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The Club PUBlication 06/29/2020

6/29/2020

Single session of exercise alters 9,815 molecules in our blood

Researchers were taken aback by the magnitude of the changes.

By Gretchen Reynolds New York Times

JUNE 18, 2020 — 9:00PM

The molecular changes due to exercise underscore how activity is critical for health.

When we exercise, the levels of thousands of substances in our bloodstream rise and drop, according to an eye-opening new study of the immediate, interior effects of working out. The study is the most comprehensive cataloging to date of the molecular changes that occur during and after exercise and underscores how consequential activity — and inactivity — may be for our bodies and health.

We have reams of evidence that exercise alters our metabolisms, muscles, genes and immune responses. But only in recent years, with the development of new techniques, have scientists been able to quantify more of the steps involved.

For the new study, published in Cell, scientists at Stanford University and other institutions tried to complete a full census of almost every molecule that changes when we work out. They already had been quantifying health data from a group of about 100 adult men and women. They chose 36 of them, representing an age range between 40 and 75 and a full spectrum of fitness and metabolic health.

After drawing blood from each volunteer before and after exercise, researchers measured the levels of 17,662 different molecules. Of these, 9,815 — or more than half — changed after exercise. The types of molecules ranged widely, with some involved in fueling and metabolism, others in immune response, tissue repair or appetite. And within those categories, molecular levels coursed and changed during the hour.

“It was like a symphony,” said Michael Snyder, the chair of the genetics department at Stanford University.

Different people’s blood followed different orchestrations. Those who showed signs of insulin resistance, for instance, tended to show smaller increases in some of the molecules related to healthy blood sugar control and higher increases in molecules involved in inflammation, suggesting that they were somewhat resistant to the general, beneficial effects of exercise.

Overall, the researchers were taken aback by the magnitude of the changes, Snyder said. “I had thought, it’s only about nine minutes of exercise, how much is going to change? A lot, as it turns out.”

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The Club PUBlication 06/22/2020

6/22/2020

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Animal interactions offer lessons for humans

Sometimes, animals seem so much more advanced than humans; other times, we learn how not to handle problems.

By Harvey Mackay Special to the Star Tribune

In the Upper Midwest, a sure sign of spring and fall is when geese fly overhead, often honking loudly. I recently discovered the reason.

Turns out that Prof. Margaret Kuhn’s research revealed that in order to fly long distances, geese rotate their leaders, and they only pick the ones that can handle turbulence. The other birds honk, not from discomfort, but to encourage their leader.

I have shared lessons from animals over the years. Sometimes, they seem so much more advanced than humans; other times, we learn how not to handle problems. Here are some examples.

If a lobster is left high and dry among rocks, it does not have enough instinct and energy to work its way back to the sea, even though it may be only a few feet away. It waits for the sea to come to it and will die in its tracks.

There are also “human lobsters” in the world who are stranded on the rocks and won’t take a risk. They choose to procrastinate instead of grabbing hold of the problems they face.

Lesson: Taking risks is part of life. Not taking risks can kill a career.

Thomas J. Watson Jr., who built IBM into a worldwide power, loved to retell a story attributed to Danish philosopher Soren Kierkegaard. Each year, a man fed wild ducks at a nearby lake before they flew south for the winter. This encouraged some of the ducks to stick around and grow fat and lazy.

The moral is that you can make wild ducks tame, but you can never make tame ducks wild again. And Watson wanted to encourage “wild ducks” at IBM to confront conformity.

Lesson: Letting someone else take care of you prevents you from maximizing your potential.

If you place a frog in a pot of boiling water, it will immediately jump out. However, if you put a frog in room-temperature water, it will stay put. But if the water temperature gradually increases by 5 to 10 degrees, the frog continues to stay and becomes groggier and groggier until it can’t climb out of the pot. The frog will sit there and boil because its sense of survival is geared to sudden changes in its environment, not slow, gradual changes.

Lesson: Pay attention to changes in your environment or prepare to get burned.

In an experiment, four monkeys were put in a room with a bunch of bananas hanging overhead. Every time a monkey tried to climb up and grab a banana, it got drenched with cold water. Eventually, the monkeys caught on, and they quit climbing up after the fruit.

But then, the monkeys were replaced one by one. As the new monkeys tried to climb up after the bananas, the older monkeys would prevent them from climbing. In time, all the original monkeys were replaced. And amazingly, none of the newer group ever tried to climb up to the bananas, even though none of them had ever been splashed with the cold water.

Lesson: Don’t avoid new opportunities just because others have failed or you have been warned not to even try.

Zookeepers found a kangaroo wandering outside its enclosure in the wee hours of the morning. They coaxed her back into the enclosure and added a few extra feet of fencing on top. They thought they had solved the issue until they found her wandering outside again the next night. They increased the fence to 20 feet and figured that would be too tall to leap over.

But the next morning, the kangaroo was free again. Another 10 feet of fencing went up, and the zookeepers thought their problem was solved.

A koala had watched the process and was more amused each day. “How high do you think those humans are going to build this cage?” he asked the kangaroo.
“Who knows?” said the kangaroo. “I wonder if they’ll take some of it down once they realize they keep leaving the gate unlocked.”

Lesson: Make sure you’re solving the right problem.

Mackay’s Moral: Who said you can’t teach an old dog new tricks?

Harvey Mackay is a Minneapolis businessman. Contact him at 612-378-6202 or e-mail harvey@mackay.com.

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The Club PUBlication 06/15/2020

6/15/2020

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Women get statins less often than men

Doctors also prescribed less aspirin, ACE inhibitors.

By LINDA SEARING Washington Post

Women are 10% less likely than men to be prescribed cholesterol-lowering statin drugs, which can lower the risk for heart attack and stroke and are among the most widely prescribed medications worldwide.

The finding, published in the Journal of the American Heart Association, is based on analysis of data from 43 international studies involving 2,264,600 men and women, most in their early 50s to late 70s who either had or were at high risk for cardiovascular disease.

Overall, the researchers found that doctors treating women prescribe medications for cardiovascular disease — heart and blood vessel ailments that can lead to a heart attack or stroke — less often than doctors treating men.
In addition to the statin differences, the study found that women are 19% less likely to be prescribed aspirin to prevent blood clots and 15% less likely to get a prescription for a blood-pressure-lowering drug called an ACE inhibitor. But they are more likely than men (by 27%) to be prescribed a diuretic for blood pressure control.

Why the differences in prescription rates exist was not determined.

Internationally, cardiovascular disease is the leading cause of death, reports the World Health Organization. That holds true in the U.S., where someone dies every 37 seconds from cardiovascular disease, about 1 in 4 deaths, said the Centers for Disease Control and Prevention.

Cardiovascular disease often develops when cholesterol builds up on the walls of arteries, forming plaque that narrows the arteries, restricting the flow of blood and potentially leading to a heart attack or stroke.

Researchers found that doctors treating women prescribe medications for cardiovascular disease less often than for men.

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The Club PUBlication 06/08/2020

6/8/2020

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How much does it take to make you sick?

It's a key question scientists can't answer, which is why they say: limit amount of virus you face.

By Apoorva Mandavilli
New York Times - JUNE 6, 2020

When experts recommend wearing masks, staying at least 6 feet away from others, washing your hands frequently and avoiding crowded spaces, what they are saying is: Try to minimize the amount of virus you encounter.

A few viral particles cannot make you sick — the immune system would kick in first. But how much virus is needed for an infection to take root? A precise answer is impossible, because it is difficult to capture the moment of infection. “The truth is, we really just don’t know,” said Angela Rasmussen, a virologist at Columbia University .

For severe acute respiratory syndrome, or SARS, also a coronavirus, the estimated infective dose is just a few hundred particles. For Middle East respiratory syndrome, or MERS, the infective dose is on the order of thousands of particles. The new coronavirus, SARS-CoV-2, is more similar to the SARS virus and, therefore, the infectious dose may be hundreds of particles, Rasmussen said.
But the virus has a habit of defying predictions.

Generally, people who harbor high levels of pathogens — whether from influenza, HIV or SARS — tend to have more severe symptoms and are more likely to pass on the pathogens to others. But in the case of the new coronavirus, people who have no symptoms seem to have viral loads — that is, the amount of virus in their bodies — just as high as those who are seriously ill.

Some people are generous transmitters; others are stingy. So-called superspreaders seem to be particularly gifted in transmitting it, although it is unclear whether that is because of their biology or their behavior.

On the receiving end, the shape of a person’s nostrils and the amount of nose hair and mucus present — as well as the distribution of certain cellular receptors in the airway that the virus needs to latch on to — can all influence how much virus it takes to become infected.

A higher dose is clearly worse, though.

The crucial dose may also vary depending on whether it is ingested or inhaled. For example, touching a contaminated surface may require millions more copies of the virus to cause an infection, compared to inhalation.

Coughing, sneezing, singing, talking and even heavy breathing can result in the expulsion of thousands of large and small respiratory droplets carrying the virus.
Larger droplets are heavy and float down quickly — unless there is a breeze or an air-conditioning blast — and cannot penetrate surgical masks. But droplets less than 5 microns in diameter, called aerosols, can linger in the air for hours. “They travel farther, last longer and have the potential of more spread than the large droplets,” said Dr. Dan Barouch, a viral immunologist at Beth Israel Deaconess Medical Center in Boston.

However, aerosols also contain much less, perhaps millions-fold less, virus than droplets of 500 microns. “It really takes a lot of these single-digit size droplets to change the risk for you,” said Dr. Joshua Rabinowitz, a quantitative biologist at Princeton University.

Three factors seem to be key to aerosol transmission: proximity to the infected person, air flow and timing. A windowless public bathroom with high foot traffic is riskier than a bathroom with a window, or a bathroom that is rarely used. A short outdoor conversation with a masked neighbor is safer than either of those scenarios.

Recently, Dutch researchers used a special spray nozzle to simulate the expulsion of saliva droplets and then tracked their movement. The scientists found that just cracking open a door or window can banish aerosols.

“Even the smallest breeze will do something,” said Daniel Bonn, a physicist at the University of Amsterdam.

Apart from avoiding crowded indoor spaces, the most effective thing people can do is wear masks, experts said. Even if masks do not fully shield you from droplets loaded with virus, they can cut down the amount you receive, and perhaps bring it below the infectious dose.

“This is not a virus for which hand washing seems like it will be enough,” Rabinowitz said. “We have to limit crowds, we have to wear masks.”

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The Club PUBlication 06/01/2020

6/1/2020

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GEARING UP FOR VACCINE TRIALS

NIH proposal outlines having 4 or 5 experimental vaccines tested on 20,000 participants in about 50 U.S. medical centers.

By ARTHUR ALLEN Kaiser Health News

If there is a silver lining to the flawed U.S. response to the corona-virus pandemic, it is this: The relatively high number of new cases being diagnosed daily — upward of 20,000 — will make it easier to test new vaccines.

I
To determine whether a vaccine prevents disease, the study’s subjects need to be exposed to the pathogen as it circulates in the population. Reopening the economy will likely result in the faster spread of the coronavirus and therefore more opportunities to test a vaccine’s efficacy in trial subjects.

Under a proposal under discussion by a committee set up by the National Institutes of Health, each of four or five experimental vaccines would be tested on about 20,000 trial participants with a placebo group of 10,000 for each vaccine. Some 50 U.S. medical centers — and perhaps an equal number overseas — would participate in these trials.

On May 18, Moderna, the biotech company, reported promising results in the first eight of 45 people enrolled in an initial test of the safety and immune responses to its vaccine.

The company is running animal and human studies simultaneously and plans to invest hundreds of millions of dollars to build laboratories where the vaccine will be produced even before it’s approved. The Food and Drug Administration has promised an accelerated review of Moderna’s vaccine, which works by injecting pieces of synthetic viral RNA into the body to stimulate an immune response to the virus.

Running a trial of the size and speed contemplated by the NIH will be an immense undertaking. Just setting up trial locations and getting common consent and data-entry forms into shape usually take months. Enrolling 30,000 people for a single vaccine trial is a big challenge.

In addition, defining success in a vaccine against COVID-19 will be no simple matter. As scientists design vaccine trials, they first have to set the “endpoints” that determine success or failure. Death? Length of illness? Hospitalization? Number of days in which a subject is infectious?

If there is little virus circulating where a trial is being run, even a vast study won’t prove anything. On the other hand, if a vaccine trial had started in early April in New York City, where roughly 10,000 cases a day were reported for weeks, 30,000 participants would have been plenty to show whether the vaccine protected against the disease.

In all likelihood, the big NIH trials will focus on rates of infection as well as clinical symptoms such as fever and cough. To discover whether the vaccine prevents severe disease, which is relatively rare, is harder. COVID-19, according to one account, kills about 0.6% of those it infects, while perhaps six times that many require hospitalization.

People who take part in a trial will be given clear instructions to protect themselves against infection through social distancing, face masks, frequent hand-washing and so on. That will lower the number of people infected during the study.

“You’d have to ask all the people enrolled in a trial to practice good hygiene,” said Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia. “You don’t want them to get infected — but you do.”

When Jonas Salk announced the successful trial of his polio vaccine in 1955, the nation celebrated a vaccine that could virtually eliminate a deadly infectious disease overnight. A new coronavirus vaccine may not provide that kind of overnight success. Instead, it may be more akin to the flu vaccine, which reduces the risk or severity of the illness but requires a new shot each year.

Vaccinating 20,000 people in a trial can reveal whether a vaccine is clearly dangerous to a general population. But when 200 million receive the same vaccine, less common side effects could still affect thousands. Botched batches of polio vaccines released after Salk’s trial permanently paralyzed 200 people and killed 10. Early vaccines against measles caused tens of thousands of cases of grave illness in the 1960s.

Maurice Hilleman, the vaccine pioneer who developed successful vaccines against measles, mumps, hepatitis A and B and other diseases, once said he never breathed a sigh of relief “until the first 3 million doses” had been delivered.

Unexpected problems naturally bedevil quick rollouts, as this one will almost certainly be as the nation searches for a way to check a pandemic that is killing tens of thousands of Americans and paralyzing the economy. But as Gregory Poland, the leader of Mayo Clinic’s vaccine research, said, “There is an irresolvable tension of speed versus safety.”

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The Club PUBlication 06/29/2020

Single session of exercise alters 9,815 molecules in our bloodResearchers were taken aback by the magnitude of the changes. ​By Gretchen Reynolds New York Times JUNE 18, 2020 — 9:00PM

The Club PUBlication 06/22/2020

Animal interactions offer lessons for humans Sometimes, animals seem so much more advanced than humans; other times, we learn how not to handle problems. ​By Harvey Mackay Special to the Star Tribune

The Club PUBlication 06/15/2020

​​Women get statins less often than menDoctors also prescribed less aspirin, ACE inhibitors.​By LINDA SEARING Washington Post

The Club PUBlication 06/08/2020

How much does it take to make you sick? It's a key question scientists can't answer, which is why they say: limit amount of virus you face. ​By Apoorva Mandavilli ​New York Times - JUNE 6, 2020

The Club PUBlication 06/01/2020

GEARING UP FOR VACCINE TRIALS NIH proposal outlines having 4 or 5 experimental vaccines tested on 20,000 participants in about 50 U.S. medical centers. By ARTHUR ALLEN Kaiser Health News

Archives

Single session of exercise alters 9,815 molecules in our blood

Researchers were taken aback by the magnitude of the changes.

By Gretchen Reynolds New York Times

JUNE 18, 2020 — 9:00PM

Animal interactions offer lessons for humans

Sometimes, animals seem so much more advanced than humans; other times, we learn how not to handle problems.

By Harvey Mackay Special to the Star Tribune

Women get statins less often than men

Doctors also prescribed less aspirin, ACE inhibitors.

By LINDA SEARING Washington Post

How much does it take to make you sick?

It's a key question scientists can't answer, which is why they say: limit amount of virus you face.

By Apoorva Mandavilli
New York Times - JUNE 6, 2020

GEARING UP FOR VACCINE TRIALS

NIH proposal outlines having 4 or 5 experimental vaccines tested on 20,000 participants in about 50 U.S. medical centers.

By ARTHUR ALLEN Kaiser Health News