Tagged research

A Living Legacy in Pediatric Cancer Research

Living With Cancer

Tyler Trent’s Living Legacy

Even as he was dying, he worked to raise awareness of pediatric cancer. Now scientists are using his cells to help others.

From left, Tyler Trent, Dr. Jamie L. Renbarger and Dr. Karen E. Pollok.
From left, Tyler Trent, Dr. Jamie L. Renbarger and Dr. Karen E. Pollok.Credit…Kelly Trent

  • Jan. 21, 2021, 5:00 a.m. ET

Approximately 85 percent of children with cancer are cured. However, about 15 percent confront the sort of aggressive disease that cut short the life of Tyler Trent at the age of 20 on Jan. 1, 2019. “One hundred years down the line, maybe my legacy could have an impact”: so Tyler said about his efforts to raise awareness of the need for further research in pediatric oncology. Two years after his death, Tyler’s physicians continue to help incurable as well as cured children lead longer and better lives.

Back in 2014, when Tyler was 15, he was found to have a rare form of osteosarcoma in his arm and underwent treatments at Riley Hospital for Children in Indianapolis. But two years later, at the end of his senior year of high school, the disease reappeared in his pelvis. Despite another surgery as well as chemotherapy, he resolved to start as a freshman at Purdue University.

Bald and on crutches, he entered Purdue with a presidential scholarship and soon became a Boilermaker football superfan as he coped with life-threatening complications caused by yet another recurrence in his spine. He was at death’s door a few days before he attended the Purdue football game against Ohio State that he correctly predicted would result in an upset Boilermaker victory and his being named honorary team captain for a game played in one of the holiday bowls. At Purdue today, an undergraduate scholarship and a student gate at the football stadium memorialize his name.

One of Tyler’s doctors, Dr. Jamie Renbarger, currently heads Riley’s Center for Cancer and Blood Disorders and the Pediatric Precision Genomics Program, which serves children with aggressive solid tumors, high risk leukemias, and relapsed cancers, all of which are associated with poor outcomes. In consultation with a child’s oncologist and with a team of scientists, Dr. Renbarger uses genetic testing to identify DNA, RNA and proteins in cancer cells that can be targeted with different treatment options specific to the child’s needs.

According to Dr. Renbarger, “in about 85 to 90 percent of cases, we’ve found something clinically relevant about the patient or the tumor as a result of testing to help further guide therapy.” Dr. Renbarger is drawn to targeted therapies because they “may have fewer side effects than previous treatments, helping the child have a better quality of life and improving survival rates.”

Her optimism has been buoyed by the breakthrough of a colleague, Karen E. Pollok, who has used the cancer cells donated by Tyler Trent — they are called TT2 — to find a combination of drugs that substantially retards tumor growth. The donors of tumor samples are generally kept anonymous, but Tyler’s parents wanted to continue honoring his activism.

Dr. Pollok, who along with Dr. Renbarger visited Tyler two weeks before he died, was inspired by the meeting: “He was busily answering texts, tweets and managing Facebook to fulfill his last mission: to raise awareness for pediatric cancer research.” Today, Dr. Pollok adds, “our lab-quote when we discuss the research using Tyler’s cells is, ‘We will never give up!’” At the start of the coronavirus pandemic, her work on Tyler’s tumor models was deemed essential. She and colleagues published research in August in the journal Cancers that demonstrated that a combination of drugs could block the growth of these aggressive cancers.

Even after Tyler suffered seizures, clogged kidney tubes, emergency operations, and fevers that landed him in hospice, he gave interviews and published essays that testified to his remarkable ability to continue expressing himself in his unique way. Though Tyler never entered full adulthood, he managed to sustain “his passion to do whatever he could, even in the midst of this crazy, horrible journey that he was on,” Dr. Renbarger says.

Children with cancer, whether or not they are cured, need to find ways to retain a sense of themselves while dealing with the deleterious side effects of cytotoxic treatments. Dr. Renbarger therefore helped to create the Karuna Precision Wellness Center, where she works with individuals during and after cancer treatments to optimize their long-term quality of life through personalized integrative and wellness plans. The areas of focus include physical functioning, mental health (cognitive and emotional), and nutrition.

Kids especially face post-therapy hurdles, Dr. Renbarger believes, for they may experience alienation from their peers, anxiety, attention deficits and cognitive disorders related to memory, mental processing and executive functioning. Reintegration into school can be challenging. Additionally, since children who have received treatment “age at a faster rate,” they can be “more susceptible to diseases associated with aging like strokes, diabetes, joint and heart problems.” In an outpatient clinic, Dr. Renbarger assembles multidisciplinary teams — specialists in cardiology, adolescent medicine and fertility as well as educational and vocational coaches — to see pediatric patients into the best possible adulthood.

A similar determination led Tyler to donate a portion of the proceeds from his book, “The Upset: Life (Sports), Death … and the Legacy We Leave in the Middle,” toward cancer research. Along with his co-author, John Driver, and others, he composed it when his entire body had surrendered to paralysis except for his right arm. The voices of his parents, brothers and spiritual advisers supplement his account and form a sort of chorus. What emerges is a multifaceted portrait of a deeply religious young man fully convinced that “There is always an opportunity to help heal others’ hurts.”

The Upset” underscores the conviction of Tyler’s parents that “when a child gets cancer, a family gets cancer” and extends his efforts to hasten that time when no family with cancer will be left behind.

Could a Smell Test Screen People for Covid?

Could a Smell Test Screen People for Covid?

A new modeling study hints that odor-based screens could quash outbreaks. But some experts are skeptical it would work in the real world.

A health worker in Altos de San Lorenzo, a neighborhood outside Buenos Aires, Argentina, administered a smell test last year.
A health worker in Altos de San Lorenzo, a neighborhood outside Buenos Aires, Argentina, administered a smell test last year.Credit…Alejandro Pagni/Agence France-Presse — Getty Images
Katherine J. Wu

  • Jan. 19, 2021, 5:49 p.m. ET

In a perfect world, the entrance to every office, restaurant and school would offer a coronavirus test — one with absolute accuracy, and able to instantly determine who was virus-free and safe to admit and who, positively infected, should be turned away.

That reality does not exist. But as the nation struggles to regain a semblance of normal life amid the uncontrolled spread of the virus, some scientists think that a quick test consisting of little more than a stinky strip of paper might at least get us close.

The test does not look for the virus itself, nor can it diagnose disease. Rather, it screens for one of Covid-19’s trademark signs: the loss of the sense of smell. Since last spring, many researchers have come to recognize the symptom, which is also known as anosmia, as one of the best indicators of an ongoing coronavirus infection, capable of identifying even people who don’t otherwise feel sick.

A smell test cannot flag people who contract the coronavirus and never develop any symptoms at all. But in a study that has not yet been published in a scientific journal, a mathematical model showed that sniff-based tests, if administered sufficiently widely and frequently, might detect enough cases to substantially drive transmission down.

Daniel Larremore, an epidemiologist at the University of Colorado, Boulder, and the study’s lead author, stressed that his team’s work was still purely theoretical. Although some smell tests are already in use in clinical and research settings, the products tend to be expensive and laborious to use and are not widely available. And in the context of the pandemic, there is not yet real-world data to support the effectiveness of smell tests as a frequent screen for the coronavirus. Given the many testing woes that have stymied pandemic control efforts so far, some experts have been doubtful that smell tests could be distributed widely enough, or made sufficiently cheat-proof, to reduce the spread of infection.

“I have been intimately involved in pushing to get loss of smell recognized as a symptom of Covid from the beginning,” said Dr. Claire Hopkins, an ear, nose and throat surgeon at Guy’s and St. Thomas’ Hospitals in the United Kingdom and an author of a recent commentary on the subject in The Lancet. “But I just don’t see any value as a screening test.”

A reliable smell test offers many potential benefits. It could catch far more cases than fever checks, which have largely flopped as screening tools for Covid-19. Studies have found that about 50 to 90 percent of people who test positive for the coronavirus experience some degree of measurable smell loss, a result of the virus wreaking havoc when it invades cells in the airway.

“It’s really like a function of the virus being in the nose at this exact moment,” said Danielle Reed, the associate director of the Monell Chemical Senses Center in Philadelphia. “It complements so much of the information you get from other tests.” Last month, Dr. Reed and her colleagues at Monell posted a study, which has not yet been published in a scientific journal, describing a rapid smell test that might be able to screen for Covid-19.

In contrast, only a minority of people with Covid-19 end up spiking a temperature. Fevers also tend to be fleeting, while anosmia can linger for many days.

A coronavirus testing site in Los Angeles. Smell tests, unlike P.C.R. and antigen tests, would not diagnose the disease nor look for the virus directly.
A coronavirus testing site in Los Angeles. Smell tests, unlike P.C.R. and antigen tests, would not diagnose the disease nor look for the virus directly.Credit…Kendrick Brinson for The New York Times

A smell test could also come with an appealingly low price tag, perhaps as low as 50 cents per card, said Derek Toomre, a cell biologist at Yale University and an author on Dr. Larremore’s paper. Dr. Toomre hopes that his version will fit the bill. The test, the U-Smell-It test, is a small smorgasbord of scratch-and-sniff scents arrayed on paper cards. People taking the test pick away at wells of smells, inhale and punch their guess into a smartphone app, shooting to correctly guess at least three of the five odors. Different cards contain different combinations of scents, so there is no answer key to memorize.

He estimated that the test could be taken in less than a minute. It is also a manufacturer’s dream, he said: A single printer “could produce 50 million of these tests per day.” Numbers like that, he argued, could make an enormous dent in a country hampered by widespread lack of access to tests that look directly for pieces of the coronavirus.

In their study, Dr. Larremore, Dr. Toomre and their collaborator Roy Parker, a biochemist at the University of Colorado, Boulder, modeled such a scenario using computational tools. Administered daily or almost daily, a smell screen that caught at least 50 percent of new infections was able to quash outbreaks nearly as well as a more accurate, slower laboratory test given just once a week.

Such tests, Dr. Larremore said, could work as a point-of-entry screen on college campuses or in offices, perhaps in combination with a rapid virus test. There might even be a place for them in the home, if researchers can find a way to minimize misuse.

“I think this is spot on,” said Dr. Carol Yan, an ear, nose and throat specialist at the University of California, San Diego. “Testing people repeatedly is going to be a valuable portion of this.”

Dr. Toomre is now seeking an emergency use authorization for the U-Smell-It from the Food and Drug Administration, and has partnered with a number of groups in Europe and elsewhere to trial the test under real-world conditions.

Translating theory into practice, however, will come with many challenges. Smell tests that can reliably identify people who have the coronavirus, while excluding people who are sick with something else, are not yet widely available. (Dr. Hopkins pointed to a couple of smell tests, developed before the pandemic, that cost about $30 each and remain in limited supply.) Should they ever be rolled out in bulk, they would inevitably miss some infected people and, unlike tests that look for the actual virus, could never diagnose disease on their own.

And smell loss, like fever, is not exclusive to Covid-19. Other infections can blunt a person’s sense of smell. So can allergies, nasal congestion from the common cold, or simply the process of aging. About 80 percent of people over the age of 75 have some degree of smell loss. Some people are born anosmic.

Moreover, in many cases of Covid-19, smell loss can linger long after the virus is gone and people are no longer contagious — a complication that could land some people in a post-Covid purgatory if they are forced to rely on smell screens to resume activity, Dr. Yan said.

There are also many ways to design a smell-based screen. Odors linked to foods that are popular in some countries but not others, such as bubble gum or licorice, might skew test results for some individuals. People who have grown up in highly urban areas might not readily recognize scents from nature, like pine or fresh-cut grass.

Smell also is not a binary sense, strictly on or off. Dr. Reed advocated a step in which test takers rate the intensity of a test’s odors — an acknowledgment that the coronavirus can drastically reduce the sense of smell but not eliminate it.

But the more complicated the test, the more difficult it would be to manufacture and deploy speedily. And no test, even a perfectly designed one, would function with 100 percent accuracy.

Dr. Ameet Kini, a pathologist at Loyola University Medical Center, pointed out that smell tests would also not be free of the problems associated with other types of tests, such as poor compliance or a refusal to isolate.

Smell screens are “probably better than nothing,” Dr. Kini said. “But no test is going to stop the pandemic in its tracks unless it’s combined with other measures.”

Could a Small Test Screen People for Covid-19?

Could a Smell Test Screen People for Covid?

A new modeling study hints that odor-based screens could quash outbreaks. But some experts are skeptical it would work in the real world.

A health worker in Altos de San Lorenzo, a neighborhood outside Buenos Aires, Argentina, administered a smell test last year.
A health worker in Altos de San Lorenzo, a neighborhood outside Buenos Aires, Argentina, administered a smell test last year.Credit…Alejandro Pagni/Agence France-Presse — Getty Images
Katherine J. Wu

  • Jan. 19, 2021, 5:49 p.m. ET

In a perfect world, the entrance to every office, restaurant and school would offer a coronavirus test — one with absolute accuracy, and able to instantly determine who was virus-free and safe to admit and who, positively infected, should be turned away.

That reality does not exist. But as the nation struggles to regain a semblance of normal life amid the uncontrolled spread of the virus, some scientists think that a quick test consisting of little more than a stinky strip of paper might at least get us close.

The test does not look for the virus itself, nor can it diagnose disease. Rather, it screens for one of Covid-19’s trademark signs: the loss of the sense of smell. Since last spring, many researchers have come to recognize the symptom, which is also known as anosmia, as one of the best indicators of an ongoing coronavirus infection, capable of identifying even people who don’t otherwise feel sick.

A smell test cannot flag people who contract the coronavirus and never develop any symptoms at all. But in a study that has not yet been published in a scientific journal, a mathematical model showed that sniff-based tests, if administered sufficiently widely and frequently, might detect enough cases to substantially drive transmission down.

Daniel Larremore, an epidemiologist at the University of Colorado, Boulder, and the study’s lead author, stressed that his team’s work was still purely theoretical. Although some smell tests are already in use in clinical and research settings, the products tend to be expensive and laborious to use and are not widely available. And in the context of the pandemic, there is not yet real-world data to support the effectiveness of smell tests as a frequent screen for the coronavirus. Given the many testing woes that have stymied pandemic control efforts so far, some experts have been doubtful that smell tests could be distributed widely enough, or made sufficiently cheat-proof, to reduce the spread of infection.

“I have been intimately involved in pushing to get loss of smell recognized as a symptom of Covid from the beginning,” said Dr. Claire Hopkins, an ear, nose and throat surgeon at Guy’s and St. Thomas’ Hospitals in the United Kingdom and an author of a recent commentary on the subject in The Lancet. “But I just don’t see any value as a screening test.”

A reliable smell test offers many potential benefits. It could catch far more cases than fever checks, which have largely flopped as screening tools for Covid-19. Studies have found that about 50 to 90 percent of people who test positive for the coronavirus experience some degree of measurable smell loss, a result of the virus wreaking havoc when it invades cells in the airway.

“It’s really like a function of the virus being in the nose at this exact moment,” said Danielle Reed, the associate director of the Monell Chemical Senses Center in Philadelphia. “It complements so much of the information you get from other tests.” Last month, Dr. Reed and her colleagues at Monell posted a study, which has not yet been published in a scientific journal, describing a rapid smell test that might be able to screen for Covid-19.

In contrast, only a minority of people with Covid-19 end up spiking a temperature. Fevers also tend to be fleeting, while anosmia can linger for many days.

A coronavirus testing site in Los Angeles. Smell tests, unlike P.C.R. and antigen tests, would not diagnose the disease nor look for the virus directly.
A coronavirus testing site in Los Angeles. Smell tests, unlike P.C.R. and antigen tests, would not diagnose the disease nor look for the virus directly.Credit…Kendrick Brinson for The New York Times

A smell test could also come with an appealingly low price tag, perhaps as low as 50 cents per card, said Derek Toomre, a cell biologist at Yale University and an author on Dr. Larremore’s paper. Dr. Toomre hopes that his version will fit the bill. The test, the U-Smell-It test, is a small smorgasbord of scratch-and-sniff scents arrayed on paper cards. People taking the test pick away at wells of smells, inhale and punch their guess into a smartphone app, shooting to correctly guess at least three of the five odors. Different cards contain different combinations of scents, so there is no answer key to memorize.

He estimated that the test could be taken in less than a minute. It is also a manufacturer’s dream, he said: A single printer “could produce 50 million of these tests per day.” Numbers like that, he argued, could make an enormous dent in a country hampered by widespread lack of access to tests that look directly for pieces of the coronavirus.

In their study, Dr. Larremore, Dr. Toomre and their collaborator Roy Parker, a biochemist at the University of Colorado, Boulder, modeled such a scenario using computational tools. Administered daily or almost daily, a smell screen that caught at least 50 percent of new infections was able to quash outbreaks nearly as well as a more accurate, slower laboratory test given just once a week.

Such tests, Dr. Larremore said, could work as a point-of-entry screen on college campuses or in offices, perhaps in combination with a rapid virus test. There might even be a place for them in the home, if researchers can find a way to minimize misuse.

“I think this is spot on,” said Dr. Carol Yan, an ear, nose and throat specialist at the University of California, San Diego. “Testing people repeatedly is going to be a valuable portion of this.”

Dr. Toomre is now seeking an emergency use authorization for the U-Smell-It from the Food and Drug Administration, and has partnered with a number of groups in Europe and elsewhere to trial the test under real-world conditions.

Translating theory into practice, however, will come with many challenges. Smell tests that can reliably identify people who have the coronavirus, while excluding people who are sick with something else, are not yet widely available. (Dr. Hopkins pointed to a couple of smell tests, developed before the pandemic, that cost about $30 each and remain in limited supply.) Should they ever be rolled out in bulk, they would inevitably miss some infected people and, unlike tests that look for the actual virus, could never diagnose disease on their own.

And smell loss, like fever, is not exclusive to Covid-19. Other infections can blunt a person’s sense of smell. So can allergies, nasal congestion from the common cold, or simply the process of aging. About 80 percent of people over the age of 75 have some degree of smell loss. Some people are born anosmic.

Moreover, in many cases of Covid-19, smell loss can linger long after the virus is gone and people are no longer contagious — a complication that could land some people in a post-Covid purgatory if they are forced to rely on smell screens to resume activity, Dr. Yan said.

There are also many ways to design a smell-based screen. Odors linked to foods that are popular in some countries but not others, such as bubble gum or licorice, might skew test results for some individuals. People who have grown up in highly urban areas might not readily recognize scents from nature, like pine or fresh-cut grass.

Smell also is not a binary sense, strictly on or off. Dr. Reed advocated a step in which test takers rate the intensity of a test’s odors — an acknowledgment that the coronavirus can drastically reduce the sense of smell but not eliminate it.

But the more complicated the test, the more difficult it would be to manufacture and deploy speedily. And no test, even a perfectly designed one, would function with 100 percent accuracy.

Dr. Ameet Kini, a pathologist at Loyola University Medical Center, pointed out that smell tests would also not be free of the problems associated with other types of tests, such as poor compliance or a refusal to isolate.

Smell screens are “probably better than nothing,” Dr. Kini said. “But no test is going to stop the pandemic in its tracks unless it’s combined with other measures.”

An 11-Minute Body-Weight Workout With Proven Fitness Benefits

Phys Ed

An 11-Minute Body-Weight Workout With Proven Fitness Benefits

Five minutes of burpees, jump squats and other calisthenics, alternating with rest, improved aerobic endurance in out-of-shape men and women.

Credit…Getty Images
Gretchen Reynolds

  • Jan. 13, 2021, 5:00 a.m. ET

Five minutes of burpees, jump squats and other calisthenics significantly improve aerobic endurance, according to one of the first randomized, controlled trials to test the effects of brief body-weight workouts. The study’s findings are predictable but reassuring, at a time when many of us are relying on short exercise sessions in our homes to gain or retain our fitness. They provide scientific assurance that these simple workouts will work, physiologically, and our burpees will not be in vain.

Last year, when the pandemic curtailed traditional gym hours and left many people hesitant to exercise outside on crowded sidewalks or paths, quite a few of us moved our workouts indoors, into our living rooms or basements, altering how we exercise. Some of us purchased stationary bicycles and started intense spin classes or turned to online personal trainers and yoga classes. But many of us started practicing some version of a body-weight routine, using calisthenics and other simple strength-training exercises that rely on our body weight to provide resistance.

Body-weight training has been a staple of exercise since almost time immemorial, of course. Usually organized as multiple, familiar calisthenics performed one after another, this type of exercise has gone by various names, from Swedish Exercises a century ago to the Royal Canadian Air Force’s Five Basic Exercises (5BX) program in the 1960s, to today’s Scientific 7-Minute Workout and its variations.

In general, one of the hallmarks of these programs is that you perform the exercises consecutively but not continuously; that is, you complete multiple repetitions of one exercise, pause and recover, then move on to the next. This approach makes the workouts a form of interval training, with bursts of intense exertion followed by brief periods of rest.

Traditional interval training has plenty of scientific backing, with piles of research showing that a few minutes — or even seconds — of strenuous intervals, repeated several times, can raise aerobic fitness substantially. But the exercise in these studies usually has involved stationary cycling or running.

Few experiments have examined the effects of brief body-weight workouts on endurance and strength, and those few had drawbacks. Most focused on people who already were fit, and almost none met the scientific gold standard of being randomized and including an inactive control group. Consequently, our faith in the benefits of short body-weight training may have been understandable, but evidence was lacking.

So, for the new study, which was published this month in the International Journal of Exercise Science, researchers at McMaster University in Hamilton, Ontario, and the Mayo Clinic in Rochester, Minn., decided to develop and test a basic body-weight routine. They modeled their version on the well-known 5BX program, which once had been used to train members of the Canadian military in remote posts. But the researchers swapped out elements from the original, which had included exercises like old-fashioned situps that are not considered particularly good for the back or effective in building endurance.

They wound up with a program that alternated one minute of calisthenics, including modified burpees (omitting the push-ups that some enthusiasts tack onto the move) and running in place, with a minute of walking, also in place. The routine required no equipment, little space and a grand total of 11 minutes, including a minute for warming up and cooling down.

They then recruited 20 healthy but out-of-shape young men and women, measured their current fitness, leg power and handgrip strength and randomly assigned half to start practicing the new program three times a week, while the others continued with their normal lives, as a control.

The exercisers were asked to “challenge” themselves during the calisthenics, completing as many of each exercise as they could in a minute, before walking in place, and then moving to the next exercise.

After six weeks, all of the volunteers returned to the lab for follow-up testing. And, to no one’s surprise, the exercisers were more fit, having upped their endurance by about 7 percent, on average. Their leg power also had grown slightly. The control group’s fitness and strength remained unchanged.

“It was good to see our expectations confirmed,” says Martin Gibala, a professor of kinesiology at McMaster University, who oversaw the new study and, with various collaborators, has published influential studies of intense interval training in the past.

“It seemed obvious” that this kind of training should be effective, he says. But “we now have evidence” that brief, basic body-weight training “can make a meaningful difference” in fitness, he says.

The study was small and quite short-term, though, and looked at the effects only among healthy young people who are capable of performing burpees and jump squats. “Some people may need to substitute” some of the exercises, Dr. Gibala says, especially anyone who has problems with joint pain or balance. (See the Standing 7-Minute Workout for examples of appropriate replacements, in that case.)

But whatever mix of calisthenics you settle on, “the key is to push yourself a bit” during each one-minute interval, he says.

Here is the full 11-minute workout used in the study, with video links of each exercise by Linda Archila, a researcher who led the experiment while a student at McMaster University.

  • 1 minute of easy jumping jacks, to warm up

  • 1 minute of modified burpees (without push-ups)

  • 1 minute of walking in place

  • 1 minute of high-knee running in place

  • 1 minute of walking in place

  • 1 minute of split squat jumps (starting and ending in the lunge position, while alternating which leg lands forward)

  • 1 minute of walking in place

  • 1 minute of high-knee running in place

  • 1 minute of walking in place

  • 1 minute of squat jumps

  • 1 minute of walking in place, to cool down

How the Right Foods May Lead to a Healthier Gut, and Better Health

How the Right Foods May Lead to a Healthier Gut, and Better Health

A diet full of highly processed foods with added sugars and salt promoted gut microbes linked to obesity, heart disease and diabetes.

Credit…Getty Images
Anahad O’Connor

  • Jan. 11, 2021, 11:00 a.m. ET

Scientists know that the trillions of bacteria and other microbes that live in our guts play an important role in health, influencing our risk of developing obesity, heart disease, Type 2 diabetes and a wide range of other conditions. But now a large new international study has found that the composition of these microorganisms, collectively known as our microbiomes, is largely shaped by what we eat.

By analyzing the diets, health and microbiomes of more than a thousand people, researchers found that a diet rich in nutrient-dense, whole foods supported the growth of beneficial microbes that promoted good health. But eating a diet full of highly processed foods with added sugars, salt and other additives had the opposite effect, promoting gut microbes that were linked to worse cardiovascular and metabolic health.

The researchers found that what people ate had a more powerful impact on the makeup of their microbiomes than their genes. They also discovered that a variety of plant and animal foods were linked to a more favorable microbiome.

One critical factor was whether people ate foods that were highly processed or not. People who tended to eat minimally processed foods like vegetables, nuts, eggs and seafood were more likely to harbor beneficial gut bacteria. Consuming large amounts of juices, sweetened beverages, white bread, refined grains, and processed meats, on the other hand, was associated with microbes linked to poor metabolic health.

“It goes back to the age-old message of eating as many whole and unprocessed foods as possible,” said Dr. Sarah E. Berry, a nutrition scientist at King’s College London and a co-author of the new study, which was published Monday in Nature Medicine. “What this research shows for the first time is the link between the quality of the food we’re eating, the quality of our microbiomes and ultimately our health outcomes.”

The findings could one day help doctors and nutritionists prevent or perhaps even treat some diet-related diseases, allowing them to prescribe personalized diets to people based on the unique makeup of their microbiomes and other factors.

Many studies suggest that there is no one-size-fits-all diet that works for everyone. The new study, for example, found that while some foods were generally better for health than others, different people could have wildly different metabolic responses to the same foods, mediated in part by the kinds of microbes residing in their guts.

“What we found in our study was that the same diet in two different individuals does not lead to the same microbiome, and it does not lead to the same metabolic response,” said Dr. Andrew T. Chan, a co-author of the study and a professor of medicine at Harvard Medical School and Massachusetts General Hospital. “There is a lot of variation.”

The new findings stem from an international study of personalized nutrition called Predict, which is the world’s largest research project designed to look at individual responses to food. Started in 2018 by the British epidemiologist Tim Spector, the study has followed over 1,100 mostly healthy adults in the United States and Britain, including hundreds of identical and nonidentical twins.

The researchers collected data on a wide range of factors that influence metabolism and disease risk. They analyzed the participants’ diets, microbiomes and body fat. They took blood samples before and after meals to look at their blood sugar, hormones, cholesterol and inflammation levels. They monitored their sleep and physical activity. And for two weeks they had them wear continuous glucose monitors that tracked their blood sugar responses to different meals.

The researchers were surprised to discover that genetics played only a minor role in shaping a person’s microbiome. Identical twins were found to share just 34 percent of the same gut microbes, while people who were unrelated shared about 30 percent of the same microbes. The composition of each person’s microbiome appeared instead to be driven more by what they ate, and the types of microbes in their guts played a strong role in their metabolic health.

The researchers identified clusters of so-called good gut bugs, which were more common in people who ate a diverse diet rich in high-fiber plants — like spinach, broccoli, tomatoes, nuts and seeds — as well as minimally processed animal foods such as fish and full-fat yogurt. They also found clusters of “bad” gut bugs that were common in people who regularly consumed foods that were highly processed. One common denominator among heavily processed foods is that they tend to contain very little fiber, a macronutrient that helps to nourish good microbes in the gut, the researchers said.

Among the “good” strains of gut microbes were Prevotella copri and Blastocystis, both of which were associated with lower levels of visceral fat, the kind that accumulates around internal organs and that increases the risk of heart disease. These microbes also appeared to improve blood sugar control, an indicator of diabetes risk. Other beneficial microbes were associated with reduced inflammation and lower spikes in blood fat and cholesterol levels after meals, all of which play a role in cardiovascular health.

The new study was funded and supported by Zoe Global, a health science company, as well as by the Wellcome Trust, a British nonprofit, and several public health groups.

Dr. Berry said the findings suggest that by looking at microbiome profiles they can identify people at high risk of developing metabolic diseases and intervene early on. She and her colleagues are now planning a clinical trial that will test whether telling people to change specific foods in their diets can alter levels of good and bad microbes in their guts and subsequently improve their health.

“We think there are lots of small changes that people can make that can have a big impact on their health that might be mediated through the microbiome,” she said.

One 18-Hour Flight, Four Coronavirus Infections

One 18-Hour Flight, Four Coronavirus Infections

An outbreak aboard a September flight from Qatar to New Zealand offers researchers, and airlines, an opportunity to study in-transit contagion.

A masked passenger on a flight out of Kansas City, Mo., last year. The study of a largely empty flight last fall suggests that airlines will need to further tighten precautions on flights.
A masked passenger on a flight out of Kansas City, Mo., last year. The study of a largely empty flight last fall suggests that airlines will need to further tighten precautions on flights.Credit…Charlie Riedel/Associated Press
Benedict Carey

  • Jan. 7, 2021, 5:50 p.m. ET

The millions of airline passengers who traveled over the holidays experienced firsthand the unsettling uncertainties that come with flying during a pandemic. The anxious glances. The awkward semi-distancing. The haphazard mask etiquette, and the absence of regular service.

In an effort to reassure, the airlines have updated and adjusted their requirements for travelers, with patchwork results. Some airlines work to maintain social distance, both at the gate and at boarding; others are less vigilant. Mask-wearing is dependent on passenger compliance, and not predictable; nor, increasingly, is flight capacity, which can range from 20 percent to nearly full.

Given the variables, infectious disease specialists have had a hard time determining the risks of flying. But a study published on Wednesday provides some clarity.

After an 18-hour flight from Dubai landed in Auckland, New Zealand, in September, local health authorities discovered evidence of an outbreak that most likely occurred during the trip. Using seat maps and genetic analysis, the new study determined that one passenger initiated a chain of infection that spread to four others en route.

Previous research on apparent in-flight outbreaks focused on flights that occurred last spring, when few travelers wore masks, planes were running near capacity and the value of preventive measures was not broadly understood. The new report, of a largely empty flight in the fall, details what can happen even when airlines and passengers are aware and more cautious about the risks.

The findings deliver a clear warning to both airlines and passengers, experts said.

“The key message here is that you have to have multiple layers of prevention — requiring testing before boarding, social distancing on the flight, and masks,” said Dr. Abraar Karan, an internal medicine physician at Brigham and Women’s Hospital and Harvard Medical School who was not part of the study team. “Those things all went wrong in different ways on this flight, and if they’d just tested properly, this wouldn’t have happened.”

The new infections were detected after the plane landed in New Zealand; the country requires incoming travelers to quarantine for 14 days before entering the community. The analysis, led by researchers at the New Zealand Ministry of Health, found that seven of the 86 passengers on board tested positive during their quarantine and that at least four were newly infected on the flight. The aircraft, a Boeing 777-300ER, with a capacity of nearly 400 passengers, was only one-quarter full.

A diagram from the study shows the seating arrangement of the seven passengers who tested positive. The open circles represent passengers who tested negative for the coronavirus after the flight. All other seats shown remained empty.
A diagram from the study shows the seating arrangement of the seven passengers who tested positive. The open circles represent passengers who tested negative for the coronavirus after the flight. All other seats shown remained empty.Credit…Centers for Disease Control and Prevention

These seven passengers came from five countries, and they were seated within four rows of one another for the 18-hour duration of the flight. Two acknowledged that they did not wear masks, and the airline did not require mask-wearing in the lobby before boarding. Nor did it require preflight testing, although five of the seven passengers who later tested positive had taken a test, and received a negative result, in the days before boarding.

The versions of the coronavirus that all seven carried were virtually identical genetically — strongly suggesting that one person among them initiated the outbreak. That person, whom the report calls Passenger A, had in fact tested negative four or five days before boarding, the researchers found.

“Four or five days is a long time,” Dr. Kamar said. “You should be asking for results of rapid tests done hours before the flight, ideally.”

Even restrictive “Covid-free” flights, international bookings that require a negative result to board, give people a day or two before departure to get a test.

The findings are not definitive, cautioned the authors, led by Dr. Tara Swadi, an adviser with New Zealand’s Health Ministry. But results “underscore the value of considering all international passengers arriving in New Zealand as being potentially infected, even if pre-departure testing was undertaken, social distancing and spacing were followed, and personal protective equipment was used in-flight,” the researchers concluded.

Previous studies of infection risk during air travel did not clearly quantify the risk, and onboard air filtration systems are thought to reduce the infection risk among passengers even when a flight includes one or more infected people. But at least two recent reports strongly suggest that in-flight outbreaks are a risk: one of a flight from Boston to Hong Kong in March; the other of a flight from London to Hanoi, Vietnam, also in March.

On the Hong Kong flight, the analysis suggested that two passengers who boarded in Boston infected two flight attendants. On the Hanoi flight, researchers found that 12 of 16 people who later tested positive were sitting in business class, and that proximity to the infectious person strongly predicted infection risk.

Airline policies vary widely, depending on the flight and the carrier. During the first months of the pandemic, most U.S. airlines had a policy of blocking off seats, or allowing passengers to reschedule if a flight was near 70 percent full. But by the holidays those policies were largely phased out, said Scott Mayerowitz, executive editor at The Points Guy, a website that covers the industry.

All carriers have a mask policy, for passengers and crew — although passengers are not always compliant.

“Even before the pandemic, passengers weren’t always the best at following rules on airplanes,” Mr. Mayerowitz said. “Something about air travel brings out the worse in people, whether it’s fighting over reclined seats, or overhead bin space, or wearing a mask properly.”

Temperature checks are uncommon and are less than reliable as an indicator of infectiousness. And coronavirus tests are not needed for boarding, at least on domestic flights. Some international flights are “Covid tested”: to fly from New York to Rome on Alitalia, for example, passengers must have received a negative test result within 48 hours of boarding. They are tested again on arrival in Rome.

Dr. Kamar said that, unless all preventive measures are in place, there will be some risk of infection on almost any flight.

“It is surprising and not surprising, on an 18-hour flight, that an outbreak would occur,” Dr. Kamar said. “It’s more than likely that more than just those two people took off their mask at some point,” and every such lapse increases the likelihood of spread.

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Sleep Better in the New Year

Sleep Better in the New Year

Advice from Well on how to get more and sounder sleep in 2021.

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CreditCredit…By Till Lauer

  • Dec. 30, 2020, 5:00 a.m. ET

For many, 2020 was a year that provided lots of worries that kept us tossing and turning at night. Tara Parker-Pope’s guide, How to Get a Better Night’s Sleep, is packed with advice:

We spend about one-third of our lives asleep, and sleep is essential to better health. But many of us are struggling with sleep. Four out of five people say that they suffer from sleep problems at least once a week and wake up feeling exhausted. So how do you become a more successful sleeper? Grab a pillow, curl up and keep reading to find out.

Here are more articles from the past year in Well that may help you start the new year with better sleep.

How Foods May Affect Our Sleep

By Anahad O’Connor

With the coronavirus pandemic, school and work disruptions and a contentious election season contributing to countless sleepless nights, sleep experts have encouraged people to adopt a variety of measures to overcome their stress-related insomnia. Among their recommendations: engage in regular exercise, establish a nightly bedtime routine and cut back on screen time and social media.

But many people may be overlooking another important factor in poor sleep: diet. A growing body of research suggests that the foods you eat can affect how well you sleep, and your sleep patterns can affect your dietary choices.

Researchers have found that eating a diet that is high in sugar, saturated fat and processed carbohydrates can disrupt your sleep, while eating more plants, fiber and foods rich in unsaturated fat — such as nuts, olive oil, fish and avocados — seems to have the opposite effect, helping to promote sound sleep.

Let the Sunshine In

By Richard Schiffman

A daily dose of sunlight won’t fend off or cure coronavirus, though researchers continue to explore the effects that warmer weather and ultraviolet rays might have on the virus. But scientists are finding that exposure to the sun has numerous other benefits that may be especially important now — including helping to elevate mood, to improve the quality of our sleep and to strengthen the body’s innate defenses against a variety of pathogens.

Exposure to daylight is critical for accurately setting our internal circadian clock, which in turn regulates sleep and waking, said Mariana Figueiro, the director of the Lighting Research Center at Rensselaer Polytechnic Institute in Troy, N.Y.

Without adequate light, we can go into a kind of permanent jet lag, Dr. Figueiro explained, where we get more easily irritated and depressed, our immune function is suppressed and our overall health may deteriorate.

Whether You Are a Night Owl or Early Bird May Affect How Much You Move

By Gretchen Reynolds

People who are evening types go to bed later and wake up later than morning types. They also tend to move around far less throughout the day, according to an interesting new study of how our innate body clocks may be linked to our physical activity habits. The study, one of the first to objectively track daily movements of a large sample of early birds and night owls, suggests that knowing our chronotype might be important for our health.

In recent years, a wealth of new science has begun explicating the complex roles of cellular clocks and chronotypes in our health and lifestyles. Thanks to this research, we know that each of us contains a master internal body clock, located in our brains, that tracks and absorbs outside clues, such as ambient light, to determine what time it is and how our bodies should react. This master clock directs the rhythmic release of hormones, such as melatonin, and other chemicals that affect sleep, wakefulness, hunger and many other physiological systems.

Their Teeth Fell Out. Was It Another Covid-19 Consequence?

Earlier this month, Farah Khemili popped a wintergreen breath mint in her mouth and noticed a strange sensation: a bottom tooth wiggling against her tongue.

Ms. Khemili, 43, of Voorheesville, N.Y., had never lost an adult tooth. She touched the tooth to confirm it was loose, initially thinking the problem might be the mint. The next day, the tooth flew out of her mouth and into her hand. There was neither blood nor pain.

Ms. Khemili survived a bout with Covid-19 this spring, and has joined an online support group as she has endured a slew of symptoms experienced by many other “long haulers”: brain fog, muscle aches and nerve pain.

There’s no rigorous evidence yet that the infection can lead to tooth loss or related problems. But among members of her support group, she found others who also described teeth falling out, as well as sensitive gums and teeth turning gray or chipping.

She and other survivors unnerved by Covid’s well-documented effects on the circulatory system, as well as symptoms such as swollen toes and hair loss, suspect a connection to tooth loss as well. But some dentists, citing a lack of data, are skeptical that Covid-19 alone could cause dental symptoms.

“It’s extremely rare that teeth will literally fall out of their sockets,” said Dr. David Okano, a periodontist at the University of Utah in Salt Lake City.

But existing dental problems may worsen as a result of Covid-19, he added, especially as patients recover from the acute infections and contend with its long-term effects.

And some experts say that doctors and dentists need to be open to such possibilities, especially because more than 47 percent of adults 30 years or older have some form of periodontal disease, including infections and inflammation of the gums and bone that surround teeth, according to a 2012 report from the Centers for Disease Control and Prevention.

“We are now beginning to examine some of the bewildering and sometimes disabling symptoms that patients are suffering months after they’ve recovered from Covid,” including these accounts of dental issues and teeth loss, said Dr. William W. Li, president and medical director of the Angiogenesis Foundation, a nonprofit that studies the health and disease of blood vessels.

While Ms. Khemili had become more diligent about her dental care, she had a history of dental issues before contracting the coronavirus. When she went to the dentist the day after her tooth came out, he found that her gums were not infected but she had significant bone loss from smoking. He referred Ms. Khemili to a specialist to handle a reconstruction. The dental procedure is likely to cost her just shy of $50,000.

The same day Ms. Khemili’s tooth fell out, her partner went on Survivor Corp, a Facebook page for people who have lived through Covid-19. There, he found that Diana Berrent, the page’s founder, was reporting that her 12-year-old son had lost one of his adult teeth, months after he had a mild case of Covid-19. (Unlike Ms. Khemili, Ms. Berrent’s son had normal and healthy teeth with no underlying disease, according to his orthodontist.)

Others in the Facebook group have posted about teeth falling out without bleeding. One woman lost a tooth while eating ice cream. Eileen Luciano of Edison, N.J., had a top molar pop out in early November when she was flossing.

“That was the last thing that I thought would happen, that my teeth would fall out,” Ms. Luciano said.

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Teeth falling out without any blood is unusual, Dr. Li said, and provides a clue that there might be something going on with the blood vessels in the gums.

The new coronavirus wreaks havoc by binding to the ACE2 protein, which is ubiquitous in the human body. Not only is it found in the lungs, but also on nerve and endothelial cells. Therefore, Dr. Li says, it’s possible that the virus has damaged the blood vessels that keep the teeth alive in Covid-19 survivors; that also may explain why those who have lost their teeth feel no pain.

It’s also possible that the widespread immune response, known as a cytokine storm, may be manifesting in the mouth.

“If a Covid long hauler’s reaction is in the mouth, it’s a defense mechanism against the virus,” said Dr. Michael Scherer, a prosthodontist in Sonora, Calif. Other inflammatory health conditions, such as cardiovascular disease and diabetes, he said, also correlate with gum disease in the same patients.

“Gum disease is very sensitive to hyper-inflammatory reactions, and Covid long haulers certainly fall into that category,” Dr. Scherer said.

Dentists haven’t seen many of these cases, and some dismiss these individual claims. But physicians like Dr. Li say Covid-19’s surprises require that the profession be on the lookout for unexpected consequences of the disease.

“Patients may be bringing in new findings,” he said, and physicians and dentists need to cooperate on understanding the effects of long-term Covid-19 on teeth.

For now, Ms. Khemili hopes her story may serve as a cautionary tale. If people aren’t taking the proper precautions to protect themselves from the coronavirus, “they could be looking at something like this.”

How Exercise May Help the Brain Grow Stronger

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Credit Getty Images

Physical activity is good for our brains. A wealth of science supports that idea. But precisely how exercise alters and improves the brain remains somewhat mysterious.

A new study with mice fills in one piece of that puzzle. It shows that, in rodents at least, strenuous exercise seems to beneficially change how certain genes work inside the brain. Though the study was in mice, and not people, there are encouraging hints that similar things may be going on inside our own skulls.

For years, scientists have known that the brains of animals and people who regularly exercise are different than the brains of those who are sedentary. Experiments in animals show that, for instance, exercise induces the creation of many new cells in the hippocampus, which is a part of the brain essential for memory and learning, and also improves the survival of those fragile, newborn neurons.

Researchers believe that exercise performs these feats at least in part by goosing the body’s production of a substance called brain-derived neurotropic factor, or B.D.N.F., which is a protein that scientists sometimes refer to as “Miracle-Gro” for the brain. B.D.N.F. helps neurons to grow and remain vigorous and also strengthens the synapses that connect neurons, allowing the brain to function better. Low levels of B.D.N.F. have been associated with cognitive decline in both people and animals. Exercise increases levels of B.D.N.F. in brain tissue.

But scientists have not understood just what it is about exercise that prompts the brain to start pumping out additional B.D.N.F.

So for the new study, which was published this month in the journal eLIFE, researchers with New York University’s Langone Medical Center and other institutions decided to microscopically examine and reverse engineer the steps that lead to a surge in B.D.N.F. after exercise.

They began by gathering healthy mice. Half of the animals were put into cages that contained running wheels. The others were housed without wheels. For a month, all of the animals were allowed to get on with their lives. Those living with wheels ran often, generally covering several miles a day, since mice like to run. The others remained sedentary.

After four weeks, the scientists looked at brain tissue from the hippocampus of both groups of animals, checking for B.D.N.F. levels. As expected, the levels were much higher in the brains of the runners.

But then, to better understand why the runners had more B.D.N.F., the researchers turned to the particular gene in the animals’ DNA that is known to create B.D.N.F. For some reason, the scientists realized, this gene was more active among the animals that exercised than those that did not.

Using sophisticated testing methods, the scientists soon learned why. In both groups of animals, the B.D.N.F. gene was partially covered with clusters of a particular type of molecule that binds to the gene, though in different amounts.

In the sedentary mice, these molecules swarmed so densely over the gene that they blocked signals that tell the gene to turn on. As a result, the B.D.N.F. genes of the sedentary animals were relatively muted, pumping out little B.D.N.F.

But among the runners, the molecular blockade was much less effective. The molecules couldn’t seem to cover and bind to the entire B.D.N.F. gene. So messages from the body continued to reach the gene and tell it to turn on and produce more B.D.N.F.

Perhaps most remarkably, the researchers also found a particular substance in the runners’ brains that fended off the action of these obstructionist molecules. The runners’ brains contained high levels of ketones, which are a byproduct of the breakdown of fat. During strenuous exercise, the body relies in part on fat for fuel and winds up creating ketones, some of which migrate to the brain. (They are tiny enough to cross the blood-brain barrier.) The brain uses these ketones for fuel when blood sugar levels grow low.

But it appears that ketones also cause the molecules that hinder the B.D.N.F. gene to loosen their grip, as the scientists realized when they experimentally added ketones to brain tissue from some of the mice. Afterward, their B.D.N.F. genes were not blocked by nearly as many of the bothersome molecules, and those genes could get on with the job of making B.D.N.F.

None of this occurred in the brains of the sedentary mice.

“It’s incredible just how pervasive and complex the effects of exercise are on the brain,” said Moses Chao, a professor at the Skirball Institute of Biomolecular Medicine at N.Y.U. who oversaw the study.

Whether the same mechanisms that occur in mice occur in our own brains when we exercise is still unknown. But, Dr. Chao pointed out, like the mice, we have more B.D.N.F. in our bodies after exercise. We also create ketones when we exercise, and those ketones are known to migrate to our brains..

Generally, however, this process requires exerting yourself vigorously for an hour or more, after which time your body, having exhausted its stores of sugar, starts burning stored fat and making ketones.

If an hour or more of intense exercise seems daunting — and it does to me — don’t despair. “We are only starting to understand” the many ways in which exercise of any kind and amount is likely to alter our brains, Dr. Chao said. For now, he says, “it’s a very good idea to just keep moving.”

A Decades-Old Study, Rediscovered, Challenges Advice on Saturated Fat

A four-decades-old study — recently discovered in a dusty basement — has raised new questions about longstanding dietary advice and the perils of saturated fat in the American diet.

The research, known as the Minnesota Coronary Experiment, was a major controlled clinical trial conducted from 1968 to 1973, which studied the diets of more than 9,000 people at state mental hospitals and a nursing home.

During the study, which was paid for by the National Heart, Lung and Blood Institute and led by Dr. Ivan Frantz Jr. of the University of Minnesota Medical School, researchers were able to tightly regulate the diets of the institutionalized study subjects. Half of those subjects were fed meals rich in saturated fats from milk, cheese and beef. The remaining group ate a diet in which much of the saturated fat was removed and replaced with corn oil, an unsaturated fat that is common in many processed foods today. The study was intended to show that removing saturated fat from people’s diets and replacing it with polyunsaturated fat from vegetable oils would protect them against heart disease and lower their mortality.

So what was the result? Despite being one of the largest controlled clinical dietary trials of its kind ever conducted, the data were never fully analyzed.

Several years ago, Christopher E. Ramsden, a medical investigator at the National Institutes of Health, learned about the long-overlooked study. Intrigued, he contacted the University of Minnesota in hopes of reviewing the unpublished data. Dr. Frantz, who died in 2009, had been a prominent scientist at the university, where he studied the link between saturated fat and heart disease. One of his closest colleagues was Ancel Keys, an influential scientist whose research in the 1950s helped establish saturated fat as public health enemy No. 1, prompting the federal government to recommend low-fat diets to the entire nation.

“My father definitely believed in reducing saturated fats, and I grew up that way,” said Dr. Robert Frantz, the lead researcher’s son and a cardiologist at the Mayo Clinic. “We followed a relatively low-fat diet at home, and on Sundays or special occasions, we’d have bacon and eggs.”

The younger Dr. Frantz made three trips to the family home, finally discovering the dusty box marked “Minnesota Coronary Survey,” in his father’s basement. He turned it over to Dr. Ramsden for analysis.

The results were a surprise. Participants who ate a diet low in saturated fat and enriched with corn oil reduced their cholesterol by an average of 14 percent, compared with a change of just 1 percent in the control group. But the low-saturated fat diet did not reduce mortality. In fact, the study found that the greater the drop in cholesterol, the higher the risk of death during the trial.

The findings run counter to conventional dietary recommendations that advise a diet low in saturated fat to decrease heart risk. Current dietary guidelines call for Americans to replace saturated fat, which tends to raise cholesterol, with vegetable oils and other polyunsaturated fats, which lower cholesterol.

While it is unclear why the trial data had not previously been fully analyzed, one possibility is that Dr. Frantz and his colleagues faced resistance from medical journals at a time when questioning the link between saturated fat and disease was deeply unpopular.

“It could be that they tried to publish all of their results but had a hard time getting them published,” said Daisy Zamora, an author of the new study and a research scientist at the University of North Carolina at Chapel Hill.

The younger Dr. Frantz said his father was probably startled by what seemed to be no benefit in replacing saturated fat with vegetable oil.

“When it turned out that it didn’t reduce risk, it was quite puzzling,” he said. “And since it was effective in lowering cholesterol, it was weird.”

The new analysis, published on Tuesday in the journal BMJ, elicited a sharp response from top nutrition experts, who said the study was flawed. Walter Willett, the chairman of the nutrition department at the Harvard T.H. Chan School of Public Health, called the research “irrelevant to current dietary recommendations” that emphasize replacing saturated fat with polyunsaturated fat.

Frank Hu, a nutrition expert who served on the government’s 2015 dietary guidelines committee, said the Minnesota trial was not long enough to show the cardiovascular benefits of consuming vegetable oil because the patients on average were followed for only about 15 months. He pointed to a major 2010 meta-analysis that found that people had fewer heart attacks when they increased their intake of vegetable oils and other polyunsaturated fats over at least four years.

“I don’t think the authors’ strong conclusions are supported by the data,” he said.

To investigate whether the new findings were a fluke, Dr. Zamora and her colleagues analyzed four similar, rigorous trials that tested the effects of replacing saturated fat with vegetable oils rich in linoleic acid. Those, too, failed to show any reduction in mortality from heart disease.

“One would expect that the more you lowered cholesterol, the better the outcome,” Dr. Ramsden said. “But in this case the opposite association was found. The greater degree of cholesterol-lowering was associated with a higher, rather than a lower, risk of death.”

One explanation for the surprise finding may be omega-6 fatty acids, which are found in high levels in corn, soybean, cottonseed and sunflower oils. While leading nutrition experts point to ample evidence that cooking with these vegetable oils instead of butter improves cholesterol and prevents heart disease, others argue that high levels of omega-6 can simultaneously promote inflammation. This inflammation could outweigh the benefits of cholesterol reduction, they say.

In 2013, Dr. Ramsden and his colleagues published a controversial paper about a large clinical trial that had been carried out in Australia in the 1960s but had never been fully analyzed. The trial found that men who replaced saturated fat with omega-6-rich polyunsaturated fats lowered their cholesterol. But they were also more likely to die from a heart attack than a control group of men who ate more saturated fat.

Ron Krauss, the former chairman of the American Heart Association’s dietary guidelines committee, said the new research was intriguing. But he said there was a vast body of research supporting polyunsaturated fats for heart health, and that the relationship between cholesterol-lowering and mortality could be deceiving.

People who have high LDL cholesterol, the so-called bad kind, typically experience greater drops in cholesterol in response to dietary changes than people with lower LDL. Perhaps people in the new study who had the greatest drop in cholesterol also had higher mortality rates because they had more underlying disease.

“It’s possible that the greater cholesterol response was in people who had more vascular risk related to their higher cholesterol levels,” he said.

Dr. Ramsden stressed that the findings by he and his colleagues should be interpreted cautiously. The research does not show that saturated fats are beneficial, he said: “But maybe they’re not as bad as people thought.”

The research underscores that the science behind dietary fat may be more complex than nutrition recommendations suggest. The body requires omega-6 fats like linoleic acid in small amounts. But emerging research suggests that in excess linoleic acid may play a role in a variety of disorders including liver disease and chronic pain.

A century ago, it was common for Americans to get about 2 percent of their daily calories from linoleic acid. Today, Americans on average consume more than triple that amount, much of it from processed foods like lunch meats, salad dressings, desserts, pizza, french fries and packaged snacks like potato chips. More natural sources of fat such as olive oil, butter and egg yolks contain linoleic acid as well but in smaller quantities.

Eating whole, unprocessed foods and plants may be one way to get all the linoleic acid your body needs, Dr. Ramsden said.

The Secrets to a Happy Life, From a Harvard Study

What does it take to live a good life?

Surveys show that most young adults believe that obtaining wealth and fame are keys to a happy life. But a long-running study out of Harvard suggests that one of the most important predictors of whether you age well and live a long and happy life is not the amount of money you amass or notoriety you receive. A much more important barometer of long term health and well-being is the strength of your relationships with family, friends and spouses.

These are some of the findings from the Harvard Study of Adult Development, a research project that since 1938 has closely tracked and examined the lives of more than 700 men and in some cases their spouses. The study has revealed some surprising – and some not so surprising – factors that determine whether people are likely to age happily and healthily, or descend into loneliness, sickness and mental decline.

The study’s current director, , outlined some of the more striking findings from the long-running project in a recent TED Talk that has garnered more than seven million views.

“We publish our findings in academic journals that most people don’t read,” Dr. Waldinger, a clinical professor of psychiatry at Harvard Medical School, said in a recent interview. “And so we really wanted people to know that this study exists and that it has for 75 years. We’ve been funded by the government for so many years, and it’s important that more people know about this besides academics.”

The study began in Boston in the 1930s with two very different groups of young men.

In one case, a team of researchers decided to track Harvard college students through adulthood to see what factors played important roles in their growth and success. “They thought there was too much emphasis placed on pathology at the time and that it would be really useful to study people who were doing well in their young adult development,” Dr. Waldinger said. The study recruited 268 Harvard sophomores and followed them closely, with frequent interviews and health examinations. In recent years the study has also incorporated brain scans, blood draws and interviews with the subjects’ spouses and adult children.

At around the same time the study began, a Harvard Law School professor named Sheldon Glueck started to study young men from some of Boston’s poorest neighborhoods, including 456 who managed to avoid delinquency despite coming from troubled homes. Eventually the two groups were merged into one study.

Over the decades, the men have gone into all walks of life. They’ve become lawyers, doctors, businessmen and — in the case of one Harvard student named John F. Kennedy — president of the United States. Others went down different paths. Some became alcoholics, had disappointing careers or descended into mental illness. Those who remain alive today are in their 90s.

Through the years, the study has produced many notable findings. It showed, for example, that to age well physically, the single most important thing you could do was to avoid smoking. It discovered that aging liberals had longer and more active sex lives than conservatives. It found that alcohol was the primary cause of divorce among men in the study, and that alcohol abuse often preceded depression (rather than the other way around).

The study has gone through several directors. Dr. Waldinger, who took over in 2003, is its fourth. He expanded the study so it focused not just on the men but also on their wives and children. The researchers began videotaping the couples in their homes, studying their interactions, and interviewing them separately about nearly every facet of their lives, even day-to-day spats.

As the researchers looked at the factors throughout the years that strongly influenced health and well-being, they found that relationships with friends, and especially spouses, were a major one. The people in the strongest relationships were protected against chronic disease, mental illness and memory decline – even if those relationships had many ups and downs.

“Those good relationships don’t have to be smooth all the time,” Dr. Waldinger said. “Some of our octogenarian couples could bicker day in and day out. But as long as they felt that they could really count on the other when the going got tough, those arguments didn’t take a toll on their memories.”

Dr. Waldinger found a similar pattern among relationships outside the home. The people who sought to replace old colleagues with new friends after retiring were happier and healthier than those who left work and placed less emphasis on maintaining strong social networks.

“Over and over in these 75 years,” Dr. Waldinger said, “our study has shown that the people who fared the best were the people who leaned into relationships with family, with friends and with community.”

Dr. Waldinger acknowledged that the research showed a correlation, not necessarily causation. Another possibility is that people who are healthier and happier to begin with are simply more likely to make and maintain relationships, whereas those who are sicker gradually become more socially isolated or end up in bad relationships.

But he said that by following the subjects for many decades and comparing the state of their health and their relationships early on, he was fairly confident that strong social bonds are a causal role in long-term health and well-being.

So what concrete actions does he recommend?

“The possibilities are endless,” he said. “Something as simple as replacing screen time with people time, or livening up a stale relationship by doing something new together, long walks or date nights. Reach out to that family member you haven’t spoken to in years — because those all-too-common family feuds take a terrible toll on the people who hold the grudges.”

To Reduce the Risk of Alzheimer’s, Eat Fish

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Salmon for sale at the Tsukiji fish market in Tokyo, Japan.

Salmon for sale at the Tsukiji fish market in Tokyo, Japan.Credit Kevin Miyazaki for The New York Times

Eating seafood is linked to a reduced risk of dementia-associated brain changes in people who carry the ApoE4 gene variation, which increases the risk for Alzheimer’s disease. Eating seafood was not linked to similar changes in those who carried other forms of the ApoE gene.

The study, published in JAMA, looked at 286 autopsied brains and also found that eating seafood was linked to increased mercury in the brain, but that mercury levels were not linked to brain abnormalities.

After controlling for age, sex, education and other factors, the researchers found that compared with those who ate less seafood, ApoE4 carriers who had one seafood meal or more a week had lower densities of the amyloid plaques and neurofibrillary tangles typical of Alzheimer’s disease. Over all, they had a 47 percent lower likelihood of having a post-mortem diagnosis of Alzheimer’s.

Consumption of fish oil supplements was not correlated with pathological brain changes.

The lead author, Martha Clare Morris, a professor of epidemiology at Rush University, said that mercury from fish appears to pose little risk for aging people. But, she said, there are studies that show that mercury consumption in pregnancy can cause cognitive problems in babies.

“Most studies in dementia have found that one seafood meal a week is beneficial,” she said, though “they haven’t found that the more you eat, the lower the risk.”