Scientists identify early signal of dangerous pregnancy complications

Good news! This could be a breakthrough!

"In a study published today [8/31/2026] ... scientists who analyzed blood samples from thousands of pregnant women found that low levels of a protein called ISM2 during the first trimester were associated with higher risk of both preeclampsia and fetal growth restriction later on.

Follow-up lab studies of placental cells showed ISM2 likely plays a causal role in the disorders, meaning the findings could help in the development of treatments, too. ...

The researchers measured blood levels of nearly 3000 proteins and found one in particular associated with both preeclampsia and fetal growth restriction: ISM2, a little-studied protein produced by the placenta. Specifically, lower blood levels of the protein at the 12-week blood test were linked to higher risks of preeclampsia, fetal growth restriction, or both. ...

What’s more, ISM2 levels were a better predictor of each condition than currently used proteins. ...

In lab experiments, the team found that blocking the production of ISM2 in stem cells that usually develop into normal, uterus-invading EVTs stopped that process from happening.

By contrast, artificially adding ISM2 into a cell line that usually lacks it induced recipient cells to migrate around lab dishes more like EVTs would. ..."

"... Both of these conditions are known to be linked to problems with the placenta not developing properly early in pregnancy, in particular a failure of specialised placental cells known as the extravillous trophoblast (EVT) to invade the mother’s womb and establish a healthy blood supply. ...

Of all mammals, humans have the deepest placental invasion, which reflects the massive demands of oxygen and nutrients required to manufacture the most complex machine ever known, the human brain. ..."

From the abstract:

"Preeclampsia and fetal growth restriction (FGR) are major causes of global morbidity and mortality. 

Both conditions are associated with impaired invasion of the uterus by extravillous trophoblast (EVT).

We performed proteomics in maternal serum obtained at ~12 weeks of gestational age in a prospective pregnancy cohort (Pregnancy Outcome Prediction Study). Here we show that low maternal serum isthmin-2 (ISM2) was the strongest protein signal (out of 2,904) in the first trimester of pregnancy for preeclampsia or FGR.

We validated the association in two independent cohorts (Pregnancy Outcome Prediction Study 2 and Improving Maternal Pregnancy And Child ouTcomes study).

ISM2 protein and mRNA are almost exclusively produced in the placenta, and, within the placenta, ISM2 mRNA is highly enriched in EVT. 

Knocking down ISM2 in cultured human trophoblast stem cells profoundly inhibited EVT invasion.

Conversely, expressing ISM2 in a cell line lacking endogenous ISM2 (HEK293 cells) promoted migration.

We conclude that ISM2 may be causally involved in the early pathophysiology of failed trophoblast invasion and that the protein and its associated pathways are potential targets for the prediction and prevention of preeclampsia and FGR."

Scientists identify early signal of dangerous pregnancy complications | Science | AAAS "Low levels of a placenta made protein predict preeclampsia and fetal growth restriction and could offer new target for prevention"

Pre-eclampsia discovery could lead to new test and treatments for at-risk pregnancies (original news release) "Cambridge scientists have identified a key protein that could act as a predictor for pre-eclampsia and fetal growth restriction, two of the major causes of stillbirth and of sickness among mothers and newborns."

Isthmin-2 is a first-trimester predictor of preeclampsia and fetal growth restriction (open access)

Fig. 2: The association between ISM2 and PE and FGR.

Fig. 3: ISM2 regulates EVT differentiation.

New soft, wearable Sleep Monitoring Device Tracks Brain Cleansing at home

Good news!

"... Sleep activates a system only discovered in 2012 that washes out brain waste. Called the glymphatic system, it’s comparable to the better-known lymphatic system that moves and filters fluids throughout your body. A healthy glymphatic system is linked to good cognitive function and could prevent neurodegenerative diseases like Alzheimer’s ...

A new wearable device ... could offer a safer and more sleep-friendly alternative. The technology shines near-infrared light to detect brain water, a soup of the fluids that constantly flood your brain. The brain-water mixture contains cerebrospinal fluid (CSF), which is what the glymphatic system uses to flush out waste particles like plaques that block in-brain communication. ..."

From the abstract:

"Sleep is a critical physiological process essential for overall brain health. Recent research shows that the glymphatic system is a key player in facilitating the metabolic waste clearance. 

However, the continuous real-time monitoring of brain water dynamics during sleep remains substantially challenging.

Here, we introduce a soft, wearable near-infrared spectroscopy (NIRS) system to detect brain water dynamics potentially linked to glymphatic activity. The device features an integration of multi-wavelength LEDs and photodetectors.

The in vivo study with multiple human subjects captures the device’s overnight sleep monitoring in a natural home environment, revealing continuous changes in brain water dynamics across different sleep stages.

Our results support the link between sleep stage-dependent water dynamics and glymphatic activity. Spectral analysis identifies several physiological rhythms during sleep, including respiration, heart rate, and oscillations linked to slow-wave activity. These advancements significantly enhance the NIRS system’s potential for a deeper understanding of brain health."

New Sleep Monitoring Device Tracks Brain Cleansing - IEEE Spectrum "Monitoring the elusive activity of the glymphatic system could aid Alzheimer’s research"

New Soft Wearable Device Could Support At-Home Sleep Monitoring (original news release) "A new Georgia Tech study shows a wireless wearable device could enable home-based monitoring of physiological changes associated with sleep and brain health."

A soft wearable near-infrared spectroscopy system for detecting brain water dynamics linked to glymphatic activity during sleep (open access)

A new device might offer a glimpse at how the brain cleans out waste during sleep.

How Exercise and physical fitness Slows Tumor Growth and progression at all stages of cancer

Good news! Cancer is history (soon)! A sedentary lifestyle and lack of physical fitness is good for cancer growth and progression!

"... In the study, ... team used metabolic tracers in mouse models of breast cancer and melanoma to learn how glucose—a nutrient that tumors use to fuel rapid cell division—is distributed when the body is active. The answer, they found, is that working muscles effectively outcompete tumors for the glucose supply. Because muscle contraction increases glucose uptake, exercise shifts metabolism, causing tumors to receive less of the fuel they need to grow. ..."

From the significance and abstract:

"Significance

It is well established from both preclinical and clinical studies that exercise protects against tumor growth and progression. However, the biomarkers of this beneficial effect are not well delineated. Here, we demonstrate using stable isotope tracer methodology and unbiased metabolomics analyses that aerobic exercise induces glucose repartitioning in rodents with breast cancer and melanoma. We further demonstrate that fitness—which can be measured along a continuum, beyond the binary “exercise/no exercise” paradigm that may not translate well to humans in practice—is a key predictor of tumor metabolism. These data highlight the importance of a nuanced, systemic view of the metabolic effects of exercise in cancer.

Abstract

Higher exercise capacity and regular exercise training improve cancer prognosis at all stages of disease. However, the metabolic adaptations to aerobic exercise training that mediate tumor–host interactions are poorly understood.

Here, we demonstrate that voluntary wheel running slows tumor growth and repartitions glucose uptake and oxidation to skeletal and cardiac muscle and away from breast and melanoma tumors in mice.

Further, prehabilitation induces repartitioning of glucose metabolism in obese mice: Uptake and oxidation of glucose are enhanced in skeletal and cardiac muscle, and reduced in tumors.

These increases in muscle glucose metabolism and reductions in tumor glucose metabolism, correlated with slower tumor progression.

Using [U-13C6] glucose infusion, we show that exercise increases the fractional contribution of glucose to oxidative metabolism in muscle while reducing it in tumors, suggesting that aerobic exercise shifts systemic glucose metabolism away from the tumor microenvironment and toward metabolically active tissues. Transcriptional analysis revealed downregulation of mTOR signaling in tumors from exercised mice.

Collectively, our findings suggest that voluntary exercise may suppress tumor progression by enhancing host tissue glucose oxidation and limiting tumor glucose availability, supporting a model in which exercise-induced metabolic competition constrains tumor energetics."

How Exercise Slows Tumor Growth | Internal Medicine

Precancer exercise capacity and metabolism during tumor development coordinate the skeletal muscle–tumor metabolic competition (no public access)

A 47 years Long-term study reveals physical ability peaks between the ages 19-35 and deteriorates and accelerates afterwards regardless of fitness or physical exercise

Bad news! Previous studies relied on cross-sectional data, while few studies are based on longitudinal data like this one. 

Aging is a bitch! Hopefully, machine learning & AI will finally make a difference in the near future.

"A 47-year study tracking over 400 people found that physical fitness and strength begin declining at age 35, with cardio endurance dropping at 45 for both men and women, regardless of previous workout habits."

"Previously, researchers relied on cross-sectional studies to gain this knowledge. The SPAF study is one of the few that, for nearly 50 years, has regularly measured fitness and strength in the same randomly selected men and women across Sweden. ...

The results show that fitness and strength begin to decline as early as age 35, regardless of training volume. After that, there is a gradual deterioration that accelerates with age. But the researchers also have positive news: individuals who started being physically active in adulthood improved their physical capacity by 5–10 percent. ..."

From the abstract:

"Background:

As we age, there is a progressive decline in skeletal muscle tissue and function that can become clinically significant in the sixth decade of life affecting independent living and health.
Longitudinal observations in elite athletes show that peak physical performance is reached before the age of about 35 years despite continuous training, suggesting that the tissue processes underlying muscle dysfunction may begin decades before they become clinically relevant. To answer the question of whether the pattern of performance decline in athletes also applies to the general population, a population-based longitudinal study is needed.

Methods:

In the Swedish population cohort (SPAF), 427 individuals (48% women) born in 1958 underwent repeated objective assessments of physical capacity from age 16 to 63 years. Linear mixed models were used to estimate age- and sex-specific changes in the original cohort during the study period.

Results:

The estimated maximal aerobic capacity and muscular endurance (bench press repetitions) peaked at ages 26-36 in both sexes and declined gradually, starting at 0.3%-0.6% per year and accelerating to 2.0%-2.5% per year (main effect of age p < 0.001 and sex p < 0.01), with no sex difference in decline rates.

Muscle power was measured using the Sargent jump test, with men having their peak at age 27, and women at age 19.

Group variance in physical performance increased markedly with age, with relative aerobic capacity showing a 25-fold increase, jump height a nearly 5-fold increase, and muscular endurance a threefold increase in variance from adolescence to age 63.

The rate of decline was small initially (0.2%-0.5% per year) but increased with age (2.2% per year), in both sexes (main effect of age p < 0.001 and sex p < 0.001), with no difference between the sexes.

The overall decline in physical capacity from peak to age 63 ranged from 30% to 48%.

Higher leisure-time physical activity at age 16 and becoming active in adulthood were associated with better performance across all outcomes (p = 0.00-0.02); having a university degree was positively associated with absolute aerobic capacity (p = 0.04) and muscular endurance (p = 0.02).

Conclusions:

The Swedish population cohort SPAF shows the same pattern of changes in physical capacity in adulthood as previously demonstrated for elite athletes. This confirms the concept that a decline in physical capacity can be observed before the age of 40, which can later lead to clinically significant physical dysfunction, especially in individuals with a sedentary lifestyle."

Long-term study reveals physical ability peaks at age 35 | Karolinska Institutet "A 47-year-long Swedish study at Karolinska Institutet reveals how fitness, strength, and muscle endurance change during adulthood. The results show that physical ability starts to deteriorate as early as age 35, but it is never too late to start exercising."

Rise and Fall of Physical Capacity in a General Population: A 47-Year Longitudinal Study (no public access)

Credits: The Flyover

Why (and how) being sick often reduces appetite

Amazing stuff!

"Key points

• Many people experience appetite loss when they’re sick.
• Researchers found that mice in similar states displayed a strong aversion to protein-rich food in particular.
• The aversion was linked to ammonia production and a gut-to-brain communication circuit.
• The findings could inform more effective post-illness diets and treatments for anorexia or cancer cachexia.

...

uncovered a gut-to-brain signaling pathway in mice that restricts appetite—specifically for protein—during recovery. ...

Many people experience appetite loss when they’re sick, and with less food intake, their bodies begin breaking down molecules like protein for energy. This is known as a catabolic state and it’s where the researchers started their work.

They offered mice that were in a catabolic state one of three diets that each had the same amounts of calories and micronutrients but different macronutrients: protein, carbohydrates, or fat. The mice given the high-carbohydrate and high-fat diets ate expected amounts, but those given the protein-rich diet ate much less than mice not in a catabolic state.

Through various experimental approaches, Jaschke and colleagues found that mice recovering from catabolic states displayed an exceptionally strong aversion to protein-rich food. ..."

From the highlights and abstract:

"Highlights

• Mice voluntarily restrict dietary protein during recovery from catabolic insults

• Three amino acids (Q, K, and T) are necessary and sufficient for protein aversion

• Gut EC sense dietary ammoniagenesis in a TRPA1-dependent manner

• TRPA1-dependent serotonin release is transduced from the gut to the brain

Summary

Dietary needs are dynamic, with optimal ranges for nutrients varying over time and across physiological states. How optimal nutrient set points are established and why they are adjusted remains largely unknown.

In our efforts to understand the physiology of recovery, we made the surprising observation that mice restrict protein intake at the expense of caloric supply. We identified three amino acids—glutamine (Q), lysine (K), and threonine (T)—within dietary protein, which are necessary and sufficient for protein aversion during recovery from catabolic states.

The anorexigenic effects of QKT are driven by ammoniagenesis in the gut, sensed by enterochromaffin cells in a TRPA1-dependent fashion and transduced to brainstem neurons via serotonin signaling, inducing anorexia. We propose that this mechanism serves as a first-line defense against ammonia toxicity.

In summary, we identified a set of adaptive food preferences during recovery (“recovery behavior”), with implications for understanding diseases of pathologic recovery and the development of therapeutic interventions deployed to enhance recovery."

Gut-to-Brain Signaling Restricts Post-Illness Protein Appetite | Yale School of Medicine

Gut-to-brain signaling restricts dietary protein intake during recovery from catabolic states (no public access)

Graphical abstract

The effects on the brain after sleep deprivation

Amazing stuff! The motto for today: Take care of your cerebrospinal fluid! This is my second blog post today covering cerebrospinal fluid (see here)!

"... A new study ... reveals what happens inside the brain as these momentary failures of attention occur. The scientists found that during these lapses, a wave of cerebrospinal fluid (CSF) flows out of the brain — a process that typically occurs during sleep and helps to wash away waste products that have built up during the day. This flushing is believed to be necessary for maintaining a healthy, normally functioning brain.

When a person is sleep-deprived, it appears that their body attempts to catch up on this cleansing process by initiating pulses of CSF flow. However, this comes at a cost of dramatically impaired attention. ..."

From the abstract:

"Sleep deprivation rapidly disrupts cognitive function and in the long term contributes to neurological disease. Why sleep deprivation has such profound effects on cognition is not well understood.

Here we use simultaneous fast fMRI–EEG to test how sleep deprivation modulates cognitive, neural and fluid dynamics in the human brain.

We demonstrate that attentional failures during wakefulness after sleep deprivation are tightly orchestrated in a series of brain–body changes, including neuronal shifts, pupil constriction and cerebrospinal fluid (CSF) flow pulsations, pointing to a coupled system of fluid dynamics and neuromodulatory state.

CSF flow and hemodynamics are coupled to attentional function within the awake state, with CSF pulsations following attentional impairment. The timing of these dynamics is consistent with a vascular mechanism regulated by neuromodulatory state.

The attentional costs of sleep deprivation may thus reflect an irrepressible need for rest periods driven by a central neuromodulatory system that regulates both neuronal and fluid physiology."

This is your brain without sleep | MIT News | Massachusetts Institute of Technology "New research shows attention lapses due to sleep deprivation coincide with a flushing of fluid from the brain — a process that normally occurs during sleep."

Attentional failures after sleep deprivation are locked to joint neurovascular, pupil and cerebrospinal fluid flow dynamics (open access)

Fig. 1: After sleep deprivation, CSF flow exhibits large sleep-like low-frequency waves during wakefulness.

Dementia linked to problems with brain’s waste clearance system

Recommendable! More evidence how the cerebrospinal fluid is involved.

"A study ... found that impaired movement of cerebrospinal fluid (CSF) – the clear liquid that cushions and cleans the brain – predicted risk of dementia later in life among 40,000 adults recruited to UK Biobank. ...

In the healthy brain, the so-called glymphatic system serves to clear out toxins and waste materials, keeping the brain healthy. Only discovered as recently as 2012, this system functions by flushing CSF through the brain along tiny channels around blood vessels known as perivascular spaces. It collects waste then drains out of the brain, helping keep it clean and healthy. ...

Until recently, it has only been possible to study glymphatic function in mice, but recent advances in MRI scanning have made it possible to study it indirectly in humans. Even so, it was only possible to do this practically in relatively small numbers, but ... developed machine learning algorithms capable of assessing glymphatic functions from MRI scans at scale.

The team applied the algorithm to MRI scans taken from around 40,000 adults in UK Biobank. They found three biomarkers – biological signatures – associated with impaired glymphatic function assessed at baseline, predicted the risk of dementia occurring over the subsequent decade. 

One of these was DTI-ALPS, a measure of the diffusion of water molecules along the perivascular spaces.

Another was the size of the choroid plexus, where the CSF is produced.

The third measure reflected the flow velocity of CSF into the brain. ...

Further analysis showed that several cardiovascular risk factors impaired glymphatic function – and hence increased dementia risk, and that this was partly via causing cerebral small vessel disease, which is visible in the MRI scans. ..."

From the highlights and abstract:

"Highlights

• We developed fully automated methods for quantifying diffusion tensor image analysis along the perivascular space (DTI-ALPS) and blood oxygen level–dependent cerebrospinal fluid (BOLD-CSF) coupling.
• Three CSF dynamics markers—BOLD-CSF coupling, DTI-ALPS, and choroid plexus (CP) volume—were predictive of incident dementia, whereas PVS volume was not.
• Magnetic resonance imaging proxies of CSF dynamics markers were associated with cardiovascular injury. CP volume and DTI-ALPS mediated the associations of both white matter hyperintensities and diabetes with dementia.

INTRODUCTION

Impaired cerebrospinal fluid (CSF) dynamics may contribute to dementia, but human evidence is limited. We examined associations between magnetic resonance imaging–based proxies of CSF dynamics and incident dementia, and whether CSF dysfunction mediates links between cardiovascular risk and dementia.

METHODS

Using the UK Biobank, we measured CSF dynamics:

perivascular space (PVS) volume, diffusion tensor image analysis along the

PVS (DTI-ALPS), blood oxygen level–dependent CSF (BOLD-CSF) coupling, and

choroid plexus (CP) volume.

We assessed cardiovascular risk factors and their associations with CSF dynamics and dementia based on general practitioner, mortality, and hospital records. Mediation analysis evaluated CSF dysfunction in cardiovascular risk–dementia relationships.

RESULTS

Lower DTI-ALPS, lower BOLD-CSF coupling, and higher CP volume predicted dementia, but PVS volume did not. DTI-ALPS and CP volume mediated the effect of white matter hyperintensities and diabetes duration on dementia.

DISCUSSION

Impaired CSF dynamics may lead to dementia and partially mediate cardiovascular risk–dementia associations."

Dementia linked to problems with brain’s waste clearance system | University of Cambridge "Problems with the brain’s waste clearance system could underlie many cases of dementia and help explain why poor sleep patterns and cardiovascular risk factors such as high blood pressure increase the risk of dementia."

MRI markers of cerebrospinal fluid dynamics predict dementia and mediate the impact of cardiovascular risk (open access)

Fig. 1 The illustration of non-invasive MRI proxies of CSF dynamics markers.

Fig. 2 The association of MRI proxies of CSF dynamics with demographics and risk factors.

A fat-storage mystery solved? May improve treatment of obesity.

Amazing stuff! Good news!

"The story scientists have long told about how fat cells function contains a puzzling paradox. An enzyme called hormone-sensitive lipase (HSL) is known to chop up fat stored in these cells, called adipocytes, to release energy. But people who can’t make HSL because of a condition called lipodystrophy don’t store excess fat and aren’t obese—in fact, they struggle to maintain adequate fat levels. HSL, it turns out,  has an unexpected second role. Rather than operating only as an enzyme in the cytoplasm as was originally thought, it also enters the nucleus of an adipocyte and controls its gene activity to maintain the health and structure of fat tissue.

Researchers found that silencing the gene for HSL in cultured human fat cells turned up the genes that drive cells’ tiny energy generators, called mitochondria; it also dialed down genes responsible for building the protein framework that gives fat tissue its structure. The cells also started to look more like fat-burning “beige” adipocytes rather than fat-storing white adipocytes, indicating they had more mitochondria. In experiments with genetically modified mice, the team confirmed that the ability to maintain normal fat stores depends on levels of nuclear, not cytoplasmic HSL.

They also found that obese lab mice tended to have excess HSL in the nucleus of their fat cells, suggesting the protein’s overactivity there could alter fat tissue structure and contribute to obesity. The findings could inform future therapies that focus on restoring fat cell function instead of just shrinking fat stores."

From the highlights and abstract:

"Highlights

• Hormone-sensitive lipase is localized within the nuclei of adipocytes

• In vivo, nuclear HSL levels regulate adipose tissue mass

• In vitro, nuclear HSL controls mitochondria and extracellular matrix gene expression

• HSL nuclear level is regulated by TGF-β and PKA signaling pathways

Summary

In adipocytes, hormone-sensitive lipase (HSL) plays a key role in hydrolyzing triacylglycerols that are stored in lipid droplets. Contrary to the expected phenotype, HSL-deficient mice and humans exhibit lipodystrophy.

Here, we show that HSL is also present in the adipocyte nucleus. Mouse models with different HSL subcellular localizations reveal that nuclear HSL is essential for the maintenance of adipose tissue.

Gene silencing in human adipocytes shows that HSL, independently of its enzymatic activity, exerts opposing effects on mitochondrial oxidative phosphorylation and the extracellular matrix.

Mechanistically, we found that HSL accumulates in the nucleus by interacting with the transforming growth factor β (TGF-β) signaling mediator, mothers against decapentaplegic homolog 3 (SMAD3).

Conversely, HSL phosphorylation induces nuclear export. In vivo, HSL accumulates in the nucleus of adipocytes during high-fat feeding with the converse effect during fasting.

Together, our data show that as both a cytosolic enzyme and a nuclear factor, HSL plays a pivotal role in adipocyte biology and adipose tissue maintenance."

ScienceAdviser

Fat-chomping enzyme that ‘moonlights’ as gene regulator could point to obesity treatments "Hormone-sensitive lipase works in the nucleus to keep fat cells healthy, new study suggests"

Nuclear hormone-sensitive lipase regulates adipose tissue mass and adipocyte metabolism (open access)

Graphical abstract

Breathing through the butt now shown safe and tolerable

Amazing stuff! Good to know! 😊

"... actually serious medical science, researchers in Japan have completed the first human trial of rectal oxygen delivery, bringing us one step closer to an emergency breathing backup system for patients with blocked airways. ..."

From the highlights and abstract:

"Context and significance

Patients with severe respiratory failure often need mechanical ventilation to survive, but these therapies can cause further lung injury. Scientists are exploring a new method called "enteral ventilation" to deliver oxygen through the intestine, which could give the lungs a chance to rest and heal. This study evaluated the safety of this method in humans for the first time, using a special liquid called perfluorodecalin with exceptional oxygen-carrying ability. In a trial with 27 healthy male volunteers, the authors found that administering this liquid rectally was safe and well tolerated. This important safety milestone paves the way for future studies to see if this technique can help patients with respiratory failure.

Highlights

• First-in-human, dose-escalation trial for intrarectal perfluorodecalin (PFD)

• Favorable tolerability profile up to 1,000 mL PFD, with all adverse events being mild

• No detectable systemic absorption of PFD (<1.0 μg/mL)

• Dose-dependent oxygen transfer predicted by pig pharmacokinetic model

Summary

Background

Enteral ventilation is an emerging approach that provides partial systemic oxygenation independent of pulmonary gas exchange, enabling lung rest. Perfluorodecalin, a clinically approved liquid with high oxygen solubility, is a promising vehicle for enteral oxygen delivery. The primary endpoint of this first-in-human trial was to assess the safety and tolerability of intrarectal perfluorodecalin administration.

Methods

This was a phase 1, single-site, open-label, non-controlled, dose-escalation trial in 27 healthy adult males aged 20–45 years. Participants received a single intrarectal dose of non-oxygenated perfluorodecalin (escalating from 25 to 1,500 mL) retained for 60 min. Safety and tolerability were assessed through monitoring of adverse events, vital signs, clinical laboratory tests, and systemic perfluorodecalin exposure. A pharmacokinetic model using large-animal data was employed to predict potential oxygen transfer.

Findings

No serious adverse events or dose-limiting toxicities occurred. Mild gastrointestinal symptoms, such as abdominal bloating and pain, were transient, dose dependent, and resolved without intervention. All clinical laboratory parameters, including liver and renal function markers, remained within normal limits. Perfluorodecalin concentrations were undetectable in blood (<1.0 μg/mL). The pharmacokinetic model predicted a dose-dependent oxygenation effect, consistent with a modest increase in peripheral oxygen saturation observed in the higher-dose group.

Conclusions

This first-in-human study demonstrates that intrarectal administration of non-oxygenated perfluorodecalin is safe, feasible, and well tolerated. These findings establish a critical safety foundation and support the continued development of enteral ventilation with fully oxygenated perfluorodecalin as an adjunctive strategy to support respiratory failure patients."

Thursday, October 23, 2025 - Join The Flyover

Human Trials Bring Us Closer to Breathing Through Our Butts

Safety and tolerability of intrarectal perfluorodecalin for enteral ventilation in a first-in-human trial (no public access)

South Korea’s Deep-Sea Diving (including pregnant) Women Show Genetic Traits for Cold Water Endurance

Amazing stuff! Genetics influences phenotype and vice versa. Some of these women appear to be working until high age (see photo below).

"Just off South Korea’s southern coast lies Jeju Island, home to a community of women divers known as Haenyeo, or “women of the sea.” These women are trained at a young age in free diving into the frigid sea to harvest shellfish, even while pregnant. As Tibetans adapted to high altitudes and Bajau divers developed underwater endurance, researchers wondered if generations of diving shaped Haenyeo physiology through training, genetics, or both. ...

a team of researchers found two gene variants associated with cold tolerance and decreased blood pressure that likely aid Haenyeo while diving. ..."

"Highlights

• Evidence of selection that may increase the safety of diving during pregnancy

• Regular diving increases the magnitude of bradycardia in response to dive stimulus

• The Haenyeo may represent the second known population evolved for diving

Summary

Natural selection and relative isolation have shaped the genetics and physiology of unique human populations from Greenland to Tibet.

Another such population is the Haenyeo, the all-female Korean divers renowned for their remarkable diving abilities in frigid waters. Apnea diving induces considerable physiological strain, particularly in females diving throughout pregnancy.

In this study, we explore the hypothesis that breath-hold diving has shaped physiological and genetic traits in the Haenyeo. We identified pronounced bradycardia during diving, a likely training effect.

We paired natural selection and genetic association analyses to investigate adaptive genetic variation that may mitigate the effects of diving on pregnancy through an associated reduction of diastolic blood pressure.

Finally, we identified positively selected variation in a gene previously associated with cold water tolerance, which may contribute to reduced hypothermia susceptibility. These findings highlight the importance of traditional diving populations for understanding genetic and physiological adaptation."

Korea’s Deep-Sea Diving Women Show Genetic Traits for Cold Water Endurance | The Scientist "Nature and nurture give Korea’s women divers, known as Haenyeo, an edge in deep-sea diving with high cold tolerance and low blood pressure."

Genetic and training adaptations in the Haenyeo divers of Jeju, Korea (open access)

Graphical abstract

Jung Sun-ja, 84, Yoon Yeon-ok, 74, and Ko Keum-sun, 69, pose after working in the sea in Busan, South Korea

The surprising reason we blink so much more than we need to

Amazing stuff! In a blink of an eye gets a whole new meaning! 😊

"... on average humans blink up to 20 times every minute, or almost 20,000 times a day. Although each blink only lasts between 0.1 and 0.4 seconds, that adds up to around [3% to ]8% of our waking hours spent walking around with our eyes closed. ...

The scientists found that the rapid motion of the eyelid during a blink changes the light patterns that stimulate the retina, sending a different type of visual signal to the brain than the kind sent when our eyes are open and focused on something. In practice, blinking helps people take in the “big picture” of a scene, and notice large-scale, slowly changing patterns. ..."

From the significance and abstract:

"Significance

Humans spend a remarkable fraction of their awake time while blinking. Here, we show that eye blinks are not simply a mechanism for refreshing the tear film but act as an information processing stage. By modulating the visual input to the retina, blinks effectively reformat spatial information in the temporal domain, yielding luminance signals that emphasize low-resolution information about the global structure of the visual scene. We show that human observers benefit from these transients and that this perceptual enhancement occurs independently from motor signals associated with blinks. Thus, contrary to common assumption, blinks facilitate—rather than disrupt—visual processing, amply compensating for the loss in stimulus exposure.

Abstract

... However, blinks also provide luminance transients rich in spatial information to neural pathways highly sensitive to temporal changes. Here, we report that the luminance modulations from blinks enhance visual sensitivity. By coupling high-resolution eye tracking in human observers with modeling of blink transients and spectral analysis of visual input signals, we show that blinking increases the power of retinal stimulation and that this effect significantly enhances visibility despite the time lost in exposure to the external scene. We further show that, as predicted from the spectral content of input signals, this enhancement is selective for stimuli at low spatial frequencies and occurs irrespective of whether the luminance transients are actively generated or passively experienced. These findings indicate that, like eye movements, blinking acts as a computational component of a visual processing strategy that uses motor behavior to reformat spatial information into the temporal domain."

The surprising reason we blink so much more than we need to

Why do we blink so much? (original news release) Researchers find that blinking plays a pivotal role in processing visual information—adding to a growing body of evidence revising our conventional views of vision.

Eye blinks as a visual processing stage (no public access)

IN PLAIN SIGHT: Owen Tu ’25 demonstrates the apparatus used to track eye movements in the lab of brain and cognitive scientist Michele Rucci.

SEEING THE BIG PICTURE: The researchers tracked eye movements in human observers and combined the data with computer models and spectral analysis. They found that blinks emphasize low spatial frequency (SF)—the overall big picture of a scene—and play an important role in allowing the brain to process visual information.

This Incredible Color-Changing Fish Can 'See' With Its Skin

Amazing stuff! How does a color changing fish, which adopts to the environment, know its current colors?

"... To do this the hogfish rely on pigment filled cells called chromatophores, like other animals that use dynamic skin color from octopus to chameleons.

Pigments within these cells huddle close together to allow the white flesh below to shine through. But as various combinations of the red, yellow or black pigments spread out, the surface level cells transform in hue and shade. ...
Research on another fish, the Nile tilapia (Oreochromis niloticus), found light sensitive molecules called opsins can influence chromatophore color. ...

They tracked down the opsin molecules to cells directly beneath the fish's chromatophores. These newly discovered opsin-producing cells are most sensitive to the short, blue wavelengths that can pass through the chromatophores. What's more, the light levels vary the amount of opsin released. ..."

From the abstract:

"Dynamic color change has evolved multiple times, with a physiological basis that has been repeatedly linked to dermal photoreception via the study of excised skin preparations. Despite the widespread prevalence of dermal photoreception, both its physiology and its function in regulating color change remain poorly understood. By examining the morphology, physiology, and optics of dermal photoreception in hogfish (Lachnolaimus maximus), we describe a cellular mechanism in which chromatophore pigment activity (i.e., dispersion and aggregation) alters the transmitted light striking SWS1 receptors in the skin. When dispersed, chromatophore pigment selectively absorbs the short-wavelength light required to activate the skin’s SWS1 opsin, which we localized to a morphologically specialized population of putative dermal photoreceptors. As SWS1 is nested beneath chromatophores and thus subject to light changes from pigment activity, one possible function of dermal photoreception in hogfish is to monitor chromatophores to detect information about color change performance. This framework of sensory feedback provides insight into the significance of dermal photoreception among color-changing animals."

This Incredible Color-Changing Fish Can 'See' With Its Skin : ScienceAlert As if changing color isn't impressive enough, hogfish can 'see' with their skin too. A new US study suggests this bizarre form of visualization is how the reef fish detect their own colors.

Dynamic light filtering over dermal opsin as a sensory feedback system in fish color change (open access)

Fig. 1: Dynamic color change of hogfish (Lachnolaimus maximus).

Electrophysiology: The Skin Battery

Recommendable! A nice overview article about the electrophysiology of the skin!

The Skin Battery | The Scientist Magazine® The “wound current” has intrigued scientists for more than a century. It could turn out to be the key to healing catastrophic injuries.

Gene variant gives mice super-powered tendons for jumping and running

Amazing stuff! When will it be available for humans? Why are some sprinters so much better than others (it is not the skin color)!

The PIEZO1 is apparently also involved with the mechanical itch.

"... have discovered a genetic mutation that gives tendons the ability to store more energy, letting mice jump higher and reach faster speeds than usual ... Preliminary data on humans suggests that the gene variant, which is in a sensor protein known as PIEZO1, might play a similar role in people. ...
potential to be a therapeutic target for treating age-related declines in physical performance ...
Mice with the genetic change in all their cells, or in tendons alone, could jump about one and a half times further than other mice. ... could reach higher top speeds. ...
Among 91 Jamaican sprinters in the Athlome database, 46% had one copy of PIEZO1 with the tendon-impacting mutation and 8% had two copies of the mutation. Among Jamaican students who had not competed in track events, 31% had one version of the mutation and only 2% had two copies. Data on Greek athletes showed similar trends, with 3 to 5 times more sprinters having two copies of the mutation than controls, and 1.3 to 1.75 times more sprinters having one copy of the mutation compared to controls. ..."

From the abstract:

"How mechanical stress affects physical performance via tendons is not fully understood. Piezo1 is a mechanosensitive ion channel, and E756del PIEZO1 was recently found as a gain-of-function variant that is common in individuals of African descent. We generated tendon-specific knock-in mice using R2482H Piezo1, a mouse gain-of-function variant, and found that they had higher jumping abilities and faster running speeds than wild-type or muscle-specific knock-in mice. These phenotypes were associated with enhanced tendon anabolism via an increase in tendon-specific transcription factors, Mohawk and Scleraxis, but there was no evidence of changes in muscle. Biomechanical analysis showed that the tendons of R2482H Piezo1 mice were more compliant and stored more elastic energy, consistent with the enhancement of jumping ability. These phenotypes were replicated in mice with tendon-specific R2482H Piezo1 replacement after tendon maturation, indicating that PIEZO1 could be a target for promoting physical performance by enhancing function in mature tendon. The frequency of E756del PIEZO1 was higher in sprinters than in population-matched nonathletic controls in a small Jamaican cohort, suggesting a similar function in humans. Together, this human and mouse genetic and physiological evidence revealed a critical function of tendons in physical performance, which is tightly and robustly regulated by PIEZO1 in tenocytes."

Gene variant gives mice super-powered tendons for jumping and running | Scripps Research Scripps Research scientists discovered that a mutation in the touch-sensitive PIEZO1 ion channel impacts tendon biology and boosts the physical performance of mice.

The mechanosensitive ion channel PIEZO1 is expressed in tendons and regulates physical performance (no public access)

Food scientists create zinc index for human body

Good news!

"... The human body needs zinc to boost immunity, regulate metabolism and to help heal wounds, but more than 1 billion people – or about 17% of the global population – suffer from dietary zinc deficiency. ...
“Because of the complexity and sophistication of zinc metabolism, it is very difficult to accurately measure zinc status.” ..."

From the abstract:

"... Widely used biomarkers of Zn status include plasma, whole blood, and urine Zn, which decrease in severe Zn deficiency; however, accurate assessment of Zn status, especially in mild to moderate deficiency, is difficult, as studies with these biomarkers are often contradictory and inconsistent. Thus, sensitive and specific biological markers of Zn physiological status are still needed. In this communication, we provide the Zn status index (ZSI) concept, which consists of a three-pillar formula: (1) the LA:DGLA ratio, (2) mRNA gene expression of Zn-related proteins, and (3) gut microbiome profiling to provide a clear assessment of Zn physiological status and degree of Zn deficiency with respect to assessing dietary Zn manipulation. ..."

Food scientists create zinc index for human body | Cornell Chronicle

Zinc Status Index (ZSI) for Quantification of Zinc Physiological Status (no public access)

Scientists confirm universal law of Peripheral Sensory Adaptation Response

Amazing stuff! An interesting meta study!

"... The findings are based on data from hundreds of unrelated independent studies, which used different methods and were performed across different time periods spanning decades. Although this is by no means absolute proof, the unified nature of this research strengthens the notion that all things process stimuli according to a universal law. ..."

From the abstract:

"Measurements of the peripheral sensory adaptation response were compared to a simple mathematical relationship involving the spontaneous, peak, and steady-state activities. This relationship is based on the geometric mean and is found to be obeyed to good approximation in peripheral sensory units showing a sustained response to prolonged stimulation. From an extensive review of past studies, the geometric mean relationship is shown to be independent of modality and is satisfied in a wide range of animal species. The consilience of evidence, from nearly 100 years of experiments beginning with the work of Edgar Adrian, suggests that this is a fundamental result of neurophysiology."

Scientists find universal law of nature that may govern all living things

Consilience in the Peripheral Sensory Adaptation Response

Figure 1. Peripheral sensory adaptation curve. An idealized sensory adaptation response showing steady-state spontaneous rate (SR) prior to introduction of stimulus, the peak response to the stimulus (PR), and the subsequent new steady-state response (SS).