Author: gettingwell4

Microwave broccoli to increase sulforaphane levels

gettingwell4 4-5 stars Advanced knowledge, Epigenetics, Immune system, Stress

This 2020 Chinese/USDA study investigated effects on sulforaphane amount from heating broccoli in water and microwaving at different power settings to different temperatures:

“Microwave treatment causes a sudden collapse of cell structure due to the increase in osmotic pressure difference over vacuole membrane. Mild heating could increase SFR [sulforaphane] level, possibly explained by the increased activity of MYR [the enzyme myrosinase] which can hydrolyze GLR [glucoraphanin] into SFR at high temperature (up to 60°C).

Microwave‐cooked broccoli had higher levels of these two compounds compared to broccoli heated in water. The broccoli sample without cooking as a control showed the least amount of GLR, indicating that microwave heating did help to release more GLR from the cell.

In the temperature range of 50–60°C, a positive correlation was observed between GLR or SFR contents and temperature. However, these two physiochemical contents were negatively correlated with temperature when it increased to 70°C.

The glucoraphanin (GLR) and sulforaphane (SFR) contents (μmol/g DW) in florets of broccoli during microwaving at 40, 50, 60, and 70°C using low power level (LL) or high power level (HL). Data are reported as the mean ± SD (n = 3). Values with different letters are significantly (p < .05) different.

[For example, sulforaphane levels of the control (raw), LL40, LL70, and HL40 conditions weren’t significantly different, and the HL70 level was significantly lower than those levels]. The microwave using high level at 60°C showed the greatest SFR level (2.45 µmol/g DW).”

Table S1 from the supporting material:

Temperature

(°C)

 Time

(S)

 Power level

(W)
Heating in water 40 185 NA
50 230
60 262
70 290
Microwave (HL) 40 65 950
50 90
60 108
70 120
Microwave (LL) 40 115 475
50 148
60 178
70 200

https://onlinelibrary.wiley.com/doi/10.1002/fsn3.1493 “Microwave cooking increases sulforaphane level in broccoli”

The researchers demonstrated a more effective method of increasing sulforaphane than did the cited and widely discussed 2004 Heating decreases epithiospecifier protein activity and increases sulforaphane formation in broccoli (not freely available). The older study methods were difficult to implement in kitchens, and evaluated heating temperature as the only factor.

The present study added microwave power level irradiation effects as a factor, and simplified heating temperature implementation. People can use Table S1 to maximize broccoli floret sulforaphane content in their kitchens. See Week 2 of Changing an inflammatory phenotype with broccoli sprouts for changes.

The study provided an optimal sulforaphane end result of “(2.45 µmol/g DW)”. I asked a study author for additional data, and they replied:

“The control GLR and SLR amount was 2.18 and 0.22 µmol/g DW, respectively, while the HL60 GLR amount was 2.78 µmol/g DW.”

Microwaving 10 grams of broccoli florets to 60°C (140°F) increased the sulforaphane amount by 1,114% (2.45 / .22)! That also increased the glucoraphanin amount by 27% (2.78 / 2.18) for further processing into sulforaphane after eating.

I replied: That’s an exciting result, increasing sulforaphane more than 11 times, while also increasing glucoraphanin! I haven’t found similar experiments with broccoli sprouts. Would you expect similar results?

The study author responded:

“We didn’t expect this result, and think microwave irradiation might help to release more conjugated forms of glucosinolates and then get hydrolyzed by released myrosinase. Further studies are being carried out.”

The study also measured broccoli stems:

“GLR and SFR were hardly detected in stems. Less than 52% of GLR was detected in the [50/50] mixture of florets and stems compared to florets.

Microwaved at 60°C, the florets had a concentration of GLR and SFR at 2.78 and 2.45 µmol/g DW, respectively, which was significantly higher than the levels detected in mixture of florets and stems (1.21 and 0.82 µmol/g DW, respectively).”

The 50% florets / 50% stems mixture’s glucoraphanin amount of 1.21 µmol was roughly comparable with the 1.08 µmol glucoraphanin amount of mature broccoli extract in item 2 below.

Reminders from Eat broccoli sprouts today:

  1. A 1 mg sulforaphane weight equals a 5.64 μmol sulforaphane amount.
  2. “Content of glucoraphanin in extract from broccoli sprouts was 16.6 μmol per gram of fresh weight. In contrast, mature broccoli extract contained 1.08 μmol per gram of fresh weight.”
  3. The bioavailability of sulforaphane in a broccoli sprout extract with the myrosinase enzyme 100 μmol gelcap was 36.1% which weighed 6.4 mg.
  4. The question of how much sulforaphane is suitable for healthy people remains unanswered.

The evidence says..

gettingwell4 Just me

Three items to follow up yesterday’s The UK downgraded COVID-19 a week ago:

1. From March 24, 2020:

Oxford Epidemiologist: Here’s Why That Doomsday Model Is Likely Way Off

“Fewer than one in a thousand who’ve been infected with COVID-19 become sick enough to need hospitalization, leaving the vast majority with mild cases or free of symptoms.”

However, that was based on “my model’s better than yours” arguments rather than sufficient evidence.

2. From March 26, 2020:

Dr. Deborah Birx Shreds Media For Salacious Claims: ‘We Don’t Have Evidence Of That’

“Birx began by highlighting the study in the U.K. that dramatically revised its projections of the total number of deaths projected in the U.K. from ‘half a million to 20,000.’

‘When people start talking about 20% of a population getting infected,’ Birx later added. ‘It’s very scary, but we don’t have data that matches that based on the experience.'”

3. From March 25, 2020: the panic model’s lead researcher offered a long non-apology to UK Parliament, which they accepted uncritically:

Witness: Professor Neil Ferguson, Director, MRC Centre for Global Infectious Disease Analysis, Imperial College London

Still don’t know exactly who is herding the US population. We wait at home for headlines to emphasize evidence.

The UK downgraded COVID-19 a week ago

gettingwell4 Just me

From https://www.gov.uk/guidance/high-consequence-infectious-diseases-hcid:

“As of 19 March 2020, COVID-19 is no longer considered to be a high consequence infectious diseases (HCID) in the UK.

The 4 nations public health HCID group made an interim recommendation in January 2020 to classify COVID-19 as an HCID.  Now that more is known about COVID-19, the public health bodies in the UK have reviewed the most up to date information about COVID-19 against the UK HCID criteria. They have determined that several features have now changed; in particular, more information is available about mortality rates (low overall), and there is now greater clinical awareness and a specific and sensitive laboratory test, the availability of which continues to increase.

Definition of HCID

  • acute infectious disease
  • typically has a high case-fatality rate
  • may not have effective prophylaxis or treatment
  • often difficult to recognise and detect rapidly
  • ability to spread in the community and within healthcare settings
  • requires an enhanced individual, population and system response to ensure it is managed effectively, efficiently and safely.”

Who is herding the US population, with demands that businesses be shut down, for a disease that the UK recognizes as not the most serious health threat?

Will their scorched earth agenda not be satisfied until the remains of US businesses are in a pile like this?

Image from Rare Historical Photos

Waiting to be officially denied

gettingwell4 Just me

Three items to follow up yesterday’s What’s next?:

1. A view from a Singapore gold dealer:

LBMA colludes with the COMEX – To lockdown the global gold market?

“LBMA [London Bullion Market Association] market-makers have a duty and obligation to make a market in gold. So where were these market makers as the spot price seized up, and why would these market makers not be making a market and providing liquidity for gold?

Is it just a management of perceptions exercise with no gold bars involved, to try to coax back the spot and futures prices by telegraphing that the gold that is backing the spot price (which is actually unallocated non-existent gold) is now also backing COMEX gold futures. While neither of the two can be delivered, the same non-gold now backs both, so voila, there is no need for any price divergence!”

2. Concurrently, from the Wall Street Journal, a new form of US currency may or may not be part of the coronavirus bailout package:

Fed Digital Dollars Are Part of Debate Over Coronavirus Stimulus

“While it may not make it to the finished coronavirus economic stimulus and support package now being weighed in Congress, there is a push from some legislators to give the Federal Reserve a new tool some believe could radically reshape how it conducts monetary policy.

At issue are so-called digital dollars and the accounts that would hold them.”

3. Private equity eyes industries crippled by coronavirus: ‘They have been waiting for this’

“‘Vulture investors, especially in private equity, are waiting in the wings to scoop up scores of struggling businesses on the cheap,’ tweeted Rohit Chopra, an FTC commissioner.”

Still no idea about exactly who are the herders. Getting a better picture of who benefits from the herd’s demise.


Charles M. Russell “Driving Buffalo Over the Cliff” 1914

Eat broccoli sprouts today!

gettingwell4 4-5 stars Advanced knowledge, Epigenetics, Immune system, Stress , , ,

This 2020 Korean letter to a journal editor cited 23 recent papers in support of sulforaphane’s positive effects, mainly in anti-cancer treatments:

“Gene expression is mediated by chromatin epigenetic changes, including DNA methylation, histone modifications, promoter-enhancer interactions, and non-coding RNA (microRNA and long non-coding RNA)-mediated regulation. Approximately 50% of all tumor suppressor genes are inactivated through epigenetic modifications, rather than by genetic mechanisms, in sporadic cancers. Accumulating evidence suggests that epigenetic modulators are important tools to improve the efficacy of disease prevention strategies.

Because sulforaphane (SFN) induces the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element pathway that induces the cellular defense against oxidative stress, SFN has received increased attention because it acts as an antioxidant, antimicrobial, anti-inflammatory, and anticancer agent.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068201/ “A recent overview on sulforaphane as a dietary epigenetic modulator”

Letters to the editor aren’t peer-reviewed, though. One of the cited papers was a 2018 Czech mini-review that included metabolism, preparation and processing evidence:

“Sulforaphane is a phytochemical that occurs in plants in the form of biological inactive precursor glucoraphanin. This precursor belongs to the group of phytochemicals – glucosinolates – that are rapidly converted to isothiocyanate by the enzyme myrosinase.

The process of transformation takes place after a disruption of plant tissues by biting, chewing, slicing, and other destruction of tissues, when myrosinase is released from plant tissues. When myrosinase is destroyed during meal preparation (during cooking, steam cooking, or microwave treatment), a likely source of isothiocyanates is microbial degradation of glucosinolates by intestinal microflora. However, hydrolysis by microflora has been reported to be not very efficient, and in humans it is very diverse and variable.

Content of glucoraphanin in extract from broccoli sprouts was 16.6 μmol per gram of fresh weight. In contrast, mature broccoli extract contained 1.08 μmol per gram of fresh weight. Total amount of glucosinolates in young broccoli sprouts is 22.7 μmol per gram of fresh weight and 3.37 μmol per gram of fresh weight for mature broccoli.

Percentage amount of sulforaphane formed from its precursor glucoraphanin in broccoli which had not been heat treated and had been lyophilized [freeze-dried] was 22.8%. Broccoli steaming (5 min) and its lyophilization decrease the amount of sulforaphane formed to 4.2%.”

https://www.liebertpub.com/doi/full/10.1089/jmf.2018.0024 “Isothiocyanate from Broccoli, Sulforaphane, and Its Properties (not freely available)

Information about 43 completed sulforaphane clinical trials is here. Among them, the 2014 Effect of Broccoli Sprouts on Nasal Response to Live Attenuated Influenza Virus in Smokers: A Randomized, Double-Blind Study was of particular interest, stating:

“Nutritional interventions aimed at boosting antioxidants may be most effective in individuals who are relatively antioxidant-deficient at baseline, a condition likely to be more prevalent in smokers.”

I didn’t notice regular supplement dosage studies. Maybe I didn’t read control group information carefully enough?

https://pubchem.ncbi.nlm.nih.gov/compound/sulforaphane lists sulforaphane’s molecular weight as 177.3 g/mol. A 1 mg sulforaphane capsule weight equals a 5.64 μmol sulforaphane amount (.001 / 177.3).

From the 2015 Sulforaphane Bioavailability from Glucoraphanin-Rich Broccoli: Control by Active Endogenous Myrosinase:

  • Figure 4 showed bioavailability of sulforaphane in a broccoli sprout extract with myrosinase 100 μmol gelcap was 36.1% which weighed 6.4 mg (36.1 / 5.64).
  • Figure 3 showed bioavailability of sulforaphane in freeze-dried broccoli sprouts in pineapple-lime juice was 40.5% in 50, 100, and 200 μmol amounts and 33.8% with 100 μmol gel caps. You do the weight math.
  • Figure 2 showed that if broccoli sprout extract didn’t have the enzyme, bioavailability of sulforaphane was 10.4% whether the amount was 69 or 230 μmol, weighing 1.27 mg (69 x .104) / 5.64 and 4.24 mg (230 x .104) / 5.64.

Bioavailability ranged from Figure 2’s 10.4% to Figure 4’s 36.1%. The question of how much sulforaphane is suitable for healthy people remains unanswered.

Deaths in Italy attributed to COVID-19

gettingwell4 2-3 stars Required further work, Beliefs, Immune system

Why have so many coronavirus patients died in Italy? from the Telegraph today:

“According to Prof Walter Ricciardi, scientific adviser to Italy’s minister of health, the country’s mortality rate is far higher due to demographics – the nation has the second oldest population worldwide – and the manner in which hospitals record deaths.

‘The age of our patients in hospitals is substantially older – the median is 67, while in China it was 46,’ Prof Ricciardi says. ‘So essentially the age distribution of our patients is squeezed to an older age and this is substantial in increasing the lethality.

But Prof Ricciardi added that Italy’s death rate may also appear high because of how doctors record fatalities.

‘The way in which we code deaths in our country is very generous in the sense that all the people who die in hospitals with the coronavirus are deemed to be dying of the coronavirus.

On re-evaluation by the National Institute of Health, only 12 per cent of death certificates have shown a direct causality from coronavirus, while 88 per cent of patients who have died have at least one pre-morbidity – many had two or three,’ he says.”

Refactoring the current 4,825 deaths in Italy attributed to COVID-19 equals 579 (4,825 x .12). That number places Italy slightly above France’s 562 current total.

Evidence-based statements wouldn’t sufficiently frighten the herd, though. The article continued on to include now-obligatory, hyperbolic, unscientific WHO statements referencing a “miracle.”

Image from “Culture Audits: We Have Been Asking the Wrong Question”

Humans individually evolve by..?

gettingwell4 0-1 star Wasted resources, Epigenetics, Primal Therapy , , ,

This 2020 UK evolutionary biology article was part of a “Fifty years of the Price equation” issue:

“Genetic and non-genetic inheritance usually produce a phenotype [the composite of an organism’s characteristics, including its developmental, biophysical, and behavioral traits] through a highly complex developmental process that also relies on many features of the world over which the parents have little, if any, control. As a consequence, the relationship between the phenotypes of parents and offspring, the offspring–parent distribution, can take on many forms and vary from one place or time to another.

The extension of transmission and quantitative genetic models retain the assumption that the relationship between inheritance and phenotypic variation is such that it is sufficient to focus on the transmissibility of inherited variants or additive variance rather than phenotype development.

The concept of heredity as a developmental process is a more significant departure from traditional notions of inheritance. The mechanisms of non-genetic inheritance, such as parental behaviour, do not only affect the parent–offspring resemblance, but also the generation of variation and individual fitness.

Any feature of the parents, including their DNA sequence, physiology and behaviour can carry information about the conditions that the offspring will encounter. That this information content itself must be an evolving property is perhaps most evident when heredity is viewed as a developmental process; a developmental perspective is particularly useful when the aim is to study how the evolutionary process itself is evolving.”

https://royalsocietypublishing.org/doi/full/10.1098/rstb.2019.0366 “Different perspectives on non-genetic inheritance illustrate the versatile utility of the Price equation in evolutionary biology”

This article and the “Fifty years of the Price equation” issue’s other articles had numerous mentions of individual evolution and behavior. They acknowledged “a diversity of perspectives” but I didn’t see my 2015 page’s perspective that it’s up to each individual to mold their own phenotype. In it, the Price equation prompted the question:

“How does a phenotype influence its own change?”

which I applied to a person individually evolving.

The article and the issue’s other articles tinkered with equations, and cited plant, animal, and human studies with frameworks that didn’t include investigating causes for the observed effects. These often wasted resources by providing solutions that addressed symptoms instead of addressing the uninvestigated causes.

For example, I didn’t see any mentions of how an individual’s pain may drive their phenotype. Pain induced by threats to survival are common parts of animal experiments that create and investigate phenotypes of epigenetic responses to stressors.

Regarding possible human applicability, how can a person remedy their undesirable traits and acquire desirable traits without addressing a root cause?

Unlike animals, people can therapeutically resolve underlying causes without the timing, duration, and intensity of efforts being externally determined. A human’s efforts to change their phenotype don’t have to mimic animal studies’ forcible approaches with drugs, etc., directed on someone else’s schedule. Addressing pain may be required for such efforts.

The article also promoted an outdated paradigm of epigenetic transgenerational inheritance:

“The transgenerational stability of some epigenetic states may fall within the same range as the stability of behaviours that are learnt from parents. Quantifying the environmental sensitivity and transgenerational stability of epigenetic variation has emerged as a major research focus over the past decade.”

As explained in Transgenerational epigenetic inheritance of thyroid hormone sensitivity:

“Observing the same phenotype in each generation is NOT required for transgenerational epigenetic inheritance to exist. Animal transgenerational studies have shown that epigenetic inheritance mechanisms may both express different phenotypes for each generation, and entirely skip a phenotype in one or more generations.”

Considering only “transgenerational stability of epigenetic variation” as proof will misinterpret this supporting evidence.

Aging as a disease

gettingwell4 4-5 stars Advanced knowledge, Epigenetics, Neurochemicals, Oxytocin, Telomeres ,

This 2020 interview was with UC Berkeley researchers:

“Lack of cure goes hand in hand with inability to accept that this [aging] is disease. For example, there was some resistance to accept tuberculosis as the actual disease. When there was no antibiotics or cure against it, people tended to discard it and said, oh, it’s just nerves, you need to go to a sanatorium and relax.

It used to be that, please do not diagnose that there’s bacterial meningitis, because there is no cure. Whatever else you can come up with, do it first. Now, diagnose it as fast as possible, so we can put patients on antibiotics immediately. My prediction is that the same will happen to aging.

We and others have demonstrated that you can, from the outside, either by some signal or blood therapy, parabiosis, something like that, some intervention, jump-start aged resident stem cells in tissue and get them to behave as, by whatever means you’re measuring it, young or a lot closer to young than they would normally be. Intrinsic capacity of them to act that way is there.

As we grow old, the environment of differentiated niche stem cells does not provide productive instruction. It provides counterproductive instruction, which, overall, tells them just to remain quiescent and do nothing.

It’s not a program to kill you. It’s the lack of a program to keep you young and healthy for longer than 90 years.

If your program was that whenever you’re a damaged, differentiated cell, you simply trigger apoptosis and activate stem cells to make new cells, we would live much longer and healthy. The program right now is to resist being dead and replaced as much as you can for as long as you can.

So cells produce too much TGF beta [transforming growth factor-β] because it helps them to keep functioning even when they’re damaged. That too much TGF beta, ironically, inhibits resident stem cells, so they are not replacing old cells with new ones. It’s almost like you have old bureaucrats that are running an organization and do not want to be replaced.

Our thoughts are probably different from most people, because we go to the data and the data show that they’re not really fully what authors wrote in the abstract or conclusion. When you look at that, my thought is that much more work needs to be done before it [partial cellular reprogramming] could be even thought to be commercialized.”

https://www.lifespan.io/news/apheresis-with-profs-irina-michael-conboy/ “Irina & Michael Conboy – Resetting Aged Blood to Restore Youth”

Keep in mind that although the interviewers’ organization had changed, their advocacy position as displayed in A blood plasma aging clock persisted. One of the interviewees is on the interviewers’ organization scientific advisory board, and they also have an interest in downgrading competing approaches.

Despite caveats, this interview was these researchers’ perspective in their decades-long investigations of aging. I included a graphic and below quote from Organismal aging and cellular senescence to note how their paradigm compared with other aging researchers:

“In our view, recent evidence that

  • Senescence is based on an unterminated developmental growth program and finding that
  • The concept of post-mitotic senescence requires activation of expansion, or ‘growth’ factors as a second hit,

favor the assumption that aging underlies a grating of genetic determination similarly to what is summarized above under the pseudo-programmed causative approach.”

Well done, WHO, carefully played

gettingwell4 2-3 stars Required further work

A follow up to The WHO has a financial incentive to declare COVID-19 a pandemic:

Today CNBC reported Investors in World Bank’s ‘pandemic bonds’ face big losses due to the coronavirus outbreak

“According to ratings agency DBRS Morningstar, investors who hold the riskier of the two bonds could be losing their entire principal amount soon, with the firm saying that the price should have dropped more than 80%.

According to the World Bank, the outbreak would need to last at least 12 weeks, and have more than 2,500 deaths for the riskier of the two bonds, and 250 deaths for the other. There must also be more than 20 deaths in a second country.

When all those conditions are fulfilled, it triggers a payout to selected countries in need of help to contain the outbreak, and investors lose some or all of their money. That date works out to be Mar. 24, going by the 12-week period, and the start date of the outbreak – Dec. 31, according to the WHO, said DBRS Morningstar.

The World Bank did not respond to CNBC’s request for comment.”

Regarding WHO terminology, from The Cyclical Nature of Disease:

“The World Health Organization (WHO) made the announcement on Wednesday, March 11, 2020, that the Coronavirus is a “pandemic” which is actually not as bad as an Epidemic which is a term that describes any problem that has grown out of control. An epidemic is therefore defined as “an outbreak of a disease that occurs over a wide geographic area and affects an exceptionally high proportion of the population.”

Consequently, an epidemic requires a high proportion of society to be infected and is an event in which a disease is actively spreading. That is clearly not the case with the coronavirus. since the proportion of society infected has not even reached 1/10th of one percent of the population.

In contrast, the term pandemic relates to geographic spread and is used to describe a disease that affects a whole country or the entire world. This has nothing to do with the proportion of the population that is infected.”

Regarding WHO timing, last week The Guardian reported:

First Covid-19 case happened in November, China government records show – report

“The first case of someone suffering from Covid-19 can be traced back to 17 November, according to media reports on unpublished Chinese government data.

The report, in the South China Morning Post, said Chinese authorities had identified at least 266 people who contracted the virus last year and who came under medical surveillance, and the earliest case was 17 November – weeks before authorities announced the emergence of the new virus.

The Chinese government was widely criticised over attempts to cover up the outbreak in the early weeks, including crackdowns on doctors who tried to warn colleagues about a new Sars-like virus which was emerging in the city of Wuhan in Hubei province.

The data obtained by the Post, which the Guardian has not been able to verify, said a 55-year-old from Hubei province could have been the first person to contract Covid-19. For about one month after that date there were one to five new cases reported each day, the report said, and by 20 December there were 60 confirmed cases.

Official statements by the Chinese government to the World Health Organisation reported that the first confirmed case had been diagnosed on 8 December.”

Looking past the headlines, we have time to ask cui bono questions while we’re sitting at home:

  • Who’s benefiting from (medical, economic, social, and political) reports on and actions taken with COVID-19?
  • Who’s suffering from these reports and actions?

Recover your sanity

gettingwell4 4-5 stars Advanced knowledge, Beliefs, Cerebrum, Memory

“Men, it has been well said:

  • Think in herds; it will be seen that
  • They go mad in herds, while
  • They only recover their senses slowly, one by one.

During the great plague, which ravaged all Europe between the years 1345 and 1350, it was generally considered that the end of the world was at hand.

‘But the facts, my dear fellow,’ said his friend, ‘the facts do not agree with your theory.’ ‘Don’t they?’ replied the philosopher, shrugging his shoulders, ‘then, tant pis pour les faits’ – so much the worse for the facts!”

Charles Mackay, 1841

https://www.gutenberg.org/ebooks/24518 “Memoirs of Extraordinary Popular Delusions and the Madness of Crowds”

Alfred Jacob Miller “Hunting buffalo” 1837

“Establishing the hidden communication networks in large self-organized groups facilitates a quantitative understanding of behavioral contagion.

An individual will be more likely to respond (is more susceptible) if it:

  • Is strongly connected to the initiator (short path length), and if it
  • Has neighbors which are strongly connected to each other.”

Why is it so difficult to live your own life?

The WHO has a financial incentive to declare COVID-19 a pandemic

gettingwell4 4-5 stars Advanced knowledge, Immune system

“The percent of the population being affected has not even reached 1/10th of one percent. When we look at this Coronavirus scare, it does not even compare to all the deaths taking place every single day from a host of other diseases nobody bothers to ever mention. This really makes me wonder just who is orchestrating this panic and is the purpose really to expand government powers?”

The Cyclical Nature of Disease

“The WHO has a financial incentive in declaring this a pandemic. It issued Pandemic Bonds paying 7% interest which now the WHO does not have to repay.”

Half-Billion $ Pandemic Derivatives

See Well done, WHO, carefully played to follow up.

Train your immune system every day!

gettingwell4 4-5 stars Advanced knowledge, Epigenetics, Immune system, Memory, Stress ,

This 2019 US review subject was β-glucan:

“β-1,3-Glucans (hereafter referred to as glucan) are natural molecules able to significantly improve our health. In human studies, the tested (and suggested) daily dose remains in the range of 100–500 mg for stimulation of the immune system, whereas for a decrease in cholesterol levels a daily dose of 3 g is recommended.

Glucan does not represent essential nutrients, but it might be successfully used not only for:

  • Improvement of immune functions, but also to improve the general quality of life via
  • Improvements of immune status,
  • Lowering cholesterol,
  • Improving blood glucose levels and
  • Reduction of stress.

ClinicalTrials.gov summarizes 177 [now 207 with 110 completed] β-glucan clinical trials, mostly in cancer, gastrointestinal tract therapy, lowering cholesterol and improvements of immune reactions.

The question is not if glucans will move from food supplement to widely accepted drug, but how soon.

Reactions known to be influenced by glucan are represented in white, reactions where glucan has no confirmed effects are shown in black. The first defensive body response to infection results from formation of the anorexia cytokines (IL-1, IL-6, IL-8, and TNF-α).”

https://www.mdpi.com/1420-3049/24/7/1251/htm “Beta Glucan: Supplement or Drug? From Laboratory to Clinical Trials”

The review is also indexed at https://www.betaglucan.org/i-p/ under “Immunomodulator”

I’m curating this review on Day 12 of a self-quarantine after coming back from Milano, Italy, Monday, February 24, 2020. The previous Friday into Saturday I flew to Milano sitting with a group of elderly Italians who were returning from vacation.

On Saturday my traveling companion and I used the Milano rail and crowded subway system to go downtown. On Sunday we used their crowded rail, crowded bus, and crowded ferry systems to visit Como, Bellagio, and Menaggio.

I don’t think we could have mixed in more with people during transits, touristing, and Carnevale celebrations.

IMG_9539

After returning to our hotel Sunday evening, we heard about the coronavirus outbreak south of Milano and the closing of ten towns. We changed flights and departed for the US early Monday morning.

Neither of us have had any signature symptoms of COVID-19 (fever, shortness of breath, dry cough). Our daily diet the past few years included β-glucan from steel-cut oats (~3 g) and from a 1/3, 1/6 yeast cell wall supplement.

Coincidence?

Each of our futures will depend on what we do Now to prepare.

Take responsibility for your one precious life.

Moonrise at sunrise with Venus

Wander into creativity?

gettingwell4 0-1 star Wasted resources, Beliefs, Primal Therapy

This 2019 US study investigated the context of creative ideas:

“Creative inspiration routinely occurs during moments of mind wandering. Approximately 20% of ideas occurred in this manner.

Although ideas that occurred while participants were both on task and mind wandering did not differ in overall quality, there were several dimensions on which they did consistently differ. Ideas that occurred while mind wandering were reported to be experienced with a greater sense of ‘aha’ and were more likely to involve overcoming an impasse.

The present findings are consistent with the view that spontaneous task-independent mind wandering represents a source of the inventive ideas that individuals have each day. This potential function of mind wandering may help to explain why a mental state that can be associated with significant negative outcomes is nevertheless so ubiquitous.”

“Would you say the idea felt like an ‘aha!’ moment?” and “How creative do you feel the idea was?” were the closest items to emotional measures. “How important do you think this idea is?” and several months later “How important has the idea proven to be overall?” were used to measure importance.

https://labs.psych.ucsb.edu/schooler/jonathan/sites/labs.psych.ucsb.edu.schooler.jonathan/files/pubs/0956797618820626.pdf “When the Muses Strike: Creative Ideas of Physicists and Writers Routinely Occur During Mind Wandering”

I came across this study from its reference in How Productivity Apps Can Make Us Less Productive (And Less Happy).

The study’s design missed opportunities to discover sources of creative ideas and feelings of importance. It focused on effects and intentionally disregarded causes, despite asserting that “mind wandering represents a source of inventive ideas.”

Experiments were subjectively biased for a framework that considered ideas as originating solely from a person’s thinking brain. A framework like Primal Therapy that demonstrated how ideas may arise as defenses against feelings wasn’t considered, although relevant.

Let’s use the finding “Ideas that occurred while mind wandering were more likely to involve overcoming an impasse” as an example for a Primal Therapy framework’s view:

  1. A person who has a seemingly unsolvable work problem probably encounters feelings of helplessness.
  2. Staying busy with tasks can distract them from these feelings.
  3. During times of less cognitive activity, though, these feelings can have more impetus.
  4. The resultant discomfort will trigger ideas to help ward off helpless feelings.

Regarding importance judgments, there are many needs a person develops and tries to satisfy as substitutes for real needs that weren’t fulfilled. I’ve focused on the need to feel important in blog posts such as Your need to feel important will run your life, and you’ll never feel satisfied.

An evolutionary view of transgenerational epigenetic inheritance

gettingwell4 2-3 stars Required further work, Epigenetics, Memory, Stress ,

This 2020 Swiss/German review mainly cited weed, worm, and yeast studies:

“RNA interference-related mechanisms can mediate the deposition and transgenerational inheritance of specific chromatin modifications in a truly epigenetic fashion.

Epigenetics was initially defined as any heritable change in gene expression patterns without changes in the DNA sequence. Now, epigenetic phenomena are often characterized as ‘gene expression changes that are mutation independent and heritable in the absence of the triggering event’, a definition we will follow in this review. We note that this definition can be expanded to include protein only-based inheritance mechanisms that do not necessarily cause changes in gene expression.

Gene silencing can persist over multiple generations in the germline of C. elegans. Gene repression is typically maintained without the initial trigger for three to seven generations and occasionally for tens of generations. In contrast, silencing of somatically expressed genes mostly affects only the subsequent generation through nonepigenetic parental effects.

In the presence of an ‘enabling’ mutation, primary siRNAs [small interfering RNAs] can trigger an RNAe [RNA-induced epigenetic silencing] response. Secondary siRNA amplification is required for transgenerational inheritance.

The fitness of a population in a dynamic environment strongly depends on the ability of individuals to adapt to the new condition as well as to remember, inherit, and forget such adaptation:

  • (A) A well-adapted population (grey) is at its maximal density (dotted line) in a given niche until an environmental change (1st stress) creates a bottleneck. Only few individuals can adapt through mutations and repopulate the niche. After the environment changes back to the initial blue state, only individuals that acquire rare counteracting mutations survive, often leading to extinction of the population.
  • (B) Individuals of a population in the red state can gain beneficial epimutations through siRNAs and repopulate the niche. When exposed again to the blue state, the epimutations can be quickly reversed and the population rapidly reaches maximal density. After recurrence of the red state, organisms establish de novo epimutations with the same low frequency as when they first encountered this state.
  • (C) In contrast, organisms that can maintain the memory of a beneficial silencing event can quickly re-establish beneficial epimutations and grow to full density. Such memory can be maintained by phenotypically neutral epimutations, marked by the continuously high production of siRNAs without substantial reductions in the expression of a gene. A population that can adapt through phenotypically plastic epimutations is predicted to have a maximal fitness advantage in a dynamic environment.”

The Concluding Remarks section included:

“RNA-mediated epigenetic responses could contribute to adaptation.

Even though RNAe may yield significant adaptive advantages, a high induction frequency could cause silencing of multiple essential genes and therefore be detrimental. Hence, it is plausible that mechanisms would have coevolved that counteract silencing.

Similarly, if constituting a bet-hedging strategy to cope with ever-changing environments, permanent fixation of an acquired silencing response would not constitute a selective advantage and mechanisms that modify and limit the duration of RNAe would be predicted.”

https://www.sciencedirect.com/science/article/pii/S0168952519302598 “Small RNAs in the Transgenerational Inheritance of Epigenetic Information”

The review’s arguments were based on evolutionary selective advantages and less-complex organisms. It predicted that there would be an endpoint generation as in the (A) case of the above graphic.

Were the mechanisms in the (B) case necessarily transgenerational throughout? The review further explained:

“Epimutations tend to occur in hot spots (e.g., in stress-related or nutritional pathway genes) and can potentially silence several homologous genes simultaneously. Incomplete penetrance of a beneficial epimutation by stochastic loss of siRNAs [59] can result in loss of adaptation in a given environment (red state), but can be beneficial if the previous blue state is re-established. However, when the environment changes back to the red state, epimutations must initiate de novo, at the same low frequency as when the population first encountered this state.”

The study cited at 59 found:

“A feedback between siRNAs and RNAi genes determines heritable silencing duration”

but not “Incomplete penetrance of a beneficial epimutation by stochastic loss of siRNAs.” Hmm.

In any event, the review stated:

“Evidence for naturally occurring RNAe-related phenomena in other animals is scarce and we should be cautious about inferring RNAe as a widely conserved phenomenon.”

It’s encouraging to read studies that find benefits to epigenetic transgenerational inheritance, albeit in organisms that are less complex than rodents and humans.