts are. Some customers leave the quarter in the cart for the next person to use.“We’re always amazed at the ‘pay-it-forward’ spirit that happens in our parking lots,” said Kate Kirkpatrick, communications director at ALDI. “As a result, we rarely run into issues with carts not being returned.”On many days, Seth Sanders, 20, a clerk at Safeway in Bellingham, Wash., can be found dodging cars as he rounds up carts that people have left in parking spaces or shoved aside in the massive lot.About a quarter of customers do not bother to return their carts, he estimated, which means he spends a lot of time doing it for them, in between bagging groceries, cleaning and finding items for customers.Mr. Sanders has wrangled carts in the cold, in the rain, and in the smoke from wildfires. One customer, in a hurry, shoved a cart in his direction with such force that it hurt his leg.“I want to say it is almost kind of selfish,” he said. “It is kind of a test of character. It is our job to pick up after people, but if it is the smallest thing you can do to help out, I feel like it is not a lot to help out a little bit.”Shirley Yu for The New York TimesEnter the Vigilantes …Of course, shopping cart slackers have their reasons.In a 2017 column in Scientific American, the anthropologist Krystal D’Costa explored why people failed to return carts. It “hit a nerve,” she wrote in a follow-up.In more than 2,000 comments on the magazine’s Facebook page, some said they were afraid to leave children unattended, or struggled with a disability, or feared making someone’s job obsolete. Within the past year, the so-called Shopping Cart Theory has become an article of faith on Reddit and other social media sites. The theory posits that the decision to return a cart is the ultimate test of moral character and a person’s capacity to be self-governing.It is a theory fully embraced by the video vigilantes known as The Cart Narcs, self-appointed enforcers who confront shoppers trying to leave without returning their carts. The series has about 500,000 followers on Facebook and YouTube.The Shopping Cart Theory has even reached academia — if middle school counts as academia. Students at the Lausanne Collegiate School in Tennessee were recently asked by Greg Graber, the school’s director of social and emotional learning, to analyze it in a class on critical thinking.One student said anyone who noticed a wayward cart should just return it. Another warned against rushing to judgment. Mr. Graber agreed.“It seems to be a popular belief now that people who leave their shopping carts in places are lacking in values and morals,” he said. But that belief “does not allow for growth or grace.”… and Here Come the LegislatorsIn April, the Shopping Cart Theory was cited in coverage of a proposed state law that would fine shoppers who did not return their carts.Paul Aronsohn, a disability ombudsman for New Jersey, had approached State Senator Kristin Corrado with the idea. He said the state needed to deter shoppers who abandon carts in the wide spaces designated for people with disabilities.Senator Corrado introduced Senate Bill No. 3705, which would impose a fine of $250 for doing so.“Apparently it is a pet peeve to a lot of people,” she said.One person who would benefit is Kelly Boyd, 41, of Hamilton Township, N.J., who has used a wheelchair since she was 9. When she drives her van to the store and lowers a ramp to disembark in her motorized chair, she often finds a cart blocking her way.So Ms. Boyd said she has to nudge it out of the way with her van, or drive to a remote part of the lot where she can use two spaces to get out. That has led to angry notes left on her car and confrontations with other drivers.“Everything I do as a person with a disability takes longer and then to have to deal with that is more frustrating,” Ms. Boyd said. “It is surprising how some people do not care.”This is not the only state legislation tackling shopping cart nuisances. Some places, like Los Angeles and Clark County, Nev., require wheels that lock when a cart is taken far from a store. Some cities in Washington impose fines on stores for wayward carts, and other cities are taking note.Last year the board of supervisors in Fairfax County, Va., met to address “the visual clutter” of stray carts with a proposal to impose $500 fines on people who wheel them off store property.“It is a real problem,” Jeffrey C. McKay told his fellow supervisors during the session. But others on the board argued that it would penalize people who are struggling economically and use the carts to get food home or carry their belongings.One of the supervisors, Dalia A. Palchik, said that had been her childhood experience.As immigrants from Argentina in 1989, Ms. Palchik said, she and her three siblings often accompanied their mother to the store and then pushed the cart to their rental house on the edge of Fairfax City. They had no car available.The memory came flooding back during the discussion. “It was one of those things I was ashamed of as a kid,” she said in an interview. “Why are we criminalizing people trying to get to the grocery store?”The ordinance is still under consideration.

In a paper published by the Journal of Sleep Research, researchers reveal how they examined data* from half a million middle-aged UK participants asked if they had trouble falling asleep at night or woke up in the middle of the night.
The report found that people with frequent sleep problems are at a higher risk of dying than those without sleep problems. This grave outcome was more pronounced for people with Type-2 diabetes: during the nine years of the research, the study found that they were 87 per cent more likely to die of any cause than people without diabetes or sleep disturbances.
The study also found that people with diabetes and sleep problems were 12 per cent more likely to die over this period than those who had diabetes but not frequent sleep disturbances.
Malcolm von Schantz, the first author of the study and Professor of Chronobiology from the University of Surrey, said:
“Although we already knew that there is a strong link between poor sleep and poor health, this illustrates the problem starkly.”
“The question asked when the participants enrolled does not necessarily distinguish between insomnia and other sleep disorders, such as sleep apnoea. Still, from a practical point of view it doesn’t matter. Doctors should take sleep problems as seriously as other risk factors and work with their patients on reducing and mitigating their overall risk.”
Professor Kristen Knutson of Northwestern University, the senior co-author of the study, said:
“Diabetes alone was associated with a 67 per cent increased risk of mortality. However, the mortality for participants with diabetes combined with frequent sleep problems was increased to 87 per cent. In order words, it is particularly important for doctors treating people with diabetes to also investigate sleep disorders and consider treatments where appropriate.”
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Scientists have observed for the first time what it looks like in the key memory region of the brain when a mistake is made during a memory trial. The findings have implications for Alzheimer’s disease research and advancements in memory storage and enhancement, with a discovery that also provides a view into differences between the physiological events in the brain during a correct memory versus a faulty one.
The study was published today in the journal Nature Communications.
In both correct and incorrect recall of a spatial memory, researchers could observe patterns of cell activation in the brain that were similar, though the pace of activation differed.
“We could see the memories activating,” said Laura Colgin, an associate professor of neuroscience at The University of Texas at Austin and lead author of the paper. “It’s like dominoes falling. One cell activates and then the next fires.”
Colgin and her team used electrophysiological recordings of rats in and out of mazes to study signals in the brain as the rats attempted to remember where a food reward was located and find it.
When rats remembered where the food reward was and located it, a specific pattern of brain cells activated with similar timing. These cells, called place cells, are associated with memories involving spatial relationships and locations and are found in the hippocampus, a section of the brain where animals including humans store most of their memories. It is also a region of the brain that experiences degeneration in patients with Alzheimer’s and related memory disorders.