76 Breast Cancer Linked Chemicals found in Food Packaging -- and in People!

It should come as no surprise – today, everyone is TOXIC, and I don’t mean they give off bad energy.  I mean that our bodies are all exposed to things that we don’t want IN our bodies.  Back in the day, people talked about leaded gasoline and paint.  So lead was taken out of gas and paint.  But interestingly, jet fuel is still leaded and exhausts continue to spew lead into the atmosphere. 

What people don’t talk about is what happened to all that lead?  Obviously, lead is heavy.  It falls (out of the sky from planes), but it used to spew out of car exhausts.  Where did it all go?

Mostly, it dropped to the pavement, or was aerosolized and carried short distances to land on some property.  And then it drained into the soil, or perhaps the water supply.  Ultimately, it ends up in the food supply, amongst other places.  Point being that it can end up in us.  

There are now over 30,000 chemicals that have been created that are “new to nature”.  The vast majority of them have not been tested for safety.  The government actually has a certification known as GRAS that specifically states it has not been tested for safety (GRAS stands for Generally Regarded as Safe – an extrapolation from some similar products previously evaluated).  Lots and lots of “stuff” gets into the environment and years later someone figures out it not good for us.   

The CNN report (don’t get political – it’s health news!) summarizes a toxicology paper that describes how food packaging materials have been demonstrated to leak into foods they are holding.  And a number of those chemicals end up in the humans that eat the food.  BPA was one of the chemicals that only relatively recently was declared as a bad actor and mostly removed from packaging (think baby bottles in the microwave!! Yikes).

These kinds of toxicities drive all kinds of health issues.  Understanding your level of personal toxic burden can be very helpful in avoiding future disasters.  Understanding your personal genetic tendencies in how well you are able to clear these toxins is another important piece of the puzzle to potentially keeping out of the TOXIC SOUP that may all await us if we keep on our current path.  

If any of these things concern you, please, let’s have a conversation.

FROM CNN HEALTH / BY SANDEE LAMOTTE

Chemicals linked to breast cancer leach into our foods, study finds

Nearly 200 chemicals connected to breast cancer are used in the making of food packaging and plastic tableware, and dozens of those carcinogens can migrate into the human body, a new study found.

“There is strong evidence that 76 known or potential breast carcinogens from food contact materials recently purchased all over the world can be found in people,” said study coauthor Jane Muncke, managing director and chief scientific officer at the Food Packaging Forum, a nonprofit foundation based in Zurich, Switzerland, that focuses on science communication and research.

“Getting rid of these known or suspected carcinogens in our food supply is a huge opportunity for cancer prevention,” Muncke said.

Of the recently detected chemicals in food packaging, 40 are already classified as hazardous by regulatory agencies around the world, according to the study.

“So many of these chemicals have already been classified as human health hazards, yet they are still allowed to be used in food contact materials, thus allowing them to migrate into the food we eat,” said Jenny Kay, a research scientist at Silent Spring Institute, a scientific research organization focused on the link between chemicals, women’s health and breast cancer. She was not involved in the study.

Rates of early-onset breast cancer in women under 50 are increasing, and experts said the trend cannot be explained by genetics alone.

“Rates of colon cancer are also rising in younger people,” said Dr. Len Lichtenfeld, former deputy chief medical officer for the American Cancer Society who was not involved in the study.

“Is it obesity? Is it alcohol? Is it the lack of physical activity? Is it environmental? There are a lot of reasons,” Lichtenfeld said, “and it’s going to take a long time to sort which has the most impact, as some of these chemicals may be high risk, some low risk.”

The Consumer Brands Association, which represents the consumer products industry, told CNN that its members adhere to the US Food and Drug Administration’s evidence-based safety standards.

“Packaging exists to protect and keep food safe for consumption,” said Sarah Gallo, the association’s senior vice president of product policy and federal affairs, in an email.

“The FDA reviews and approves food contact substances through their science and risk-based system before they go to market,” Gallo said. “The agency’s post market review also provides continuous safety analysis and regulation of the approved substances.”

The FDA has been under fire for its failure to act quickly on health concerns about some 14,000 chemicals known to be added to food. The agency will hold a public meeting Wednesday to present its ideas on how to improve its post-market food analyses.

Possible breast carcinogens

In 2007, Silent Spring published a list of 216 chemicals that can cause mammary tumors in rodents — a key method for determining toxicity, according to experts.

A January 2024 update to that list found 921 possibly carcinogenic chemicals, including 642 that may stimulate estrogen or progesterone production, another known risk factor for breast cancer.

“The fact that so many potential breast carcinogens are present in food packaging and can migrate into our food is just one example of how many chemicals we are unwittingly exposed to every day,” said Kay, who coauthored the 2024 study update published in Environmental Health Perspectives.

“Many of the mammary carcinogens are hormone disruptors, too, and many of the chemicals on our list can also damage DNA,” she said. “Consumers should not have to keep track of all of the scientific literature on what chemicals to avoid. It should be on regulators to recognize the danger and take action.”

Carcinogens in plastic, paper and cardboard

The new study, published Tuesday in the journal Frontiers in Toxicology, compared the Silent Springs database of known carcinogens for breast cancer with the Database on Food Contact Chemicals Monitored in Humans, or FCChumon.

FCChumon, created by the Food Packaging Forum, is a list of food contact chemicals that have been detected in human breast milk, blood, urine and tissues.

“The new study took our list of potential breast carcinogens and compared it to their list of chemicals that have been found in food contact materials to find out which of potential breast carcinogens could be getting into people’s diets,” Kay said. “That’s a great way to prioritize chemicals for regulatory action.”

The study found such chemicals as benzene, a known carcinogen connected to breast cancers in animals and people; 4,4’-Methylenebis-(2-Chloroaniline), a probable carcinogen linked to bladder cancer; 2,4-Toluenediamine, found to cause breast and other cancers in animals; and 3,3′-Dimethylbenzidine and o-Toluidine, which are dyes used to color plastic and paper.

“Dyes can be used in plastics, paper, cardboard and the like and can have some pretty toxic properties,” Kay said. “Plastics are not the only culprit.”

In fact, while the study found most of the exposure to carcinogens came from plastics used in food packaging, 89 suspected carcinogens were found in paper and cardboard containers.

“Paper has additives such as emulsifiers and adhesives, say if papers are glued together, or there’s a plastic layer glued to the paper,” Muncke said.

PFAS, phthalates and other worrisome chemicals are used to make plastic soft and flexible and to produce grease-proof food containers.

A number of the chemicals found in the study were bisphenols, phthalates or perfluoroalkyl and polyfluoroalkyl substances, known as PFAS — worrisome chemicals that have been linked to many health concerns.

Often called “forever chemicals” because they do not break down in the environment, PFAS are used in food packaging to prevent grease and water from soaking through food wrappers and beverage cups. PFAS can also be found in the ink used to print logos and instructions on food containers.

Chemicals in the PFAS family are linked to high cholesterol, cancer and various chronic diseases as well as a limited antibody response to vaccines in both adults and children, according to a report by the National Academies of Sciences, Engineering, and Medicine.

Phthalates have been linked to childhood obesity, asthma, cardiovascular issues, cancer and premature death in people ages 55 to 64.

Bisphenol A, or BPA, is an endocrine disruptor that has been linked to fetal abnormalities, low birth weight, and brain and behavior disorders in infants and children. In adults, the chemical has been linked to the development of diabetes, heart disease, erectile dysfunction, cancer and a 49% higher risk of early death within 10 years.

Steps to take to reduce exposure

While it’s up to regulatory agencies to make sweeping changes to protect the food supply, there are steps consumers can take to reduce the risk of toxic chemicals and carcinogens, according to Silent Spring.

To Live Longer, Get to Know Your Toes

I mentioned sometime in the past a study that tied standing on one leg to mortality risk.  The same guy has worked out more details around flexibility and mortality.  Over 13 years, the difference between being pretty flexible and not being flexible is translated into a difference from 1% up to 18-26%!! That’s a crazy difference, but, as usual, you really need to parse this result.  They plainly admit that they didn’t stratify people with regards to activity or lifestyle going into the study, so it might be that the less flexible group was already sicker and that contributed to the difference.  The difference varied by gender –flexible vs less flexible translated into a doubling of mortality for men, a 5-fold increase for women.  

What this doesn’t tell us is whether or not stretching regimens will help these statistics, but it’s clear other aspects of this kind of thing does make a difference – balance training, strength training, etc all translate to better outcomes.  It mostly follows (though not a given) that stretching would be beneficial, if not for mortality, at least for quality of life.  

An easy way to start is with sun salutations – a cornerstone of yoga.  A great, comprehensive review of how to start is here: https://www.youtube.com/watch?v=L4Z7lix6Qao&ab_channel=YouAligned

Get STRETCHING!

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FROM MEDSCAPE / BY BRENDA SANDBURG

The more flexible you are as you age, the longer you're likely to live.

That's the conclusion of a new study that associated increased flexibility in middle age with a lower odds of mortality over the next dozen or so years.

The prospective cohort study, which evaluated the flexibility of more than 3100 men and women in Brazil, found body flexibility was strongly and inversely associated with mortality risk over a 13-year follow-up period.

Claudio Gil Araújo, MD, PhD, the research director of the Exercise Medicine Clinic-CLINIMEX in Rio de Janeiro, who led the study, said his group was not surprised by the results. "We found what we expected. Reduced flexibility was related to poor survival," he said.

The findings, published today in the Scandinavian Journal of Medicine & Science in Sports, used data from 2087 men and 1052 women who underwent a medical-functional evaluation at CLINIMEX. They received a body flexibility score, called the Flexindex, based on range of motion in 20 movements in seven joints, with a minimum score of 0 and a maximum score of 80.

Among the 3139 participants, there were 302 deaths (9.6%) during a mean follow-up of 12.9 years with cardiovascular diseases and cancer the most common underlying causes in men and women, respectively.

"The probability of death during nearly 13 years of follow-up was close to 1% when Flexindex scores exceed 49 for men and 56 for women," Araújo told Medscape Medical News. "On the other hand, for men and women placed in the lower 10th percent of Flexindex scores, death rates were, respectively, 26.9% and 18.2%."

Barry Franklin, PhD, director of preventive cardiology and cardiac rehabilitation at Corewell Health William Beaumont University Hospital in Royal Oak, Michigan, and a co-author of the new study, said men with the poorest flexibility were nearly twice as likely to die over the follow-up period than men with high flexibility. Women with the poorest flexibility were almost five times more likely to die than those with high flexibility.

Flexibility Assessment and Training

Araújo opened CLINIMEX in 1994, and since then, its staff of five physicians have evaluated more than 10,000 individuals using the Flexitest. Araújo has published two previous studies on flexibility. The first showed that the ability to rise from a sitting position on the floor is a strong predictor of longevity, and the second demonstrated that the inability to stand on one leg for at least 10 seconds is linked to an increased risk for death over 7 years.

Araújo and his colleagues believe the current study is the first to assess the association between levels of body flexibility and mortality. But the observational analysis was unable to establish causality, and therefore, they could not show a definitive mechanism to explain the association between low levels of flexibility and premature mortality.

The authors noted several limitations of their study. The participants were primarily affluent Whites, and the researchers did not control for the time of day flexibility was measured or for variables such as diet and physical activity. They also acknowledged reduced flexibility may be a consequence of poor lifestyle habits rather than a causal risk factor for mortality.

Jonathan Bonnet, MD, MPH, an exercise expert at the Stanford Center on Longevity Lifestyle Medicine in California, said the researchers used a more robust evaluation of flexibility than a traditional sit-and-reach test. However, he expressed concern that the primary comparisons were of the upper and lower 10% of performers and that the average differences in Flexindex scores between people who died and those who survived were only a handful of points in an 80-point test.

"People who are not flexible probably have other health-related issues that limit their mobility and those who are very flexible are either genetically different from inflexible individuals or are doing something to maintain or increase their flexibility to a high level," Bonnet said. "Not knowing how active or inactive people are at baseline when flexibility was assessed or over the duration of the study limits how confident we can be that flexibility is the cause of mortality."

Bonnet, a member of the American College of Lifestyle Medicine, noted that the latest guidelines on physical activity from the US Department of Health and Human Services do not include recommendations on stretching, given the lack of data demonstrating its specific health benefits. While maintaining mobility and range of motion in joints is important for long-term health, he said the new study does not provide sufficient evidence to recommend stretching as a way to reduce mortality.

"Until there are more data that can show a cause-and-effect relationship with stretching and health outcomes, time is better spent doing aerobic and muscle-strengthening activities," Bonnet said.

Franklin said future studies could better account for missing potential confounders like physical activity and whether individuals were taking protective medications, such as aspirin, cholesterol-lowering drugs, or beta-blockers. Studies also are needed to assess whether training-induced gains in flexibility are specifically related to increases in survival and whether their findings apply to people over the age of 65, he said.

The current findings "give us some additional ammo to say, 'Wow, being more flexible may, in fact, improve long-term survival or outcomes'," Franklin said. Regardless, flexibility still "improves quality of life, it improves balance and reduces the potential for falls, and all those things make it worthy of better recognition or appreciation by the general public and clinicians," he added.

Araújo said he would like his research to influence people's health. "While to exercise regularly is advisable, what really matters is to be physically fit and not only in aerobic or strength fitness but also in flexibility," he said. "The study is adding a new and, I believe, important 'relevant for survival' label on flexibility assessment and training."

Recommended Stretches for Increased Mobility and Flexibility

Matthew Accetta, MS, exercise physiologist at Hospital for Special Surgery in New York City

Matthew Accetta, MS

Hip Hug Stretch

This stretch effectively targets the gluteal muscles, piriformis, and other deep hip rotators, which can become tight from prolonged sitting or lack of movement. Tight hips can contribute to lower back pain. By stretching the hip muscles, you can reduce tension and pressure on the lower back. Regularly performing this stretch helps to improve hip joint mobility, which is essential for maintaining functional movement and preventing stiffness as you age.

• Start by sitting and crossing one leg over the other.

• Hug your knee to your chest.

• Focus on keeping your chest up to feel the stretch in the glute.

• Hold for 20-30 seconds.

• Repeat on the opposite side.

Half Kneeling Hip Flexor Stretch

As people age, they often spend more time sitting, which can lead to tight hip flexors. This stretch specifically targets these muscles, helping to alleviate tightness and improve mobility. Tight hip flexors can contribute to poor posture by pulling the pelvis into an anterior tilt, which can lead to lower back pain and other postural issues. Stretching these muscles helps to counteract this effect and promote better posture.

• Kneel on a pad (the side you kneel on is the side being stretched); position the front leg far enough away so the front knee stays behind the toes.

• With a tall posture, engage your abdominals and tuck your tailbone by engaging your glutes until a stretch is felt in the front of the thigh on the kneeling leg.

• Hold for 20-30 seconds.

• Repeat on the opposite side.

Calf Stretch at a Wall

Tight calf muscles can lead to discomfort and limit the range of motion in the ankles. Stretching the calves helps to maintain and improve flexibility in these muscles. Flexible calf muscles contribute to better mobility in the ankles and feet, making daily activities like walking, climbing stairs, and running more comfortable. Tight calves can increase the risk for strains, Achilles tendonitis, and other injuries. Stand facing a wall with your hands on the wall at about eye level. Put the leg you want to stretch about a step behind your other leg.

• Stand in a staggered stance in front of a wall with your arms stretched out.

• Keeping your back heel on the floor, bend your front knee until you feel a stretch in the back leg.

• Hold the stretch for 15-30 seconds.

• Repeat on the opposite side.

Standing Quad Stretch

Regularly stretching the quadriceps helps maintain and improve flexibility in these muscles, which is crucial for overall lower body mobility. Flexible quadriceps are less prone to strains and injuries. Tight quadriceps can contribute to knee pain and discomfort by exerting excessive pressure on the knee joint. Stretching these muscles helps alleviate this pressure and reduce knee pain.

• While standing, hold onto a countertop or chair back to assist in balance.

• Bend your knee by grasping your ankle with one hand and moving your foot toward your buttocks.

• Gently pull on your ankle to bend your knee as far as possible.

• Maintain the position for 30 seconds.

• Repeat on the opposite side.

Seated Hamstring Stretch

Regularly stretching the hamstrings helps maintain and improve their flexibility, which is crucial for the overall mobility of the lower body. Tight hamstrings can contribute to lower back pain by pulling on the pelvis and causing an anterior pelvic tilt. Stretching these muscles can help alleviate tension and reduce back pain. Hamstring flexibility helps to contribute to a better range of motion in the hip and knee joints, making daily activities such as walking, bending, and reaching easier.

• Sit on the front half of a firm chair with your back straight.

• Extend one leg out in front of you with your heel on the floor and your toes pointed up.

• Bend the opposite knee so that your foot is flat on the floor.

• Center your chest over your straight leg.

• Slowly lean forward at the hips until you feel a stretch in the back of your thigh.

• Hold the stretch for 30 seconds.

• Slowly return to your original position and repeat on the opposite side.

Does Time Restricted Eating (some call it Intermittent Fasting) result in weight loss?

In recent months the excitement about fasting has died down a bit, but there’s lots of interesting data surrounding it’s utility.  Most of the excitement centered around, you guessed it – the possibility that it would drive weight loss.

We’ve talked about this a bit in the past – it’s important to get the terminology right.  Many/most Americans fail to get a full 12 hour fast overnight.  To me, that’s an absolute necessity – you’ve got to NOT eat for more time than you DO eat (if you eat late - 8 or 10pm, then you shouldn’t eat again until the earliest at 8 am or 10 am, respectively).  Time Restricted Eating (TRE) is when you restrict your eating window to shorter than 10 hours, all the way down to OMAD (one meal a day) with a 2 hour eating window.  Intermittent Fasting (IF) is when you DON’T eat for 24 hours at a stretch.  These fasts may be repeated a few times a week.  Fasting is when there is no food for extended periods, usually 3 to 5 days.  Each of these have some benefits, but with the longer fasting windows resulting in ever increasing risks, some of which are nearly impossible to overcome as the patient gets older.   

As I’ve mentioned, NOT eating for more than 12 hours a day is a good thing.  Most people can easily tolerate 14 hours of not eating – most women don’t benefit from longer daily fasts, though some do.  Many men do well around 16 hours (8 hour eating window).  Once you’re used to it, it becomes pretty easy and there are definite benefits that have been described elsewhere.  

There continues to be some very real questions about what are the specific benefits of daily temporal restriction of caloric intake – this study does answer some of that uncertainty.  

Previous studies have suggested that merely restricting the eating window would end up restricting calories because people had less time to eat, resulting in weight loss.  Sounds silly, but it turns out that that is exactly what seems to be happening.  There was no weight loss associated with TRE versus the exact calorie match of usual eating.  They go on to make some interesting points about confounders (the TRE group went to bed earlier, so less active and thus, less calorie burn) – why stay up if you’re not going to have a snack watching TV?!?

Most people feel better and sleep better if they don’t eat late – stop eating at least 90 minutes before bed, and better yet, 2 hours plus.  These folks got virtually all of their calories before 1 pm – now that’s an early dinner!  The Blue Light special becomes a midnight snack….

FROM MEDSCAPE / BY DIANA SWIFT

Time-Restricted Eating Fails for Weight Loss and Glucose Homeostasis

In the setting of isocaloric eating, time-restricted eating (TRE) did not reduce weight or improve glucose homeostasis relative to a usual eating pattern (UEP), a small randomized controlled trial found.

The results suggested that any effects of TRE on weight observed in prior studies may be due to reductions in caloric intake and not timing, according to Nisa M. Maruthur, MD, MHS, of the Division of General Internal Medicine at the Johns Hopkins School of Medicine in Baltimore, and colleagues.

Published in Annals of Internal Medicine, the 12-week trial randomly assigned 41 adults aged 18-69 years with obesity and prediabetes or diet-controlled diabetes 1:1 as follows: To TRE, involving a 10-hour eating window with 80% of calories consumed before 1 PM, or to UEP, involving a ≤ 16-hour window, with at least 50% of calories consumed after 5 PM. The regimen in each group was based on the OmniHeart unsaturated fat diet and the SPICE study.

"The diet was similar to the DASH [Dietary Approaches to Stop Hypertension] diet for hypertension and maybe a bit higher in unsaturated fat and micronutrients," said study co-author Scott J. Pilla, MD, MHS, an assistant professor of medicine at the Johns Hopkins Bloomberg School of Public Health, Baltimore, in an interview. For each participant, macro- and micronutrient content remained constant throughout the study period, with total calories individually determined at baseline and ranging from 1600 to 3500 kcal/d. "That differs from some TRE studies in which calories were adjusted according to whether participants lost or gained weight," he said. "This was a purely mechanistic study to determine the impact of time of eating alone with no change in calories." 

Although the current findings revealed no weight loss advantage, some evidence suggests that limiting the food consumption window to 4-10 hours naturally reduces energy intake by approximately 200-550 calories per day and can result in a loss of 3%-5% of baseline body weight for 2-12 months. In addition, TRE has been shown to improve metabolic risk factors, such as insulin resistance, blood pressure, and triglyceride concentrations — but not in this study.

The Cohort

The mean age was 59 years, 93% of patients were women, and 93% were Black. The mean body mass index was 36, and the mean baseline weight was 96.2 kg — 95.6 kg in the TRE group and 103.7 kg in the UEP group.

At 12 weeks, weight decreased comparably by 2.3 kg (95% CI, 1.0-3.5) in the TRE group and by 2.6 kg (95% CI, 1.5-3.7) in the UEP group. Change in glycemic measures did not differ between the two groups.

Interestingly, self-reporting questionnaires revealed a slight reduction in physical activity in the TRE group, an effect that requires further study. "We don't know why but anecdotally, some TRE participants said they tended to go to bed earlier," Pilla said. Earlier bedtimes may put an end sooner to the daily eating pattern.

Subanalyses of the data are ongoing and will be published later.

"In the context of several clinical trials that suggest a benefit of TRE, our findings suggest that if or when TRE interventions induce weight loss, it is likely in part due to a reduction in energy intake, and therefore, clinicians can counsel patients that TRE may help them lose weight by decreasing their caloric intake," the authors wrote.

In an accompanying editorial, Krista A. Varady, PhD, and Vanessa M. Oddo, PhD, of the Department of Kinesiology and Nutrition at the University of Illinois Chicago, said the study results have important clinical implications. "Many patients stop following standard-care diets (such as daily calorie restriction) because they become frustrated with having to monitor food intake vigilantly each day," they wrote.

Although TRE is no more effective than other diet interventions for weight reduction, it offers a simplified approach to treat obesity by omitting the need for calorie counting. "TRE bypasses this requirement simply by allowing participants to 'watch the clock' instead of monitoring calories, while still producing weight loss," they wrote.

The straightforward nature of this diet makes it well suited for remote delivery, which can reduce the scheduling and financial barriers associated with inpatient visits, they added. "Moreover, TRE does not require the purchase of expensive food products and allows a person to continue consuming familiar foods, making it a high accessible diet for lower-resource populations."

Gastroenterologists and Obesity

Of late, support has grown for gastroenterologists to become actively involved in obesity treatment — even to "take ownership" of this field.

In a 2023 article in Gut, Michael Camilleri, MD, AGAF, a gastroenterologist at the Mayo Clinic in Rochester, Minnesota, made the case for the natural fit between gastrointestinal (GI) specialists and obesity management. He noted that obesity is a significant risk factor for GI, pancreatic, and liver diseases. It can even affect inflammatory bowel disease.

"Treating obesity starting when patients present in gastroenterology and hepatology clinics has potential to impact serious consequences of obesity such as cardiovascular risks," he wrote.

Gastroenterologists already treat GI conditions with pharmacologic and surgical interventions that can also be used to treat obesity and improve glycemic control. These include pancreatic lipase inhibitors and incretin, bariatric endoscopy and surgery, and combination therapies targeting metabolic problems.

Not Kidding: Yellow Dye 5 May Be the Key to Invisibility

This is about as crazy as it gets.

Rub Twinkie dye on skin and it “disappears”.  Imagine watching your insides sloshing around!  Yikes!

But if you could actually see what’s going on without surgery, maybe Twinkie dye isn’t all bad?  

Have trouble when they need to get blood at the lab – not anymore!  

Well, it’s a little ways away, but the possibilities are interesting.

FROM MEDSCAPE / BY SARI HARRAR

The same dye that gives Twinkies their yellowish hue could be the key to invisibility. 

Applying the dye to lab mice made their skin temporarily transparent, allowing Stanford University researchers to observe the rodents' digestive system, muscle fibers, and blood vessels, according to a study published September 5 in Science.

"It's a stunning result," said senior author Guosong Hong, PhD, who is assistant professor of materials science and engineering at Stanford. "If the same technique could be applied to humans, it could offer a variety of benefits in biology, diagnostics, and even cosmetics." 

The work drew upon optical concepts first described in the early 20th century to form a surprising theory: Applying a light-absorbing substance could render skin transparent by reducing the chaotic scattering of light as it strikes proteins, fats, and water in tissue. 

A search for a suitable light absorber led to FD&C Yellow 5, also called tartrazine, a synthetic color additive certified by the US Food and Drug Administration for use in foods, cosmetics, and medications. 

Rubbed on live mice (after areas of fur were removed using a drugstore depilatory cream), tartrazine rendered skin on their bellies, hind legs, and heads transparent within 5 minutes. With the naked eye, the researchers watched a mouse's intestines, bladder, and liver at work. Using a microscope, they observed muscle fibers and saw blood vessels in a living mouse's brain — all without making incisions. Transparency faded quickly when the dye was washed off.

Someday, the concept could be used in doctors' offices and hospitals, Hong said. 

"Instead of relying on invasive biopsies, doctors might be able to diagnose deep-seated tumors by simply examining a person's tissue without the need for invasive surgical removal," he said. "This technique could potentially make blood draws less painful by helping phlebotomists easily locate veins under the skin. It could also enhance procedures like laser tattoo removal by allowing more precise targeting of the pigment beneath the skin."

From Cake Frosting to Groundbreaking Research

Yellow 5 food dye can be found in everything from cereal, soda, spices, and cake frosting to lipstick, mouthwash, shampoo, dietary supplements, and house paint. Although it's in some topical medications, more research is needed before it could be used in human diagnostics, said Christopher J. Rowlands, PhD, a senior lecturer in the Department of Bioengineering at Imperial College London, UK, where he studies biophotonic instrumentation — ways to image structures inside the body more quickly and clearly. 

But the finding could prove useful in research. In a commentary published in Science, Rowlands and his colleague Jon Gorecki, PhD, an experimental optical physicist also at Imperial College London, note that the dye could be an alternative to other optical clearing agents currently used in lab studies, such as glycerol, fructose, or acetic acid. Advantages are the effect is reversible and works at lower concentrations with fewer side effects. This could broaden the types of studies possible in lab animals, so researchers don't have to rely on naturally transparent creatures like nematodes and zebrafish. 

The dye could also be paired with imaging techniques such as magnetic resonance imaging (MRI) or electron microscopy. 

"Imaging techniques all have pros and cons," Rowlands said. "MRI can see all the way through the body albeit with limited resolution and contrast. Electron microscopy has excellent resolution but limited compatibility with live tissue and penetration depth. Optical microscopy has subcellular resolution, the ability to label things, excellent biocompatibility but less than 1 millimeter of penetration depth. This clearing method will give a substantial boost to optical imaging for medicine and biology."

The discovery could improve the depth imaging equipment can achieve by tenfold, according to the commentary. 

Brain research especially stands to benefit. "Neurobiology in particular will have great use for combinations of multiphoton, optogenetics, and tissue clearing to record and control neural activity over (potentially) the whole mouse brain," he said.

Refraction, Absorption, and The Invisible Man

The dye discovery has distant echoes in H.G. Wells' 1897 novel The Invisible Man, Rowlands noted. In the book, a serum makes the main character invisible by changing the light scattering — or refractive index (RI) — of his cells to match the air around him.

The Stanford engineers looked to the past for inspiration, but not to fiction. They turned to a concept first described in the 1920s called the Kramers-Kronig relations, a mathematical principle that can be applied to relationships between the way light is refracted and absorbed in different materials. They also read up on Lorentz oscillation, which describes how electrons and atoms inside molecules react to light. 

They reasoned that light-absorbing compounds could equalize the differences between the light-scattering properties of proteins, lipids, and water that make skin opaque. 

With that, the search was on. The study's first author, postdoctoral researcher Zihao Ou, PhD, began testing strong dyes to find a candidate. Tartrazine was a front-runner. 

"We found that dye molecules are more efficient in raising the refractive index of water than conventional RI-matching agents, thus resulting in transparency at a much lower concentration," Hong said. "The underlying physics, explained by the Lorentz oscillator model and Kramers-Kronig relations, reveals that conventional RI matching agents like fructose are not as efficient because they are not 'colored' enough."

What's Next

Though the dye is already in products that people consume and apply to their skin, medical use is years away. In some people, tartrazine can cause skin or respiratory reactions. 

The National Science Foundation (NSF), which helped fund the research, posted a home or classroom activity related to the work on its website. It involves painting a tartrazine solution on a thin slice of raw chicken breast, making it transparent. The experiment should only be done while wearing a mask, eye protection, lab coat, and lab-quality nitrile gloves for protection, according to the NSF.

Meanwhile, Hong said his lab is looking for new compounds that will improve visibility through transparent skin, removing a red tone seen in the current experiments. And they're looking for ways to induce cells to make their own "see-through" compounds. 

"We are exploring methods for cells to express intensely absorbing molecules endogenously, enabling genetically encoded tissue transparency in live animals," he said.

Clickbait? -- Regular Cell Phone Use Linked to Higher Heart Disease Risk

Sometimes even the medical media aggregators get lazy and put up stories with titles that don’t tell the story as it is written.  

I hope people have come to understand the difference between association and causation.  

“Ice Cream causes drowning”.   Huh?  

In the summer, people eat more ice cream, they go swimming more, there are more drownings.  Association, obviously not causation.

This story, through a convoluted discussion, reports that regular cell phone users have greater risk of heart disease (it’s about a 4-11% increase).  But in the next sentence they talk about how sleep issues, psychological distress and neuroticism has substantial impact on those risks.  Is anyone surprised that they also say that smoking and diabetes act to increase the risk associated with cell phone use?  

The study doesn’t look at level of use – a cell phone user is defined as a weekly user – seriously??  

The commentary makes the point – take care of the stuff that really matters – don’t smoke, control sugar, blood pressure, get sleep, do exercise and the cell phone issue will likely not be enough to worry about.  

Are there people for whom using a cell phone is a problem – sure – remember “it depends”!

FROM MEDSCAPE / BY MARILYNN LARKIN

Regular Cell Phone Use Linked to Higher Heart Disease Risk

Using a cell phone for at least one call per week is linked to a higher risk for cardiovascular disease (CVD), especially among smokers and patients with diabetes, according to a new UK Biobank analysis.

"We found that a poor sleep pattern, psychological distress, and neuroticism significantly mediated the positive association between weekly mobile phone usage time and the risk for incident CVD, with a mediating proportion of 5.11%, 11.50%, and 2.25%, respectively," principal investigator Xianhui Qin, MD, professor of nephrology at Southern Medical University, Guangzhou, China, told Medscape Medical News.

Poor sleep patterns and poor mental health could disrupt circadian rhythms and endocrine and metabolic functions, as well as increase inflammation, he explained.

In addition, chronic exposure to radiofrequency electromagnetic fields (RF-EMF) emitted from cell phones could lead to oxidative stress and an inflammatory response. Combined with smoking and diabetes, this exposure "may have a synergistic effect in increasing CVD risk," Qin suggested

Risk Underestimated?

The researchers aimed to examine the association of regular cell phone use with incident CVD and explore the mediating effects of sleep and mental health using linked hospital and mortality records.

Their analysis included 444,027 participants (mean age, 56 years; 44% men) without a history of CVD from the UK Biobank. A total of 378,161 participants were regular cell phone users.

Regular cell phone use was defined as at least one call per week. Weekly use was self-reported as the average time of calls per week during the previous 3 months.

The primary outcome was incident CVD. Secondary outcomes were each component of CVD (ie, coronary heart disease, stroke, atrial fibrillation, and heart failure) and increased carotid intima media thickness (CIMT).

Compared with nonregular cell phone users, regular users were younger, had higher proportions of current smokers and urban residents, and had lower proportions of history of hypertension and diabetes. They also had higher income, Townsend deprivation index, and body mass index and lower education levels.

During a median follow-up of 12.3 years, 56,181 participants developed incident CVD. Compared with nonregular cell phone users, regular users had a significantly higher risk for incident CVD (hazard ratio, 1.04) and increased CIMT (odds ratio, 1.11).

Among regular cell phone users, the duration of cell phone use and hands-free device/speakerphone use during calls was not significantly associated with incident CVD. Yet a significant and positive dose-response relationship was seen between weekly cell phone usage time and the risk for CVD. The positive association was stronger in current vs noncurrent smokers and people with vs without diabetes.

To different extents, sleep patterns (5.11%), psychologic distress (11.5%), and neuroticism (2.25%) mediated the relationship between weekly cell phone usage time and the risk for incident CVD.

"Our study suggests that despite the advantages of mobile phone use, we should also pay attention to the potential harm of mobile phone use to cardiovascular health," Qin said. "Future studies to assess the risk-benefit balance will help promote mobile phone use patterns that are conducive to cardiovascular health."

Meanwhile, he added, "We encourage measures to reduce time spent on mobile phones to promote the primary prevention of CVD. On the other hand, improving sleep and mental health status may help reduce the higher risk of CVD associated with mobile phone use."

There are several limitations to the study in addition to its observational nature, which cannot show cause and effect. The questionnaires on cell phone use were restricted to phone calls; other use patterns of cell phones (eg, messaging, watching videos, and browsing the web) were not considered. Although the researchers adjusted for many potential confounders, unmeasured confounding bias (eg, the type of cell phone used and other sources of RF-EMF) cannot be eliminated.

Weak Link?

Commenting on the study for Medscape Medical News, Nicholas Grubic, MSc, a PhD student in epidemiology at the University of Toronto, Toronto, Ontario, Canada, and co-author of a related editorial, said, "I found it interesting that there was a connection observed between mobile phone use and CVD. However, it is crucial to understand that this link appeared to be much weaker compared with other well-known cardiovascular risk factors, such as smoking, diabetes, and high blood pressure. For now, mobile phone use should not be a major concern for most people."

Nevertheless, clinicians should encourage patients to practice healthy habits around their screen time, he advised. "This could include limiting mobile phone use before bedtime and taking regular breaks to engage in activities that promote heart health, such as exercising or spending time outdoors.

"For the time being, we probably won't see mobile phone use included in standard assessments for cardiovascular risk or as a focal point of cardiovascular health promotion initiatives," he added. Instead, clinicians should "focus on established risk factors that have a stronger impact on patients' cardiovascular health."

Nieca Goldberg, MD, a clinical associate professor of medicine at NYU Grossman School of Medicine in New York City and American Heart Association volunteer expert, had a similar message. "You don't have to go back to using a land line," she said. "Instead, patients should be more mindful of how much phone use is taking away from their physical activity, keeping them from sleeping, and causing them stress." Clinicians should also remember to counsel smokers on smoking cessation.

"It would be important for future studies to look at time spent on the phone and the type of activities patients are doing on their phones, such as social media, calls, texts, movies, or streaming TV shows," she said. "It would be important to see how phone use is leading to a sedentary lifestyle" and what that means for a larger, more diverse population.

Coffee Again -- Too Much of a Good Thing?

Back some time ago we talked about studies that showed coffee intake has a broad array of benefits.  At that time, the study suggested that the more coffee, the better you did, with some exceptions.  What they figured out was that most people who drank lots of coffee (more than 5 cups a day) had associated addictive tendencies that, not surprisingly, independently led to other problems.  If you excluded those addictive characters, the heavy coffee drinkers did the best.  

Now there’s an observational study that shows that the best option is around 3 cups of coffee a day – more is worse.  But is it really?  

Turns out that this study never controlled for other confounding factors – think, for example, smoking or alcohol or other addictive issues.  So is this really new news?  Not convinced.  

Of course, I’ve always thought that 3 cups is probably a good number.  After all, past that, you’re talking about a lot of caffeine, if nothing else!

Interestingly, this also talks about tea (no distinction between green or black) – and here it doesn’t make any difference once you get past 1 cup per day.  But that one cup definitely helps.

FROM MEDSCAPE / BY PAULINE ANDERSON

Too Much Coffee Linked to Accelerated Cognitive Decline

Drinking more than three cups of coffee a day is linked to more rapid cognitive decline over time, results from a large study suggest.

Investigators examined the impact of different amounts of coffee and tea on fluid intelligence — a measure of cognitive functions including abstract reasoning, pattern recognition, and logical thinking.

"It's the old adage that too much of anything isn't good. It's all about balance, so moderate coffee consumption is okay but too much is probably not recommended," study investigator Kelsey R. Sewell, PhD, Advent Health Research Institute, Orlando, told Medscape Medical News. 

The findings of the study were presented on July 30 at the Alzheimer's Association International Conference (AAIC) 2024. 

One of the World's Most Widely Consumed Beverages

Coffee is one of the most widely consumed beverages around the world. The beans contain a range of bioactive compounds, including caffeine, chlorogenic acid, and small amounts of vitamins and minerals.

Consistent evidence from observational and epidemiologic studies indicates that intake of both coffee and tea has beneficial effects on stroke, heart failure, cancers, diabetes, and Parkinson's disease. 

Several studies also suggest that coffee may reduce the risk for Alzheimer's disease, said Sewell. However, there are limited longitudinal data on associations between coffee and tea intake and cognitive decline, particularly in distinct cognitive domains.

Sewell's group previously published a study of cognitively unimpaired older adults that found greater coffee consumption was associated with slower cognitive decline and slower accumulation of brain beta-amyloid.

Their current study extends some of the prior findings and investigates the relationship between both coffee and tea intake and cognitive decline over time in a larger sample of older adults.

This new study included 8451 mostly female (60%) and White (97%) cognitively unimpaired adults older than 60 (mean age, 67.8 years) in the UK Biobank, a large-scale research resource containing in-depth, de-identified genetic and health information from half a million UK participants. Study subjects had a mean body mass index (BMI) of 26, and about 26% were apolipoprotein epsilon 4 (APOE e4) gene carriers.

Researchers divided coffee and tea consumption into tertiles: high, moderate, and no consumption.

For daily coffee consumption, 18% reported drinking four or more cups (high consumption); 58% reported drinking one to three cups (moderate consumption); and 25% reported that they never drink coffee. For daily tea consumption, 47% reported drinking four or more cups (high consumption); 38% reported drinking one to three cups (moderate consumption); and 15% reported that they never drink tea.

The study assessed cognitive function at baseline and at least two additional patient visits. 

Researchers used linear mixed models to assess the relationships between coffee and tea intake and cognitive outcomes. The models adjusted for age, sex, Townsend deprivation index (reflecting socioeconomic status), ethnicity, APOE e4 status, and BMI.

Steeper Decline 

Compared with high coffee consumption (four or more cups daily), people who never consumed coffee (beta = 0.06; SE = 0.02; P = .005) and those with moderate consumption (beta = 0.07; SE = 0.02; P = < .001) had slower decline in fluid intelligence after an average of 8.83 years of follow-up.

"We can see that those with high coffee consumption showed the steepest decline in fluid intelligence across the follow up, compared to those with moderate coffee consumption and those never consuming coffee," said Sewell, referring to illustrative graphs.

At the same time, "our data suggest that across this time period, moderate coffee consumption can serve as some kind of protective factor against cognitive decline," she added.

For tea, there was a somewhat different pattern. People who never drank tea had a greater decline in fluid intelligence compared with those who had moderate consumption (beta = 0.06; SE = 0.02; P = .0090) or high consumption (beta = 0.06; SE = 0.02; P = .003).

Because this is an observational study, "we still need randomized controlled trials to better understand the neuroprotective mechanism of coffee and tea compounds," said Sewell.

Responding later to a query from a meeting delegate about how moderate coffee drinking could be protective, Sewell said there are probably "different levels of mechanisms," including at the molecular level (possibly involving amyloid toxicity) and the behavioral level (possibly involving sleep patterns).

Sewell said that she hopes this line of investigation will lead to new avenues of research in preventive strategies for Alzheimer's disease. 

"We hope that coffee and tea intake could contribute to the development of a safe and inexpensive strategy for delaying the onset and reducing the incidence for Alzheimer's disease."

A limitation of the study is possible recall bias, because coffee and tea consumption were self-reported. However, this may not be much of an issue because coffee and tea consumption "is usually quite a habitual behavior," said Sewell.

The study also had no data on midlife coffee or tea consumption and did not compare the effect of different preparation methods or types of coffee and tea — for example, green tea vs black tea. 

When asked if the study controlled for smoking, Sewell said it didn't but added that it would be interesting to explore its impact on cognition.

Bad Sleep = Bad Health / Chronic Disease

I’ve been using an OURA ring for nearly 3 years now – it’s the best sleep data available to consumers and you can learn a lot about what certain behaviors do to your sleep quality – alcohol, cigars, altering sleep time, eating meals close to bedtime all will mess you up.  It then becomes up to you whether or not that behavior is “worth it.” 

If you’ve been reading my stuff, then you know I believe that sleep is critical.  Sleep is probably more important than anything.  Exercise comes in a close second.  Diet is obviously important, but it pales in comparison – you can eat a tremendous amount of bad stuff, but if you exercise regularly and get enough sleep, you probably get away with it a lot more often than if you don’t sleep or don’t get any exercise.  Yes, it will all catch up with you, but I’m trying to make a point.

So why do we care about sleep?  One major thing to understand is that the brain’s sewer system (the glymphatic system) increases it’s flow by over 40% when you sleep.  We make junk systematically all day long and if we don’t clear it out, we’re in trouble.  And this doesn’t even take into account all the ideas around solidifying memories,  processing experiences, etc.  

Now we have a study that confirms that sleep quality ties directly to development of chronic diseases.  I kind of this qualifies as a “DUH”, but some folks need “proof”. 

If you want to talk about measuring sleep quality, or other health trackers, I’m always happy to have the conversation – because “it depends” which one you should get!  

If you want $40 off an OURA ring – use this link (it’s possible I’ll get a tee shirt, but I think that promotion is long over 😊):

ouraring.com/raf/d120a63065?utm_medium=iac_raf

FROM MEDSCAPE / BY HEIDI SPLETE

Wearable Monitors Confirm Impact of Sleep Patterns on Chronic Disease

Rapid eye movement (REM) sleep, deep sleep, and sleep irregularity were significantly associated with increased risk for a range of chronic diseases, based on a new study of > 6000 individuals. 

"Most of what we think we know about sleep patterns in adults comes from either self-report surveys, which are widely used but have all sorts of problems with over- and under-estimating sleep duration and quality, or single-night sleep studies," said corresponding author Evan L. Brittain, MD, of Vanderbilt University, Nashville, Tennessee, in an interview. 

The single-night study yields the highest quality data but is limited by extrapolating a single night's sleep to represent habitual sleep patterns, which is often not the case, he said. In the current study, published in Nature Medicine, "we had a unique opportunity to understand sleep using a large cohort of individuals using wearable devices that measure sleep duration, quality, and variability. The All of Us Research Program is the first to link wearables data to the electronic health record at scale and allowed us to study long-term, real-world sleep behavior," Brittain said.

The timing of the study is important because the American Heart Association now recognizes sleep as a key component of heart health, and public awareness of the value of sleep is increasing, he added. 

The researchers reviewed objectively measured, longitudinal sleep data from 6785 adults who used commercial wearable devices (Fitbit) linked to electronic health record data in the All of Us Research Program. The median age of the participants was 50.2 years, 71% were women, and 84% self-identified as White individuals. The median period of sleep monitoring was 4.5 years.

REM sleep and deep sleep were inversely associated with the odds of incident heart rhythm and heart rate abnormalities. Each percent increase in REM sleep was associated with a reduced incidence of atrial fibrillation (odds ratio [OR], 0.86), atrial flutter (OR, 0.78), and sinoatrial node dysfunction/bradycardia (OR, 0.72). A higher percentage of deep sleep was associated with reduced odds of atrial fibrillation (OR, 0.87), major depressive disorder (OR, 0.93), and anxiety disorder (OR, 0.94). 

Increased irregular sleep was significantly associated with increased odds of incident obesity (OR, 1.49), hyperlipidemia (OR, 1.39), hypertension (OR, 1.56), as well as major depressive disorder (OR, 1.75), anxiety disorder (OR, 1.55), and bipolar disorder (OR, 2.27). 

The researchers also identified J-shaped associations between average daily sleep duration and hypertension (P for nonlinearity = .003), as well as major depressive disorder and generalized anxiety disorder (both P < .001). 

The study was limited by several factors including the relatively young, White, and female study population. However, the results illustrate how sleep stages, duration and regularity are associated with chronic disease development, and may inform evidence-based recommendations on healthy sleeping habits, the researchers wrote.

Findings Support Need for Sleep Consistency 

"The biggest surprise for me was the impact of sleep variability of health," Brittain told Medscape Medical News. "The more your sleep duration varies, the higher your risk of numerous chronic diseases across the entire spectrum of organ systems. Sleep duration and quality were also important but that was less surprising," he said. 

The clinical implications of the findings are that sleep duration, quality, and variability are all important, Brittain told Medscape Medical News. "To me, the easiest finding to translate into the clinic is the importance of reducing the variability of sleep duration as much as possible," he said. For patients, that means explaining that they need to go to sleep and wake up at roughly the same time night to night, he said. 

"Commercial wearable devices are not perfect compared with research grade devices, but our study showed that they nonetheless collect clinically relevant information," Brittain added. "For patients who own a device, I have adopted the practice of reviewing my patients' sleep and activity data which gives objective insight into behavior that is not always accurate through routine questioning," he said.

As for other limitations, "Our cohort was limited to individuals who already owned a Fitbit; not surprisingly, these individuals differ from a random sample of the community in important ways, both demographic and behavioral, and our findings need to be validated in a more diverse population," said Brittain. 

Looking ahead, "we are interested in using commercial devices as a tool for sleep interventions to test the impact of improving sleep hygiene on chronic disease incidence, severity, and progression," he said.

Device Data Will Evolve to Inform Patient Care

"With the increasing use of commercial wearable devices, it is crucial to identify and understand the data they can collect," said Arianne K. Baldomero, MD, a pulmonologist and assistant professor of medicine at the University of Minnesota, Minneapolis, in an interview. "This study specifically analyzed sleep data from Fitbit devices among participants in the All of Us Research Program to assess sleep patterns and their association with chronic disease risk," said Baldomero, who was not involved in the study. 

The significant relationships between sleep patterns and risk for chronic diseases were not surprising, said Baldomero. The findings of an association between shorter sleep duration and greater sleep irregularity with obesity and sleep apnea validated previous studies in large-scale population surveys, she said. Findings from the current study also reflect data from the literature on sleep duration associated with hypertension, major depressive disorder, and generalized anxiety findings, she added.

"This study reinforces the importance of adequate sleep, typically around 7 hours per night, and suggests that insufficient or poor-quality sleep may be associated with chronic diseases," Baldomero told Medscape Medical News. "Pulmonologists should remain vigilant about sleep-related issues, and consider further investigation and referrals to sleep specialty clinics for patients suspected of having sleep disturbances," she said.

"What remains unclear is whether abnormal sleep patterns are a cause or an effect of chronic diseases," Baldomero noted. "Additionally, it is essential to ensure that these devices accurately capture sleep patterns and continue to validate their data against gold standard measures of sleep disturbances," she said.

HEY - Are you in there? Anybody Home?

When people are unconscious, it’s pretty clear that they are legitimately unresponsive -- they don’t know what’s going on around them.  But what about when someone is in a coma?  Are they still “conscious” but just can’t move?  Should you be holding someone’s hand, talking to them, encouraging them, etc.?  Does that make any difference?

I’ve attached an interesting article detailing how ¼ of coma patients show clear evidence that they know what’s going on around them.  This has profound implications for how they should be cared for and how, as caregivers/supporters, we should interact with these loved ones if they should unfortunately be stuck in a coma.  Be aware that everything that you say or do in earshot of this patient may be heard – and remembered!

Realize that this does not apply to patients that might be considered brain-dead – there is no electrical activity in those cases.  In coma cases there is still brain activity, but no conscious activity. 

FROM MEDPAGE TODAY / BY JUDY GEORGE

One in Four Brain Injury Patients Who Appear Unresponsive Respond Covertly

— Functional MRI and EEG detect awareness in coma or vegetative states

Key Takeaways

• One in four severe brain injury patients had cognitive-motor dissociation detected on EEG or fMRI.

• Despite appearing unresponsive, these patients repeatedly showed covert consciousness.

• Younger age, longer time since injury, and brain trauma were associated with cognitive-motor dissociation.

Cognitive-motor dissociation -- a phenomenon that occurs when patients who appear unresponsive perform cognitive tasks that can be detected on functional MRI (fMRI) or electroencephalography (EEG) -- occurred in one in four people with severe brain injury, a prospective cohort study found.

The study evaluated 241 unresponsive patients with brain injury who were given verbal commands -- to imagine playing tennis, or to imagine opening and closing their hand, for example.

Of these, 60 patients (25%) repeatedly showed brain activation on fMRI or EEG indicating they were covertly following instructions, reported Nicholas Schiff, MD, of Weill Cornell Medicine in New York City, and co-authors in the New England Journal of Medicine.

Cognitive-motor dissociation was associated with younger age, longer time since injury, and brain trauma as an etiologic factor. In total, 11 patients with cognitive-motor dissociation were assessed with fMRI only, 13 were assessed with EEG only, and 36 with both techniques.

"This research shows that a substantial fraction of apparently unresponsive, severely brain-injured persons are aware and can engage in sustained cognitive activity," Schiff told MedPage Today. "These findings importantly point to the need to establish infrastructure to evaluate patients and to begin efforts to test possible therapies to help them."

Persons with cognitive-motor dissociation have cognitive abilities that exceed their motor abilities, Schiff noted. "They show a sharp dissociation with a high level of retained cognitive ability and limited or no motor responses," he said.

Earlier work reported that cognitive-motor dissociation occurred in 15% to 20% of brain-injured patients who seemed unresponsive. One study suggested that detecting it soon after injury may predict recovery.

"The percentage of participants with cognitive motor dissociation is 5 to 10 percentage points higher in our study than in previous studies," Schiff and co-authors pointed out.

"This finding may be due to our multimodal approach, which classified the participants who underwent assessment with both techniques on the basis of responses on either fMRI or EEG," they wrote. "The percentage of participants with cognitive motor dissociation may have been even higher if all the participants had been assessed with both imaging techniques."

Schiff and colleagues evaluated 353 adults with disorders of consciousness at six sites from 2006 to 2023. Some sites recruited participants from intensive care units soon after severe brain injury trauma, stroke, or cardiac arrest; others included participants who had brain injury years ago.

The researchers conducted behavioral assessments using the Coma Recovery Scale-Revised (CRS-R). They divided participants into two groups based on whether responses to verbal commands or intelligible speech were observed during CRS-R evaluations.

Participants had a median age of about 38. The median time between brain injury and CRS-R assessment was 7.9 months; 25% of participants had a CRS-R evaluation within 28 days after injury. Brain trauma was an etiologic factor in 50% of cases.

Overall, 241 patients had a behavioral diagnosis of coma, vegetative state, or minimally conscious state-minus (i.e., they showed signs of awareness but not responses to commands or intelligible verbal output). The other 112 patients had observable responses to verbal commands.

In the group with observable response to verbal commands, fMRI or EEG detected covert responses in only 43 of 112 patients (38%).

"The paradigms used in studies of task-based fMRI and EEG may require more cognitive resources (e.g., short-term memory, selective attention, and mental persistence) than in typical command-following trials performed at the bedside," Schiff and co-authors suggested. "Although this hypothesis has not been proven, it is supported by our finding that responses on fMRI and EEG were detected in only 38% of the participants with an observable response to commands at the bedside."

American Academy of Neurology guidelines note that the natural history of disorders of consciousness is not well-defined and prognosis can be challenging. Recently, a propensity score analysis led by co-author Yelena Bodien, PhD, of Mass General Brigham in Boston, suggested that some patients with severe traumatic brain injury who had life support withdrawn may have survived and achieved at least partial independence.

"Our team's recent studies suggest there is a benefit to waiting before decisions are made to withdraw life support, because some patients may be more conscious than they appear, and patients with even the most severe injuries may recover and regain independence," Bodien told MedPage Today. "Our papers highlight the need for improved access to advanced testing, like with fMRI, long-term monitoring of recovery, and evidence-based medical guidelines so doctors do not have to rely on their past experiences to establish prognosis."

Survival bias may have influenced outcomes in this study, Schiff and colleagues said. Participating sites used heterogeneous strategies to acquire, analyze, and interpret fMRI and EEG data, they acknowledged.

"Our findings may therefore not be generalizable across all centers," the researchers wrote. "Large-scale validation studies are needed to improve data acquisition and analysis for clinical translation."

Skin Cancer Protection -- Is the FDA too slow (again)? As usual, it depends.

Many people have had complaints about the FDA’s regulatory processes.  Examples of “too fast” can be directed at numerous surgical products, like joint replacements and even cardiac tools, but also the recent challenges related to COVID vaccinations.  “Too slow” used to be attached (back in the day) to HIV-related treatments, but now one that could hit home to people you know – sunscreen protective agents.  As stated in the article, 2 Americans die every hour from skin cancer, with more skin cancers diagnosed than all other cancers combined.  Seems like we should take this seriously.

Meanwhile, in the US, we’re using old sunscreen agents for decades, most of which have never been fully tested.  That’s not to safe they’re unsafe – they have just been used starting before the tests were even initiated.  But any newer products are required to be fully tested before approval.  So agents that have been used worldwide (excluding the US) for over a decade are still not approved, and thus not sold here.  And people keep getting skin cancer…

I guess there isn’t a strong enough skin cancer lobby – not as sexy as breast cancer, I guess.  But one of the issues, I think, is that these products are non-prescription, so as a consumer product there are different hoops to jump through.  Plus, you can’t charge $10,000 a tube like you can for a drug.  

Supposedly we’re on track to have superior sun protection by 2025.  In the meantime – hats, sleeves, umbrellas, and lots of the old sunscreen.  Remember, 5 sunburns doubles your risk of melanoma, the deadliest form of skin cancer.

FROM NBC NEWS / BY MICHAEL SCATURRO

What's keeping the U.S. from allowing better sunscreens?

Products sold in Europe, Japan and South Korea offer more protection from the sun. In the U.S., the key ingredients aren't FDA-approved.

When dermatologist Dr. Adewole “Ade” Adamson sees people spritzing sunscreen as if it’s cologne at the pool where he lives in Austin, Texas, he wants to intervene. “My wife says I shouldn’t,” he said, “even though most people rarely use enough sunscreen.”

At issue is not just whether people are using enough sunscreen, but what ingredients are in it.

The Food and Drug Administration’s ability to approve the chemical filters in sunscreens that are sold in countries such as Japan, South Korea, and France is hamstrung by a 1938 U.S. law that requires sunscreens to be tested on animals and classified as drugs, rather than as cosmetics as they are in much of the world. So Americans are not likely to get those better sunscreens — which block the ultraviolet rays that can cause skin cancer and lead to wrinkles — in time for this summer, or even the next.

Sunscreen makers say that requirement is unfair because companies including BASF Corp. and L’Oréal, which make the newer sunscreen chemicals, submitted safety data on sunscreen chemicals to the European Union authorities some 20 years ago.

Steven Goldberg, a retired vice president of BASF, said companies are wary of the FDA process because of the cost and their fear that additional animal testing could ignite a consumer backlash in the European Union, which bans animal testing of cosmetics, including sunscreen. The companies are asking Congress to change the testing requirements before they take steps to enter the U.S. marketplace.

In a rare example of bipartisanship last summer, Sen. Mike Lee (R-Utah) thanked Rep. Alexandria Ocasio-Cortez (D-N.Y.) for urging the FDA to speed up approvals of new, more effective sunscreen ingredients. Now a bipartisan bill is pending in the House that would require the FDA to allow non-animal testing.

“It goes back to sunscreens being classified as over-the-counter drugs,” said Carl D’Ruiz, a senior manager at DSM-Firmenich, a Switzerland-based maker of sunscreen chemicals. “It’s really about giving the U.S. consumer something that the rest of the world has. People aren’t dying from using sunscreen. They’re dying from melanoma.”

Every hour, at least two people die of skin cancer in the United States. Skin cancer is the most common cancer in America, and 6.1 million adults are treated each year for basal cell and squamous cell carcinomas, according to the Centers for Disease Control and Prevention. The nation’s second-most-common cancer, breast cancer, is diagnosed about 300,000 times annually, though it is far more deadly.

Though skin cancer treatment success rates are excellent, 1 in 5 Americans will develop skin cancer by age 70. The disease has cost the health care system $8.9 billion a year, according to CDC researchers. One study found that the annual cost of treating skin cancer in the United States more than doubled from 2002 to 2011, while the average annual cost for all other cancers increased by just 25%. And unlike many other cancers, most forms of skin cancer can largely be prevented — by using sunscreens and taking other precautions.

But a heavy dose of misinformation has permeated the sunscreen debate, and some people question the safety of sunscreens sold in the United States, which they deride as “chemical” sunscreens. These sunscreen opponents prefer “physical” or “mineral” sunscreens, such as zinc oxide, even though all sunscreen ingredients are chemicals.

“It’s an artificial categorization,” said E. Dennis Bashaw, a retired FDA official who ran the agency’s clinical pharmacology division that studies sunscreens.

Innisfree's Daily UV Defense Sunscreen, made in South Korea, is sold in the U.S. and doesn't contain bemotrizinol.Chelsea Stahl and Elise Wrabetz / NBC News

Still, such concerns were partly fed by the FDA itself after it published a study that said some sunscreen ingredients had been found in trace amounts in human bloodstreams. When the FDA said in 2019, and then again two years later, that older sunscreen ingredients needed to be studied more to see if they were safe, sunscreen opponents saw an opening, said Nadim Shaath, president of Alpha Research & Development, which imports chemicals used in cosmetics.

“That’s why we have extreme groups and people who aren’t well informed thinking that something penetrating the skin is the end of the world,” Shaath said. “Anything you put on your skin or eat is absorbed.”

Adamson, the Austin dermatologist, said some sunscreen ingredients have been used for 30 years without any population-level evidence that they have harmed anyone. “The issue for me isn’t the safety of the sunscreens we have,” he said. “It’s that some of the chemical sunscreens aren’t as broad spectrum as they could be, meaning they do not block UVA as well. This could be alleviated by the FDA allowing new ingredients.”

Ultraviolet radiation falls between X-rays and visible light on the electromagnetic spectrum. Most of the UV rays that people come in contact with are UVA rays that can penetrate the middle layer of the skin and that cause up to 90% of skin aging, along with a smaller amount of UVB rays that are responsible for sunburns.

The sun protection factor, or SPF, rating on American sunscreen bottles denotes only a sunscreen’s ability to block UVB rays. Although American sunscreens labeled “broad spectrum” should, in theory, block UVA light, some studies have shown that they fail to meet the European Union’s higher UVA-blocking standards.

“It looks like a number of these newer chemicals have a better safety profile in addition to better UVA protection,” said David Andrews, deputy director of Environmental Working Group, a nonprofit that researches the ingredients in consumer products. “We have asked the FDA to consider allowing market access.”

The FDA defends its review process and its call for tests of the sunscreens sold in American stores as a way to ensure the safety of products that many people use daily, rather than just a few times a year at the beach.

“Many Americans today rely on sunscreens as a key part of their skin cancer prevention strategy, which makes satisfactory evidence of both safety and effectiveness of these products critical for public health,” Cherie Duvall-Jones, an FDA spokesperson, wrote in an email.

D’Ruiz’s company, DSM-Firmenich, is the only one currently seeking to have a new over-the-counter sunscreen ingredient approved in the United States. The company has spent the past 20 years trying to gain approval for bemotrizinol, a process D’Ruiz said has cost $18 million and has advanced fitfully, despite attempts by Congress in 2014 and 2020 to speed along applications for new UV filters.

Bemotrizinol is the bedrock ingredient in nearly all European and Asian sunscreens, including those by the South Korean brand Beauty of Joseon and Bioré, a Japanese brand.

D’Ruiz said bemotrizinol could secure FDA approval by the end of 2025. If it does, he said, bemotrizinol would be the most vetted and safest sunscreen ingredient on the market, outperforming even the safety profiles of zinc oxide and titanium dioxide.

As Congress and the FDA debate, many Americans have taken to importing their own sunscreens from Asia or Europe, despite the risk of fake products.

“The sunscreen issue has gotten people to see that you can be unsafe if you’re too slow,” said Alex Tabarrok, a professor of economics at George Mason University. “The FDA is just incredibly slow. They’ve been looking at this now literally for 40 years. Congress has ordered them to do it, and they still haven’t done it.”

Avoiding a Heart Attack -- Timing CAN BE Everything!

When am I supposed to take my blood pressure pill if I want to avoid a heart attack?  Well…. Are you a night-owl or a morning lark?  It matters – and it seems to matter A LOT!

Night owls (up late in the morning and to bed late in the evening) should take their pills at night – 34% lower risk of heart attack hospitalization.  What’s crazy, though, is that if those people take their medication in the morning – there’s a 62% INCREASED risk of the same. The reverse is mostly true for the morning larks – better risk for pills in the morning and worse risk for pills at night.  So, oddly enough – IT DEPENDS on who you are and recommendations need to be tailored to the individual.  

There’s more in the article – Chronotherapy is the whole concept to timing for one’s specific circadian rhythm or body clock.  Lots more yet to learn.

FROM MEDSCAPE INTERNAL MEDICINE / BY SARI HARRAR

Chronotherapy: Why Timing Drugs to Our Body Clocks May Work

Do drugs work better if taken by the clock?

A new analysis published in this month's issue of The Lancet journal's eClinicalMedicine suggests: Yes, they do — if you consider the patient's individual body clock. The study is the first to find that timing blood pressure drugs to a person's personal "chronotype" — that is, whether they are a night owl or an early bird — may reduce the risk for a heart attack.

The findings represent a significant advance in the field of circadian medicine or "chronotherapy" — timing drug administration to circadian rhythms. A growing stack of research suggests this approach could reduce side effects and improve the effectiveness of a wide range of therapies, including vaccines, cancer treatments, and drugs for depression, glaucoma, pain, seizures, and other conditions. Still, despite decades of research, time of day is rarely considered in writing prescriptions.

"We are really just at the beginning of an exciting new way of looking at patient care," said Kenneth A. Dyar, PhD, whose lab at Helmholtz Zentrum München's Institute for Diabetes and Cancer focuses on metabolic physiology. Dyar is co-lead author of the new blood pressure analysis.

"Chronotherapy is a rapidly growing field," he said, "and I suspect we are soon going to see more and more studies focused on 'personalized chronotherapy,' not only in hypertension but also potentially in other clinical areas."

The 'Missing Piece' in Chronotherapy Research

Blood pressure drugs have long been chronotherapy's battleground. After all, blood pressure follows a circadian rhythm, peaking in the morning and dropping at night.

That healthy overnight dip can disappear in people with diabetes, kidney disease, and obstructive sleep apnea. Some physicians have suggested a bed-time dose to restore that dip. But studies have had mixed results, so "take at bedtime" has become a less common recommendation in recent years.

But the debate continued. After a large 2019 Spanish study found that bedtime doses had benefits so big that the results drew questions, an even larger, 2022 randomized, controlled trial from the University of Dundee in Dundee, Scotland — called the TIME study — aimed to settle the question.

Researchers assigned over 21,000 people to take morning or night hypertension drugs for several years and found no difference in cardiovascular outcomes.

"We did this study thinking nocturnal blood pressure tablets might be better," said Thomas MacDonald, MD, professor emeritus of clinical pharmacology and pharmacoepidemiology at the University of Dundee and principal investigator for the TIME study. "But there was no difference for heart attacks, strokes, or vascular death."

So, the researchers then looked at participants' chronotypes, sorting outcomes based on whether the participants were late-to-bed, late-to-rise "night owls" or early-to-bed, early-to-rise "morning larks."

Their analysis of these 5358 TIME participants found the following results: Risk for hospitalization for a heart attack was at least 34% lower for "owls" who took their drugs at bedtime. By contrast, owls' heart attack risk was at least 62% higher with morning doses. For "larks," the opposite was true. Morning doses were associated with an 11% lower heart attack risk and night doses with an 11% higher risk, according to supplemental data.

The personalized approach could explain why some previous chronotherapy studies have failed to show a benefit. Those studies did not individualize drug timing as this one did. But personalization could be key to circadian medicine's success.

"Our 'internal personal time' appears to be an important variable to consider when dosing antihypertensives," said lead author Filippo Pigazzani, MD, PhD, clinical senior lecturer and honorary consultant cardiologist at the University of Dundee School of Medicine, who conceived the study. "Chronotherapy research has been going on for decades. We knew there was something important with time of day. But researchers haven't considered the internal time of individual people. I think that is the missing piece."

The analysis has several important limitations, the researchers said. A total of 95% of participants were White. And it was an observational study, not a true randomized comparison. "We started it late in the original TIME study," MacDonald said. "You could argue we were reporting on those who survived long enough to get into the analysis." More research is needed, they concluded.

Looking Beyond Blood Pressure

What about the rest of the body? "Almost all the cells of our body contain 'circadian clocks' that are synchronized by daily environmental cues, including light-dark, activity-rest, and feeding-fasting cycles," said Dyar.

An estimated 50% of prescription drugs hit targets in the body that have circadian patterns. So, experts suspect that synching a drug with a person's body clock might increase effectiveness of many drugs.

A handful of US Food and Drug Administration–approved drugs already have time-of-day recommendations on the label for effectiveness or to limit side effects, including bedtime or evening for the insomnia drug Ambien, the HIV antiviral Atripla, and cholesterol-lowering Zocor. Others are intended to be taken with or after your last meal of the day, such as the long-acting insulin Levemir and the cardiovascular drug Xarelto. A morning recommendation comes with the proton pump inhibitor Nexium and the attention-deficit/hyperactivity disorder drug Ritalin.

Interest is expanding. About one third of the papers published about chronotherapy in the past 25 years have come out in the past 5 years. The May 2024 meeting of the Society for Research on Biological Rhythms featured a day-long session aimed at bringing clinicians up to speed. An organization called the International Association of Circadian Health Clinics is trying to bring circadian medicine findings to clinicians and their patients and to support research.

Moreover, while recent research suggests minding the clock could have benefits for a wide range of treatments, ignoring it could cause problems.

In a Massachusetts Institute of Technology study published in April in Science Advances, researchers looked at engineered livers made from human donor cells and found more than 300 genes that operate on a circadian schedule, many with roles in drug metabolism. They also found that circadian patterns affected the toxicity of acetaminophen and atorvastatin. Identifying the time of day to take these drugs could maximize effectiveness and minimize adverse effects, the researchers said.

Timing and the Immune System

Circadian rhythms are also seen in immune processes. In a 2023 study in The Journal of Clinical Investigation of vaccine data from 1.5 million people in Israel, researchers found that children and older adults who got their second dose of the Pfizer mRNA COVID vaccine earlier in the day were about 36% less likely to be hospitalized with SARS-CoV-2 infection than those who got an evening shot.

"The sweet spot in our data was somewhere around late morning to late afternoon," said lead researcher Jeffrey Haspel, MD, PhD, associate professor of medicine in the Division of Pulmonary and Critical Care Medicine at Washington University School of Medicine in St. Louis.

In a multicenter, 2024 analysis of 13 studies of immunotherapy for advanced cancers in 1663 people, researchers found treatment earlier in the day was associated with longer survival time and longer survival without cancer progression.

"Patients with selected metastatic cancers seemed to largely benefit from early [time of day] infusions, which is consistent with circadian mechanisms in immune-cell functions and trafficking," the researchers noted. But "prospective randomized trials are needed to establish recommendations for optimal circadian timing."

Other research suggests or is investigating possible chronotherapy benefits for depression, glaucoma, respiratory diseases, stroke treatment, epilepsy, and sedatives used in surgery. So why aren't healthcare providers adding time of day to more prescriptions? "What's missing is more reliable data," Dyar said.

Should You Use Chronotherapy Now?

Experts emphasize that more research is needed before doctors use chronotherapy and before medical organizations include it in treatment recommendations. But for some patients, circadian dosing may be worth a try:

Night owls whose blood pressure isn't well-controlled. Dyar and Pigazzani said night-time blood pressure drugs may be helpful for people with a "late chronotype." Of course, patients shouldn't change their medication schedule on their own, they said. And doctors may want to consider other concerns, like more overnight bathroom visits with evening diuretics.

In their study, the researchers determined participants' chronotype with a few questions from the Munich Chronotype Questionnaire about what time they fell asleep and woke up on workdays and days off and whether they considered themselves "morning types" or "evening types." (The questions can be found in supplementary data for the study.)

If a physician thinks matching the timing of a dose with chronotype would help, they can consider it, Pigazzani said. "However, I must add that this was an observational study, so I would advise healthcare practitioners to wait for our data to be confirmed in new RCTs of personalized chronotherapy of hypertension."

Children and older adults getting vaccines. Timing COVID shots and possibly other vaccines from late morning to mid-afternoon could have a small benefit for individuals and a bigger public-health benefit, Haspel said. But the most important thing is getting vaccinated. "If you can only get one in the evening, it's still worthwhile. Timing may add oomph at a public-health level for more vulnerable groups."