Laughter acts as a stress buffer -- and even smiling helps
July 30, 2020
Science Daily/University of Basel
People who laugh frequently in their everyday lives may be better equipped to deal with stressful events -- although this does not seem to apply to the intensity of laughter. These are the findings reported by a research team from the University of Basel in the journal PLOS ONE.
It is estimated that people typically laugh 18 times a day -- generally during interactions with other people and depending on the degree of pleasure they experience. Researchers have also reported differences related to time of day, age, and gender -- for example, it is known that women smile more than men on average. Now, researchers from the Division of Clinical Psychology and Epidemiology of the Department of Psychology at the University of Basel have recently conducted a study on the relationship between stressful events and laughter in terms of perceived stress in everyday life.
Questions asked by app
In the intensive longitudinal study, an acoustic signal from a mobile phone app prompted participants to answer questions eight times a day at irregular intervals for a period of 14 days. The questions related to the frequency and intensity of laughter and the reason for laughing -- as well as any stressful events or stress symptoms experienced -- in the time since the last signal.
Using this method, the researchers working with the lead authors, Dr. Thea Zander-Schellenberg and Dr. Isabella Collins, were able to study the relationships between laughter, stressful events, and physical and psychological symptoms of stress ("I had a headache" or "I felt restless") as part of everyday life. The newly published analysis was based on data from 41 psychology students, 33 of whom were women, with an average age of just under 22.
Intensity of laughter has less influence
The first result of the observational study was expected based on the specialist literature: in phases in which the subjects laughed frequently, stressful events were associated with more minor symptoms of subjective stress. However, the second finding was unexpected. When it came to the interplay between stressful events and intensity of laughter (strong, medium or weak), there was no statistical correlation with stress symptoms. "This could be because people are better at estimating the frequency of their laughter, rather than its intensity, over the last few hours," says the research team.
https://www.sciencedaily.com/releases/2020/07/200730110114.htm
Hedonism leads to happiness
July 27, 2020
Science Daily/University of Zurich
Relaxing on the sofa or savoring a delicious meal: Enjoying short-term pleasurable activities that don't lead to long-term goals contributes at least as much to a happy life as self-control, according to new research from the University of Zurich and Radboud University in the Netherlands. The researchers therefore argue for a greater appreciation of hedonism in psychology.
We all set ourselves long-term goals from time to time, such as finally getting into shape, eating less sugar or learning a foreign language. Research has devoted much time to finding out how we can reach these goals more effectively. The prevailing view is that self-control helps us prioritize long-term goals over momentary pleasure and that if you are good at self-control, this will usually result in a happier and more successful life.
"It's time for a rethink," says Katharina Bernecker, researcher in motivational psychology at the University of Zurich. "Of course self-control is important, but research on self-regulation should pay just as much attention to hedonism, or short-term pleasure." That's because Bernecker's new research shows that people's capacity to experience pleasure or enjoyment contributes at least as much to a happy and satisfied life as successful self-control.
Distraction disrupts pleasure
Bernecker and her colleague Daniela Becker of Radboud University developed a questionnaire to measure respondents' capacity for hedonism, i.e. their ability to focus on their immediate needs and indulge in and enjoy short-term pleasures. They used the questionnaire to find out whether people differ in their capacity to pursue hedonic goals in a variety of contexts, and whether this ability is related to well-being.
They found that certain people get distracted by intrusive thoughts in moments of relaxation or enjoyment by thinking about activities or tasks that they should be doing instead. "For example, when lying on the couch you might keep thinking of the sport you are not doing," says Becker. "Those thoughts about conflicting long-term goals undermine the immediate need to relax." On the other hand, people who can fully enjoy themselves in those situations tend to have a higher sense of well-being in general, not only in the short term, and are less likely to suffer from depression and anxiety, among other things.
More isn't always better
"The pursuit of hedonic and long-term goals needn't be in conflict with one another," says Bernecker. "Our research shows that both are important and can complement each other in achieving well-being and good health. It is important to find the right balance in everyday life."
Unfortunately, simply sitting about more on the sofa, eating more good food and going to the pub with friends more often won't automatically make for more happiness. "It was always thought that hedonism, as opposed to self-control, was the easier option," says Bernecker. "But really enjoying one's hedonic choice isn't actually that simple for everybody because of those distracting thoughts."
Conscious planning of downtime
This is currently a topical issue with more people working from home, as the environment where they normally rest is suddenly associated with work. "Thinking of the work you still need to do can lead to more distracting thoughts at home, making you less able to rest," says Bernecker.
So what can you do to enjoy your downtime more? More research is needed, but the researchers suspect that consciously planning and setting limits to periods of enjoyment could help to separate them more clearly from other activities, allowing pleasure to take place more undisturbed.
https://www.sciencedaily.com/releases/2020/07/200727114739.htm
Wealthier men are more likely to develop high blood pressure
July 26, 2020
Science Daily/European Society of Cardiology
Working men with higher incomes are more likely to develop high blood pressure, reports a study presented at the 84th Annual Scientific Meeting of the Japanese Circulation Society (JCS 2020).
JCS 2020 takes place online from 27 July to 2 August in conjunction with the Asian Pacific Society of Cardiology Congress 2020 (APSC 2020). Joint scientific sessions are being held by the European Society of Cardiology (ESC) and JCS as part of the ESC Global Activities programme.
"Men with higher incomes need to improve their lifestyles to prevent high blood pressure," said study author Dr. Shingo Yanagiya of the Hokkaido University Graduate School of Medicine, Sapporo, Japan. "Steps include eating healthily, exercising, and controlling weight. Alcohol should be kept to moderate levels and binge drinking avoided."
More than one billion people have high blood pressure worldwide.2 Around 30-45% of adults are affected, rising to more than 60% of people over 60 years of age. High blood pressure is the leading global cause of premature death, accounting for almost 10 million deaths in 2015. Of those, 4.9 million were due to ischaemic heart disease and 3.5 million were due to stroke.
Japan alone has more than 10 million people with high blood pressure, and the number continues to rise. Dr. Yanagiya said: "High blood pressure is a lifestyle-related disease. As a physician seeing these patients I wanted to know if risk varies with socioeconomic class, to help us focus our prevention efforts."
This analysis of the J-HOPE3 study examined the relationship between household income and high blood pressure in Japanese employees. A total of 4,314 staff (3,153 men and 1,161 women) with daytime jobs and normal blood pressure were enrolled in 2012 from 12 workplaces.
Workers were divided into four groups according to annual household income: less than 5 million, 5 to 7.9 million, 8 to 9.9 million, and 10 million or more Japanese yen per year. The researchers investigated the association between income and developing high blood pressure over a two-year period.
Compared to men in the lowest income category, men in the highest income group were nearly twice as likely to develop high blood pressure. Men in the 5 to 7.9 million and 8 to 9.9 million groups had a 50% higher risk of developing high blood pressure compared to men with the lowest incomes, although the positive association did not reach statistical significance in the 8 to 9.9 million group.
The findings were consistent regardless of age, and were independent of baseline blood pressure, worksite, occupation, number of family members, and smoking. The relationships were slightly weakened after accounting for alcohol consumption and body mass index (BMI; kg/m2), both of which were higher for men in the higher income groups.
In women, there was no significant link between income and blood pressure. However, women with higher household income tended to have a lower risk of developing high blood pressure.
"Some previous Japanese surveys have reported that higher household income is associated with more undesirable lifestyles in men, but not in women," said Dr. Yanagiya. "Our study supports this: men, but not women, with higher household incomes were more likely to be obese and drink alcohol every day. Both behaviours are major risk factors for hypertension."
He concluded: "Men with high-paying daytime jobs are at particular risk of high blood pressure. This applies to men of all ages, who can greatly decrease their chance of a heart attack or stroke by improving their health behaviours."
Dr. Yusuke Yoshikawa, public relations coordinator for JCS 2020, said: "Hypertension is one of the most important risk factors of cardiovascular disease in Japan, because the average daily salt intake in Japan (approx. 10 g/day) is much higher than desired. As the current guidelines2 strongly recommend healthy lifestyle to control high blood pressure, this study suggests a potential key to successful intervention for those who are at risk of heart disease and stroke."
https://www.sciencedaily.com/releases/2020/07/200726214837.htm
Remember the first time you...? Mysterious brain structure sheds light on addiction
Cocaine-addicted mice shed light on claustrum's role in associating reward with context
July 23, 2020
Science Daily/The Hebrew University of Jerusalem
Do you remember where you were when you first heard that two planes had crashed into New York's Twin Towers? Or where you had your first kiss? Our brains are wired to retain information that relates to the context in which highly significant events occurred. This mechanism also underlies drug addiction and is the reason why hanging out in an environment or with people associated with memories of drug use often leads to relapse.
How our brains create this strong association, however, is less clear. Now, new research by Professor Ami Citri and PhD student Anna Terem at Hebrew University of Jerusalem (HU)'s Edmond and Lily Safra Center for Brain Sciences and the Alexander Silberman Institute of Life Science, shows that a relatively obscure brain region known as the claustrum plays a significant role in making these connections. They published their findings in the latest edition of Current Biology.
The researchers' findings fit the idea of "incentive salience," the process that determines the desirability of an otherwise neutral stimulus. For example, a candy store façade becomes very attractive to kids after repeated associations with the rewarding treats that lie within. In time, children unconsciously learn to "want" to see the store stimulus, which is separate from their "liking" the actual candy reward. Taking a closer look at how context becomes associated with cocaine, the researchers found a group of neurons within the claustrum that lit up during cocaine use. Further, these neurons are pivotal in the formation of an incentive salience that links context with the pleasure of cocaine.
To determine when and how the claustrum participates in incentive salience, Citri and his team employed a conditioned-place preference (CPP) test for a group of lab mice. During this test, the mice learned to associate reward with context. The researcher administered cocaine to the mice and placed them in an area with distinctive flooring (rugged) and wall patterns (dots), ones that a mouse would notice, as the drug started to kick in. After a few times of this, when placed in a room where the mice could choose either to hang out in a region similar to the one paired with cocaine (rugged floors and dots wall) or a neutral area (smooth floor and striped walls), the mice would quickly congregate in the area where their drug high had played out.
To test the claustrum's involvement in how a context becomes associated with a given reward, Citri and his team observed the changes in mice behavior when they inhibited these claustral neurons. They found that the inhibition of these neurons inhibited the mice's behavioral responses to cocaine, meaning they no longer preferred hanging out in the cocaine-paired environment. On the other hand, activating these neurons -- even in the absence of any cocaine -- caused the mice to develop a preference for this context.
Importantly, the team found that the activity of the claustrum was not necessary for retrieval of the cocaine memory. Once the mice had been placed in a cocaine-paired context several times to enjoy their cocaine high, the memory for this context was encoded and inhibition of the claustrum had no effect on their preference for the cocaine-paired context. "These findings boosted our confidence that the claustrum is indeed integral to incentive salience, heightening the awareness of the mouse to the context in which it experienced the drug high" shared Citri.
As the number of deaths caused by drug overdose increases from year to year, this new study has wide-ranging implications towards a better understanding of the nature of addiction and the importance of breaking contextual cues before they develop. "By recognizing that the claustrum plays a pivotal role in creating a context association for reward, it becomes a structure of interest for the field of addiction. We hope this knowledge will lead to the development of new diagnostic tools to identify populations susceptible to addiction, as well as new therapeutic approaches," concluded Terem.
https://www.sciencedaily.com/releases/2020/07/200723115904.htm
When it comes to happiness, what's love got to do with it?
July 23, 2020
Science Daily/Michigan State University
How accurate was William Shakespeare when he said, "'Tis better to have loved and lost than never to have loved at all"? Researchers from Michigan State University conducted one of the first studies of its kind to quantify the happiness of married, formerly married and single people at the end of their lives to find out just how much love and marriage played into overall well-being.
The study -- published in the Journal of Positive Psychology -- examined the relationship histories of 7,532 people followed from ages 18 to 60 to determine who reported to be happiest at the end of their lives.
"People often think that they need to be married to be happy, so we asked the questions, 'Do people need to be in a relationship to be happy? Does living single your whole life translate to unhappiness? What about if you were married at some point but it didn't work out?,'" said William Chopik, MSU assistant professor of psychology and co-author of the paper. "Turns out, staking your happiness on being married isn't a sure bet."
Chopik and Mariah Purol, MSU psychology master's student and co-author, found that participants fell into one of three groups: 79% were consistently married, spending the majority of their lives in one marriage; 8% were consistently single, or, people who spent most of their lives unmarried; and 13% had varied histories, or, a history of moving in and out of relationships, divorce, remarrying or becoming widowed. The researchers then asked participants to rate overall happiness when they were older adults and compared it with the group into which they fell.
"We were surprised to find that lifelong singles and those who had varied relationship histories didn't differ in how happy they were," said Purol. "This suggests that those who have 'loved and lost' are just as happy towards the end of life than those who 'never loved at all.'"
While married people showed a slight uptick in happiness, Purol said the margin was not substantial -- nor what many may expect. If the consistently married group answered a 4 out of 5 on how happy they were, consistently single people answered a 3.82 and those with varied history answered a 3.7.
"When it comes to happiness, whether someone is in a relationship or not is rarely the whole story," Chopik said. "People can certainly be in unhappy relationships, and single people derive enjoyment from all sorts of other parts of their lives, like their friendships, hobbies and work. In retrospect, if the goal is to find happiness, it seems a little silly that people put so much stock in being partnered."
If someone longs for a lifelong partner to start a family and build a happy life together, Chopik and Purol's research suggests that if that individual isn't completely happy to begin with, getting married won't likely dramatically change it all.
"It seems like it may be less about the marriage and more about the mindset," Purol said. "If you can find happiness and fulfillment as a single person, you'll likely hold onto that happiness -- whether there's a ring on your finger or not."
https://www.sciencedaily.com/releases/2020/07/200723115833.htm
Health and happiness depend on each other
July 22, 2020
Science Daily/Association for Psychological Science
Good health and a happy outlook on life may seem like equally worthy yet independent goals. A growing body of research, however, bolsters the case that a happy outlook can have a very real impact on your physical well-being.
New research published in the journal Psychological Scienceshows that both online and in-person psychological interventions -- tactics specifically designed to boost subjective well-being -- have positive effects on self-reported physical health. The online and in-person interventions were equally effective.
"Though prior studies have shown that happier people tend to have better cardiovascular health and immune-system responses than their less happy counterparts," said Kostadin Kushlev, a professor in Georgetown University's Department of Psychology and one of the authors of the paper, "our research is one of the first randomized controlled trials to suggest that increasing the psychological well-being even of generally healthy adults can have benefits to their physical health."
Intervention for Healthy Outcomes
Over the course of six months, Kushlev and his colleagues at the University of Virginia and the University of British Columbia examined how improving the subjective well-being of people who were not hospitalized or otherwise undergoing medical treatment affected their physical health.
A group of 155 adults between the ages of 25 and 75 were randomly assigned either to a wait-list control condition or a 12-week positive psychological intervention that addressed three different sources of happiness: the "Core Self," the "Experiential Self," and the "Social Self."
The first 3 weeks of the program focused on the Core Self, helping individuals identify their personal values, strengths, and goals. The next 5 weeks focused on the Experiential Self, covering emotion regulation and mindfulness. This phase also gave participants tools to identify maladaptive patterns of thinking. The final 4 weeks of the program addressed the Social Self, teaching techniques to cultivate gratitude, foster positive social interactions, and engage more with their community.
The program, called Enduring Happiness and Continued Self-Enhancement (ENHANCE), consisted of weekly modules either led by a trained clinician or completed individually using a customized online platform. None of the modules focused on promoting physical health or health behaviors, such as sleep, exercise, or diet.
Each module featured an hour-long lesson with information and exercises; a weekly writing assignment, such as journaling; and an active behavioral component, such as guided meditation.
"All of the activities were evidence-based tools to increase subjective well-being," Kushlev noted.
When the program concluded, the participants were given individual evaluations and recommendations of which modules would be most effective at improving their happiness in the long term. Three months after the conclusion of the trial, researchers followed up with the participants to evaluate their well-being and health.
A Happy Future
Participants who received the intervention reported increasing levels of subjective well-being over the course of the 12-week program. They also reported fewer sick days than control participants throughout the program and 3 months after it ended.
The online mode of administering the program was shown to be as effective as the in-person mode led by trained facilitators.
"These results speak to the potential of such interventions to be scaled in ways that reach more people in environments such as college campuses to help increase happiness and promote better mental health among students," Kushlev said.
https://www.sciencedaily.com/releases/2020/07/200722170142.htm
Meditation linked to lower cardiovascular risk
Survey data from more than 61,000 people points to heart benefits
July 15, 2020
Science Daily/Veterans Affairs Research Communications
Meditation was linked to lower cardiovascular risk in a data analysis by Veterans Affairs researchers and colleagues.
The results appeared online June 30 in the American Journal of Cardiology.
Previous studies have suggested that meditation may have beneficial effects on a number of conditions. A 2017 American Heart Association scientific statement suggests that meditation may be of benefit for cardiovascular risk reduction. Data show that it may help with blood pressure, cholesterol level, quitting smoking, and overall cardiovascular health. However, this connection is far from definitive. By using a large national database with many participants, the authors of the new study sought further evidence on how meditation impacts cardiovascular risk.
Lead researcher Dr. Chayakrit Krittanawong -- of the Michael E. DeBakey VA Medical Center, Baylor College of Medicine, and the Icahn School of Medicine at Mount Sinai -- and his colleagues studied data from the National Health Interview Survey, conducted annually by the National Center for Health Statistics. It collects information on a wide range of health topics from a nationally representative sample.
The researchers looked at data on more than 61,000 survey participants. Of those, almost 6,000 (nearly 10%) said they participated in some form of meditation.
The researchers found that people who meditated had lower rates of high cholesterol, high blood pressure, diabetes, stroke, and coronary artery disease, compared with those who did not meditate.
The greatest difference was in coronary artery disease. Those who meditated were 51% as likely as those who didn't to have the disease. The prevalence of other cardiovascular risks in the meditation group compared with the non-meditation group was 65% for high cholesterol, 70% for diabetes, 76% for stroke, and 86% for high blood pressure.
The researchers controlled for other factors connected to cardiovascular risk, such as age, sex, cigarette smoking, and body mass index. After adjusting for these factors, the effect of meditation was still significant.
Many types of meditation exist. Most focus on attention and awareness. Meditation has been shown to increase physical and mental relaxation. "I believe in meditation, as it can give us a sense of calm, peace, and stress reduction, leading to improvement of our emotional well-being," explained Krittanawong.
Practicing meditation has been linked to decreased stress, greater mindfulness, and improved psychological health. It may even lead to long-term functional and anatomical changes in the brain. Meditation is also simple, cost-effective, and low-risk.
Krittanawong and colleagues did note several limitations to the study. First, the survey did not capture what type of meditation people were using. Some types of meditation may offer more cardiovascular benefit than others, say the researchers. The survey also did not ask about the duration or intensity of that meditation. It is possible that those who practice longer and more frequently will get more benefit, but the study cannot measure these effects.
Also, the researchers cannot definitively say that meditation directly decreases cardiovascular risk. It could be that people who are in better cardiovascular health to begin with are more likely to practice meditation, rather than the other way around.
Other life activities might also obscure the link between meditation and cardiovascular health. The researchers found factoring in alcohol consumption and physical activity lowered the significance of the relationship between meditation and cardiovascular risk.
Considering all these factors, the researchers concluded that meditation is "probably" associated with lower prevalence of cardiovascular risk. Krittanawong notes that, while the results suggest that meditation can improve cardiovascular health, "we would need a powerful study such as a clinical trial to determine whether meditation could benefit cardiovascular health in veterans."
Meanwhile, the study adds to a growing body of research on the potential benefits of meditation, they say.
https://www.sciencedaily.com/releases/2020/07/200715135734.htm
Apathy not depression helps to predict dementia
July 13, 2020
Science Daily/University of Cambridge
Apathy offers an important early warning sign of dementia in individuals with cerebrovascular disease, but depression does not, new research led by the University of Cambridge suggests.
Depression is often thought to be a risk factor for dementia but this may be because some depression scales used by clinicians and researchers partially assess apathy, say scientists from the universities of Cambridge, King's College London, Radboud and Oxford.
The study, published on 11 July in the Journal of Neurology, Neurosurgery & Psychiatry is the first to examine the relationships between apathy, depression, and dementia in individuals with cerebral small vessel disease (SVD). SVD may occur in one out of three elderly individuals, causes about a quarter of all strokes, and is the most common cause of vascular dementia.
The team studied two independent cohorts of SVD patients, one from the UK and the other from the Netherlands.* Across both cohorts, they found that individuals with higher baseline apathy, as well as those with increasing apathy over time, had a greater risk of dementia. In contrast, neither baseline depression nor change in depression had any detectable influence on dementia risk.
These findings were consistent despite variation in the severity of participants' symptoms, suggesting that they could be generalised across a broad spectrum of SVD cases. The relationship between apathy and dementia remained after controlling for other well-established risk factors for dementia including age, education, and cognition.
Lead author, Jonathan Tay, from Cambridge's Department of Clinical Neurosciences said: "There has been a lot of conflicting research on the association between late-life depression and dementia. Our study suggests that may partially be due to common clinical depression scales not distinguishing between depression and apathy."
Apathy, defined as a reduction in 'goal-directed behaviour', is a common neuropsychiatric symptom in SVD, and is distinct from depression, which is another symptom in SVD. Although there is some symptomatic overlap between the two, previous MRI research linked apathy, but not depression, with white matter network damage in SVD.
Jonathan Tay said: "Continued monitoring of apathy may be used to assess changes in dementia risk and inform diagnosis. Individuals identified as having high apathy, or increasing apathy over time, could be sent for more detailed clinical examinations, or be recommended for treatment."
Over 450 participants -- all with MRI-confirmed SVD -- recruited from three hospitals in South London and Radboud University's Neurology Department in the Netherlands, were assessed for apathy, depression and dementia over several years.
In the UK cohort, nearly 20% of participants developed dementia, while 11% in the Netherlands cohort did, likely due to the more severe burden of SVD in the UK cohort. In both datasets, patients who later developed dementia showed higher apathy, but similar levels of depression at baseline, compared to patients who did not.
The study provides the basis for further research, including the mechanisms that link apathy, vascular cognitive impairment, and dementia. Recent MRI work suggests that similar white matter networks underlie motivation and cognitive function in SVD. Cerebrovascular disease, which can be caused by hypertension and diabetes, can lead to network damage, resulting in an early form of dementia, presenting with apathy and cognitive deficits. Over time, SVD-related pathology increases, which is paralleled by increasing cognitive and motivational impairment, eventually becoming severe enough to meet criteria for a dementia state.
Jonathan Tay says: "This implies that apathy is not a risk factor for dementia per se, but rather an early symptom of white matter network damage. Understanding these relationships better could have major implications for the diagnosis and treatment of patients in the future."
https://www.sciencedaily.com/releases/2020/07/200713120022.htm
Long-studied protein could be a measure of traumatic brain injury
Cathepsin B in brain and cerebral spinal fluid is a biomarker for traumatic brain injury
July 13, 2020
Science Daily/Walter Reed Army Institute of Research
Scientists at the Walter Reed Army Institute for Research (WRAIR) have recently demonstrated that cathepsin B, a well-studied protein important to brain development and function, can be used as biomarker, or indicator of severity, for traumatic brain injury.
Traumatic brain injury (TBI) or brain trauma results from blows to the head, leading to life-changing disruption of the brain and a cascade of long-term health conditions. A leading cause of disability and death worldwide, TBI may occur due to an open-skull injury, like a gunshot wound, a fall, or an automobile accident. Athletes, the elderly, children, and military service members are particularly vulnerable.
Biomarkers are a source of great interest to researchers due to their potential to dramatically improve both the diagnosis and categorization of severity of TBI. Furthermore, they have the potential to validate treatment strategies by indicating whether drugs have reached their proposed targets and achieved therapeutic benefits.
In their publication in the Journal of Neurotrauma, the researchers showed that levels of cathepsin B were increased in areas of the injured brain relevant to controlling the senses, language, memory and other critical executive functions. In healthy cells, cathepsin B has a range of roles, including helping to eliminate damaged cells, maintaining metabolic homeostasis, and degrading improperly produced proteins. When the level of cathepsin B is not tightly controlled, it is linked to inflammation and tissue death. This publication reports the first results demonstrating the ability to use cathepsin B as a blood-based biomarker to capable of identifying TBI severity within different brain regions as well as cerebral spinal fluid.
"Biomarker tests that accurately reflect the extent and severity of injury can dramatically improve the standard of care, minimizing the need for resource-intensive diagnostics like CT or MRI scans in favor of more portable tests," said Dr. Angela Boutte, lead author and section chief of molecular biology and proteomics within the Brain Trauma Neuroprotection Branch at WRAIR. "This would allow for early, accurate detection of TBI, whether at the side of the road after an accident or, most importantly, on the battlefield to help guide medical decisions."
https://www.sciencedaily.com/releases/2020/07/200713154950.htm
Does eating fish protect our brains from air pollution?
July 15, 2020
Science Daily/American Academy of Neurology
Older women who eat more than one to two servings a week of baked or broiled fish or shellfish may consume enough omega-3 fatty acids to counteract the effects of air pollution on the brain, according to a new study published in the July 15, 2020, online issue of Neurology®, the medical journal of the American Academy of Neurology.
Researchers found that among older women who lived in areas with high levels of air pollution, those who had the lowest levels of omega-3 fatty acids in their blood had more brain shrinkage than women who had the highest levels.
"Fish are an excellent source of omega-3 fatty acids and easy to add to the diet," said study author Ka He, M.D., Sc.D., of Columbia University in New York. "Omega-3 fatty acids have been shown to fight inflammation and maintain brain structure in aging brains. They have also been found to reduce brain damage caused by neurotoxins like lead and mercury. So we explored if omega-3 fatty acids have a protective effect against another neurotoxin, the fine particulate matter found in air pollution."
The study involved 1,315 women with an average age of 70 who did not have dementia at the start of the study. The women completed questionnaires about diet, physical activity, and medical history.
Researchers used the diet questionnaire to calculate the average amount of fish each woman consumed each week, including broiled or baked fish, canned tuna, tuna salad, tuna casserole and non-fried shellfish. Fried fish was not included because research has shown deep frying damages omega-3 fatty acids.
Participants were given blood tests. Researchers measured the amount of omega-3 fatty acids in their red blood cells and then divided the women into four groups based on the amount of omega-3 fatty acids in their blood.
Researchers used the women's home addresses to determine their three-year average exposure to air pollution. Participants then had brain scans with magnetic resonance imaging (MRI) to measure various areas of the brain including white matter, which is composed of nerve fibers that send signals throughout the brain, and the hippocampus, the part of the brain associated with memory.
After adjusting for age, education, smoking and other factors that could affect brain shrinkage, researchers found that women who had the highest levels of omega-3 fatty acids in the blood had greater volumes of white matter than those with the lowest levels. Those in the highest group had 410 cubic centimeters (cm3) white matter, compared to 403 cm3 for those in the lowest group. The researchers found that for each quartile increase in air pollution levels, the average white matter volume was 11.52 cm3 smaller among people with lower levels of omega-3 fatty acids and 0.12 cm3 smaller among those with higher levels.
Women with the highest levels of omega-3 fatty acids in the blood also had greater volumes of the hippocampus.
"Our findings suggest that higher levels of omega-3 fatty acids in the blood from fish consumption may preserve brain volume as women age and possibly protect against the potential toxic effects of air pollution," said He. "It's important to note that our study only found an association between brain volume and eating fish. It does not prove that eating fish preserves brain volume. And since separate studies have found some species of fish may contain environmental toxins, it's important to talk to a doctor about what types of fish to eat before adding more fish to your diet."
A limitation of the study was that most participants were older white women, so the results cannot be generalized to others. Also, researchers were only able to examine exposures to later-life air pollution, not early or mid-life exposures, so future studies should look at exposures to air pollution across a person's lifespan.
https://www.sciencedaily.com/releases/2020/07/200715163555.htm
High-fat diet with antibiotic use linked to gut inflammation
Combining Western diet and antibiotic use is a pre- IBD risk factor
July 15, 2020
Science Daily/University of California - Davis Health
UC Davis researchers have found that combining a Western-style high-fat diet with antibiotic use significantly increases the risk of developing pre-inflammatory bowel disease (pre-IBD). The study, published July 14 in Cell Host and Microbe, suggests that this combination shuts down the energy factories (mitochondria) in cells of the colon lining, leading to gut inflammation.
Irritable bowel syndrome (IBS) affects approximately 11% of people worldwide. It is characterized by recurring episodes of abdominal pain, bloating and changes in bowel habits. IBS patients with mucosal inflammation and changes in the gut's microbial composition are considered pre-IBD.
Antibiotic usage with high-fat diet is a risk factor
The study included 43 healthy adults and 49 adult patients diagnosed with IBS. The researchers measured fecal calprotectin, a biomarker for intestinal inflammation, of participants. Elevated levels of fecal calprotectin indicated a pre-IBD condition. The study identified 19 patients with IBS as pre-IBD.
The researchers found that all participants who consumed high-fat diet and used antibiotics were at 8.6 times higher risk for having pre-IBD than those on low-fat diet and no recent history of antibiotic use. Participants with the highest fat consumption were about 2.8 times more likely to have pre-IBD than those with the lowest fat intake. A history of recent antibiotic usage alone was associated with 3.9 times higher likelihood of having pre-IBD.
"Our study found that a history of antibiotics in individuals consuming a high-fat diet was associated with the greatest risk for pre-IBD," said Andreas Bäumler, professor of medical microbiology and immunology and lead author on the study. "Until now, we didn't appreciate how different environmental risk factors can synergize to drive the disease."
Shutting the cell's powerhouse promotes gut microbial growth
Using mouse models, the study also tested the effect of high-fat diet and antibiotics use on the cells in the intestinal lining. It found that high-fat diet and antibiotics cooperate to disrupt the work of the cell's mitochondria, shutting its ability to burn oxygen. This disruption causes reduction in cell's oxygen consumption and leads to oxygen leakage into the gut.
The body's beneficial bacteria thrive in environments lacking oxygen such as the large intestine. Higher oxygen levels in the gut promote bacterial imbalances and inflammation. With the disruption in the gut environment, a vicious cycle of replacing the good bacteria with potentially harmful proinflammatory microbes that are more oxygen tolerant begins. This in turn leads to mucosal inflammation linked to pre-IBD conditions.
The study also identified 5-aminosalicylate (mesalazine), a drug that restarts the energy factories in the intestinal lining, as a potential treatment for pre-IBD.
"The best approach to a healthy gut is to get rid of the preferred sustenance of harmful microbes," Lee said. "Our study emphasized the importance of avoiding high fat food and abuse of antibiotics to avoid gut inflammation."
https://www.sciencedaily.com/releases/2020/07/200715142400.htm
Regular physical activity seems to enhance cognition in children who need it most
July 15, 2020
Science Daily/University of Tsukuba
Researchers re-analyzed data from three experiments that tested whether physical activity interventions lead to improved cognitive skills in children. They found that (1) the benefits of regular exercise on cognition were greater in children who have poor cognitive performance before the intervention and (2) spending time on physical activity did not hinder cognition in children who already had good cognitive performance before the intervention.
A common school-age stereotype is that smart kids are unathletic. However, as a recent study lead by Associate Professor Keita Kamijo at the University of Tsukuba and Assistant Professor Toru Ishihara at Kobe University shows, physical activity is linked to better cognitive ability, which is in turn related to academic performance in school. Understanding the effects of physical activity on cognition has been difficult for several reasons. "Previous studies looked at the issue too broadly," explains Professor Kamijo, "When we broke down the data, we were able to see that physical activity helps children the most if they start out with poor executive function."
Executive functions refer to three types of cognitive skills. The first is the ability to suppress impulses and inhibit reflex-like behaviors or habits. To assess this ability, children were asked to indicate the color in which words like "red" and "blue" were displayed on a computer screen. This is easy when the words and colors match ("red" displayed in red font), but often requires inhibition of a reflex response when they don't ("red" displayed in blue font). The second skill is the ability to hold information in working memory and process it. This was evaluated by testing how well children could remember strings of letters that vary in length. The third cognitive skill is mental flexibility. This was measured by asking children to frequently switch the rules for categorizing colored circles and squares from shape-based to color-based.
Professor Kamijo and Professor Ishihara, and their colleagues re-analyzed the data from previous experiments in which executive function was assessed in children before and after several months of daily intervention with physical activity, such as aerobic activities, ball games, and playing tag. They looked at a factor that was missed in the initial analyses. That is, they considered whether the effectiveness of the intervention depended on the initial baseline scores.
The researchers found that cognitive skills, which have been shown to closely associate with academic performance, improved most in children whose skills were initially poor. The team also found that increased time spent doing regular physical activity did not negatively affect cognitive function in children who started out with better cognitive functions.
The finding that daily physical activity can improve executive function in children who might need it the most has some practical implications. "Because the cognitive functions evaluated in our study are related to academic performance," says Professor Kamijo, "we can say that daily physical activity is critical for school-aged children. Our findings can help educational institutions design appropriate systems for maximizing the effects of physical activity and exercise."
https://www.sciencedaily.com/releases/2020/07/200715111421.htm
Early life stress is associated with youth-onset depression for some types of stress but not others
July 15, 2020
Science Daily/Elsevier
A study in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP), published by Elsevier, reports that individuals exposed to early life stress (ELS) were more likely to develop a major depressive disorder (MDD) in childhood or adolescence than individuals who had not been exposed to ELS.
Examining the association between eight different types of ELS and youth-onset depression, the authors found that while some types of ELS (e.g., poverty) were not associated with MDD, other types of stress, including emotional abuse, were associated more strongly with MDD than a broader assessment of ELS.
"Researchers have documented that early life stress increases the risk for developing depression in adulthood. We wanted to know the degree to which it was associated with depression earlier in life -- specifically during childhood or adolescence," said lead author Joelle LeMoult, PhD, a researcher at the University of British Columbia, Vancouver, Canada. "Given that earlier onsets of depression often mean a more recurrent course across the lifespan. We found that exposure to early life stress more than doubled the likelihood someone will develop youth-onset depression.
"These findings indicate that there is a narrow window between adversity and depression during which we have the opportunity to intervene."
The findings are based on a meta-analysis of data from 62 journal articles and over 44,000 unique participants. Studies that assessed early life stress and the presence or absence of MDD before the age of 18 years were also included.
Compared to youth who were not exposed to ELS, youth who were exposed to ELS were 2.5 times more likely to develop MDD (OR=2.50; 95% CI [2.08, 3.00]).
The authors also conducted eight additional meta-analyses to examine the association between different types of ELS and a diagnosis of MDD during childhood or adolescence. Sexual abuse, physical abuse, death of a family member, domestic violence, and emotional abuse were associated with significantly higher risk for youth-onset MDD; in contrast, poverty, illness/injury, and exposure to a natural disaster were not.
Several variables moderated the association between ELS and youth-onset MDD. For example, studies that used interview-based assessments or included larger sample sizes reported stronger associations between ELS and depression.
Taken together, findings provide evidence that the adverse effects of ELS on risk for MDD manifests early in development, before adulthood, and varies by type of ELS. Further, findings support recommendations to use best-practice methods in early life stress research.
https://www.sciencedaily.com/releases/2020/07/200715142326.htm
Two paths of aging: New insights on promoting healthspan
Master aging circuit identified
July 16, 2020
Science Daily/University of California - San Diego
Molecular biologists and bioengineers at the University of California San Diego have unraveled key mechanisms behind the mysteries of aging. They isolated two distinct paths that cells travel during aging and engineered a new way to genetically program these processes to extend lifespan.
The research is described July 17 in the journal Science.
Our lifespans as humans are determined by the aging of our individual cells. To understand whether different cells age at the same rate and by the same cause, the researchers studied aging in the budding yeast Saccharomyces cerevisiae, a tractable model for investigating mechanisms of aging, including the aging paths of skin and stem cells.
The scientists discovered that cells of the same genetic material and within the same environment can age in strikingly distinct ways, their fates unfolding through different molecular and cellular trajectories. Using microfluidics, computer modeling and other techniques, they found that about half of the cells age through a gradual decline in the stability of the nucleolus, a region of nuclear DNA where key components of protein-producing "factories" are synthesized. In contrast, the other half age due to dysfunction of their mitochondria, the energy production units of cells.
The cells embark upon either the nucleolar or mitochondrial path early in life, and follow this "aging route" throughout their entire lifespan through decline and death. At the heart of the controls the researchers found a master circuit that guides these aging processes.
"To understand how cells make these decisions, we identified the molecular processes underlying each aging route and the connections among them, revealing a molecular circuit that controls cell aging, analogous to electric circuits that control home appliances," said Nan Hao, senior author of the study and an associate professor in the Section of Molecular Biology, Division of Biological Sciences.
Having developed a new model of the aging landscape, Hao and his coauthors found they could manipulate and ultimately optimize the aging process. Computer simulations helped the researchers reprogram the master molecular circuit by modifying its DNA, allowing them to genetically create a novel aging route that features a dramatically extended lifespan.
"Our study raises the possibility of rationally designing gene or chemical-based therapies to reprogram how human cells age, with a goal of effectively delaying human aging and extending human healthspan," said Hao.
The researchers will now test their new model in more complex cells and organisms and eventually in human cells to seek similar aging routes. They also plan to test chemical techniques and evaluate how combinations of therapeutics and drug "cocktails" might guide pathways to longevity.
"Much of the work featured in this paper benefits from a strong interdisciplinary team that was assembled," said Biological Sciences Professor of Molecular Biology Lorraine Pillus, one of the study's coauthors. "One great aspect of the team is that we not only do the modeling but we then do the experimentation to determine whether the model is correct or not. These iterative processes are critical for the work that we are doing."
https://www.sciencedaily.com/releases/2020/07/200716144732.htm
Blood iron levels could be key to slowing aging
July 16, 2020
Science Daily/University of Edinburgh
Genes linked to ageing that could help explain why some people age at different rates to others have been identified by scientists.
The international study using genetic data from more than a million people suggests that maintaining healthy levels of iron in the blood could be a key to ageing better and living longer.
The findings could accelerate the development of drugs to reduce age-related diseases, extend healthy years of life and increase the chances of living to old age free of disease, the researchers say.
Scientists from the University of Edinburgh and the Max Planck Institute for Biology of Ageing in Germany focused on three measures linked to biological ageing -- lifespan, years of life lived free of disease (healthspan), and being extremely long-lived (longevity).
Biological ageing -- the rate at which our bodies decline over time -- varies between people and drives the world's most fatal diseases, including heart disease, dementia and cancers.
The researchers pooled information from three public datasets to enable an analysis in unprecedented detail. The combined dataset was equivalent to studying 1.75 million lifespans or more than 60,000 extremely long-lived people.
The team pinpointed ten regions of the genome linked to long lifespan, healthspan and longevity. They also found that gene sets linked to iron were overrepresented in their analysis of all three measures of ageing.
The researchers confirmed this using a statistical method -- known as Mendelian randomisation -- that suggested that genes involved in metabolising iron in the blood are partly responsible for a healthy long life.
Blood iron is affected by diet and abnormally high or low levels are linked to age-related conditions such as Parkinson's disease, liver disease and a decline in the body's ability to fight infection in older age.
The researchers say that designing a drug that could mimic the influence of genetic variation on iron metabolism could be a future step to overcome some of the effects of ageing, but caution that more work is required.
The study was funded by the Medical Research Council and is published in the journal Nature Communications.
Anonymised datasets linking genetic variation to healthspan, lifespan, and longevity were downloaded from the publically available Zenodo, Edinburgh DataShare and Longevity Genomics servers.
Dr Paul Timmers from the Usher Institute at the University of Edinburgh, said: "We are very excited by these findings as they strongly suggest that high levels of iron in the blood reduces our healthy years of life, and keeping these levels in check could prevent age-related damage. We speculate that our findings on iron metabolism might also start to explain why very high levels of iron-rich red meat in the diet has been linked to age-related conditions such as heart disease."
Dr Joris Deelen from the Max Planck Institute for Biology of Ageing in Germany, said: "Our ultimate aim is to discover how ageing is regulated and find ways to increase health during ageing. The ten regions of the genome we have discovered that are linked to lifespan, healthspan and longevity are all exciting candidates for further studies."
https://www.sciencedaily.com/releases/2020/07/200716101548.htm
Super-agers show resistance to tau and amyloid accumulation
July 15, 2020
Science Daily/Society of Nuclear Medicine and Molecular Imaging
Super-agers, or individuals whose cognitive skills are above the norm even at an advanced age, have been found to have increased resistance to tau and amyloid proteins, according to research presented at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2020 Annual Meeting. An analysis of positron emission tomography (PET) scans has shown that compared to normal-agers and those with mild cognitive impairment, super-agers have a lower burden of tau and amyloid pathology associated with neurodegeneration, which probably allows them to maintain their cognitive performance. An image showing the comparison of tau and amyloid distribution patterns in these different cognitive aging trajectories has been selected as SNMMI's 2020 Image of the Year.
"Our cognition reflects who we are as individuals. As we age, most of us lose some of that ability," said SNMMI's Scientific Program Committee chair, Umar Mahmood, MD, PhD. "The Image of the Year provides us with insight into how we can use these PET imaging biomarkers to understand behaviors and therapies that may allow more of us age better and retain more of our cognitive abilities as we get older."
Each year, SNMMI chooses an image that best exemplifies the most promising advances in the field of nuclear medicine and molecular imaging. The state-of-the-art technologies captured in these images demonstrate the capacity to improve patient care by detecting disease, aiding diagnosis, improving clinical confidence and providing a means of selecting appropriate treatments. This year, the SNMMI Henry N. Wagner, Jr., MD, Image of the Year was chosen from more than two thousand abstracts submitted to the meeting and voted on by reviewers and the society leadership.
"The phenomenon of super-aging suggests that cognitively high-functioning individuals have extraordinary mechanisms that resist brain aging processes and neurodegeneration," said Dr. Merle Hoenig, Research Center Juelich & University Hospital Cologne, Germany. Some insights have been collected on amyloid pathology in super-agers, but there is no in vivo evidence on tau pathology due to the former lack of available imaging techniques. "We know that tau pathology is more closely associated with cognitive decline than amyloid pathology," Hoenig continued, "thus, the resistance, in particular against tau pathology, likely allows these individuals to perform cognitively above average even at advanced age."
Data from the Alzheimer's Disease Neuroimaging Initiative was utilized to create three age- and education-matched groups of 25 super-agers, 25 normal-agers and 25 patients with mild cognitive impairment, all above 80 years old. In addition, 18 younger, cognitively normal, amyloid-negative controls were included in the comparison as a reference group. 18F-AV-1451 and 18F-AV-45 PET images obtained for all individuals and researchers compared the tau and amyloid burden between the four groups. A logistic regression was performed to identify genetic and pathophysiological factors best predicting aging processes.
No significant differences between super-agers and the younger control group were observed in terms of in vivo tau and amyloid burden. The normal-ager group exhibited tau burden in inferior temporal and precuneal areas and no significant differences in amyloid burden, when compared to the younger control group. Patients with mild cognitive impairment showed both high amyloid and high tau pathology burden. Differences in amyloid burden dissociated the normal-agers from those with mild cognitive impairment, whereas lower tau burden and lower polygenic risk predicted super-agers from mild cognitive impairment patients.
"While super-agers may be able to resist aging-associated proteinopathies, in particular tau pathology, normal-agers may not and are thus exposed to inevitable cognitive decline due to the accumulation of neurotoxic tau tangles and the advancing aging process," noted Hoenig. "Moving further to the other extreme of aging, namely mild cognitive impairment, the synergistic effects of both amyloid and tau may accelerate the pathological aging process."
These results motivate further research to determine responsible resistance factors, which may also inspire the development of novel treatment concepts. "Given the multitude of factors involved in the aging process, it will certainly be challenging to develop therapeutics to tackle the factors involved. However, if we understand which individuals are resistant to dementia, this will help us identify potential pathways that promote successful aging -- protecting against not only Alzheimer's disease but also other aging-associated diseases, such as vascular disease and other forms of dementia," said Hoenig.
https://www.sciencedaily.com/releases/2020/07/200715111447.htm
Type 1 interferon deficiency: Biomarker of patients at risk of severe COVID-19
July 17, 2020
Science Daily/INSERM (Institut national de la santé et de la recherche médicale)
Which patients will develop a severe form of Covid-19? This is a key question that needs to be answered to improve the individual management and prognosis of patients. In a study published in Science on July 13, teams from AP-HP, Inserm, Université of Paris, Institut Pasteur and Institut Imagine describe a unique and unexpected immunological phenotype in severe and critical patients, consisting of a severely impaired response of interferon (IFN) type I, associated with a persistent blood viral load and an excessive inflammatory response. These data suggest that IFN type I deficiency in the blood could be a hallmark of severe forms of Covid-19. It also supports the potential value of therapeutic approaches that combine early administration of IFN, with appropriate anti-inflammatory therapy targeting IL-6 or TNF-α, in patients preventing severe disease forms.
Approximately 5% of people with Covid-19 progress to a severe or critical form, including the development of severe pneumonia that progresses to acute respiratory distress syndrome. While these forms sometimes occur early in the course of the disease, clinical observations generally describe a two-stage progression of the disease, beginning with a mild to moderate form, followed by respiratory aggravation 9 to 12 days after the onset of the first symptoms. This sudden progression suggests deregulation of the host inflammatory response.
A growing number of indications suggest that this aggravation is caused by a large increase in cytokines. This runaway inflammatory response is correlated with massive infiltration in the lungs of innate immune cells, namely neutrophils and monocytes, creating lung damage and acute respiratory distress syndrome.
By analogy with a genetic disease leading to a similar pulmonary pathology identified at Institut Imagine by the team of Inserm researcher Frédéric Rieux-Laucat, the initial hypothesis assumed excessive production of interferon (IFN) type I, a marker of the response to infections. However, in seriously ill patients, the teams of Darragh Duffy (Dendritic Cell Immunobiology Unit, Institut Pasteur/Inserm), Frédéric Rieux-Laucat (Laboratory of Immunogenetics of Pediatric Autoimmune Diseases at Institut Imagine -- Inserm/Université de Paris), Solen Kernéis (Mobile Infectiology Team, AP-HP. Centre -- Université of Paris) and Benjamin Terrier (Department of Internal Medicine, AP-HP. Centre -- Université of Paris) show that the production and activity of type-I IFN are strongly reduced in the most severe forms of Covid-19.
In addition, there is a persistent blood viral load, indicating poor control of viral replication by the patient's immune system which leads to an ineffective and pathological inflammatory response. The inflammation, caused by the transcription factor NF-kB, also leads to increased production and signaling of tumor necrosis factor (TNF)-alpha and the pro-inflammatory cytokine interleukin IL-6.
Distinct type-I IFN responses may be characteristic of each stage of the disease
This low signature of type-I IFN differs from the response induced by other respiratory viruses such as human respiratory syncitial virus or influenza A virus, both of which are characterized by high production of type-I IFN.
The study also showed that low levels of type-I IFN in plasma precede clinical worsening and transfer to intensive care. Levels of circulating Type 1 IFN could even characterize each stage of disease, with the lowest levels observed in the most severe patients. These results suggest that in SARS-CoV-2 infection, the production of type-I IFN is inhibited in the infected host, which could explain the more frequent severe forms in individuals with low production of this cytokine, such as the elderly or those with co-morbidities.
Therefore, type-I IFN deficiency could be a signature of severe forms of COVID-19 and could identify a high-risk population.
These results further suggest that the administration of IFN-alpha/Beta combined with anti-inflammatory therapy targeting IL-6 or TNF-α, or corticosteroids such as dexamethasone, in the most severe patients could be a therapeutic avenue to be evaluated for severe forms of COVID-19.
https://www.sciencedaily.com/releases/2020/07/200717101015.htm
Chest x-rays show more severe COVID-19 in non-white patients
July 16, 2020
Science Daily/Radiological Society of North America
Racial/ethnic minority patients admitted to the hospital with COVID-19 infection are more likely to have more severe disease on chest X-rays than white/non-Hispanic patients, increasing the likelihood of adverse outcomes, such as intubation or death, according to a study published in the journal Radiology.
Emerging data show that racial/ethnic minorities have been disproportionately affected by COVID-19. Socioeconomic factors and pre-existing medical conditions like hypertension are likely contributing factors to this disparity. Furthermore, limited English proficiency may introduce additional linguistic and health literacy barriers to care, potentially resulting in delays seeking medical attention and greater severity of disease at the time of admission to the hospital with COVID-19 infection.
Radiologists from Massachusetts General Hospital (MGH) saw these disparities firsthand in April among patients admitted to the hospital with confirmed COVID-19 infection, and at one of the hospital's respiratory infection clinics in Chelsea, a city just north of Boston that is home to a predominantly Spanish-speaking Hispanic community. A significant proportion of the patients who visited the Chelsea clinic had COVID-19, and the level of disease the radiologists observed on chest imaging was markedly more severe than that seen at other respiratory infection clinics in Boston. These disparities were more evident among patients admitted to the hospital with confirmed COVID-19 infection.
"It got to the point where half of our patient population admitted with COVID-19 were underrepresented minorities," said study coauthor Efren J. Flores, M.D., a radiologist at MGH.
Dr. Flores and colleagues set out to study these observed disparities in greater detail with an eye toward developing a better understanding of some of the factors involved. They hope to use this information to guide risk mitigation strategies and improve outcomes among racial/ethnic minority groups. They looked at data from 326 patients hospitalized with confirmed COVID-19 infection between March 27 and April 10, 2020. Analysis of chest X-ray results revealed that non-white patients had significantly more severe lung disease on admission than white/non-Hispanic patients. Increased disease severity on chest X-rays increased the likelihood of adverse clinical outcomes, including admission to the intensive care unit, intubation and death.
As expected, the increased severity of lung disease on chest X-rays among non-white patients correlated with a combination of factors, including delay in seeking care at the hospital, higher prevalence of pre-existing comorbidities and limited English proficiency.
"Limited English proficiency is an additional socioeconomic factor that really influences many aspects of access to care," Dr. Flores said. "When we were first learning how the disease spreads, there was all this rapidly evolving information coming out that was not available in languages other than English, and that lag in availability of actionable health information for non-English speaking individuals was really critical for many patients trying to navigate a complex medical system with a disease from a virus that is so aggressive."
The connection between limited English proficiency and disease severity underscores the importance of having multilingual, culturally tailored health information available, Dr. Flores said, especially as the number of infections climbs in different parts of the country.
Disparities in access to care and disease severity are not limited to linguistic barriers. Racial/ethnic non-white communities disproportionately experience lower socioeconomic status, adding another layer of complexity when accessing care. Living and working arrangements also likely played a role in the severity of COVID-19 among these patients, the study authors said. Racial and ethnic minority populations tend to live in multigenerational households and communities of higher population density, making social distancing difficult. In addition, they are more often employed in jobs not conducive to remote work with limited paid time off, thus increasing their exposure to COVID-19.
"Many of these patients delay their care because they're considered essential workers and they don't have a lot of sick leave, but also it's difficult for them to leave because they are living on a weekly paycheck and have other dependents," Dr. Flores said. "It wasn't uncommon for us to go into the medical record when we were interpreting their exams and see that many of them worked at grocery stores or warehouses."
The study findings highlight the important role radiologists play in providing earlier identification of higher-risk patients and developing multidisciplinary collaborations to help address these disparities, according to Dr. Flores.
"Health equity is every medical specialty's responsibility, but I believe radiology is uniquely positioned to take a bigger role not only in population health but in public health efforts," he said. "Our ability to provide care in different settings is what allowed us to make the clinical observation that patients coming to this one particular clinic and those being admitted to the hospital were presenting with a higher rate of positive findings that were also more severe. That really offered a window into the disparities that were translating into greater disease severity and worse outcomes."
Moving forward, the findings of this study could assist radiologists in the development of algorithms to identify vulnerable and at-risk populations. This could spur collaborations with other medical specialties, community stakeholders, and public health initiatives to enhance the effectiveness of public health interventions that increase access to care.
"We did this study not only to gain a better understanding of these emerging disparities, but also to discover how we can use this information to craft a better path towards equity together," Dr. Flores said.
https://www.sciencedaily.com/releases/2020/07/200716144710.htm
Dangerous blood clots form in leg arteries of COVID-19 patients
July 16, 2020
Science Daily/Radiological Society of North America
COVID-19 is associated with life-threatening blood clots in the arteries of the legs, according to a study published in Radiology. Researchers said COVID-19 patients with symptoms of inadequate blood supply to the lower extremities tend to have larger clots and a significantly higher rate of amputation and death than uninfected people with the same condition.
COVID-19's association with blood clots in the pulmonary arteries is well-established. Less is known about the virus' connection to lower extremity arterial thrombosis, a condition characterized by blood clots in the arteries that impede the flow of oxygenated blood to the lower extremities.
During the peak of the COVID-19 pandemic in New York City, radiologists at the city's Montefiore Medical Center observed an increase in patients testing positive for lower extremity arterial thrombosis on CT angiography exams. The patients had arrived at hospitals with coldness, pain or discoloration of their legs. Frequently these symptoms of leg ischemia, a condition in which blood flow to the lower extremities is restricted, were accompanied by respiratory distress, cough, fever and altered mental status.
The alarming trend prompted the researchers to look more closely at a possible connection between COVID-19 and lower extremity arterial thrombosis and whether people with the virus had a worse prognosis.
In March and April 2020, they identified 16 COVID-19-positive patients, average age 70, who underwent CT angiography of the lower extremities for symptoms of leg ischemia. These patients were compared with 32 COVID-19-negative patients, average age 71, who underwent CT angiography with similar symptoms in previous years and who were well matched with COVID-19 cohort for demographic and clinical characteristics.
All patients with COVID-19 infection undergoing lower extremity CT angiography had at least one clot in the leg, compared with only 69% of controls. The clots in the COVID-19 patients were significantly larger and affected arteries higher up in the leg with greater frequency than those in controls. Death or limb amputation was more common in the COVID-19 patients.
"We found that arterial thrombosis associated with COVID-19 infection was characterized by dire outcomes, namely strikingly increased rates of amputation and death, which in our series were 25% and 38%, respectively," said study lead author Inessa A. Goldman, M.D., a radiologist at Montefiore and assistant professor at Albert Einstein College of Medicine in New York City. "For comparison, the rate of both amputation and death was only 3% among controls. It is unclear whether the patients' concurrent COVID-19-related pneumonia, the virulence of the COVID-19-related clotting disorder or delayed initial arrival to the hospital contributed to these outcomes."
COVID-19 patients presenting with symptoms of leg ischemia only were more likely to avoid amputation or death than patients who had symptoms of ischemia and systemic symptoms including cough, respiratory distress or failure, hypoxia, fever, or altered mental status.
"In our cohort none of the five patients presenting with complaints pertaining to leg symptoms only, such as pain or discoloration, without systemic symptoms sustained amputation or died," Dr. Goldman said.
Dr. Goldman noted that with infection rates rising in many parts of the country, it is important that physicians be mindful of the connection between COVID-19 and lower extremity arterial thrombosis.
"Awareness of lower extremity arterial thrombosis as a possible complication of COVID-19 infection is important for all providers who take care of these patients, because early diagnosis is usually crucial for limb preservation in lower extremity ischemia," she said.
COVID-19's association with lower extremity arterial thrombosis is likely related to a combination of factors, Dr. Goldman said, including an increased tendency of the blood to clot, damage to the lining of the arteries, and immune reactions tied to the SARS-CoV-2 virus and COVID-19 infection.
"This continues to be an area of intense study around the world," she said.
https://www.sciencedaily.com/releases/2020/07/200716144706.htm
Vaccine additives can enhance immune flexibility -- Implications for flu and SARS-CoV-2
July 16, 2020
Science Daily/Emory Health Sciences
A vaccine additive known as an adjuvant can enhance responses to a vaccine containing the exotic avian flu virus H5N1, so that both rookie and veteran elements of the immune response are strengthened, according to results from an Emory Vaccine Center study.
The findings have implications for the effort to develop vaccines against multiple strains of flu, as well as the current push for vaccines against SARS-CoV-2. The Emory study was a test of what happens when the body sees something new -- in contrast to seasonal flu vaccination, which often re-activates the same memory B cells the immune system relied upon in past years.
The study provides guidance on how adjuvants might become part of a proposed "universal" flu vaccine, aimed at protecting people against a wider variety of influenza strains. In addition, vaccine designers are considering how to optimize immune responses against SARS-Cov-2, which few had encountered before 2020.
The results were published online July 13 by Proceedings of the National Academy of Sciences.
"We saw that an adjuvant makes it possible to efficiently engage both memory and naive B cells, expanding the repertoire of the antibody immune response to influenza," says first author Ali Ellebedy, PhD, who did the study while he was a postdoctoral fellow in Rafi Ahmed's lab at Emory Vaccine Center.
"For a new pathogen like SARS-CoV-2, nobody has immunity," Ahmed says. "So the important thing is to have the vaccine bring out good responses from naïve B cells, whose frequency is low."
"For universal flu, the situation is more complicated. You want to bring out both the cross-reactive memory cells and the naïve strain-specific cells," adds Ahmed, whose lab is part of a NIH-funded consortium developing flu vaccine candidates. "Looking ahead, adjuvants are going to be an important element of universal flu vaccine research."
The particular adjuvant studied in the paper is called AS03, whose manufacturer GlaxoSmithKline is making it available for COVID-19 vaccine trials. The AS03 adjuvant could be relevant for extending the efficacy of limited doses of protein or viral subunit-based vaccines, but less so for newer mRNA-based vaccines, Ahmed says.
The Hope Clinic study recruited 50 healthy young adults, who were (most likely) exposed to other flu viruses and vaccines earlier in their lives. The H5N1 vaccine, with AS03, was approved by the FDA in 2013 and is part of the national stockpile in case of pandemic flu. More information about the AS03-adjuvanted flu vaccine is available from the FDA.
Emory researchers had previously observed that when the immune system encounters an unfamiliar flu virus, which occurred for many during the 2009 H1N1 pandemic, the antibodies produced are able to neutralize a broader range of viruses. This came from the skew of the antibodies toward the "stem" (or stalk) region of the viral hemagglutinin protein, versus the "head." The stem region doesn't mutate and change as much as the head from year to year.
A similar phenomenon occurred in the H5N1 study, because the head region of the virus was unfamiliar, but the stem region was not. Without an adjuvant, the immune response to a low dose of the H5N1 flu vaccine was poor, the researchers found.
But with the adjuvant, immune responses changed markedly between the first and second dose. A week after the first adjuvanted vaccine dose, broadly cross-reactive antibodies produced by the immune system were mostly directed against the stem. This first wave came mostly from pre-existing memory B cells. After the second dose, the antibodies were more directed against the head, coming from strain-specific naïve B cells.
The researchers also offered an explanation for the shift in the antibody response after the second dose: essentially, the immune system is getting in its own way. After the second vaccination, the antibodies against the stem region are still in the body and they appear to be covering up those parts of the viral hemagglutinin protein, a phenomenon called "epitope blocking."
"This is something that many flu vaccine studies have observed, but now we have a possible mechanistic explanation and good evidence for it," Ahmed says.
https://www.sciencedaily.com/releases/2020/07/200716122917.htm