Sunday, December 26, 2021

 

The best way to follow through on your New Year's resolution? Make an 'old year's resolution'

The best way to follow through on your New Year's resolution? Make an 'old year's resolution'
Benjamin Franklin recorded his slip-ups over the course of a week. Credit: The Huntington Library, Art Museum, and Botanical Gardens

If you've made a New Year's resolution, your plot for self-improvement probably kicks into gear sometime on Jan. 1, when the hangover wears off and the quest for the "new you" begins in earnest.

But if research on habit change is any indication, only about half of New Year's resolutions are likely to make it out of January, much less last a lifetime.

As experts in positive psychology and literature, we recommend an unconventional but more promising approach.

We call it the "old year's resolution."

It combines insights from psychologists and America's first self-improvement guru, Benjamin Franklin, who pioneered a habit-change model that was way ahead of its time.

With the "old year" approach, perhaps you can sidestep the inevitable challenges that come with traditional New Year's resolutions and achieve lasting, positive changes.

A period to practice—and fail

Research has highlighted two potential pitfalls with New Year's resolutions.

First, if you lack the confidence to invest in a full-fledged effort, failure to achieve the goal may become a self-fulfilling prophesy. Furthermore, if you maintain the change but perceive progress as unacceptably slow or inadequate, you may abandon the effort.

The old year's resolution is different. Instead of waiting until January to start trying to change your life, you do a dry run before the New Year begins.

How does that work?

First, identify a change you want to make in your life. Do you want to eat better? Move more? Sock away more savings? Now, with Jan. 1 days away, start living according to your commitment. Track your progress. You might stumble now and then, but here's the thing: You're just practicing.

If you've ever rehearsed for a play or played scrimmages, you've used this kind of low-stakes practice to prepare for the real thing. Such experiences give us permission to fail.

Psychologist Carol Dweck and her colleagues have shown that when people see failure as the natural result of striving to achieve something challenging, they are more likely to persist to the goal.

However, if people perceive failure as a definitive sign that they are not capable—or even deserving—of success, failure can lead to surrender.

If you become convinced that you cannot achieve a goal, something called "learned helplessness" can result, which means you're likely to abandon the endeavor altogether.

Many of us unintentionally set ourselves up for failure with our New Year's resolutions. On Jan. 1, we jump right into a new lifestyle and, unsurprisingly, slip, fall, slip again—and eventually never get up.

The old year's resolution takes the pressure off. It gives you permission to fail and even learn from failure. You can slowly build confidence, while failures become less of a big deal, since they're all happening before the official "start date" of the resolution.

A gardener weeding one bed at a time

Long before he became one of America's greatest success stories, Franklin devised a method that helped him overcome life's inevitable failures—and could help you master your old year's resolutions.

When he was still a young man, Franklin came up with what he called his "bold and arduous project of arriving at moral perfection." With charming confidence, he set out to master 13 virtues, including temperance, frugality, chastity, industry, order and humility.

In a typically Franklinian move, he applied a little strategy to his efforts, concentrating on one virtue at a time. He likened this approach to that of a gardener who "does not attempt to eradicate all the bad herbs at once, which would exceed his reach and his strength, but works on one of the beds at a time."

In his autobiography, where he described this project in detail, Franklin did not say that he tied his project to a new year. He also did not give up when he slipped once—or more than once.

"I was surpris'd to find myself so much fuller of faults than I had imagined; but I had the satisfaction of seeing them diminish," Franklin wrote.

He made his progress visible in a book, where he recorded his slip-ups. One page—perhaps only a hypothetical example—shows 16 of them tied to "temperance" in a single week. (Instead of marking faults, we recommend recording successes in line with the work of habit expert B.J. Fogg, whose research suggests that celebrating victories helps to drive habit change.)

Repeated failures might discourage someone enough to abandon the endeavor altogether. But Franklin kept at it—for years. To Franklin, it was all about perspective: This effort to make himself better was a "project," and projects take time.

'A better and a happier man'

Many years later, Franklin admitted that he never was perfect, despite his best efforts. His final assessment, however, is worth remembering: "But, on the whole, tho' I never arrived at the perfection I had been so ambitious of obtaining, but fell far short of it, yet I was, by the endeavor, a better and a happier man than I otherwise should have been if I had not attempted it."

Treating self-improvement as a project with no rigid time frame worked for Franklin. In fact, his scheme probably helped him succeed wildly in business, science and politics. Importantly, he also found immense personal satisfaction in the endeavor: "This little artifice, with the blessing of God," he wrote, was the key to "the constant felicity of his life, down to his 79th year, in which this is written."

You can enjoy the same success Franklin did if you start on your own schedule—now, during the old year—and treat self-improvement not as a goal with a starting date but as an ongoing "project."

It might also help to remember Franklin's note to himself on a virtue he called, coincidentally, "Resolution": "Resolve to perform what you ought; perform without fail what you resolve."

Provided by The Conversation 

 

A 10-minute run can boost brain processing

A 10-minute run can boost brain processing
Credit: Pressmaster/Shutterstock

Running may be a useful activity to undertake for better mental health. University of Tsukuba researchers have found that only 10 minutes of moderate-intensity running increases local blood flow to the various loci in the bilateral prefrontal cortex—the part of the brain that plays an important role in controlling mood and executive functions. These findings may contribute to the development of a wider range of treatment recommendations to benefit mental health.

26 dec 2021--There's clear evidence that physical activity has many benefits, such as the ability to improve mood, but in previous studies, cycling was often the form of exercise studied. Running, however, has always played an important role in the well-being of humans. The unique form and efficiency of human running, which includes the ability to sustain this form of exertion (i.e., by jogging as opposed to sprinting), and the evolutionary success of humans are closely linked.

Despite this fact, researchers had not yet looked closely at the effects of running on brain regions that control mood and executive functions. "Given the extent of executive control required in coordinating balance, movement, and propulsion during running, it is logical that there would be increased neuronal activation in the prefrontal cortex and that other functions in this region would benefit from this increase in brain resources," explains Professor Hideaki Soya.

To test their hypothesis, the research team used the well-established Stroop Color-Word Test and captured data on hemodynamic changes associated with brain activity while participants were engaged in each task. For example, in one task, incongruent information was shown, i.e., the word "red" written in green, and the participant must name the color rather than read out the word. To do so, the brain must process both sets of information and inhibit the extraneous information. The Stroop interference effect was quantified by the difference in response times for this task and those for a simpler version of the task—stating the names of color swatches.

The results demonstrated that, after 10 minutes of moderate-intensity running, there was a significant reduction in Stroop interference effect time. Furthermore, bilateral prefrontal activation had significantly increased during the Stroop task. After running, participants reported being in a better mood. "This was supported by findings of coincident activations in the prefrontal cortical regions involved in mood regulation," first author Chorphaka Damrongthai adds.

Given that many characteristics of the human prefrontal cortex are uniquely human, this study not only sheds light on the present benefits of running but also on the possible role that these benefits may have played in the evolutionary past of humans.


More information: Chorphaka Damrongthai et al, Benefit of human moderate running boosting mood and executive function coinciding with bilateral prefrontal activation, Scientific Reports (2021). DOI: 10.1038/s41598-021-01654-z
Provided by University of Tsukuba 

 

Self-administered cognition test predicts early signs of dementia sooner

Self-administered cognition test predicts early signs of dementia sooner
Dr. Douglas Scharre reviews the results of a patient's cognitive test at The Ohio State University Wexner Medical Center. A new study finds the SAGE test he developed accurately identifies early signs of dementia at least six months earlier than standard testing, allowing treatment to start sooner. Credit: The Ohio State University Wexner Medical Center

Many people experience forgetfulness as they age, but it's often difficult to tell if these memory issues are a normal part of aging or a sign of something more serious. A new study finds that a simple, self-administered test developed by researchers at The Ohio State University Wexner Medical Center, College of Medicine and College of Public Health can identify the early, subtle signs of dementia sooner than the most commonly used office-based standard cognitive test.

26 dec 2021--This earlier detection by the Self-Administered Gerocognitive Examination (SAGE test) is critical to effective treatment, especially as new therapeutics for dementia and Alzheimer's disease are being developed and approved.

"New disease modifying therapies are available and others are currently being evaluated in clinical trials, and we know that the earlier cognitive impairment is detected, the more treatment choices a patient has and the better the treatments work," said Dr. Douglas Scharre, director of the Division of Cognitive Neurology at Ohio State Wexner Medical Center and lead author of the study published in the journal Alzheimer's Research & Therapy.

While the test does not definitively diagnose problems like Alzheimer's, it allows doctors to get a baseline of their patients' cognitive functioning, and repeat testing allows them to follow their memory and thinking abilities over time. "Often primary care physicians may not recognize subtle cognitive deficits during routine office visits," Scharre said.

The eight-year study followed 665 consecutive patients in Ohio State's Center for Cognitive and Memory Disorders. Researchers found that the SAGE test accurately identified patients with mild cognitive impairment who eventually progressed to a dementia diagnosis at least six months earlier than the most commonly used testing method called the Mini-Mental State Examination (MMSE).

Among the 164 patients with baseline mild cognitive impairment, 70 patients converted to dementia. This is a 43% conversion rate over three to four years which is similar to rates from other academic center-based studies, Scharre said. The distribution of dementia diagnoses included 70% Alzheimer's disease dementia, 7% Lewy body dementia, and 9% pure or mixed vascular dementia.

The test can be taken anywhere whenever there are cognitive concerns. It takes only about 10-15 minutes to complete, and the four interchangeable forms are designed to reduce learning effects from recurrent testing over time. The cognitive domains tested with the 11-item test include orientation, language, calculations, memory, abstraction, executive function, and constructional abilities. The MMSE does not test abstractions or executive function abilities.

"Any time you or your family member notices a change in your brain function or personality you should take this test," Scharre said. "If that person takes the test every six months and their score drops two or three points over a year and a half, that is a significant difference, and their doctor can use that information to get a jump on identifying the causes of the cognitive loss and to make treatment decisions."

Self-administered cognition test predicts early signs of dementia sooner
Frank Rupnik looks at family photos with his wife, Nancy, in their Delaware, Ohio home. Frank was diagnosed with early-stage Alzheimer's disease and takes the digital Brain Test on a tablet every six months that informs his neurologist about any changes in cognition or needed adjustments in treatment. Credit: The Ohio State University Wexner Medical Center

Scharre has worked closely with BrainTest Inc SEZC to develop a scientifically validated digital version of the SAGE test called BrainTest that can be taken anywhere on a tablet or touch screen computer. This digital version will also be integrated with the Ohio State Wexner Medical Center's electronic medical records system to better facilitate self-testing, storing and reviewing results for patients and their health care providers.

"Based on cognitive score changes, clinicians and families may decide it is time to act on safety and supervision needs. This might include, for example, medication oversight, financial assistance, driving limitations, setting up durable Powers of Attorney and other legal arrangements/trusts, change in living arrangements, and enhanced caregiving support," Scharre said.

More than 6 million Americans have Alzheimer's disease, and those numbers are expected to rise to more than 13 million by 2050. Deaths from Alzheimer's and other dementias have increased 16% during the COVID-19 pandemic, according to the Alzheimer's Association.

Access SAGE or BrainTest at wexnermedical.osu.edu/SAGE.

Scharre is a member of the Scientific Advisory Board and is Head of Medical Affairs for BrainTest.

More information: Douglas W. Scharre et al, Self-Administered Gerocognitive Examination: longitudinal cohort testing for the early detection of dementia conversion, Alzheimer's Research & Therapy (2021). DOI: 10.1186/s13195-021-00930-4
Provided by Ohio State University Medical Center 

 

Antipsychotic drugs may increase risk of breast cancer

pink pills
Credit: Pixabay/CC0 Public Domain

Tracking medications provided to over a half million U.S. women, researchers at Washington University School of Medicine in St. Louis have found that many commonly prescribed older antipsychotic medications, and some newer ones, are associated with a significant increase in risk of breast cancer. Antipsychotics are prescribed for a broad range of conditions, including depression, bipolar disorder, schizophrenia, dementia and autism spectrum disorders.

26 dec 2021--While earlier studies have uncovered links between antipsychotic drug use and breast cancer risk, this is the first study to compare newer antipsychotics to older drugs, and to look at how the drugs affect levels of a hormone called prolactin. Increased levels of prolactin have been associated with breast cancer.

Prolactin is an important hormone involved in puberty, pregnancy and breastfeeding. However, many antipsychotics elevate prolactin levels and can produce side effects such as menstrual cycle irregularities, abnormal breast milk production and abnormal breast tissue growth.

The findings will be published in the February issue of the Journal of Clinical Psychopharmacology but are available online.

"Many women with psychiatric illnesses such as schizophrenia and bipolar disorder will take antipsychotics for decades, and they are essential to keeping symptoms in check," said the paper's first author, Tahir Rahman, MD, associate professor of psychiatry. "But both older antipsychotic medicines and some newer drugs raise levels of prolactin and increase the risk of breast cancer, which is concerning. Our study confirms findings from a smaller European study that advised women and their doctors to first try drugs that don't affect prolactin levels. We agree with that advice and believe psychiatrists should start to monitor prolactin levels in their patients taking antipsychotics."

The researchers classified antipsychotic drugs into three categories, based on their established effects on prolactin. Category 1 included drugs associated with high prolactin levels, such as haloperidol, paliperidone and risperidone. Category 2 drugs, which had mid-range effects on prolactin, included the drugs iloperidone, lurasidone and olanzapine. Category 3 included drugs with less of an effect on prolactin levels, such as aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, quetiapine and ziprasidone.

The researchers compared the effects of all three categories of antipsychotic drugs to anticonvulsant drugs and lithium, which also often are prescribed to treat psychiatric disorders. When compared with those drugs, the relative risk of breast cancer was 62% higher for women who took Category 1 drugs and 54% higher for those taking Category 2 drugs, whereas Category 3 antipsychotics were not associated with any increase in breast cancer risk.

"Certain drugs are known to elevate prolactin, and the women taking those drugs were more likely to have breast cancer," Rahman said. "But we didn't detect any increased risk in women taking antipsychotics that don't raise prolactin levels."

In mouse models, prolactin can contribute to a weakening of cellular systems that keep precancerous lesions from becoming breast cancer. In people, prolactin levels tend to be lower in women who have had more children at a younger age than in women who have fewer children or wait until they are older to do so.

In this study using data collected from 2012 through 2016, the research team performed a retrospective, observational study of breast cancer risk in women ages 18 through 64 who took antipsychotics. The data came from the IBM MarketScan and Multi-State Medicaid databases, which contain anonymized medical information on more than 170 million people.

Rahman and his colleagues used billing codes from the databases to learn which patients were treated for breast cancer during a 12-month period. Next, they matched that information to patients taking antipsychotic drugs. Of the 540,737 women in the database taking antipsychotics, only 914 were identified as having breast cancer. But a significant number of those women were taking drugs known to increase prolactin.

"Antipsychotic medications can be lifesaving for patients who have psychotic episodes where they experience symptoms such as hallucinations and delusions," Rahman said. "In recent years, the drugs have been approved to treat other conditions, too, including depression and bipolar disorder. As those high-prolactin agents are used more widely, the number at risk could increase. We've been advising against using these high-prolactin agents in women who already have breast cancer, but we'd like to investigate whether keeping prolactin levels lower even might prevent some of these cancers."

In another recent study, his team analyzed blood samples from women who took the antipsychotic drug aripiprazole (Abilify) as an add-on treatment for depression. They found that their prolactin levels did not increase and that a few women who began the study with high prolactin levels experienced decreases in prolactin levels after 12 weeks of treatment.

Those findings—combined with preclinical evidence of the anticancer effects of some antipsychotics—have inspired Rahman and his colleagues to propose repurposing some antipsychotic drugs in the fight against breast cancer.

"We don't want to alarm patients taking antipsychotic drugs for life-threatening mental health problems, but we also think it is time for doctors to track prolactin levels and vigilantly monitor their patients who are being treated with antipsychotics," Rahman said.


More information: Tahir Rahman et al, Risk of Breast Cancer With Prolactin Elevating Antipsychotic Drugs, Journal of Clinical Psychopharmacology (2021). DOI: 10.1097/JCP.0000000000001513
Provided by Washington University School of Medicine in St. Louis 

 

Medicines for anxiety and antidepressants trigger post-surgery delirium

Medicines for anxiety and antidepressants trigger post-surgery delirium
Credit: DOI: 10.1007/s40264-021-01136-1

Older people taking a medicine used to treat anxiety and insomnia—nitrazepam—as well as those on antidepressants, are twice as likely to suffer postoperative delirium after hip and knee surgery, a new Australian study has found.

26 dec 2021--The finding has prompted calls by University of South Australia (UniSA) researchers for older patients to temporarily cease these medications or change to safer alternatives prior to surgery.

In a study published in the international journal Drug Safety, UniSA scientists scanned data from 10,456 patients aged 65 years and older who had undergone knee or hip surgery in the past 20 years. A quarter of them (2614 people) had experienced delirium after surgery.

Apart from nitrazepam, five medications—commonly prescribed for depression and various anxiety disorders including obsessive-compulsive disorder and post-traumatic stress disorder—were associated with delirium, although not to the same extent. They included mirtazapine, sertraline, venlafaxine, citalopram and fluvoxamine.

Lead researcher Dr. Gizat Kassie says no link was found between pain-relieving opioids and delirium.

"Our findings show that some medicine types within the same classes of medicines are riskier than others when it comes to causing delirium after surgery, and the older the patients are, the greater the risk," he says.

Smoking, alcohol use, multiple health conditions, polypharmacy (taking five or more medications), male gender, older age and impaired cognition also put people at risk.

Many of these factors can't be altered but we can do something about medications.

"Delirium affects up to 55 percent of older patients undergoing hip surgery and is associated with an increased risk of death, prolonged hospital stays and cognitive decline. Delirium is costly to manage and puts enormous stress on the healthcare system, health professionals and families," Dr. Kassie says.

An earlier study found that older people who developed delirium following hip surgery had a 10 percent higher death rate within one year compared to patients who were not affected.

The UniSA study is the first to investigate the link between specific medications and delirium after surgery. Previous studies have been broader in scope, considering a range of factors predisposing older patients to delirium.

The researchers hope that evidence-based recommendations can be implemented into clinical practice so that delirium risk by medicines can be reduced.

"In people undergoing elective procedures it should be practical to taper specific medications well in advance. It's important that people are weaned off these riskier drugs well before surgery because abrupt withdrawal can have even worse consequences," Dr. Kassie says.

"The Risk of Preoperative Central Nervous System-Acting Medications on Delirium Following Hip or Knee Surgery: A Matched Case-Control Study" is published in Drug Safety.


More information: Gizat M. Kassie et al, The Risk of Preoperative Central Nervous System-Acting Medications on Delirium Following Hip or Knee Surgery: A Matched Case-Control Study, Drug Safety (2021). DOI: 10.1007/s40264-021-01136-1
Provided by University of South Australia 

 

'Supermeres' may carry clues to cancer, Alzheimer's disease and COVID-19

cells
Credit: CC0 Public Domain

Researchers at Vanderbilt University Medical Center have discovered a nanoparticle released from cells, called a "supermere," which contains enzymes, proteins and RNA associated with multiple cancers, cardiovascular disease, Alzheimer's disease and even COVID-19.

26 dec 2021--The discovery, reported in Nature Cell Biology, is a significant advance in understanding the role extracellular vesicles and nanoparticles play in shuttling important chemical "messages" between cells, both in health and disease.

"We've identified a number of biomarkers and therapeutic targets in cancer and potentially in a number of other disease states that are cargo in these supermeres," said the paper's senior author, Robert Coffey, MD. "What is left to do now is to figure out how these things get released."

Coffey, the Ingram Professor of Cancer Research and professor of Medicine and Cell & Developmental Biology, is internationally known for his studies of colorectal cancer. His team is currently exploring whether the detection and targeting of cancer-specific nanoparticles in the bloodstream could lead to earlier diagnoses and more effective treatment. 

In 2019 Dennis Jeppesen, Ph.D., a former research fellow in Coffey's lab who is now a research instructor in Medicine, used advanced techniques to isolate and analyze small membrane-enclosed extracellular vesicles called "exosomes." 

That year, using high-speed ultracentrifugation, another of Coffey's colleagues, Qin Zhang, Ph.D., research assistant professor of Medicine, devised a simple method to isolate a nanoparticle called an "exomere" that lacks a surface coat.

In the current study, Zhang took the "supernatant," or fluid that remains after the exomeres have been spun into a "pellet," and spun the fluid faster and longer. 

The result was a pellet of nanoparticles isolated from the supernatant of the exomere spin—which the researchers named supermeres. "They're also super-interesting," Coffey quipped, "because they contain many cargo previously thought to be in exosomes."

For one thing, supermeres carry most of the extracellular RNA released by cells and which is found in the bloodstream. Among other functional properties, cancer-derived supermeres can "transfer" drug resistance to tumor cells, perhaps via the RNA cargo they deliver, the researchers reported.

Supermeres are important carriers of TGFBI, a protein that in established tumors promotes tumor progression. TGFBI thus may be a useful marker in liquid biopsies for patients with colorectal cancer, the researchers noted.

They also carry ACE2, a cell-surface receptor that plays a role in cardiovascular disease and is the target of the COVID-19 virus. This raises the possibility that ACE2 carried by supermeres could serve as a "decoy" to bind the virus and prevent infection. 

Another potentially important cargo is APP, the amyloid-beta precursor protein implicated in the development of Alzheimer's disease. Supermeres can cross the blood-brain barrier, suggesting that their analysis could improve early diagnosis or possibly even targeted treatment of the disease.

"The identification of this rich plethora of bioactive molecules … raises interesting questions about the function of supermeres, and heightens interest in the potential of these particles as biomarkers for diseases," researchers at the University of Notre Dame noted in a review published with the paper.


More information: Qin Zhang et al, Supermeres are functional extracellular nanoparticles replete with disease biomarkers and therapeutic targets, Nature Cell Biology (2021). DOI: 10.1038/s41556-021-00805-8

 

Margarines now nutritionally better than butter after hydrogenated oil ban

butter
Credit: CC0 Public Domain

In the U.S. the year-end holidays are here, which not only makes it the season of joy and celebration, but also of butter as many Americans make batches of cookies and creamy comfort foods to celebrate. In 2018, the Food and Drug Administration (FDA) banned partially hydrogenated oils from food products such as margarines in order to reduce the amount of heart-damaging trans fats people consume. A new study from the University of Minnesota School of Public Health recently compared the nutrition composition of margarine products to butter to see which is now the healthier choice in terms of cardiovascular health.

26 dec 2021--"What we found is that in the U.S. marketplace today, margarines are now a better option than butter for your health," said study lead author and public health nutrition student Cecily Weber. "In the past there was a lot of debate about which product was better for you, but now that trans fats have been removed from margarines, they're the best choice in terms of heart health."

The study, led by Weber and co-authored by Professor Lisa Harnack, is the first to comprehensively look at margarine versus butter since the FDA ban went into effect. The details of the study were recently published in the journal Public Health Nutrition.

Weber examined the fatty acid profiles and relevant vitamin and mineral content of 83 margarine/margarine-like and butter blend products available in the U.S. marketplace in 2020 and compared them to butter. Weber collected the information using the Food and Nutrient Database from the University of Minnesota Nutrition Coordinating Center (NCC), which is a database detailing the nutritional content of thousands of foods. Harnack is the director of the NCC.

The study found:

  • Following the ban, margarine and butter blend products contain substantially less saturated fat and cholesterol in comparison to butter, and contain no man-made trans fat.
  • Softer tub and squeeze-tube margarine products were found to contain less saturated fat than stick margarines, making them the better nutritional choice among margarine products.

"The findings are particularly important for registered dietitians and other nutrition-related health professionals so that they can update their advice and offer people the best options in order to promote heart health," says Weber.

Weber says the news is also important for consumers so that they know it's nutritionally wisest to choose tub and squeeze-tube margarines in particular over butter when shopping for food. Tub and squeeze-tube margarines typically contain the least amount of saturated fats, which makes them softer than stick products at room temperature. Weber also added that food manufacturers are to be commended for reformulating their products to eliminate trans fats and maintain their taste and quality while keeping their saturated fat content low.

"It's a public health success story," says Weber. "Consumers no longer have to worry about reading product nutritional labels to see if they contain hydrogenated oils and trans fats. They can just know that they no longer do."


More information: Cecily Weber et al, Nutrient comparisons of margarine/margarine-like products, butter blend products and butter in the US marketplace in 2020 post-FDA ban on partially hydrogenated oils, Public Health Nutrition (2021). DOI: 10.1017/S1368980021004511
Provided by University of Minnesota 

 

SARS-CoV-2 protein interacts with Parkinson's protein, promotes amyloid formation

SARS-CoV-2 protein interacts with Parkinson's protein, promotes amyloid formation
The SARS-CoV-2 N-protein can interact with α-synuclein in the test tube and help it form amyloid fibrils, a hallmark of Parkinson's disease. Credit: Adapted from ACS Chemical Neuroscience 2021, DOI: 10.1021/acschemneuro.1c00666

Case reports of relatively young COVID-19 patients who developed Parkinson's disease within weeks of contracting the virus have led scientists to wonder if there could be a link between the two conditions. Now, researchers reporting in ACS Chemical Neuroscience have shown that, at least in the test tube, the SARS-CoV-2 N-protein interacts with a neuronal protein called α-synuclein and speeds the formation of amyloid fibrils, pathological protein bundles that have been implicated in Parkinson's disease.

26 dec 2021--In addition to respiratory symptoms, SARS-CoV-2 can cause neurological problems, such as loss of smell, headaches and "brain fog." However, whether these symptoms are caused by the virus entering the brain, or whether the symptoms are instead caused by chemical signals released in the brain by the immune system in response to the virus, is still controversial. In Parkinson's disease, a protein called α-synuclein forms abnormal amyloid fibrils, leading to the death of dopamine-producing neurons in the brain. Interestingly, loss of smell is a common premotor symptom in Parkinson's disease. This fact, as well as case reports of Parkinson's in COVID-19 patients, made Christian Blum, Mireille Claessens and colleagues wonder whether protein components of SARS-CoV-2 could trigger the aggregation of α-synuclein into amyloid. They chose to study the two most abundant proteins of the virus: the spike (S-) protein that helps SARS-CoV-2 enter cells, and the nucleocapsid (N-) protein that encapsulates the RNA genome inside the virus.

In test tube experiments, the researchers used a fluorescent probe that binds amyloid fibrils to show that, in the absence of the coronavirus proteins, α-synuclein required more than 240 hours to aggregate into fibrils. Adding the S-protein had no effect, but the N-protein decreased the aggregation time to less than 24 hours. In other experiments, the team showed that the N- and α-synuclein proteins interact directly, in part through their opposite electrostatic charges, with at least 3–4 copies of α-synuclein bound to each N-protein. Next, the researchers injected N-protein and fluorescently labeled α-synuclein into a cell model of Parkinson's disease, using a similar concentration of N-protein as would be expected inside a SARS-CoV-2-infected cell. Compared to control cells with only α-synuclein injected, about twice as many cells died upon injection of both proteins. Also, the distribution of α-synuclein was altered in cells co-injected with both proteins, and elongated structures were observed, although the researchers could not confirm that they were amyloid. It's unknown whether these interactions also occur within neurons of the human brain, but if so, they could help explain the possible link between COVID-19 infection and Parkinson's disease, the researchers say.


More information: Slav A. Semerdzhiev et al, Interactions between SARS-CoV-2 N-Protein and α-Synuclein Accelerate Amyloid Formation, ACS Chemical Neuroscience (2021). DOI: 10.1021/acschemneuro.1c00666
Provided by American Chemical Society

 

Uncovered: Key to how exercise protects against consequences of ageing

Uncovered: Key to how exercise protects against consequences of ageing
Staining showing mitochondria within individual muscle fibres. Credit: Monash University

Monash University, Australia scientists have discovered an enzyme that is key to why exercise improves our health. Importantly this discovery has opened up the possibility of drugs to promote this enzyme's activity, protecting against the consequences of aging on metabolic health, including type 2 diabetes.

26 dec 2021--The proportion of people worldwide over 60 years old will double in the next three decades and by 2031, more than six million Australians will be over 65 years old. The incidence of type 2 diabetes increases with age so this aging population will also result in an increased incidence of the disease globally.

One of the main reasons for the increased prevalence of type 2 diabetes with age is the development of insulin resistance, or an inability for the body to respond to insulin, and this is often caused by reduced physical activity as we age.

However, the precise mechanisms by which physical inactivity facilitates the development of insulin resistance has remained a mystery.

Now researchers from Monash University in Australia have discovered how  actually enhances insulin responsiveness and in turn promotes metabolic health. Importantly, the enzymes they have discovered that are key to this mechanism have the potential to be targeted by drugs to protect against consequences of aging such as muscle wasting and diabetes.

The team of scientists at the Monash University Biomedicine Discovery Institute (BDI), led by Professor Tony Tiganis, reveals that reductions in skeletal  reactive oxygen species (ROS) generation during aging is instrumental in the development of insulin resistanceAccording to Professor Tiganis, skeletal muscle constantly produces ROS and this is increased during exercise.

"Exercise-induced ROS drives adaptive responses that are integral to the health-promoting effects of exercise," he said.

In a paper published today (15 December) in the journal, Science Advances, the research team show how an enzyme called NOX-4 is essential for exercise-induced ROS and the adaptive responses that drive metabolic health.

In mice the researchers found that NOX4 is increased in skeletal muscle after exercise and that this then leads to increased ROS which elicits adaptive responses that protect mice from the development of insulin resistance, which otherwise occurs with aging or diet induced-obesity.

Importantly, the scientists have shown that the levels of NOX4 in skeletal muscle are directly related to age-associated decline in insulin sensitivity. "In this study we have shown, in animal models, that skeletal muscle NOX 4 abundance is decreased with aging and that this leads to a reduction in insulin sensitivity," Professor Tiganis said.

"Triggering the activation of the adaptive mechanisms orchestrated by NOX4 with drugs, might ameliorate key aspects of aging, including the development of insulin resistance and type 2 diabetes," he said.

"One of these compounds is found naturally, for instance, in cruciferous vegetables, such as broccoli or cauliflower, though the amount needed for anti-aging effects might be more than many would be willing to consume."


More information: Chrysovalantou Xirouchaki et al, Skeletal muscle NOX4 is required for adaptive responses that prevent insulin resistance, Science Advances (2021). DOI: 10.1126/sciadv.abl4988www.science.org/doi/10.1126/sciadv.abl4988
Provided by Monash University 

 

How diet influences taste sensitivity and preference

food
Credit: CC0 Public Domain

What you eat influences your taste for what you might want to eat next. So claims a University of California, Riverside, study performed on fruit flies.

26 dec 2021--The study, published in the Journal of Neuroscience, offers a better understanding of neurophysiological plasticity of the taste system in flies.

To maintain ideal health, animals require a balanced  with optimum amounts of different nutrients. Macronutrients like carbohydrates and proteins are essential; indeed, an unbalanced intake of these nutrients can be detrimental to health. Flies require macronutrients such as sugars and amino acids for survival. They use the gustatory system, the sensory system responsible for the perception of taste, to sense these nutrients and begin feeding.

In their experiments in the lab, the researchers Anindya Ganguly and Manali Dey, led by Anupama Dahanukar, fed adult flies different diets: A balanced diet, a sugar-reduced and protein-enriched diet, and a sugar-enriched and protein-depleted diet. They ensured that all three diets were similar in total calorie content and tested the flies daily for a week to examine modifications in their food choice and taste sensitivity. 

The researchers report that diet affects dopamine and insulin signaling in the brain, which, in turn, affects the flies' peripheral sensory response, which is comprised of neurons directly involved in detecting external stimuli. This response then influences what the flies eat next.

"We found diet changed the flies' taste preference," said Dahanukar, an associate professor of molecular, cell and systems biology. "For a diet with excess protein at the expense of carbohydrates, the flies' taste sensitivity changed so that they mounted a compensatory behavioral response in the short term to eat more carbohydrates and less protein in order to regain a balanced diet."

What this may mean for other animals, including humans, is that conserved signaling pathways could play a role in mounting similar diet-induced changes in taste. Individuals on a high sugar diet could see a dampening of sugar taste, making sugars less palatable at least for the short term. Similarly, a low protein diet would enhance umami taste, increasing the value of protein-rich foods to be consumed next.

"Changes in gene expression appear to be involved," said Ganguly, a former graduate student at UC Riverside and now a postdoctoral researcher at UC Santa Barbara. "We see these changes in flies based on dietary exposure for just a day or two."

Interestingly, when the flies that were fed unbalanced diets were returned to a balanced diet, their taste sensitivity returned to baseline levels, suggesting that changes in taste preference are reversible. 

"Our work shows that imbalances in diet affect your taste preferences in a way that help you in the short term at least," said Dey, a graduate student in Dahanukar's lab. "They help you change your taste so that you prefer foods that benefit you, foods that would help you achieve metabolic homeostasis again."

Dahanukar cautioned, however, that long term effects on consumption may be more complex. For example, research by other scientists has shown that while flies raised on a high sugar diet saw their sugar response decrease in the short term, flies maintained on that diet consumed more of that food in the long term.

Dahanukar, Ganguly, and Dey were joined in the study by Christi Scott and Vi-Khoi Duong. Scott is a former graduate student and postdoctoral researcher at UCR. She helped analyze transcriptome data. Duong is a former undergraduate student who did his honors thesis in Dahanukar's lab. He is now in dental school.


More information: Anindya Ganguly et al, Dietary Macronutrient Imbalances Lead to Compensatory Changes in Peripheral Taste via Independent Signaling Pathways, The Journal of Neuroscience (2021). DOI: 10.1523/JNEUROSCI.2154-20.2021
Provided by University of California - Riverside 

 

Men aged 40-80 more likely to die after surgery than women of the same age, German study finds

surgery
Credit: CC0 Public Domain

Middle-aged men are around 50% more likely to die after surgery than middle-aged women, according to new research being presented at Euroanaesthesia, the annual meeting of the European Society of Anaesthesiology and Intensive Care (ESAIC), held online this year. The study of more than 100,000 non-cardiac patients at a leading German hospital found that mortality rates are higher in men in their 40s and 50s, as well as those in their 60s and 70s.

26 dec 2021--Some previous studies have found that sex affects the risk of complications after surgery but the results have been mixed. One1 showed that men were at higher risk of complications and death after non-cardiac surgery, while another2 found that survival rates after some types of vascular surgery were lower in women than men. A third study3, of ICU patients, found no difference in death rates between the sexes.

To find out more, Dr. Dimislav Andonov and colleagues at the Technical University of Munich, Munich, Germany, analyzed data on 107,471 patients who had undergone non-cardiac surgery at the university's hospital between January 2014 and March 2020.

The procedures included a wide range of elective (planned) operations, such as hip replacements and cancer surgery, and emergency surgeries, such as acute appendicitis and operations on victims of car accidents.

Outpatient and day cases were excluded, as were diagnostic procedures under anaesthesia, electroconvulsive therapy and patients that were in ICU before their operation.

The patients' average age was 53.8 and just over half (54.1%) were male.

No link was found between a patient's sex and the likelihood of them being admitted to the post-anaesthesia care unit or PACU for prolonged post-operative follow-up (Patients who stay more than four hours in the post-anaesthesia recovery room are defined as being in PACU).

Nor was there any link between sex and ICU admission, the need to be put on a ventilator or death before being discharged from hospital in those under 40.

But, in the 41-80 age group, men were more likely to be admitted to ICU, need ventilation and die before discharge than women of the same age.

Men aged 41-60 were 22% more likely to be admitted to ICU than women of the same age, 37% more likely to need ventilation and 54% more likely to die.

Those aged 61-80 were 20% more likely to be admitted to ICU than women of the same age, 31% more likely to need ventilation and 38% more likely to die.

After the age of 80, men's risk of ICU admission, ventilation and death reverted to being the same as that of women of the same age.

The researchers say: "This work demonstrates that male patients aged between 40 and 80 are at higher risk of death in the days after their operation. They are also more likely to be admitted to ICU and to need to be ventilated."

It isn't clear why the risks are higher for men aged 41-80 but one possibility is that higher rates of cardiovascular problems in males make surgical complications more likely.

Plus, the results may be skewed by the inclusion of trauma cases, such as injuries from car accidents, which are often life-threatening and are more common in men.

Male reluctance to go to the doctor may also play a part. Dr. Andonov says: "Men undergo health checks less often than women and, thus, their health problems (for example cancer) may be discovered at a later stage.

"We plan to do more research to clarify the reasons. If we find that men's higher risk isn't being driven by trauma cases, we can think about how to best raise men's awareness of their health.

"And while it isn't yet clear whether males are at higher risk of cardiovascular complications, our findings do suggest that more attention should be paid to cardiovascular risk factors during pre-operative assessments."


More information: 1. Moodley, Y. and B.M. Biccard, S Afr Med J, 2015. 105(2): p. 126-9.

2. Grootenboer, N., et al., Eur J Vasc Endovasc Surg, 2011. 42(4): p. 510-6.

3. Zettersten, E., et al., J Crit Care, 2020. 55: p. 22-27

Provided by The European Society of Anaesthesiology and Intensive Care (ESAIC)

 

Twins study indicates environmental factors significant in Alzheimer's pathology

Twins study indicates environmental factors significant in Alzheimer's pathology
Cerebral autopsy specimen of a patient diagosed having Alzheimer Disease. In the HE stain numerous plaque formations within the neuropil background are visible. Credit: Jensflorian/Wikimedia Commons, CC BY-SA 3.0

The question of genetic vs environmental influences plays a major role in research into brain aging, with researchers from UNSW Sydney's Centre for Healthy Brain Aging (CHeBA) revealing new insights into one of the hallmarks of Alzheimer's disease—amyloid plaques—by looking at the brains of identical and non-identical twins.

26 dec 2021--The world first study, led by Dr. Rebecca Koncz and published in the Journal of Neurology, Neurosurgery & Psychiatry, used a special type of imaging called amyloid PET, or 'position emission tomography' to determine what proportion of amyloid accumulation is determined by genes, and what proportion is determined by environmental, or modifiable risk factors such as high blood pressure and high cholesterol.

"Amyloid is a protein that accumulates in the brain very early in the development of Alzheimer's disease," said Dr. Koncz. "It is a hallmark feature of the condition that starts to accumulate decades before memory problems become apparent."

According to Professor Perminder Sachdev, co-director of CHeBA and leader of the Older Australian Twins Study, twins provide a unique opportunity to investigate the relative importance of genetic and lifestyle factors for Alzheimer's disease, because monozygotic twins share 100 percent of their genetic material, and dizygotic twins share an estimated 50 percent. Australia has one of the world's leading twin registries—Twin Research Australia—members of which participated in the study. The amyloid PET imaging was done in collaboration with the Department of Molecular Imaging and Therapy, Austin Hospital, Melbourne, and the Department of Nuclear Medicine and PET at Prince of Wales Hospital in Sydney.

The researchers discovered that the heritability of amyloid is moderate—meaning genes play only a moderate role in determining the variation in amyloid build up in the brain.

"This is significant, because it tells us that whilst genes are important, there is actually a major environmental contribution that may respond well to intervention," said Dr. Koncz.

"With respect to modifiable risk factors, we examined whether vascular risk factors such as hypertension, diabetes, high cholesterol, or a history of heart disease were significantly associated with amyloid burden or had any shared genetic basis," said Dr. Koncz.

While the study did not find an association between vascular risk factors and amyloid, larger studies are required.

"Identifying modifiable risk factors will lead us to interventions that reduce the risk of amyloid accumulation—and ultimately risk reduction of developing Alzheimer's disease," said Professor Perminder Sachdev.


More information: Rebecca Koncz et al, The heritability of amyloid burden in older adults: the Older Australian Twins Study, Journal of Neurology, Neurosurgery & Psychiatry (2021). DOI: 10.1136/jnnp-2021-326677
Provided by CHeBA