The Neuroscience of Bubbles -- they do more than tickle your nose

Gabriel Lepousez is a neuroscientist working in perception and memory and asked the question” “Why does your brain love bubbles?”

Sparkling drinks have long been popular.  I did not know, for example, that 12 liters of CO2 is dissolved in a pressurized bottle of champagne.  He talks about the smell of the product being increased 10 fold from the microexplosions as the bubbles pop.  There’s reference to the mustard receptor that suggests there’s a pain response.  Taste is made acidic by the production of hydrogen ions.  Ultimately, the “bubbly” engages all five senses, and that’s what grabs us!  Salud!  Cin Cin!  L’Chiam!

FROM MEDSCAPE UK / ANNE-GAËLLE MOULUN

Our Brain Loves Bubbles: CO2 Stimulates All Five Senses

In a video published on the Pasteur Institute website on January 2, neuroscientist Gabriel Lepousez, from the Perception and Memory Unit, explores the question: “Why does our brain love bubbles?”

Lepousez studied olfactory sensory perception and its health implications, particularly mental health and body-brain communication. While he does not focus exclusively on CO2, he acknowledges its role as an olfactory stimulus.

“It is one of many sensory stimuli, but not the subject of specific research,” he explained. However, inspired by the sparkling drinks that take centre stage during end-of-year celebrations, he decided to share insights into the neuroscience of bubbles.

Bubble Formation

The effervescence in sparkling drinks results from dissolved CO2; however, their formation also depends on external factors.

“In a pressurized bottle, such as champagne, 12 L of CO₂ remain dissolved. But once the bottle is opened and pressure decreases, the gas returns to its gaseous form, creating bubbles in the glass,” Lepousez explained.

“Interestingly, bubble formation is triggered by impurities on the glass surface, such as dust, microfibres, and microcracks, which serve as points of nucleation and formation of bubble columns. If you poured a carbonated drink into a perfectly clean, smooth glass, you might see no bubbles at all,” he emphasised.

“The magic of these drinks lies in the ability of CO2 to engage all five senses,” he said. “The bubbles capture our attention as they animate the liquid, making it appear alive and dynamic — unlike a still, flat drink. They also stimulate our hearing — the pop of a champagne cork, the hiss of a can opening, and the fizzing sound of bubbles rising in the glass all contribute to the sensory experience,” noted Lepousez.

Sensory Stimulation

Bubbles do more than just provide a captivating sight and sound. “Bubbles also stimulate our noses because each time a bubble finishes rising and bursts on the surface of the drink, its explosion triggers the projection of micro-aerosols into the air, which, like a mist, actively spray micro-droplets of perfumed liquid towards our nostrils and increasing 10-fold the vaporisation of odours in the air. This excess sensory stimulation directly activates our brain and increases the 10-fold intensity felt, which can be observed in functional brain imaging of a taster,” Lepousez explained.

CO2 is also an irritant gas that stimulates the same receptors as mustard. He noted, “That’s why it stings.”

The transient receptor potential ankyrin 1 receptor, commonly known as the mustard receptor, detects irritant compounds and plays a role in pain and inflammation. In the mouth, it is strongly expressed in the nerve endings of the trigeminal nerve, which innervates the oral and nasal cavities.

When exposed to a CO2-rich solution, these nerve endings are activated and transmit pain signals to the brain. This phenomenon can be studied in vitro using neuronal cultures, allowing precise control over molecular interactions and direct recording of their effects.

Taste and Texture

Bubbles also contribute to texture, creating a foam that adds thickness between the tongue and the palate. In addition, CO2 activates acid-detecting cells in the tongue.

“Does sparkling water taste more acidic and refreshing than still water? This is due to a chemical reaction between CO2 and water on the surface of our taste buds, producing hydrogen ions that trigger a mild acidic flavour. The simple CO2 molecule is unique in its ability to act on our five senses: Olfactory, gustatory, tactile, visual, and auditory — a true multisensory enhancer,” Lepousez concluded.

Slow Alzheimer's? You got it -- Get MOVING!

Here’s a quick take on a study from France and Monaco.  Folks over 70 were recruited from “memory centers” with complaints of memory issues, slow walking speed and issues with activities of daily living.  They were excluded if they were more restricted, or had dementia.  P-tau181, a known marker for Alzheimer’s was measured over time, as well as assessing physical activity and cognitive scores.  Even low levels of moderate to vigorous physical activity showed slower increases in the biomarker, though if the patients started with higher levels of p-tau181 there was no clear association.  

Don’t wait until things start going south – GET MOVING NOW!

FROM MEDPAGE UK / EDITED BY ANUSHREE CHAPHALKAR

Physical Activity May Slow Alzheimer's Pathology

— Lower risk of all-cause and cardiovascular mortality observed only among morning drinkers

TOPLINE:

Increased levels of moderate to vigorous physical activity were associated with a delayed rise in the concentration of phosphorylated tau181 (p-tau181) in blood over time in older adults with memory complaints, a study found. The cognitive benefits were attenuated at elevated baseline p-tau181 concentrations.

METHODOLOGY:

• This post hoc secondary analysis of the MAPT trial included 558 adults with memory complaints aged 70 years or older, recruited from 13 memory centres in France and Monaco between 2008 and 2011.

• Participants were eligible if they had spontaneous memory complaints, a gait speed ≤ 0.77 m/s, or a limitation in instrumental activities of daily living. Individuals with a diagnosis of dementia, Mini Mental State Examination scores < 24, or limitations in basic activities were excluded.

• Concentrations of p-tau181 in blood were measured at baseline, 3 years, or both, and self-reported moderate to vigorous physical activity and cognitive composite scores were assessed at baseline, 6 months, and 1, 2, and 3 years.

TAKEAWAY:

• Compared with inactive individuals, those with low or high levels of moderate to vigorous physical activity showed a slower increase in p-tau181 concentrations over time (regression coefficient [β], −0.109; P = .028 for low activity × time; β, −0.114; P = .018 for high activity × time).

• Physical activity was not positively associated with cognitive composite scores when baseline p-tau181 concentrations exceeded 9.36 pg/mL for cross-sectional association and 3.5 pg/mL for longitudinal association.

• No association was found between baseline concentrations of p-tau181 and baseline levels of moderate to vigorous physical activity.

IN PRACTICE:

"These findings support the current recommendation of increasing physical activity as a preventive tool against neurodegeneration, but further investigations are needed," the authors wrote.

SOURCE:

The study was led by Jérémy Raffin, PhD, Institut du Vieillissement, Gérontopôle de Toulouse, Centre Hospitalo-Universitaire de Toulouse, Toulouse, France. It was published online on February 24 in The Lancet Healthy Longevity.

LIMITATIONS:

The study was limited by the use of subjective tools for assessing physical activity levels, which are prone to recall and response biases. Light-intensity physical activity was not considered and data on sedentary time were not collected. The study population was limited to adults aged 70 years or older, reducing generalisability. The assessment of education may not have fully captured variability. Additionally, factors such as fasting status were not controlled for, and the statistical analyses may have been influenced by missing confounder data and unmeasured confounding.

DISCLOSURES:

The study was supported by grants from Toulouse Gérontopôle, the French Ministry of Health, and the Pierre Fabre Research Institute. One author reported receiving multiple research grants, consulting for pharmaceutical and diagnostic companies, contributing to educational programs, and co-founding a biomarker company. Details are provided in the original article.

Are We Going to Talk about Coffee Again? Yup!

I’m virtually certain you heard about this one – morning coffee saves lives, but not in the afternoon – or something like that!  

It’s been up and down for coffee, but really it’s a solid yes for everyone who doesn’t hate it or have a negative reaction to it.  So what’s new with this one?   Honestly, not much.  Years ago I wrote about how the more coffee you drank the longer you lived (ok, there’s a bit more to it than that), so long as you didn’t have an addictive personality.  That’s kind of what this says – if you drink coffee all day, you’re probably doing other things that will kill you sooner, so the coffee is “diluted”.

Recommendation --- 1 to 3 cups in the morning is fine.  Realize that the benefits come from the flavonoids and phytochemicals, not from caffeine.  Essentially, if you start pushing your caffeine into the afternoon, you might be looking for trouble, effecting sleep quality.  If you avoid that, knock yourself out.  

I personally like a decaf espresso at lunch (I know, it seems like you’re defeating the purpose, but at least it’s not like grandma’s decaf!)

Alla Salute!

FROM MEDPAGE TODAY / BY NICOLE LU

Coffee Drinking Tied to Better Survival, but Timing Matters

— Lower risk of all-cause and cardiovascular mortality observed only among morning drinkers

Key Takeaways

• Lower risks of all-cause mortality and cardiovascular mortality were observed in people who mostly drank coffee in the morning.

• Study is consistent with other literature showing an inverse association between moderate coffee consumption and mortality risk.

• Definitive long-term trials to validate the present study findings deemed unlikely.

Any presumed health benefits of coffee may be limited to morning cups of joe, according to an observational study based on the National Health and Nutrition Examination Survey (NHANES).

Compared with non-coffee drinkers, those who mostly drank coffee in the morning had a lower risk of all-cause mortality (adjusted HR 0.84, 95% CI 0.74-0.95) and cardiovascular mortality (HR 0.69, 95% CI 0.55-0.87) when followed over a median 9.8 years.

It appeared that survival was particularly improved with morning consumers drinking moderate (>1 to 2 cups and >2 to 3 cups/day) and heavy (>3 cups/day) amounts of coffee rather than lesser amounts, reported Lu Qi, MD, PhD, epidemiologist of Tulane University in New Orleans and Harvard T.H. Chan School of Public Health in Boston, and colleagues in European Heart Journalopens in a new tab or window.

In contrast, people who kept drinking coffee later in the day, the all-day type, had no reduction in all-cause mortality (HR 0.96, 95% CI 0.83-1.12) and cardiovascular mortality (HR 0.82, 95% CI 0.61-1.10) regardless of how much they consumed.

Neither coffee drinking pattern was tied to more or less cancer-specific mortality.

"We found that coffee drinking timing was associated with all-cause mortality risk and [cardiovascular disease]-specific mortality risk independent of the amounts of coffee intake," Qi's group concluded. "Our findings highlight the importance of considering drinking timing in the association between the amounts of coffee intake and health outcomes."

The authors suggested two potential mechanisms that could explain their findings. One is that all-day caffeine consumption can disrupt circadian rhythms. Secondly, there may be anti-inflammatory substances within coffee that can counteract the body's pro-inflammatory cytokines when they are typically at their highest levels in the morning.

"Why would time of the day matter? In the morning hours there is commonly a marked increase in sympathetic activity as we wake up and get out of bed, an effect that fades away during the day and reaches its lowest level during sleep. Thus, it is possible, as the authors point out, that coffee drinking in the afternoon or evening disrupts the circadian rhythm of sympathetic activity," agreed Thomas Lüscher, MD, cardiologist of Royal Brompton and Harefield Hospitals in London and the University of Zurich, writing in an accompanying editorialopens in a new tab or window.

Previously, multiple observational studies had shown that moderate coffee consumptionopens in a new tab or window has an inverse association with mortality risk and risk of type 2 diabetes and other chronic conditions. At the same time, the data are mixed regarding heavy coffee consumption.

None of the work so far can establish causal relationships between coffee drinking and survival.

"We don't typically give advice about timing in our dietary guidance, but perhaps we should be thinking about this in the future," Qi nevertheless said in a press release. "Further studies are needed to validate our findings in other populations, and we need clinical trials to test the potential impact of changing the time of day when people drink coffee."

That may be easier said than done, however. "[T]hese cohorts are not randomized trials, probably as nobody wanted to be in the placebo group ... Be that as it may, it is unlikely that we will see a large, randomized trial over prolonged periods of time," Lüscher wrote.

"Overall, we must accept the now substantial evidence that coffee drinking, particularly in the morning hours, is likely to be healthy," he urged. "Thus, drink your coffee, but do so in the morning!"

Qi and colleagues performed their study using the 1999-2018 cycles of NHANES, a nationally representative cohort that includes health exams and lab tests. There were 40,725 adult participants identified who had completed 24-hour dietary recalls.

Reported coffee habits were fed into a cluster analysis that split participants into morning type (36%) and all-day types (16%) of coffee drinkers, the remainder considered non-coffee drinkers. These coffee drinking patterns were validated in 1,463 adults from the Women's and Men's Lifestyle Validation Study who had complete data on 7-day dietary records.

Compared with non-coffee drinkers, the morning and all-day types were older, more likely to be white, had higher family income, and a higher prevalence of diabetes, hypertension, and high cholesterol. Among coffee drinkers, the morning-type pattern was associated with more tea and caffeinated soda drinking but lower overall quantities of coffee than the all-day pattern.

The authors tried to adjust their mortality analyses to account for between-group differences in caffeinated and decaffeinated coffee intake amounts, sleep hours, and other confounders.

"Indeed, it is possible that coffee drinkers differ from non-drinkers in many aspects," Lüscher cautioned. "Of note, dietary and lifestyle habits, in particular smoking, may affect any of the observed associations. Some may work against the hypothesis provided in the current study as coffee drinkers are more likely to smoke than non-drinkers. This may particularly be the case of all-day drinkers who may be somewhat more addicted to this habit that may annihilate the protective effects of coffee drinking."

Other limitations to the study include the possibility of recall bias and measurement errors. Whether the findings can be generalized to other countries and other cultures is unknown.

Insulin Pumps and the World Traveler - Public Service Announcement

More and more people are becoming diabetic, and consequently more people are ending up using insulin pumps.  The technology is now fantastic and even type 1 diabetics whose sugars have been all over the place are now controlled.  But those people have realized that traveling wreaks havoc with glucose control.  Now we know why – BUBBLES!  For most people it’s not a big deal, but for some, it can be.  

Please forward this to anyone you know who uses an insulin pump.  They’ll find it useful.

FROM MEDSCAPE / BY MIRIAM E. TUCKER

Air Travel Alters Insulin Pump Delivery on Takeoff, Landing

MADRID — Airplane travel consistently causes insulin pumps to over-deliver a little over half a unit on takeoff and under-deliver a bit less on landing, new research found.

This phenomenon is due to air bubble formation and reabsorption in the insulin caused by ambient pressure changes in the airplane's cabin. It has nothing to do with the pump itself and happens with all insulin pumps, including those in hybrid closed-loop systems, Bruce King, MD, said at the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.

The extent to which this affects people with diabetes who use insulin pumps depends on their dose and insulin sensitivity among other factors, but all who fly should be aware of the possibility and take precautions, particularly with children, King, a pediatric endocrinologist at John Hunter Children's Hospital, Newcastle, Australia, told Medscape Medical News.

"Basically, the pumps are very safe in flight, but they deliver a little bit of extra insulin when you go up and stop delivery when you come back down again. There are a couple of simple steps that people can take to make sure that they don't have problems during the flight," he said.

Specifically, he advised that for pumps with tubing, wearers can disconnect just prior to takeoff and reconnect when the plane reaches cruising altitude, about 20 minutes into the flight. The insulin will still come out, but it won't be delivered to the person, King said.

On descent, they can disconnect after landing and prime the line to remove the insulin deficit.

With the Omnipod, which can't be disconnected, the only solution is to eat a small snack on takeoff. And on landing, eat another small snack such as a banana, and give a bolus for it to overcome the blockage of insulin delivery.

In any case, King said, "One of the most important things is informing people with diabetes about this effect so they're aware of it and can act appropriately when they fly."

Asked to comment, Nicholas B. Argento, MD, a practicing endocrinologist in Columbia, Maryland, and author of the American Diabetes Association's book Putting Your Patients on the Pump, called the issue a "minor effect," adding, "While I think it would be reasonable to make those changes…it seems like a lot of effort for a difference of 0.6 units extra on ascent and 0.5 units less on descent."

He noted there is a risk that the individual might forget to reattach the pump after 20 minutes, leading to hyperglycemia and even diabetic ketoacidosis. Instead, "one could put the pump on suspend for 1 hour on ascent. That would not stop the extra insulin but would net less insulin during that time period."

And after descent, "you have to walk a lot in most cases, so I don't think they need to take this into consideration. So many other factors change in air travel that I don't think this is a significant enough effect to make the effort."

A Known Phenomenon, the Manufacturers Are Aware

This phenomenon has been described previously, including by King in a 2011 Diabetes Care paper. The new research is among a series of experiments funded by the European Union Aviation Safety Agency in collaboration with the pump manufacturers Medtronic (MiniMed), Tandem (t:slim), and Insulet (Omnipod), primarily aimed at establishing safety parameters for airline pilots with insulin-treated diabetes.

Both the Omnipod DASH and Omnipod 5 User Guides include warnings about unintended insulin delivery during flight, and both advise users to check their blood glucose levels frequently while flying.

In a statement, Jordan Pinsker, MD, Chief Medical Officer at Tandem Diabetes Care, told Medscape Medical News, "While it has long been known that routine air travel pressure changes can cause minor fluctuations in insulin pump delivery, the impact of these variations have been found to be generally minor as it relates to glycemic control."

Pinsker added that the Tandem Mobi user manual includes a warning related to significant pressure changes in specific air travel situations and offers guidance to disconnect. However, "the t:slim X2 pump's microdelivery technology limits how much extra insulin can get delivered from air pressure changes due to a mechanism between the tubing and the contents of the bag inside the cartridge."

Medtronic's user guide says that the 780G system has not been tested at altitudes higher than 10,150 feet.

Hypobaric Chamber Used to Simulate Flight

The study was conducted in vitro, in a hypobaric chamber designed to mimic atmospheric changes during commercial flight. A total of 10 Medtronic MiniMed 780G, 10 Tandem t:slim X2, and six Insulet Omnipod DASH pumps were tested.

The hypobaric chamber was depressurized to 550 mm Hg over a 20-minute ascent, maintained at a 30-minute cruise, followed by a 20-minute descent to ground (750 mm Hg). During the simulated flights, insulin infusion was set at 0.6 units per hour, a rate typical for both adults and children, to allow accurate measurements with multiple flights.

Insulin delivery rates and bubble formation were recorded by attaching infusion sets to open-ended 100 µL capillary tubes against 1-mm grid paper.

Full cartridges — Medtronic: 3 mL, t:slim: 3 mL, and Omnipod: 2 mL — all over-delivered 0.60 units of insulin over a 20-minute ascent compared with delivery at ground level. And during descent, the cartridges under-delivered 0.51 units of insulin.

But if There's Rapid Decompression…

In a separate protocol, insulin infusion sets without pumps were tested in a simulation of rapid decompression. Insulin delivery during both ascent and descent showed statistically significant differences compared with delivery at ground level (both P < .001). In this scenario, fluid delivery was equivalent to 5.6 units of excess insulin.

King pointed out that while these are rare events, about 40-50 occur annually. One was the widely publicized Alaska Airlines flight in January 2024 when the door fell off in midair.

Argento commented, "The catastrophic decompression is of note, and I would want patients to be aware of this, but it is asking a lot for someone thinking they are going to die to remember to disconnect as it starts."

The researchers are investigating this phenomenon further in people, including airline pilots.

Depression and Ice Cream

Headlines often conflate associations into causation, essentially as click-bait.  What does that mean?  

My favorite example is “Ice Cream Causes Drowning”.  No – I don’t mean the kids went swimming too soon after eating (that’s a myth, too, by the way).  Drowning increases when more people go swimming.  More people go swimming when it’s hot; more people eat ice cream when it’s hot, ergo – ice cream causes drowning.  Duh --- NO!  Association is not causation.

Here we have more steps equals less depression.  But how do we know that the more depressed on is, the less likely they are to walk lots of steps?  Meta-analyses group together lots of studies that may look at different questions, but have data that can be examined from a different angle.  Opportunities to point to causation is extremely limited.  Most of the articles these days are in this category, so be careful in the conclusions you draw.

What can we say?  If you walk more, you’re less likely to be depressed.  Does walking more decrease depressive symptoms?  The answer to that is YES – just not from this meta-analysis.

FROM MEDSCAPE / BY ANUSHREE CHAPHALKAR

Can Walking More Steps Per Day Help Keep Depression Away?

TOPLINE:

Walking 7000 or more steps per day is associated with fewer depressive symptoms and a 31% lower risk for depression than taking fewer steps, a new meta-analysis shows.

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis of 33 observational studies that included more than 96,000 adults aged 18-91 years.

• Data were obtained from 27 cross-sectional and 6 longitudinal studies and from 5 major databases through May 2024.

• Objectively measured daily step counts and depression data were collected via various assessment tools.

TAKEAWAY:

• The number of daily steps had a significant inverse correlation with depressive symptoms in both cross-sectional (correlation coefficient [r], −0.12; 95% CI, −0.20 to −0.04) and panel studies (r, −0.17; 95% CI, −0.28 to −0.04).

• Participants achieving 7000 steps per day or more showed a lower risk for depression than those achieving less than 7000 steps per day (risk ratio [RR], 0.69; 95% CI, 0.62-0.77).

• An additional increase of 1000 steps per day was associated with a 9% lower risk for depression (RR, 0.91; 95% CI, 0.87-0.94).

• Cross-sectional analysis showed that, compared with walking less than 5000 steps per day, walking 5000-7499 steps per day, 7500-9999 steps per day, and at least 10,000 steps per day were all significantly associated with fewer depressive symptoms (standardized mean difference, −0.17, −0.27, and −0.26, respectively).

IN PRACTICE:

"The objective measurement of daily steps may represent an inclusive and comprehensive approach to public health that has the potential to prevent depression. Small amounts of PA [physical activity] may be particularly relevant for specific populations, such as older adults and individuals with limited activities of daily living, for whom daily steps emerge as an accessible PA strategy," the investigators wrote.

SOURCE:

The study was led by Bruno Bizzozero-Peroni, PhD, Health and Social Research Center, Universidad de Castilla-La Mancha, Cuenca, Spain. It was published online December 16 in JAMA Network Open.

LIMITATIONS:

Reverse associations were possible, and causal inferences could not be made from the findings. In addition, the analysis showed substantial between-study heterogeneity in some pooled estimates, partially explained by differences in participant characteristics and step-counting devices. Most studies also lacked robust methods, potentially affecting result reliability, and the meta-analysis comparing high vs low daily step counts may have been susceptible to publication bias.

DISCLOSURES:

The study was funded by the University of Castilla-La Mancha, National Agency for Research and Innovation, Ministry of Economy and Competitiveness of Spain, Carlos III Health Institute, European Regional Development Fund, and European Union's Next Generation EU initiative. No conflicts of interest were reported.

Women WIN -- when it comes to a Little Exercise

Surprise – we’re talking about exercise again!

And the good news only applies to women, and we don’t know why, but we think it’s related to intensity.

Anyway – If women can get even less than 2 minutes of vigorous exercise a day had a reduction in MACE (major adverse cardiovascular events), heart attack and heart failure.  As the vigorous exercise went up, the rate of events went down.  For men the benefits were not statistically significant (men didn’t get their heart rate up as high with their activity seems to be the reason). 

So, again, time to get moving.  But you have to work hard – for 20 or 30 seconds at a time, a few times a day – is that so bad?  Come on!  Let’s go!

FROM MEDSCAPE / BY CAROLYN BROWN

Just Minutes of Daily Vigorous Exercise Improve Heart Health

Middle-aged women who did many short bursts of vigorous-intensity exercise — amounting to as little as 3 min/d — had a 45% lower risk for major adverse cardiovascular events, reported investigators.

This doesn’t mean just a walk in the park, explained Emmanuel Stamatakis, PhD, a researcher with the University of Sydney in Sydney, Australia. He said the activity can be as short as 20-30 seconds, but it must be high intensity — “movement that gets us out of breath, gets our heart rate up” — and repeated several times daily.

Stamatakis and his colleagues call this type of exercise vigorous intermittent lifestyle physical activity, and it involves intense movement in very short bouts that are part of daily life, like a quick stair climb or running for a bus.

In their study, published in the British Journal of Sports Medicine, most exercise bursts were less than a minute, and few were over 2 minutes.

This is the third study in which the international network of researchers has shown the health benefits of vigorous physical activity. They are upending the common view that “any physical activity under 10 minutes doesn’t count for health,” said Stamatakis.

Bursts of Energy

The three studies looked at data for thousands of middle-aged men and women aged 40-69 years collected in the UK Biobank. Their daily activity was measured using accelerometers worn on the wrist for 7 days. This is preferable to survey data, which Stamatakis said is often unreliable.

The analysis looked at people who reported that they did not do any other exercise, taking no more than a single walk during the week. Then their cardiovascular health was tracked for almost 8 years.

Previous studies of the same data have shown benefits of vigorous physical activity for risk for cancer and for risk for death, both overall and due to cardiovascular disease or cancer.

In this study, women who did even less than 2 minutes of vigorous physical activity a day but no other exercise had a lower risk for all major cardiovascular events and for heart attack and heart failure. Women who did the median daily vigorous exercise time — 3.4 minutes — had an even lower risk. In fact, in women, there was a direct relationship between daily exercise time and risk reduction.

In men, the study showed some benefit of vigorous physical activity, but the relationship was not as clear, said Stamatakis. “The effects were much subtler and, in most cases, did not reach statistical significance.”

Good News for Women

Stamatakis said it is unclear why there was such a gap in the benefits between men and women. “Studies like ours are not designed to explain the difference,” he added.

“This study does not show that [vigorous physical activity] is effective in women but not men,” said Yasina Somani, PhD, an exercise physiology researcher at the University of Leeds, Leeds, England, who was not involved in the work. Because the study just observed people’s behavior, rather than studying people in controlled conditions such as a lab, she said you cannot reach conclusions about the benefits for men. “You still need some further research.”

Somani pointed out that a study like this one cannot determine how vigorous physical activity protects the heart. In her research, she has studied the ways that exercise exerts effects on the heart. Exercise stresses the cardiovascular system, leading to physiological adaptation, and this may differ between men and women.

“Seeing this article motivates me to understand why women are responding even more than men. Do men need a greater volume of this exercise? If you’re carrying a 10-pound grocery bag up a flight of stairs, who is getting the greater stimulus?”

In fact, the study researchers think women’s exercise bursts might simply be harder for them. For some of the sample, the researchers had data on maximal oxygen consumption (VO2 max), a measure of cardiovascular fitness. During vigorous physical activity bouts, this measure showed that the effort for women averaged 83.2% of VO2 max, whereas it was 70.5% for men.

Somani said, “For men, there needs to be more clarity and more understanding of what it is that provides that stimulus — the intensity, the mode of exercise.”

“People are very surprised that 20-30 seconds of high-intensity exercise several times a day can make a difference to their health,” said Stamatakis. “They think they need to do structured exercise,” such as at a gym, to benefit.

He said the message that even quick exercise hits are beneficial can help healthcare professionals foster preventive behavior. “Any health professional who deals with patients on a regular basis knows that physical activity is important for people’s overall well-being and prevention of chronic disease.” The difficulty is that many people cannot or simply do not exercise. “Some people cannot afford it, and some do not have the motivation to stick to a structured exercise program.”

But anyone can do vigorous physical activity, he said. “The entry level is very low. There are no special preparations, no special clothes, no money to spend, no time commitment. You are interspersing exercise across your day.”

The researchers are currently studying how to foster vigorous physical activity in everyday behavior. “We are codesigning programs with participants, engaging with middle-aged people who have never exercised, so that the program has the highest chance to be successful.” Stamatakis is looking at encouraging vigorous physical activity through wearable devices and coaching, including online options.

Somani said the study adds weight to the message that any exercise is worthwhile. “These are simple choices that you can make that don’t require engaging in more structured exercise. Whatever you can do — little things outside of a gym — can have a lot of benefit for you.”

Another Chocolate Story -- it's back to Dark!

Wait long enough, and there will be another study on chocolate to talk about.  This time is back to Dark as the winner!  Studies go back and forth – it’s pretty much always good news –chocolate lowers mortality, certain diseases, etc, but while dark seems to always benefit, milk doesn’t always.  Well, it’s like that again today.

Eating dark chocolate 5 or more servings a week drops the risk of type 2 diabetes by 21%, where eating milk chocolate doesn’t do anything – well, not entirely true.  Eating more milk chocolate IS associated with weight gain!  Milk chocolate actually has more sugar than cocoa, and, as a consequence, has less of the good stuff (flavanols).  

Of course it’s never that simple – intake of dark chocolate also coincides with better food choices… so is it really the chocolate?

FROM MEDPAGE TODAY / BY SOPHIE PUTKA

New Study Teases Out Chocolate and Diabetes Connection

— Eating more dark chocolate was associated with a lower risk of type 2 diabetes

Eating more dark chocolate was associated with a lower risk of type 2 diabetes, an analysis of prospective cohort studies suggested.

Among participants across three studies of healthcare workers, those who consumed ≥5 servings per week of dark chocolate had a 21% lower risk of type 2 diabetes compared with those who never or rarely consumed dark chocolate (P=0.006 for trend), reported Qi Sun, MD, ScD, of the Harvard T.H. Chan School of Public Health in Boston, and colleagues in The BMJ.

There was no significant association between consumption of milk chocolate and type 2 diabetes, but intake of milk chocolate was positively associated with weight gain, while this was not the case for dark chocolate.

"We were surprised to see a stark contrast between dark and milk chocolate," co-author Binkai Liu, MS, also of Harvard T.H. Chan School of Public Health, told MedPage Today. "While dark chocolate was associated with a lower risk of type 2 diabetes, milk chocolate showed no such benefit and was even associated with weight gain. This difference underscores the importance of chocolate type and its nutrient composition."

"Advising patients to enjoy dark chocolate occasionally as part of a balanced and nutrient-rich diet could be a way to integrate these insights into practical recommendations," she added.

Chocolate is high in polyphenols, including flavanols (part of the larger flavonoid group), and previous studies have shown an association between higher dietary flavonoid consumption and decreased type 2 diabetes risk.

Though flavonoids may confer antioxidant, anti-inflammatory, and vasodilatory benefits, the relationship between chocolate consumption and diabetes remains "controversial," the authors wrote, due to observational studies with inconsistent findings, and a lack of inquiry into health effects by chocolate subtype.

"We made efforts to adjust for various dietary, lifestyle, and socioeconomic variables, but residual confounding remains a possibility," Liu said.

Simin Liu, MD, ScD, of the University of California Irvine, who was not involved in the study, told MedPage Today that "the new findings, while promising, should be interpreted with caution. Observational studies like this can show associations but cannot definitively prove cause and effect."

"It's plausible that the flavanols in dark chocolate may contribute to improved insulin sensitivity and glucose metabolism, which could offer some protection against type 2 diabetes," he noted. "However, it's important to consider other lifestyle factors that may be influencing the results."

For this analysis, Sun and team used data from the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHSII) (both all female), as well as the Health Professionals Follow-up Study (HPFS; all male). Total chocolate consumption baselines for the NHS and HPFS were in 1986, and in 1991 for the NHSII, when comprehensive food frequency questionnaires were first implemented. The second baseline, for chocolate subtype analyses, were in 2006 for the NHS and HPFS and 2007 for the NHSII, when the survey added questions about chocolate types.

Participants' diets were assessed every 4 years, with questions about average consumption of a standard portion size of chocolate in the past year, with nine frequency levels ("never, or less than once per month" to "≥6 per day"). Starting in later years, participants were asked, "How often do you consume milk chocolate (bar or pack)?" and "How often do you consume dark chocolate?"

Other variables assessed included race/ethnicity, body weight, waist circumference, smoking status, alcohol consumption, multivitamin use, menopausal status and postmenopausal hormone use, oral contraceptive use, hypertension, hypercholesterolemia, and family history of diabetes. Physical activity and body mass index were measured over time. Diabetes was self-reported in biennial questionnaires and confirmed by study doctors with a supplementary questionnaire, which collected more details about diagnoses and treatment.

In total, 192,208 participants were included from the three trials in the total chocolate intake analysis, with 111,654 included in the analysis on chocolate types. The mean ages at first baseline were 52.3, 36.1, and 53.1 for the NHS, NHSII, and HPFS, respectively. For baseline 2, they were 70.4, 52.3, and 68.3, respectively. Most participants were non-Hispanic white.

In the analysis on total chocolate intake, participants who consumed ≥5 servings per week of any chocolate had a 10% lower relative risk of type 2 diabetes compared with those who never or rarely consumed chocolate, but this was not a significant trend (P=0.07).

Participants with higher chocolate intake had higher energy, saturated fat, and added sugar intakes. Higher levels of dark chocolate consumption were associated with higher-quality diet, as assessed by the Alternate Healthy Eating Index-2010 (based on food frequency questionnaire responses), and greater consumption of fruit and vegetables, epicatechin, and total flavonoids. The opposite was true for milk chocolate consumption.

The authors were limited by potential confounding, and a limited number of people with type 2 diabetes in the higher chocolate consumption groups. Most of the participants in the chocolate subtype analyses were white adults over 50 at baseline, which could limit the generalizability of the findings to other populations.

Moreover, chocolate consumption in the overall study population was low compared with the national average, which was another limitation.

Pooping makes you Faster...and Smarter!

Recently there’s been a lot of talk about a gut-brain connection, but is this taking things a little too far?

Turns out, no, there’s actually data supporting the idea that not only are the bowels and the brain connected, but if you want to be faster and smarter – use the toilet!

If you empty your bowels prior to a triathlon, you’ll perform better.  In this case, they gave athletes a magnesium oxide laxative to ensure “performance” prior to the race.  Each one also improved they race “performance” and cognitive test result.  Even 69% of the athletes who did not get the laxative saw Stroop test improvement, confirming the rectal-brain connection.  

I’m sure there’s a joke in there, but I just can’t seem to….oh, never mind.

FROM SCIENCE ALERT / BY MICHELLE STARR

Pooping Before You Exercise Has an Incredible Effect on Performance

If you're looking to improve your performance, both cognitively and physically, you need to start by giving a crap.

No, quite literally. Go to the toilet and empty your bowel. If you're about to compete in a triathlon, it will make you both faster and smarter, according to two recent studies.

The latest research involved 13 triathletes, a cognitive test called the Stroop test, and a magnesium oxide laxative.

The result? The athletes performed measurably better on the cognitive test after voiding their large intestines, a finding that suggests an underexplored link between the rectum and cognitive function. This potential link has interesting implications, not just for peak performance, but for understanding cognitive decline.

"The most striking finding of this study is the unequivocal improvement observed in Stroop test performance for all participants consuming magnesium oxide," writes a team of researchers led by biochemist Chen-Chan Wei of the University of Taipei in a new paper.

"Even in the absence of magnesium oxide, defecation led to improved Stroop test results for 9 out of 13 individuals."

A Stroop test is one that presents you with a visual of conflicting information. The word "red" might appear in blue text, for example; the test participant needs to say aloud the color of the text, not the color word that is written. It evaluates cognitive flexibility and response time.

A 2022 study found that patients with early-stage Parkinson's disease can exhibit mild cognitive impairment when constipated, suggesting a link between the rectum and the brain. Such a concept isn't without precedent. Your gut contains hundreds of millions of neurons, and the gut microbiome may play a role in your mood, as well as neurological and mental health disorders.

Wei and colleagues wanted to investigate the link for athletes. Triathlons, involving three different sports disciplines, are taxing on both mind and body. The athlete needs to make fast decisions to navigate the course, have the fortitude to last the distance, and in the process try to best their fellow athletes.

The researchers previously showed that having a poop before getting on a bike resulted in improved performance – and improved blood flow in the prefrontal cortex region of the brain – in triathletes. The next step, after establishing a link between an empty bowel and increased physical performance, was to try to identify if there was a similar link to cognitive performance.

"When you do exercise, especially long-distance exercise, your brain is going to be sending high amounts of commands to the muscles," explains physiologist Chia-Hua Kuo of the University of Taipei.

"Whether or not you can sustain muscle contraction is not really depending on whether your muscle has wrung out the energy, it's whether your brain is able to challenge your muscle."

Each of the 13 triathletes in the study participated in three sessions of Stroop testing. For the first session, the test was taken without a prior bowel movement. For the second session, after a careful diet, the test was administered an hour after a bowel movement. Finally, for the third session, the athletes were given magnesium oxide; they took the test 13 hours after taking the laxative, and an hour after defecation.

More than two thirds of participants performed better on the test with empty bowels in the second session. Intriguingly, 100 percent saw improvement after a laxative-aided defecation.

Although the sample size was small, the difference in performance between the sessions suggests that emptying one's bowels could be linked to improved cognition.

The link and the reasons for it have not been definitively established, but the researchers believe that it may have something to do with finite resources in the body. When you have material in your digestive tract, blood and oxygen are used to help break it down. With no material to digest, those resources can be used elsewhere.

Near-infrared spectroscopy images highlighting real-time oxygenation and blood distribution. Arrows indicate the position of spectroscopy detector probes. (Wei et al., SMHS, 2024)

In fact, insufficient resourcing during exercising is thought to be the cause of the well-known phenomenon of runners' diarrhea, in which athletes lose control of their bowels while engaged in intense exercise.

In a 2012 review, scientists found that "During physical exercise, the increased activity of the sympathetic nervous system redistributes blood flow from the splanchnic organs to the working muscles… A severely reduced splanchnic blood flow may frequently cause gastrointestinal ischemia."

That means that the body redirects blood away from the gastrointestinal organs to work on the exercise; and the reduced blood flow causes gastrointestinal pyrotechnics.

It's all connected in strange and wonderful ways. Or, as Kuo puts it: "Our spirit is not only inside the skull, but also in other parts. And the rectum is also part of the brain."

The researchers caution against taking laxative drugs. If you are having issues maintaining gastrointestinal regularity, seek help from a medical professional.

The findings have been published in Sports Medicine and Health Science.

"There's a great future in plastics"... In Us?!?

In 1967, “The Graduate” reported that there was a great future in plastics.  I doubt they meant that the future of plastics was “in us”.  But that’s what it’s looking like.  Back several years ago there was an article that said people were eating the equivalent of a credit card in microplastics every week.  Turns out that was wrong – we only eat a credit card every year.  But it never goes away….

Those microplastics range from 5 ½ microns up to 26 microns (a human hair averages around 70 microns) and have now been found in the olfactory bulb (your nose smell center – part of your brain).

But it’s not just them being there – we can’t break them down and excrete them – they can degrade and potentially spread through the body and, since those substance are known to be toxic, potentially make who knows what kind of mess!  

The real question I ask is not IF you are toxic, but rather, how TOXIC are you?  If you have stuff that doesn’t fit the usual scenarios, this might be the very question you need to answer.

FROM MEDSCAPE / by Deborah Brauser

Microplastics Have Been Found in the Human Brain. Now What?

Microplastics have been found in the lungs, liver, blood, and heart. Now, researchers report they have found the first evidence of the substances in human brains.

In a recent case series study that examined olfactory bulb tissue from deceased individuals, 8 of the 15 decedent brains showed the presence of microplastics, most commonly polypropylene, a plastic typically used in food packaging and water bottles.

Measuring less than 5 mm in size, microplastics are formed over time as plastic materials break down but don’t biodegrade. Exposure to these substances can come through food, air, and skin absorption.

While scientists are learning more about how these substances are absorbed by the body, questions remain about how much exposure is safe, what effect — if any — microplastics could have on brain function, and what clinicians should tell their patients.

What Are the Major Health Concerns?

The Plastic Health Council estimates that more than 500 million metric tons of plastic are produced worldwide each year. In addition, it reports that plastic products can contain more than 16,000 chemicals, about a quarter of which have been found to be hazardous to human health and the environment. Microplastics and nanoplastics can enter the body through the air, in food, or absorption through the skin.

As previously reported by Medscape Medical News, a study published in March showed that patients with carotid plaques and the presence of microplastics and nanoplastics were at an increased risk for death or major cardiovascular events.

Other studies have shown a link between these substances and placental inflammation and preterm births, reduced male fertility, and endocrine disruption — as well as accelerated spread of cancer cells in the gut.

There is also evidence suggesting that microplastics may facilitate the development of antibiotic resistance in bacteria and could contribute to the rise in food allergies.

And now, Thais Mauad, MD, PhD, and colleagues have found the substances in the brain.

How Is the Brain Affected?

The investigators examined olfactory bulb tissues from 15 deceased Sao Paulo, Brazil, residents ranging in age from 33 to 100 years who underwent routine coroner autopsies. All but three of the participants were men.

Exclusion criteria included having undergone previous neurosurgical interventions. The tissues were analyzed using micro–Fourier transform infrared spectroscopy (µFTIR).

In addition, the researchers practiced a “plastic-free approach” in their analysis, which included using filters and covering glassware and samples with aluminum foil.

Study findings showed microplastics in 8 of the 15 participants — including in the centenarian. In total, there were 16 synthetic polymer particles and fibers detected, with up to four microplastics detected per olfactory bulb. Polypropylene was the most common polymer found (44%), followed by polyamide, nylon, and polyethylene vinyl acetate. These substances are commonly used in a wide range of products, including food packaging, textiles, kitchen utensils, medical devices, and adhesives.

The microplastic particles ranged in length from 5.5 to 26 microns (one millionth of a meter), with a width that ranged from 3 to 25 microns. The mean fiber length and width was 21 and 4 microns, respectively. For comparison, the diameter of one human hair averages about 70 microns, according to the US Food and Drug Administration (FDA).

“To our knowledge, this is the first study in which the presence of microplastics in the human brain was identified and characterized using µFTIR,” the researchers wrote.

How Do Microplastics Reach the Brain?

Although the possibility of microplastics crossing the blood-brain barrier has been questioned, senior investigator Mauad, associate professor in the Department of Pathology, the University of Sao Paulo, Sao Paulo, Brazil, noted that the olfactory pathway could offer an entry route through inhalation of the particles.

This means that “breathing within indoor environments could be a major source of plastic pollution in the brain,” she said in a press release.

“With much smaller nanoplastics entering the body with greater ease, the total level of plastic particles may be much higher. What is worrying is the capacity of such particles to be internalized by cells and alter how our bodies function,” she added.

Mauad told Medscape Medical News that although questions remain regarding the health implications of their findings, some animal studies have shown that the presence of microplastics in the brain is linked to neurotoxic effects, including oxidative stress.

In addition, exposure to particulate matter has been linked previously to such neurologic conditions as dementia and neurodegenerative conditions such as Parkinson’s disease “seem to have a connection with nasal abnormalities as initial symptoms,” the investigators noted.

While the olfactory pathway appears to be a likely route of exposure the researchers noted that other potential entry routes, including through blood circulation, may also be involved.

The research suggests that inhaling microplastics while indoors may be unavoidable, Mauad said, making it unlikely individuals can eliminate exposure to these substances.

“Everything that surrounds us is plastic. So we can’t really get rid of it,” she said.

Are Microplastics Regulated?

The most effective solution would be stricter regulations, Mauad said.

“The industry has chosen to sell many things in plastic, and I think this has to change. We need more policies to decrease plastic production — especially single-use plastic,” she said.

Federal, state, and local regulations for microplastics are “virtually nonexistent,” reported the Interstate Technology and Regulatory Council (ITRC), a state-led coalition that produces documents and trainings related to regulatory issues.

In 2021, the ITRC sent a survey to all US states asking about microplastics regulations. Of the 26 states that responded, only four said they had conducted sampling for microplastics. None of the responders indicated they had established any criteria or standards for microplastics, although eight states indicated they had plans to pursue them in the future.

Although federal regulations include the Microbead-Free Waters Act of 2015 and the Save Our Seas Act 2.0, the rules don’t directly pertain to microplastics.

There are also no regulations currently in place regarding microplastics or nanoplastics in food. A report issued in July by the FDA claimed that “the overall scientific evidence does not demonstrate that levels of microplastics or nanoplastics found in foods pose a risk to human health.”

International efforts to regulate microplastics are much further along. First created in 2022, the treaty would forge an international, legally binding agreement.

While it is a step in the right direction, the Plastic Health Council has cautioned about “the omission of measures in draft provisions that fully address the impact of plastic pollution on human health.” The treaty should reduce plastic production, eliminate single-use plastic items, and call for testing of all chemicals in plastics, the council argues.

The final round of negotiations for the UN Global Plastic Treaty is set for completion before the end of the year.

What Should Clinicians Know?

Much remains unknown about the potential health effects of microplastic exposure. So how can clinicians respond to questions from concerned patients?

“We don’t yet have enough evidence about the plastic particle itself, like those highlighted in the current study — and even more so when it comes to nanoplastics, which are a thousand times smaller,” Phoebe Stapleton, PhD, associated professor in the Department of Pharmacology and Toxicology at the Ernest Mario School of Pharmacy at Rutgers University, Piscataway, New Jersey, told Medscape Medical News.

“But we do have a lot of evidence about the chemicals that are used to make plastics, and we’ve already seen regulation there from the EPA. That’s one conversation that clinicians could have with patients: about those chemicals,” she added.

Stapleton recommended clinicians stay current on the latest research and be ready to respond should a patient raise the issue. She also noted the importance of exercising caution when interpreting these new findings.

While the study is important — especially because it highlights inhalation as a viable route of entry — exposure through the olfactory area is still just a theory and hasn’t yet been fully proven.

In addition, Stapleton wonders whether there are tissues where these substances are not found. A discovery like that “would be really exciting because that means that that tissue has mechanisms protecting it, and maybe, we could learn more about how to keep microplastics out,” she said.

She would also like to see more studies on specific adverse health effects from microplastics in the body.

Mauad agreed.

“That’s the next set of questions: What are the toxicities or lack thereof in those tissues? That will give us more information as it pertains to human health. It doesn’t feel good to know they’re in our tissues, but we still don’t have a real understanding of what they’re doing when they’re there,” she said.

Does your Heart have a "Brain"?

Never to be one that stays in my lane, here’s some obscurity that is not only interesting, but may have real implications down the road.

There’s lots of evidence that says the heart is the heart of everything – that’s why we call it the heart!  Discussions of interactions between heart and brain are fascinating – like why are there many more signals going from the heart to the brain than the other way around?  Is the heart in charge or the brain? 

A  “mini-brain” has been confirmed in the heart of a zebrafish (why a zebrafish?  Turns out it’s closer to a human heart than a mouse heart), and unlike what was previously believed, it functions independently from the brain.  This complex mini-brain can independently effect heart rate, but it’s more than that -- zebrafish neurons are known to produce substances that activate stem cells in bones, skin, and even the nervous system.  How will this information shake out?

Who knows – but I think it’s pretty cool! 

FROM MEDSCAPE / BY Tatum Anderson

The heart’s “mini-brain” is independent and highly localized, according to researchers at the Karolinska Institutet in Stockholm, Sweden. The findings could lead to new research into arrhythmia, dementia, and Parkinson’s disease.

Although controlled by the brain, the heart has a separate, smaller intracardiac nervous system (IcNS) embedded within the superficial layers of the heart wall. Nicknamed the mini-brain by researchers decades ago, the IcNS was assumed to be a simple structure capable only of relaying simple information from the brain to the heart.

The neurons in the mini-brain, however, have been under-researched, said Konstantinos Ampatzis, principal researcher and assistant professor of neuroscience at the Karolinska Institutet. “Cardiologists know that neurons exist but never study them because their first concern is the cardiac muscle cells, or cardiomyocytes, that are responsible for the heartbeat,” he explained. “Neuroscientists understand and decode neurons but don’t know about neurons in the heart.”

Ampatzis’s team mapped the exact composition, organization, and function of neurons in the IcNS using zebrafish as an animal model. “The heart of the zebrafish is closer to that of humans than the mouse heart is,” he explained. “The heart rate of a zebrafish is exactly the same.”

Several techniques were used to characterize these neurons. Electrophysiology determined their function, and researchers at Columbia University in New York City helped identify their molecular signatures using single-cell RNA sequencing. Ampatzis and his team also analyzed neurotransmitters that the neurons release to communicate with each other. Researchers in Sweden and New York worked on this project in their spare time because they had no additional funding.

Ampatzis expected to see ganglions or relay neurons capable only of receiving or sending information. “But we found a very diverse set of neurons in a small network,” he said. Their findings included sympathetic, parasympathetic, and sensory neurons with apparent neurochemical and functional diversity. Most surprising was a subset of pacemaker neurons. “You cannot have a network that produces a rhythm without these neurons, and we didn’t expect exactly that, to be honest,” he said.

Pacemaker neurons are usually associated with so-called central pattern generator networks within the central nervous system. These independent, highly localized neuronal networks generate and control complex rhythmic behaviors such as respiration, mastication, urination, and ejaculation. “Most importantly, we found that this neuronal network works in an isolated heart, without brain information, and can change the rhythm of the heart and the regularity by itself,” said Ampatzis.

Further studies confirmed that neurons do not produce the rhythm, which is controlled by the cardiomyocytes. The neurons’ main function is to regulate the speed of the heartbeat. In other words, this smaller localized network acts as a kind of insurance system to safeguard the brain’s control of the heartbeat. “From an evolutionary perspective, I think that the system is like this because the heartbeat defines life,” Ampatzis added.

With the neurons of the heart mapped, medical researchers now have a toolbox of molecular markers, neurotransmitters, and other information on how such neurons function. These findings could become the basis of new research. It might be possible to investigate heart arrhythmia by modulating pacemaker neurons, Ampatzis suggested. “You could even repurpose or find specific drugs that can interfere with this local network of the heart,” he said, adding that this might be a less invasive option than is possible today.

Arrhythmia affects millions of people, said Oliver Guttmann, MD, a consultant cardiologist at The Wellington Hospital and honorary associate professor of cardiology at University College London, both in London, England. Beta-blockers remain the drug of choice for arrhythmia, but other options can be invasive. “We do ablations to try and burn or freeze certain areas of the heart to get rid of a rhythm because often this comes from hyperactive cells somewhere,” he said. Pacemakers and defibrillators are also needed to modulate dangerous rhythms. Innovation is focusing on making interventions far less invasive than they are today by creating smaller and smaller pacemakers, for example.

Moving from zebrafish to more complex mammalian systems will be the next big step, said David Paterson, DPhil, head of the Department of Physiology, Anatomy, and Genetics and honorary director of Burdon Sanderson Cardiac Science Centre at the University of Oxford, Oxford, England. “If you can find the molecular road map of dysregulation, then that could be a potential target for a gene therapy or cell therapy or for neuromodulation therapy,” he explained. Interest in this field, which is sometimes called bioelectronic medicine, is mounting. “It’s like pharmaceutics, but there’s no drug. You’re tapping into the wiring of the nervous system,” he added.

More radical research pathways might look at ways to tackle neurodegenerative disorders from dementia to Parkinson’s disease. “If neurons die in the brain, then they die in the heart and can affect the rhythm of the heart,” said Ampatzis. But zebrafish neurons are now known to produce substances that induce a proliferation of stem cells in bones, skin, and even the nervous system. “We think those neurons of the heart could perhaps contribute to the regeneration of the heart,” he said.