#mitochondrial function

[blueoaknx]

Reclaim Vitality: The Science Behind Mitochondrial Biogenesis

Mitochondrial biogenesis is the cellular process of increasing the number of mitochondria, the organelles responsible for generating energy. This process is essential for maintaining cellular health and vitality, particularly in tissues with high energy demands, such as muscles. Mitochondrial biogenesis is often triggered by increased energy demand, usually resulting from exercise, caloric restriction, or the intake of specific nutrients.

Mitochondria are the energy producers of the cell, generating ATP, the energy currency of the cell, through oxidative phosphorylation. As cells face greater energy demands, they need more mitochondria to meet these requirements efficiently. The increase in mitochondrial numbers allows cells to produce more energy and better adapt to stress, thus enhancing overall health, recovery, and performance.

Key Factors Involved in Mitochondrial Biogenesis

Several molecular regulators drive mitochondrial biogenesis, with the most important being:

PGC-1α ActivationPGC-1α (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha) is recognized as the master regulator of mitochondrial biogenesis. This protein plays a pivotal role in controlling the transcription of nuclear genes that encode mitochondrial proteins. When activated by external stimuli like exercise, PGC-1α interacts with transcription factors like NRF-1 and NRF-2 to drive the production of new mitochondria. This results in increased mitochondrial DNA (mtDNA) replication and the synthesis of mitochondrial proteins necessary for energy production and cellular respiration.

AMPK & SirtuinsAMPK (AMP-activated protein kinase) is another critical regulator that responds to low energy levels within the cell (a high AMP ratio). It activates PGC-1α, which, in turn, increases the number of mitochondria. AMPK is activated during energy-demanding activities such as endurance exercise and fasting. Sirtuins (SIRT1) are a class of NAD+-dependent enzymes that also regulate mitochondrial biogenesis. Sirtuins, especially SIRT1, deacetylate PGC-1α, further activating it to promote the transcription of mitochondrial genes. Both AMPK and sirtuins respond to energy deprivation, whether through physical exertion or caloric restriction, helping cells increase energy efficiency and prolong cellular longevity.

Antioxidant Defense and Cellular ResilienceOne of the benefits of mitochondrial biogenesis is the enhancement of cellular resilience through improved antioxidant defences. Mitochondria are not only energy producers but also sources of reactive oxygen species (ROS), which can damage cells if not adequately managed. By increasing the number of healthy mitochondria, cells improve their ability to manage oxidative stress. New mitochondria are typically more efficient at energy production and less likely to produce excess ROS, reducing overall cellular damage. This process helps to protect cells from age-related decline and stress-induced damage.

How Mitochondrial Biogenesis Impacts Health and Performance

Mitochondrial biogenesis is essential for maintaining optimal energy production, particularly during periods of increased physical activity or stress. In muscle cells, the increased number of mitochondria leads to improved ATP generation, enhancing endurance and reducing fatigue during prolonged exercise. This is particularly important for athletes or individuals who engage in regular physical activity, as their muscles require a constant supply of energy for performance and recovery.

For general health, mitochondrial biogenesis supports metabolic efficiency and longevity. In metabolic disorders like type 2 diabetes and obesity, mitochondrial dysfunction often results in impaired energy metabolism and increased oxidative stress. By promoting mitochondrial biogenesis, cells can restore normal mitochondrial function, improving insulin sensitivity and energy balance. Furthermore, mitochondrial biogenesis may help reduce the risk of chronic diseases related to ageing by maintaining cellular energy production and reducing oxidative stress.

Beyond exercise and metabolic health, mitochondrial biogenesis is also a key factor in the body’s ability to adapt to various stressors, whether environmental or nutritional. The increase in mitochondrial capacity allows cells to better handle changes in energy demand, supporting recovery and cellular adaptation. For instance, during periods of caloric restriction, mitochondrial biogenesis helps the body use energy more efficiently, contributing to longer-term health benefits, including improved longevity and resistance to age-related diseases.

Supporting Mitochondrial Biogenesis with Nutraceuticals

In addition to lifestyle factors like exercise and caloric restriction, certain nutraceuticals can support mitochondrial biogenesis. Mitokatlyst™-E is one such product that targets mitochondrial function, optimising energy production, and promoting muscle recovery. By stimulating the molecular pathways involved in mitochondrial biogenesis, such products can enhance the body’s ability to adapt to stress, recover more efficiently, and improve overall cellular function.

Conclusion

Mitochondrial biogenesis is a vital process that supports energy production, cellular health, and adaptability to environmental and physical stressors. By regulating pathways such as PGC-1α, AMPK, and sirtuins, cells can increase mitochondrial content to meet higher energy demands, promote muscle recovery, and improve overall vitality. Products like Mitokatlyst™-E are designed to optimise mitochondrial function, helping the body adapt to stress and maintain optimal cellular health. By supporting mitochondrial biogenesis, we can improve energy efficiency, enhance physical performance, and promote long-term health and resilience.

[mehmetyildizmelbourne-blog]

Boosting Mitochondrial Health: How to Tame Chronic Inflammation with DAMPs Know-How

Exploring Mitochondrial Damage Signals and Practical Steps to Reduce Inflammation for Optimal Cellular Health I talk a lot about Mitochondria, as they matter. Every cell needs them, and their dysfunction is associated with all metabolic diseases, cancers, and neurodegenerative disorders. They are extra critical for energy organs like the brain and the heart. So, if our mitochondria malfunction,…

[haggishlyhagging]

Because I feel that I am a woman, therefore you must treat me as if I actually am, otherwise you are transphobic. As I insist on participating as a woman in your groups, gatherings, or spaces you also must forgo discussing anything about your female socialization, female anatomy, or female functions because it hurts my feelings. It hurts my feelings because I was neither socialized as a girl nor am I capable of experiencing what the female body experiences from cradle to grave. But if you speak about this I am then reminded that I am not female, and therefore not really a woman. My experience of feeling like a woman must not be invalidated by your experiences of being a woman, therefore I will shame you for being female, teach you in university to estrange your body from your mind, make your distinct physicality and oppression that is specific to your sex irrelevant in the laws of the land or anything that names our differences until there is only the mind. Now only how I think about your body is real. Mind over body. Mind over matter. Spirit over matter/mater/mother. A woman is anyone who says they are a woman. My word is now more real than your mitochondrial DNA. Accept that by my word, you really don't exist.

-Ruth Barrett, “Gyn-ocide Revisited” in Female Erasure

[mindblowingscience]

Researchers at the Department of Cell and Molecular Biology, Karolinska Institutet have made a major discovery in how human cells produce energy. Their study, published in The EMBO Journal, reveals the detailed mechanisms of how mitochondria process transfer RNA (tRNA) molecules, which are essential for energy production. Mitochondria need properly processed tRNAs to make proteins for energy. Problems in tRNA processing can lead to serious mitochondrial diseases. Until now, the exact process of tRNA maturation in mitochondria was not well understood. "Our study reveals, at a molecular level, how the mitochondrial RNase Z complex recognizes and processes tRNA molecules," said Genís Valentín Gesé, the first author of the study. "By using advanced cryo-electron microscopy, we've been able to visualize the complex in action, capturing snapshots of tRNA at different stages of maturation. This is a significant step forward in understanding how our cells produce energy and maintain healthy function."

Continue Reading.

[transmutationisms]

these tags annoyed me to be honest

1. PCOS is a bad point of comparison because despite the name, diagnosis is not *supposed to be* done on the primary basis of finding cysts in the ovaries; these are common and not inherently of concern. instead, the more indicative biomarker is the hormone test (high levels of testosterone *throughout the menstrual period*, with corresponding disruption to the expected/typical fluctuations in estrogen/progesterone) but often diagnosis is done more on the basis of a physical exam ('exam') confirming characteristics such as hairiness or adiposity. this absolutely DOES result in PCOS overdiagnosis for some demographics; while a real biological condition, PCOS is also a load-bearing diagnostic term in the enforcement of very specific standards of (white) femininity and its use also frequently masks, for example, the frequency of hypothalamic amenorrhea (HA) secondary to chronic energy deficiency (as in anorexia), which doctors are loathe to diagnose because they view weight loss as prima facie good

2. the reason it matters that psychiatric diagnoses do not have a 'biology' is not because every disease must have a single specific biomarker; it is correct that some do not. however, the way patient complaints are sifted into categories labelled 'psychiatric' versus '(otherwise) medical' begins essentially with determining whether the distress is 'physical' or 'mental'. in other words, in the case of, say, the chronic fatigue syndrome (famously, lacking a known specific biomarker), the symptoms being investigated by the non-psychiatrist physician are still physical (PEM; mast cell dysregulation; pain; etc) whereas a diagnosis of depression may be accompanied by, but requires no, physical symptoms or presentation. the psychiatric claim that its diagnoses have biological causes and correlates is specifically a claim about the role of neurobiology in the causation of affective states; thus, the comparison to physical complaints is meaningless here

3. this person goes on to claim that depressives do in fact share, though not universally, certain biomarkers such as mitochondrial dysregulations. such claims typically come from various imaging studies plagued with systemic problems in the selection and definition of patient populations as well as the subjectivity of result interpretation and analysis. these claims are not well supported and typically rely on circular selection and definition of patient populations

4. speaking philosophically, it is in fact often correct to challenge the notion that a physical 'disease' chronically lacking a specific biomarker is indeed a disease, in any sense besides the colloquial one. that is, diseases that cannot be correlated with one cause or presentation are often better understood as 'syndromes', which is to say, as a taxonomical heuristic that is likely grouping together multiple disparate physical (anatomical, physiological, functional, &c) problems with multiple disparate causes. this is almost certainly the case for chronic fatigue syndrome, for example. this is a philosophical distinction that matters for research and understanding, and does not mean or imply anything to minimise or contradict the patient experience of the syndrome or symptoms. it matters because, for instance, CFS triggered by the epstein-barr virus may indeed turn out to have different disease mechanisms to CFS triggered by, say, covid-19, or may have different specific mechanisms when running in certain families, and so on. distinguishing these much more specific presentations, and possibly distinct diseases, from the current discursive schema of the overlying syndrome is potentially very good for patients, who likely have different needs and treatments to one another despite currently all sharing the same label in their charts

5. which goes back to an overlying point, which is that (despite frequent defensiveness to the contrary), whether or not something is a disease does not inherently tell us anything about its reality, its severity, its cause, the moral status of its sufferers, &c

[foxgirlinfohazard]

new fetish: mitochondrial vore. the prey is eaten by the pred and instead of being digested they add a useful function to the pred while being trapped inside them

[willowreader]

Excellent article from a scientist who does great research and has her own lab.

[transgenderer]

So I'm birds the heterogamous sex is the female, males have ZZ chromosomes and females have ZW chromosomes. Some of the key respiratory proteins are on the Z chromosome, so all the genes for them come from the father, but the mitochondria come from the mother. Therefore, the mother must be unusually selective in mates, if she picks a mate with bad respiratory proteins, or proteins that don't match her mitochondria, her female offspring will all die. And it seems this might explain bright plumage in male birds! Plumage patterns are sensitive to differences between groups, signalling mismatch, and it turns out bright red color reflects mitochondria functionality!

[covid-safer-hotties]

Also preserved in our archive

From August 2023

By Mary Van Beusekom, MS

The COVID-19 International Research Team (COV-IRT) and the Children's Hospital of Philadelphia (CHOP) report that they have identified abnormal mitochondrial function in the heart, kidneys, and liver after SARS-CoV-2 infection, which leads to long-term damage and may help explain long COVID.

Mitochondria are the so-called "powerhouses" of cells, and the researchers noted that previous studies have shown that SARS-CoV-2 proteins can bind to mitochondrial proteins in host cells, possibly leading to dysregulation.

The team analyzed mitochondrial gene expression in tissues from COVID-19 patients' nose and throat, along with tissues from deceased patients and hamsters and mice. The results were published today in Science Translational Medicine.

"The tissue samples from human patients allowed us to look at how mitochondrial gene expression was affected at the onset and end of disease progression, while animal models allowed us to fill in the blanks and look at the progression of gene expression differences over time," first author Joseph Guarnieri, PhD, a postdoctoral research at CHOP, said in a hospital news release.

Research identifies potential therapeutic target In autopsy tissue, mitochondrial gene expression had recovered in the lungs, but not in the heart, kidneys, and liver. The rodent tissue and measurement of the time of peak viral load in the lungs showed that mitochondrial gene expression was suppressed in the cerebellum, even though SARS-CoV-2 wasn't found in the brain. The cerebellum coordinates and regulates muscle activity.

Other animal models showed signs of recovery of mitochondrial function in the lungs during the mid-phase of COVID-19 infection.

Co-senior author Douglas Wallace, PhD, of CHOP, said that the study offers strong evidence that COVID-19 is a systemic disease that affects multiple organs rather than strictly an upper respiratory illness. "The continued dysfunction we observed in organs other than the lungs suggests that mitochondrial dysfunction could be causing long-term damage to the internal organs of these patients," he said in the release.

The results also identified a potential therapeutic target, microRNA 2392, which was shown to regulate mitochondrial function in the human tissue samples, said co-senior author Afshin Beheshti, PhD, president of COV-IRT and a visiting researcher at the Broad Institute.

"This microRNA was upregulated in the blood of patients infected by SARS-CoV-2, which is not something we normally would expect to see," he said. "Neutralizing this microRNA might be able to impede the replication of the virus, providing an additional therapeutic option for patients who are at risk for more serious complications related to the disease."

The researchers said they will use these data to conduct future studies on how systemic immune and inflammatory responses may lead to more severe illness in some patients.

Study link: www.science.org/doi/10.1126/scitranslmed.abq1533

[tulipscomeinallsortsofcolors]

so what im getting is that trudi is the most emotionally competent and functional person in this family for Multiple generations. love that for her honestly she deserves it

toby's genes were enough to produce one (1) half-chill person but could not stand up to gretas mitochondrial DNA any longer than that

[blueoaknx]

Salugenesis in Mitochondria: Enhancing Cellular Health and Energy Production

The field of salugenesis—focused on promoting natural healing and optimizing health—finds a particularly vital area of application in mitochondrial function. Mitochondria, known as the powerhouses of the cell, generate the energy required for cellular processes through oxidative phosphorylation. As such, they are fundamental to cellular health and play a critical role in the body’s capacity to repair, maintain balance, and regenerate. Salugenesis in mitochondria involves optimizing mitochondrial function, enhancing bioenergetics, and addressing cellular aging and disease, with the ultimate aim of boosting cellular resilience and overall health.

Mitochondria’s Role in Salugenesis: The Cellular Powerhouse and Beyond

Mitochondria are essential not only for energy production but also for regulating metabolic homeostasis, immune response, and apoptosis (programmed cell death). Given their central role, mitochondria are a key target in salugenesis, with a focus on:

ATP Production and Energy: Mitochondria generate ATP through oxidative phosphorylation (OXPHOS), which fuels cellular functions. Salugenic approaches aim to support and enhance ATP production to increase cellular energy levels.

ROS and Oxidative Stress: Mitochondria produce reactive oxygen species (ROS) as byproducts of energy production. While ROS are part of normal cell signaling, excessive levels can lead to oxidative damage. Salugenesis aims to manage ROS production, supporting mitochondrial health without triggering oxidative damage.

Mitochondrial Biogenesis: This is the process by which new mitochondria are formed. Encouraging mitochondrial biogenesis is a key aspect of salugenesis, as more mitochondria enhance cellular energy output and resilience to stress.

Apoptosis and Cellular Repair: Mitochondria regulate apoptosis, a process critical to removing damaged or dysfunctional cells. By supporting efficient cellular turnover, salugenesis in mitochondria contributes to overall tissue health.

Mechanisms of Salugenesis in Mitochondria

Salugenesis in mitochondria can be achieved by targeting several key cellular and molecular mechanisms:

Mitochondrial Biogenesis Pathways: Stimulating mitochondrial biogenesis through pathways like PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) helps increase mitochondrial numbers. Salugenesis promotes biogenesis through interventions such as exercise, caloric restriction, and compounds like resveratrol and NAD+ boosters.

Mitophagy and Autophagy: Mitophagy is the process by which damaged mitochondria are selectively degraded, allowing the cell to maintain a healthy pool of mitochondria. Autophagy can be activated by fasting, certain types of exercise, and compounds that stimulate cellular cleanup. Salugenic approaches aim to enhance mitophagy, thus preventing the buildup of dysfunctional mitochondria.

Support of Mitochondrial Membrane Potential: The inner mitochondrial membrane’s electrochemical gradient, essential for ATP production, is maintained through optimal function of electron transport chain (ETC) complexes. Salugenesis supports membrane integrity with nutrient-rich diets, antioxidant supplements, and healthy lifestyle habits to maintain efficient ATP synthesis.

Nutritional Support for Mitochondria: Certain nutrients and cofactors are integral to mitochondrial function. Coenzyme Q10 (CoQ10), L-carnitine, alpha-lipoic acid, and B vitamins are essential for energy production. Salugenesis recommends incorporating these nutrients through diet or supplementation to maintain optimal mitochondrial health.

Hormesis and Controlled Stressors: Mild stressors, like heat, cold exposure, and intermittent fasting, activate mitochondrial biogenesis and increase resilience. These hormetic stressors are central to salugenesis, as they encourage mitochondria to adapt, thereby enhancing cellular health and longevity.

Practical Applications: Salugenic Interventions for Mitochondrial Health

Exercise: Physical activity, particularly endurance and resistance training, stimulates mitochondrial biogenesis and enhances ATP production. Exercise-induced PGC-1α activation supports energy production and cellular repair.

Dietary Interventions: Diets rich in antioxidants (such as vitamins C and E), polyphenols (e.g., resveratrol), and omega-3 fatty acids help protect mitochondria from oxidative damage. Caloric restriction and intermittent fasting have also been shown to stimulate mitochondrial biogenesis.

Supplementation: NAD+ boosters (like nicotinamide riboside), CoQ10, alpha-lipoic acid, and L-carnitine directly support mitochondrial energy metabolism and reduce oxidative stress.

Red and Near-Infrared Light Therapy: Photobiomodulation, using red or near-infrared light, penetrates cells to stimulate mitochondrial ATP production and improve cellular function, aiding in tissue repair and energy production.

Hormetic Stress Therapies: Cold therapy (cryotherapy) and sauna therapy activate stress-response pathways in mitochondria, encouraging adaptations that improve cellular health and resilience.

Mitochondrial Dysfunction and Implications for Health

Mitochondrial dysfunction is associated with numerous age-related and chronic diseases, including neurodegenerative conditions (e.g., Parkinson’s and Alzheimer’s), cardiovascular disease, and metabolic disorders. Dysfunctional mitochondria lead to reduced ATP production, increased ROS production, and compromised cellular integrity. Salugenic interventions target mitochondrial health to address or prevent these conditions by supporting mitochondrial efficiency and reducing cellular stress.

Salugenesis in Mitochondrial Research and Future Directions

Research in salugenesis and mitochondria continues to advance, with a focus on uncovering precise mechanisms by which mitochondrial function can be optimised. Future directions include:

Mitochondrial Medicine: Developing therapies specifically targeting mitochondrial pathways, such as pharmacological agents that mimic the effects of caloric restriction, NAD+ supplementation, and mitochondrial transplantation.

Gene Therapy: Exploring genetic interventions to enhance mitochondrial function, targeting nuclear and mitochondrial genes associated with energy production, ROS management, and mitophagy.

Precision Mitochondrial Care: Personalized approaches using genetic and metabolic profiling to determine the most effective interventions for optimizing mitochondrial health on an individual basis.

Anti-Aging Research: Extending mitochondrial health could play a significant role in anti-aging, slowing cellular senescence, and enhancing tissue repair.

Conclusion

Salugenesis in mitochondria offers an innovative approach to health by focusing on cellular energy, repair, and resilience. By supporting mitochondrial biogenesis, enhancing antioxidant defenses, and promoting optimal mitochondrial dynamics, salugenesis paves the way for improved health, longevity, and disease resistance. As research continues to shed light on the dynamic relationship between mitochondria and overall health, salugenic practices may become essential components in preventive medicine and longevity science.

[mehmetyildizmelbourne-blog]

How Does Ketosis Impact Mitochondrial Health?

An overview of mitochondrial bioenergetics activation with practical tips Ketosis can induce changes in metabolism, leading to increased production of ketone bodies, such as beta-hydroxybutyrate, acetoacetate, and acetone. These ketone bodies can serve as alternative energy substrates for cells, particularly in tissues or organs with high energy demands, such as the brain. Ketones are…

[briarpatch-kids]

Denied again by social security. I don't get how they expected me to work with a 70% mental health rating by the military and fucking mitochondrial myopathy.

Like this is the requirement for 70% mental health rating:

70% rating: The veteran is unable to function in most social and work areas with symptoms such as:

obsessive behaviors

illogical speech

persistent severe depression and panic

suicidal thinking

inability to control impulses (including becoming violent without provocation)

neglecting self-care such as basic hygiene

inability to handle stress, and

being unable to maintain relationships.

[learnwithmearticles]

Moon Missions

What’s going on with the moon?

The United States recently had a solar eclipse on April 8th, 2024, and some might be surprised to learn that the moon is, in fact, affected by solar radiation. The charged particles emitted by the sun, called the solar wind, reach the moon with no interruption from its atmosphere, as it has none. It also has no global magnetic field, another layer of protection that Earth does have, in comparison.

The moon does, however, have small areas of magnetic fields. We can see this because these areas remain lighter in photos whereas chemical reactions from radiation darken the unprotected areas.

Fortunately, most of these charged particles cannot pass through the hulls of space stations, so astronauts are safe in orbit. Cosmic rays, made of stronger and faster-moving particles, are more dangerous. Even on Earth, under the atmosphere and magnetosphere, cosmic radiation reaches humans, though not enough to be considered damaging to our health.

A lander and rover launched in 2018 delivered the first measurements of radiation levels on the moon 4. Based on those data, astronauts on the moon can be exposed to up to 150 times higher radiation levels than on Earth.

Radiation is a leading reason for the pause in lunar landing missions. It raises risks of cataracts, heart diseases, radiation illness, cancer, and other ailments. Longer missions, of course, would heavily exacerbate these radiation doses.

Other Health Concerns

Cosmic rays contain High-Energy (HZE) ions. In different exposure such as from nuclear accidents or irradiation therapy, HZE ions have been found to cause dysregulation in the mitochondria and damage to DNA. Because of this, prolonged exposure is linked to health effects often associated with aging, such as hippocampus synapse loss and metabolic disruption caused by damage to mitochondrial DNA.

Long-duration space flights have also been linked to cardiovascular disorders. For astronauts on the Apollo missions, heart attack was “the second leading cause of death” 8. For additional space flights outside of Earth’s magnetosphere, astronauts also had a higher mortality rate due to cardiovascular diseases.

In a previous article, we discussed the relationship between circadian rhythms and health. These rhythms are another thing that space travel can impact, causing sleep and mental health disturbances in astronauts 9.

While various studies are investigating the conditions of these health risks, a current NASA mission is specifically investigating radiation protection.

Long-term Mission

NASA plans on eventually returning to human-manned missions to the moon.

First, they have to address the issues discussed above.

In November of 2022, Artemis I launched with two manikins bearing radiation detectors. From this mission, NASA was able to confirm the success of the intended trajectory, launch of ground systems, and the Orion spacecraft. The radiation results from this mission are still being analyzed.

The Artemis missions are intended to explore more of the moon than ever before, and lay groundwork for eventual missions to Mars.

Artemis II will not launch any earlier than September of 2025. It is planned to last ten days, consist of a 4-person crew, and be a lunar flyby to ensure the proper functioning of the spacecraft’s systems.

It has seemed for years that lunar exploration has halted. Manned missions have indeed been paused, for good reasons. Ensuring the safety of astronauts is a priority, and they face serious health risks even when missions go as expected. But NASA intends to continue exploring space, the moon, and Mars. The current Artemis missions are discovering improved, new ways to ensure the safety of astronauts while making scientific progress.

Additional Resources

1. https://science.nasa.gov/moon/solar-wind/

2. https://phys.org/news/2012-01-solar-flares-astronauts.html

3. https://arxiv.org/ftp/arxiv/papers/1211/1211.3962.pdf

4. https://link.springer.com/article/10.1007/s11214-020-00725-3

5.https://www.nasa.gov/missions/artemis/orion/orion-passengers-on-artemis-i-to-test-radiation-vest-for-deep-space-missions/

6.https://www.smithsonianmag.com/science-nature/how-space-radiation-threatens-lunar-exploration-180981415/

7.https://www.nasa.gov/humans-in-space/analysis-confirms-successful-artemis-i-moon-mission-reviews-continue-2/

8.https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2020.00955/full

9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818606/