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Today’s Videos:

Meta-analysis finds that omega-3 fatty acids improved cardiovascular outcomes

Reduction in cardiovascular risk was greatest for eicosapentaenoic acid (EPA) alone rather than combination of EPA and another omega-3 fatty acid

Brigham and Women’s Hospital, July 9, 2021

For decades, there has been great interest in whether omega-3 fatty acids can lower rates of cardiovascular events. In 2018, results from the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) were published in the New England Journal of Medicine and showed that a high dose of a purified ethyl ester of eicosapentaenoic acid (EPA) in patients at elevated cardiac risk significantly reduced cardiovascular events. Results from the trial led to US. Food and Drug Administration, Health Canada, and European Medicines Agency approval of the prescription drug icosapent ethyl for reducing cardiovascular risk in patients with elevated triglycerides, as well as updates to worldwide guidelines. But prior and subsequent studies of omega-3 fatty acid supplements that combine EPA and docosahexaenoic acid (DHA) have had mixed results. Investigators from Brigham and Women’s Hospital and elsewhere conducted a systematic review and meta-analysis of 38 randomized controlled trials of omega-3 fatty acids. Overall, they found that omega-3 fatty acids improved cardiovascular outcomes. Results, now published in eClinical Medicine, showed a significantly greater reduction in cardiovascular risk in studies of EPA alone rather than EPA+DHA supplements.

“REDUCE-IT has ushered in a new era in cardiovascular prevention,” said senior author Deepak L. Bhatt, MD, MPH, the executive director of Interventional Cardiovascular Programsat the Brigham and lead investigator of the REDUCE-IT trial. “REDUCE-IT was the largest and most rigorous contemporary trial of EPA, but there have been other ones as well. Now, we can see that the totality of evidence supports a robust and consistent benefit of EPA.”

Bhatt and colleagues performed a meta-analysis of 38 randomized clinical trials of omega-3 fatty acids, including trials of EPA monotherapy and EPA+DHA therapy. In total, these trials included more than 149,000 participants. They evaluated key cardiovascular outcomes, including cardiovascular mortality, non-fatal cardiovascular outcomes, bleeding, and atrial fibrillation. Overall, omega-3 fatty acids reduced cardiovascular mortality and improved cardiovascular outcomes. The trials of EPA showed higher relative reductions in cardiovascular outcomes compared to those of EPA+DHA.

The researchers note that there are crucial biological differences between EPA and DHA — while both are considered omega-3 fatty acids, they have different chemical properties that influence their stability and strength of the effect that they can have on cholesterol molecules and cell membranes. No trials to date have studied the effects of DHA alone on cardiovascular outcomes.

“This meta-analysis provides reassurance about the role of omega-3 fatty acids, specifically prescription EPA,” said Bhatt. “It should encourage investigators to explore further the cardiovascular effects of EPA across different clinical settings.”

Salt nanoparticles are toxic to cancer cells, say researchers

University of Georgia, July 7, 2021

A study led by University of Georgia researchers found that salt nanoparticles could kill cancer cells and confer anti-cancer immunity. Published in the journal Advanced Materials, the study showed that sodium chloride nanoparticles (SCNPs) could stealthily enter cancer cells and rip them apart from within, causing cell death. The cells’ death could then trigger an immune response that enables the body to ward off new tumor growth.

“This technology is well suited for localized destruction of cancer cells,” said chemist and co-author Jin Xie. “We expect it to find wide applications in treatment of bladder, prostate, liver, and head and neck cancer.”

Salt nanoparticles act as a Trojan horse

Unlike other inorganic nanoparticles, the therapeutic potential of SCNPs and other electrolyte nanoparticles is massively understudied due to a notion that they are not effective.

The underlying assumption is that electrolyte nanoparticles will quickly dissolve in water and become salts. As salts, they won’t be able to enter cells because cell membranes keep sodium ions out. Cell membranes do this to maintain ion homeostasis – that is, to maintain low sodium concentrations inside cells and high sodium concentrations outside cells.

However, Xie and his colleagues theorized that SCNPs should be able to pass through because the nanoparticle form should prevent cell membranes from recognizing sodium ions.

“Sodium chloride nanoparticles can be exploited as a Trojan horse strategy to deliver ions into cells and disrupt the ion homeostasis,” the researchers wrote.

Once inside a cell, SCNPs should dissolve into sodium and chloride ions, which will overwhelm the cell’s protective mechanisms and ultimately cause the cell membrane to rupture. Once this rupturing happens, molecules that leak out alert the immune system that there’s tissue damage, causing an immune response that enables the body to fight pathogens.

Exploring salt nanoparticles for cancer treatment

The researchers treated mice with cancer with the nanoparticles to test their theory. They injected cancer cells with SCNPs and compared their growth to those in mice that received the same quantity of sodium chloride in a solution, instead of as nanoparticles.

They found that SCNPs suppressed tumor growth by 66 percent compared to the mice that received the sodium chloride solution. On top of this, there were no signs that the nanoparticles caused damage to any organ.

The cancer cells also seemed to be more susceptible to SCNPs than healthy cells. The researchers attributed this to the fact that cancer cells contain higher levels of sodium to begin with, making them more vulnerable to sodium overload.

As part of another experiment, the researchers injected mice with cancer cells that were already killed by SCNPs. After the injection, the animals became more resistant to developing new cancer, which the researchers explained was due to the immune response triggered by the death of cancer cells earlier.

The researchers also performed an experiment in isolated tumor tissues. They injected primary tumors with SCNPs and left secondary tumors untreated. They found that the secondary tumors in treated mice grew much slower than secondary tumors whose primary tumors were not injected with the nanoparticles. (Related: You’re golden: Researchers look at gold nanoparticles for improved cancer detection.)

In sum, these findings suggested that SCNPs could kill cancer cells and confer anti-cancer immunity. Xie also noted that the nanoparticles are safe for human use since they turn into salts after rupturing a cell. They would then merge harmlessly with the body’s fluid system. He added that SCNPs are best suited for localized rather than systemic therapy because they dissolve relatively easily in water.

Purpose in life by day linked to better sleep at night

 Northwestern University and Rush University Medical Center, July 10, 2021

Having a good reason to get out of bed in the morning means you are more likely to sleep better at night with less sleep apnea and restless leg syndrome, reports a new Northwestern Medicine and Rush University Medical Center study based on older adults.

This is the first study to show having a purpose in life specifically results in fewer sleep disturbances and improved sleep quality and over a long period of time. Previous research showed having a purpose in life generally improves overall sleep when measured at a single point in time.

Although the participants in the study were older, researchers said the findings are likely applicable to the broader public.

“Helping people cultivate a purpose in life could be an effective drug-free strategy to improve sleep quality, particularly for a population that is facing more insomnia,” said senior author Jason Ong, an associate professor of neurology at Northwestern University Feinberg School of Medicine. “Purpose in life is something that can be cultivated and enhanced through mindfulness therapies.”

The paper will be published in the journal Sleep Science and Practice.

Individuals have more sleep disturbances and insomnia as they get older. Clinicians prefer to use non-drug interventions to improve patients’ sleep, a practice now recommended by the American College of Physicians as a first line treatment for insomnia, Ong said.

The next step in the research should be to study the use of mindfulness-based therapies to target purpose in life and resulting sleep quality, said Arlener Turner, the study’s first author and a former postdoctoral fellow in neurology at Feinberg.

The 823 participants—non-demented individuals 60 to 100 years old with an average age of 79—were from two cohorts at Rush University Medical Center. More than half were African American and 77 percent were female.

People who felt their lives had meaning were 63 percent less likely to have sleep apnea and 52 percent less likely to have restless leg syndrome. They also had moderately better sleep quality, a global measure of sleep disturbance.

For the study, participants answered a 10-question survey on purpose in life and a 32-question survey on sleep. For the purpose in life survey, they were asked to rate their response to such statements as, “I feel good when I think of what I’ve done in the past and what I hope to do in the future.”

The next step in the research should be to study the use of mindfulness-based therapies to target purpose in life and resulting sleep quality, Turner said.

Poor sleep quality is related to having trouble falling asleep, staying asleep and feeling sleepy during the day. Sleep apnea is a common disorder that increases with age in which a person has shallow breathing or pauses in breathing during sleep several times per hour. This disruption often makes a person feel unrefreshed upon waking up and excessively sleepy during the day.

Restless leg syndrome causes uncomfortable sensations in the legs and an irresistible urge to move them. Symptoms commonly occur in the late afternoon or evening hours and are often most severe at night when a person is resting, such as sitting or lying in bed.

Study reveals source of remarkable memory of “superagers”

For the first time, researchers have used fMRI to understand how some older adults can learn and remember new information as well as a 25-year-old.

Massachusetts General Hospital, July 6, 2021

As we age, our brains typically undergo a slow process of atrophy, causing less robust communication between various brain regions, which leads to declining memory and other cognitive functions. But a rare group of older individuals called “superagers” have been shown to learn and recall novel information as well as a 25-year-old. Investigators from Massachusetts General Hospital (MGH) have now identified the brain activity that underlies superagers’ superior memory. “This is the first time we have images of the function of superagers’ brains as they actively learn and remember new information,” says Alexandra Touroutoglou, PhD, director of Imaging Operations at MGH’s Frontotemporal Disorders Unit and senior author of the paper published in Cerebral Cortex.

In 2016, Touroutoglou and her fellow researchers identified a group of adults older than 65 with remarkable performance on memory tests. The superagers are participants in an ongoing longitudinal study of aging at MGH led by Bradford Dickerson, MD, director of the Frontotemporal Disorders Unit at MGH, and Lisa Feldman Barrett, PhD, a research scientist in Psychiatry at MGH. “Using MRI, we found that the structure of superagers’ brains and the connectivity of their neural networks more closely resemble the brains of young adults; superagers had avoided the brain atrophy typically seen in older adults,” says Touroutoglou.

In the new study, the investigators gave 40 adults with a mean age of 67 a very challenging memory test while their brains were imaged using functional magnetic resonance imaging (fMRI), which, unlike typical MRI, shows the activity of different brain areas during tasks. Forty-one young adults (mean age of 25) also took the same memory test while their brains were imaged. The participants first viewed 80 pictures of faces or scenes that were each paired with an adjective, such as a cityscape paired with the word “industrial” or a male face paired with the word “average.” Their first task was to determine whether the word matched the image, a process called encoding. After 10 minutes, participants were presented with the 80 image-word pairs they had just learned, an additional 40 pairs of new words and images, and 40 rearranged pairs consisting of words and images they had previously seen. Their second task was to recall whether they had previously seen each specific word-picture pair, or whether they were looking at a new or rearranged pair.

While the participants were in the scanner, the researchers paid close attention to the visual cortex, which is the area of the brain that processes what you see and is particularly sensitive to aging. “In the visual cortex, there are populations of neurons that are selectively involved in processing different categories of images, such as faces, houses or scenes,” says lead author Yuta Katsumi, PhD, a postdoctoral fellow in Psychiatry at MGH. “This selective function of each group of neurons makes them more efficient at processing what you see and creating a distinct memory of those images, which can then easily be retrieved.”

During aging, this selectivity, called neural differentiation, diminishes and the group of neurons that once responded primarily to faces now activates for other images. The brain now has difficulty creating unique neural activation patterns for different types of images, which means it is making less distinctive mental representations of what the person is seeing. That’s one reason older individuals have trouble remembering when they may have seen a television show, read an article, or eaten a specific meal.

But in the fMRI study, the superagers’ memory performance was indistinguishable from the 25-year-olds’, and their brains’ visual cortex maintained youthful activity patterns. “The superagers had maintained the same high level of neural differentiation, or selectivity, as a young adult,” says Katsumi. “Their brains enabled them to create distinct representations of the different categories of visual information so that they could accurately remember the image-word pairs.”

An important question that researchers still must answer is whether “superagers’ brains were always more efficient than their peers, or whether, over time, they developed mechanisms to compensate for the decline of the aging brain,” says Touroutoglou.

Previous studies have shown that training can increase the selectivity of brain regions, which may be a potential intervention to delay or prevent the decline in neural differentiation in normal aging adults and make their brains more like those of superagers. Currently the researchers are conducting a clinical trial to evaluate whether noninvasive electromagnetic stimulation, which delivers an electrical current to targeted areas of the brain, can improve memory in older adults. The researchers also plan to study different brain regions to further understand how superagers learn and remember, and they will examine lifestyle and other factors that might contribute to superagers’ amazing memory.

Exercise prompts cells to react in a way that could protect against bone cancer and other bone-related illnesses

Nottingham Trent University (UK), July 8 2021

Scientists at Nottingham Trent University say that such occurrences in the bone cells is also likely to play an important role in helping to limit the risk of other bone illnesses, such as osteoporosis.

The research team, which included musculoskeletal biologists and cancer researchers, aimed to identify the mechanisms involved in bone tissue regeneration and the cancer-protective actions of exercise.

They show for the first time that, following exercise, human bone cells trigger a series of events in the body linked to the cell cycle, DNA repair and cancer—including the ‘P53’ gene, which is a known tumor suppressor.

They found that exercised bone cells secreted proteins which are implicated in ossification, the natural process of bone formation and remodeling.

The researchers argue that the process of new bone formation and remodeling as a result of exercise could potentially leave little room for cancer cells, such as breast or prostate cancer, to invade the bones and to become established through metastasis.

This same process could also contribute to the maintenance of bone mass and therefore limit the progression of osteoporosis.

Metastasis is the spreading of cancer from its original site to other parts of the body, such as other organs, or bones.

The survival of cancer patients could be significantly improved by stopping the spread of cancer to the bones.

The research pinpoints two potential mechanisms driving this cancer protective effect, the researchers say.

For the study, the researchers used human bone cells, cultured in a bioreactor to mimic the mechanical load that cells experience when someone is exercising.

While exercise is known for its regenerative and cancer protective effects, until now the underpinning mechanisms for this in relation to metastatic bone cancer and potentially other bone illnesses had not been established.

Investigating tissue regeneration in this way—by seeing how the bones cells respond to mechanical loading to mimic exercise—is a new area of study and helps to overcome the significant challenges which would be involved in using volunteers.

“The signaling pathways and biological processes we observed in this process in response to exercise were significant,” said lead researcher Dr. Lívia Santos, an expert in musculoskeletal biology in Nottingham Trent University’s School of Science and Technology.

She said “Our findings are important from a clinical perspective because they will help to inform regenerative rehabilitation protocols for patients with bone conditions or metastatic cancer. From a motivational standpoint we hope that a better understanding of the therapeutic benefits of exercise might motivate more patients to engage in such physical activities.

“This is a new area of study, our work was a cell-based model replicating the mechanical load experienced by someone exercising. Further work with other bone cells would be required to explore whether it is impact-type exercise, or other forms of exercise, which might best active these processes.”

Senior researcher Dr. David Boocock, an expert in proteomics and cancer in Nottingham Trent University’s John Van Geest Cancer Research Centre, added: “A better understanding of the incredibly complex changes that occur in the body after even only a single bout of exerciseand the implications on disease is an important area of research, and we have the tools available today to do this.”

The study is published in the journal npj Regenerative Medicine.

Western-style diet linked to state-dependent memory inhibition

Macquarie University (Australia) July 12, 2021

Obesity may ultimately be a disease of the brain, involving a progressive deterioration of various cognitive processes that influence eating. Researchers at Macquarie University have now shown that memory inhibition – the useful ability to ‘block out’ memories that are no longer useful, which depends on a brain area called the hippocampus – is linked to dietary excess. Usually, food-related memories should be at the forefront during hunger but then inhibited during fullness, so that thoughts of food are set aside when eating is no longer top priority. Prior animal studies have shown that a Western diet – one high in fats and sugars and low in fruit, vegetable and fiber – impairs the memory inhibition abilities of the hippocampus. Practically, this could mean that a Western-style diet makes it harder to inhibit pleasant memories triggered by seeing or smelling palatable food. This would make it hard to resist delicious treats even if one were full.

The Macquarie researchers have now found evidence for this problem in humans, they reported this week at the annual meeting of the Society for the Study of Ingestive Behavior (SSIB), the foremost society for research into all aspects of eating and drinking behaviour. The study supported by the Australian Research Council and led by PhD student Tuki Attuquayefio looked at healthy young people, some of whom ate a Western-style diet. Participants completed learning and memory tests that depend on the hippocampus and also rated their liking and wanting of palatable snack foods before and after a filling lunch. Participants who habitually ate a Western-style diet were slower at learning and poorer at remembering than those who ate a healthier diet, and more importantly showed much smaller reductions in wanting palatable snacks when tested full compared to hungry. The key finding is that memory performance and snack food ratings were linked. “Even though they were full, they still wanted to eat the sweet and fatty junk food”, explained Tuki Attuquayefio. “What was even more interesting was that this effect was strongly related to their performance on the learning and memory task, suggesting that there is a link between the two via the hippocampus.”

In agreement with the animal research, people with greater intake of a high fat, high sugar diet may do more poorly on the learning and memory tests because of how the diet impacts the hippocampus. The Macquarie University researchers believe inability to inhibit food memories when in a satiated physiological state could then explain the persistent desire for snacks. For otherwise healthy, lean, young people who routinely consume high-fat high-sugar diets, compromised hippocampal function may make it harder to regulate food intake and set them upon the road towards obesity.

Yoga helps reduce work-related stress

Nevada Health District Lab, July 9, 2021

Physical relaxation through yoga or other practices can help reduce work-related stress, according to an analysis of studies conducted in healthcare staff.

The analysis, which is published in the Journal of Occupational Health, included 15 randomized clinical trials with a total of 688 healthcare workers. The studies examined the effects of yoga, massage therapy, progressive muscle relaxation, and stretching on alleviating stress and improving physical and mental health.

Overall, the physical relaxation methods reduced measures of occupational stress compared with no intervention. More detailed analyses indicated that only yoga and massage therapy were more effective than no intervention, with yoga being the best method.

“Work-related stress has been linked with cardiovascular disease, diabetes, depression, and other serious causes of morbidity. Our results suggest that physical relaxation methods are helpful in reducing occupational stress,” said lead author Michael Zhang, MD, of the Southern Nevada Health District. “Yoga is particularly effective and can be delivered virtually, making it convenient for employers to offer distance options to promote worker health.”