Dr. Wakefield Sues Brian Deer and BMJ's Fiona Godlee
That’s My Boy!

The Inflammation Highway: aka Autism

  Tummy-ache-abdominal-pain-t13513By Lisa Goes

"The one thing about my husband and I...we laugh...A lot. We find a way. We really do. Poop filled sleepless nights, injuries, missed appointments, clutter everywhere, missing paperwork...sometimes all you can do is laugh. But today, looking at the dark circles we've seen so many times under our children's eyes, seeing the suffering, the real genuine human suffering that we have worked for three years to alleviate...to see it reach these depths...there is no laughing today. There is sadness. Even the fight is gone. I should be sleeping, but I have to read up on one of our new remedies. Maybe this will be the one that touches his immune damage and regulates him? Maybe. Maybe, it will work for him like it has for THOUSANDS of other children. Maybe. I can't sleep when this could be it and I could be calling the next doctor tomorrow and we could have one less day of this. Plus, I already have an appointment to see a doctor tomorrow and I will need him to know that I know what I'm talking about. If there is one thing you learn as an autism parent it is that YOU MUST KNOW WHAT YOU ARE TALKING ABOUT WITH DOCTORS. You must learn to speak their language. If you don't you will get dismissed. Must read, now.



But, before I go, just need to let everyone know the women who work for us are angels from God. They were hurt today. Two of them. In their sweetest voices they kept repeating, "nice hands." And "time to get down monkey" when he climbed on the counter for the 27th time on their shift. He is 50 lbs now. Very fast and very strong. They get him. They see the real Noah in there, fighting like hell. He is mad. In fact, that's what he said in therapy today, "I'm MAD!" His therapists were thrilled. They were so excited to see him emote appropriately. I agree with them, it's encouraging. It's just that, he's mad he's sick. He's mad his head hurts all the time. He's mad his three year old brother can use the toliet and he cannot. He's mad that his body is rebelling against him and everything hurts. He's mad that in addition to not getting to go where everyone else goes and doing all the fun things other 5 year olds do, he also cannot EAT anything they do. It seems cruel doesn't it? It is.

Autism is the cruelest most malicious, devious, conniving, heinous disease. If you fear the chicken pox or diarrhea more you are in big, big trouble. Because I guarantee with the new schedule autism will come a knocking at your door. And it will get in. It finds a way. Sometimes it looks like OCD, sometimes it looks like ADHD, even arthritis. "That's nuts!", you say. Not really. It should all just be called autism. Because any time pharma causes inflammation they don't want you to find out about, they just make up a word for it. Autism. Asthma. ADD. Just made up words for inflammation. Off to read ABOUT AUTISM . It's a good one, you might want to check it out yourself... Much hope for all our beautiful children. xo lj "

Lisa Goes is Contributing Editor to Age of Autism.

Comments

Visitor IH

"When the Rain Washes You Clean You'll Know"

Alison Krauss - When You Say Nothing At All

https://www.youtube.com/watch?v=1SCOimBo5tg

Visitor IH

God Moves In Mysterious Ways.

There are four things that are too mysterious for me to understand:
an eagle flying in the sky,
a snake moving on a rock,
a ship finding its way over the sea,
and a man and a woman falling in love.

we have come a ways, but the last one still puzzles me a bit.

Home Free - When A Man Loves A Woman

https://www.youtube.com/watch?v=-pygPmfGQvU

May the Lord Guide You Austin, I wish it were not so...all the best to all of Home Free.

Benedetta

Thank you Nick.
That was a wonderful tribute to Easter, with the panoramic view of Russia I suppose. Easter sunrise and Till we meet again song.

visitor IH

For all the believers in need due to autism and for our fellow believers in Russia. Love to those who do not seek peace in Russia, God loves you.

Simon Khorolskiy – God Be with You

https://www.youtube.com/watch?v=ZGWOKT7Hfvs

Visitor IH

We rest on Thee

1
We rest on Thee, our Shield and our Defender;
We go not forth alone against the foe;
Strong in Thy strength, safe in Thy keeping tender.
We rest on Thee, and in Thy Name we go.
2
Yea, in Thy Name, O Captain of salvation!
In Thy dear Name, all other names above;
Jesus our Righteousness, our sure Foundation,
Our Prince of glory and our King of love.
3
We go in faith, our own great weakness feeling,
And needing more each day Thy grace to know:
Yet from our hearts a song of triumph pealing;
We rest on Thee, and in Thy Name we go.
4
We rest on Thee, our Shield and our Defender:
Thine is the battle, Thine shall be the praise
When reigning in the Kingdom of Thy splendor;
Victors, we rest with Thee, through endless days.

God be with you Benedetta.

Benedetta

Visitor Nick;
LadyHawke holds special memories. Thank you for sharing. .

Visitor IH

Names of God - Give Me Jesus

https://www.youtube.com/watch?v=qedj7hANnmI

Visitor IH

Ladyhawke • I'll Stand By You • The Pretenders

https://www.youtube.com/watch?v=T8-SKY2bdtY

Visitor IH

Lady Gaga - Hold My Hand

https://www.youtube.com/watch?v=O2CIAKVTOrc

Visitor IH

From something with Frank to somewhere with Eva.

Eva Cassidy - Over The Rainbow

https://www.youtube.com/watch?v=2rd8VktT8xY

Visitor IH

All I am and have learned is laid at the feet of the Lord Jesus blessing his holy name for his love to me and his unspeakable grace and mercy. Praise the Lord God, Glory to God in the Highest!!!

In my life I say this with Love toward all. Autism may be challenge, but being without Jesus Christ is horrid. Thou shall Love the Lord thy God.. come unto Me the Lord says.

Bach - St Matthew Passion BWV 244 - Van Veldhoven | Netherlands Bach Society

https://www.youtube.com/watch?v=ZwVW1ttVhuQ

Benedetta

Keep and never doubt your faith again. Congratulations. I rejoice with you .

Visitor

I have returned fully to my faith and Lord. Anyone who has read my posts please forgive any sinful and loveless remarks I have uttered. The goodness of God have saved and preserved my spirit through all of this. I ask forgiveness for ay I have hurt or offended. May the gracious Love and Goodness of the Lord be with you. God is awesome and Amazing. I have only Jesus to thank.

Jesus is Lord.

For thine is the kingdom, The power, and the glory, For ever and ever. Amen.

Visitor IH

Please post my final song.

The sacrifice will make it all worthwhile. Praise the Lord Jesus, my savior, the light in the darkness.

Sarah McLachlan - Wintersong

https://www.youtube.com/watch?v=tuTWA6SBupY

Benedetta

It is hard. I am sorry Nick.
Life is just so brief, even a long one the stretches into the 90s.

Visitor IH

She's Gone

https://www.youtube.com/watch?v=JUkbC2ZrlHs

Its been 27 years, but the reality catches up to me from time in time.

The experience has given me understanding beyond imagination. I was not prepared.

Visitor IH

My precious wife was born in Canada and Gordon Lightfoot and Joni Mitchell are also Canadian. I learned a lot about the nation through my wife. She has been a dual citizen of the USA and Canada. I visited her in Canada while dating though she has no memory of it. I still honor Canadians because of this, I so loved the work of Gordon before I met her, but he helped form me. God speed Gordon. OH Canada. His passing has meaning to me.

Gordon Lightfoot - Saying Goodbye

https://www.youtube.com/watch?v=RsA7NlY1gtA

Visitor IH

Somewhere In Time (Main Theme)

https://www.youtube.com/watch?v=nzmprUUqryM

https://www.youtube.com/watch?v=MBDm9qWUFLQ

Visitor IH

"In sickness and in health"

Clint Black - When I Said I Do

https://www.youtube.com/watch?v=ZgalAdgEd-E

Benedetta

Yeah, I saw that lightfoot died the other day at 80.
I always loved that song, great song!

Visitor

Gordon Lightfoot - Wreck Of The Edmund Fitzgerald

https://www.youtube.com/watch?v=FuzTkGyxkYI

Visitor IH

Michael Pangilinan - How Am I Supposed To Live Without You

https://www.youtube.com/watch?v=eNanwOD94Uw

Visitor IH

The angels among us shining.

Collin Raye - She's With Me

https://www.youtube.com/watch?v=oj6GXVTAOiU

Visitor IH

Taylor Dayne - Love Will Lead You Back

https://www.youtube.com/watch?v=MO6xhLtfwW0

Visitor IH

Hi Benedetta,

I am fighting being taken over by the world. The song in discussion is beautiful to me, though I find earlier decades of songs more creative and beautiful to a great degree. The song we are discussing was released in: November 1971.

Here is another that just sweeps me into bliss.

Ambrosia - Biggest Part of Me

https://www.youtube.com/watch?v=bOm0Dq_kKNU

Benedetta

Visitor what a beautiful song with such pretty lyrics! Thank you. I feel like poems, words put together so perfect today.

Interesting about urinary tract infections after DPT vaccines. Those are suppose to be rare in babies, but I noticed that they are not. I had one when I was very small and ended up in the hospital with it.
It began on a really wonderful day. Mother took my sister, I and my father to her university to watch her graduate with her four year degree. She was the first in our entire family.

We wore our pink laced, matching dresses. We got to play in a special play ground with swings and slides. I watched the whole class march down the side walk into the beautiful, Roman column building.

We sat really high up on bleachers as we watched and that was when I began to hurt.

Mother always wondered why? So now we have our answer.
If you live long enough, answers will come.

Visitor IH

Al Green - Let's Stay Together

https://www.youtube.com/watch?v=XXx6RDzR6eM

Visitor IH

“‘“The Lord bless you
and keep you;
25 the Lord make his face shine on you
and be gracious to you;
26 the Lord turn his face toward you
and give you peace.”’
God is good. Love to all.

Visitor IH

An infant does not have to die from SIDS to have systemic developmental issues arise from an environmental insult while having a genetic predisposition to damage from said insult. The scenarios in these to reports describe effects that many who survive with Autism appear to have.

Possible pathomechanisms of sudden infant death syndrome: key role of chronic hypoxia, infection/inflammation states, cytokine irregularities, and metabolic trauma in genetically predisposed infants

Abstract
"Chronic hypoxia, viral infections/bacterial toxins, inflammation states, biochemical disorders, and genetic abnormalities are the most likely trigger of sudden infant death syndrome (SIDS). Autopsy studies have shown increased pulmonary density of macrophages and markedly more eosinophils in the lungs accompanied by increased T and B lymphocytes. The elevated levels of immunoglobulins, about 20% more muscle in the pulmonary arteries, increased airway smooth muscle cells, and increased fetal hemoglobin and erythropoietin are evidence of chronic hypoxia before death. Other abnormal findings included mucosal immune stimulation of the tracheal wall, duodenal mucosa, and palatine tonsils, and circulating interferon. Low normal or higher blood levels of cortisol often with petechiae on intrathoracic organs, depleted maternal IgG antibodies to endotoxin core (EndoCAb) and early IgM EndoCAb triggered, partial deletions of the C4 gene, and frequent IL-10-592*A polymorphism in SIDS victims as well as possible hypoxia-induced decreased production of antiinflammatory, antiimmune, and antifibrotic cytokine IL-10, may be responsible for the excessive reactions to otherwise harmless infections. In SIDS infants, during chronic hypoxia and times of infection/inflammation, several proinflammatory cytokines are released in large quantities, sometimes also representing a potential source of tissue damage if their production is not sufficiently well controlled, eg, by pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP). These proinflammatory cytokines down-regulate gene expression of major cytochrome P-450 and/or other enzymes with the specific effects on mRNA levels, protein expression, and enzyme activity, thus affecting metabolism of several endogenous lipophilic substances, such as steroids, lipid-soluble vitamins, prostaglandins, leukotrienes, thromboxanes, and exogenous substances. In SIDS victims, chronic hypoxia, TNF-alpha and other inflammatory cytokines, and arachidonic acid (AA) as well as n-3 polyunsaturated fatty acids (FA), stimulated and/or augmented superoxide generation by polymorphonuclear leukocytes, which contributed to tissue damage. Chronic hypoxia, increased amounts of nonheme iron in the liver and adrenals of these infants, enhanced activity of CYP2C9 regarded as the functional source of reactive oxygen species (ROS) in some endothelial cells, and nicotine accumulation in tissues also intensified production of ROS. These increased quantities of proinflammatory cytokines, ROS, AA, and nitric oxide (NO) also resulted in suppression of many CYP450 and other enzymes, eg, phosphoenolpyruvate carboxykinase (PEPCK), an enzyme important in the metabolism of FA during gluconeogenesis and glyceroneogenesis. PEPCK deficit found in SIDS infants (caused also by vitamin A deficiency) and eventually enhanced by PACAP lipolysis of adipocyte triglycerides resulted in an increased FA level in blood because of their impaired reesterification to triacylglycerol in adipocytes. In turn, the overproduction and release of FA into the blood of SIDS victims could lead to the metabolic syndrome and an early phase of type 2 diabetes. This is probably the reason for the secondary overexpression of the hepatic CYP2C8/9 content and activity reported in SIDS infants, which intensified AA metabolism. Pulmonary edema and petechial hemorrhages often present in SIDS victims may be the result of the vascular leak syndrome caused by IL-2 and IFN-alpha. Chronic hypoxia with the release of proinflammatory mediators IL-1alpha, IL-1beta and IL-6, and overloading of the cardiovascular and respiratory systems due to the narrowing airways and small pulmonary arteries of these children could also contribute to the development of these abnormalities. Moreover, chronic hypoxia of SIDS infants induced also production of hypoxia-inducible factor 1alpha (HIF-1alpha), which stimulated synthesis and release of different growth factors by vascular endothelial cells and intensified subclinical inflammatory reactions in the central nervous system, perhaps potentiated also by PACAP and VIP gene mutations. These processes could lead to the development of brainstem gliosis and disorders in the release of neuromediators important for physiologic sleep regulation. All these changes as well as eventual PACAP abnormalities could result in disturbed homeostatic control of the cardiovascular and respiratory responses of SIDS victims, which, combined with the nicotine effects and metabolic trauma, finally lead to death in these often genetically predisposed children."

https://pubmed.ncbi.nlm.nih.gov/15543094/

Urinary tract diseases revealed after DTP vaccination in infants and young children: cytokine irregularities and down-regulation of cytochrome P-450 enzymes induced by the vaccine may uncover latent diseases in genetically predisposed subjects

Abstract
"Prophylactic vaccinations may sometimes shorten the incubation period of some illnesses and/or convert a latent infection/inflammation into a clinically apparent disease. Cytokines play a major role in mediating the inflammatory process in various clinical entities and represent a potential source of tissue damage if their production is not sufficiently well controlled. It seems that irregularities in production of proinflammatory cytokines may be responsible for the abnormalities associated with full-blown clinical symptoms of various urinary tract diseases observed after DTP vaccination in 13 infants and young children hospitalized over the past 24 years. On admission, upper respiratory tract diseases, atopic dermatitis, and/or latent urinary tract infection/inflammation were found in these children. It is suggested that the whole-cell pertussis present in DTP vaccine, acting as an excessive stimulus in these patients, produced symptoms reminiscent of biologic responses to circulating proinflammatory monokines such as IL-1beta, TNF-alpha, and IL-6 because earlier it was reported that in vitro the whole-cell vaccine induced significantly more such cytokine production than did the acellular pertussis or diphtheria-tetanus-only vaccine. Analysis of the cellular immune disturbances previously reported in urinary tract infection/inflammation (increased serum and/or urinary IL-1alpha, IL-1 receptor antagonist, IL-6 and IL-8), steroid-sensitive nephrotic syndrome (increased IL-2, IFN-gamma, TNF-alpha, and decreased or increased IL-4, depending on the cells studied), and atopic dermatitis (decreased IFN-gamma and increased IL-4 production), may suggest that similar subclinical chronic cytokine-mediated abnormalities produced in the course of latent diseases revealed in our patients, combined with those caused by DTP vaccination stimulus, were responsible for the pathomechanism of these clinical entities. This speculation is in agreement with the reports on the long-lasting induction of cytokine release and down-regulation of hepatic cytochrome P-450 isoenzyme activities after administration of DTP vaccine to mice and may be supported by the fact that TH1 phenotype is associated with the up-regulation of intercellular adhesion molecule-1 and RANTES, whereas TH2 phenotype is associated with the up-regulation of the vascular cell adhesion molecule and P-selectin, which are key players in the migration into inflamed tissues and localization of lymphocytes and other allergic effector and inflammatory cells. Because several inflammatory cytokines down-regulate gene expression of major cytochrome P-450 and/or other enzymes with the specific effects on mRNA levels, protein expression, and enzyme activity, thus affecting the metabolism of several endogenous lipophilic substances such as steroids, lipid-soluble vitamins, prostaglandins, leukotrienes, thromboxanes, and exogenous substances, their irregularities in the body may eventually lead to the flare of latent diseases in some predisposed subjects. Also, interleukin genetic polymorphisms, especially the constellation of TNF-alpha and IL-6 genetic variants, might predispose some infants with infection to a more than usually intense inflammatory response in the kidneys after vaccination. It seems that the aforementioned pathomechanism may also be responsible for some cases of sudden infant death syndrome, which is often preceded by infection/inflammation."

https://pubmed.ncbi.nlm.nih.gov/15356430/

Visitor IH

Benedetta,

We share things that manifest themselves in the unassuming mind. That has left us searching and trusting, while hoping. Trios IV and I appreciate you and wish you and I well. I do hope you are finding good in life as you do what is blessed and I feel you have done your best. I too find you thoughtful and a kindred spirit.

SINCE I have done my best, I do
Not fear the outcome; here I stand
Prepared for judgment when men view
The labor of my heart and hand.
If good, then happy I shall be,
If not, contented I'll abide,
And though the prize is not for me,
My joy shall be in having tried.

Since I have done my best, there is
No cause for me to sit and sigh,
Although the laurel wreath I miss,
My eyes shall smiling be and dry;
No vain excuses shall I make
For failing, and no vain regret,
But bravely judgment I shall take,
And say: 'A better man I've met.'

Since I have done my best, I'll go
Whenever God shall summon me,
Contented, for right well I know
However poor my record be
That, having nothing to regret,
No shame that I would seek to hide,
The Master's praises I shall get
For honest effort when I tried.

Edgar Albert Guest

Beneath Still Waters"
From 1979's 'Blue Kentucky Girl

https://youtu.be/TQ4jehpLCT0

Kate C

What a gorgeous piece of music! I’ve always loved the bass viol, it adds so much depth to music.

Benedetta

Visitor:
I meant to respond to your thoughts on hypothalamus repair.
Mostly a thank you for your thoughtfulness .

2007 was a very, very busy time in my life , so I did not even know that Delp was dead! Great song though.

I swear I loved the new music coming out even up into 2007, but right now; nothing that is new on the radio seems appealing

Visitor IH

I want to know are we...Boston - More Than A Feeling. The lead singer killed himself. Did he know something? I have always absolutely adored this song. What the hell are we?

Boston - More Than A Feeling

https://www.youtube.com/watch?v=zOILAZHf2pE

Visitor IH

Hi Kate C,

I'm glad you're glad.

Bach - Violin Concerto in E major BWV 1042 - Sato | Netherlands Bach Society

https://www.youtube.com/watch?v=QyZIU--9q88


Kate C

So glad to see you back posting articles. I will read this several times, but the findings on first reading are so interesting. Inflammation, inflammation, inflammation! Kate C

Visitor IH

Wrong address for second report in last post. Correct one is:

Understanding Brain Diseases: From Receptor Dysregulation to Neurodegeneration, Neuroinflammation and Memory Impairment

https://www.ingentaconnect.com/content/ben/cn/2023/00000021/00000002/art00003?crawler=true&mimetype=application/pdf

Visitor IH

Excellent report.

Neuron-specific transcriptomic signatures indicate neuroinflammation and altered neuronal activity in ASD temporal cortex

Significance
We present a comprehensive assessment of neuronal cell-type-specific gene expression and alternative splicing changes in ASD cortex, directly comparing RNA-seq results from bulk tissue with isolated neurons. We observe strong signatures of cell stress and neural-immune/inflammatory pathway activation present within ASD neurons—a signal that is typically attributed to astrocyte/microglial populations. Our findings also provide further evidence for the hypothesized imbalance of excitatory to inhibitory neuronal activity in the brains of individuals with ASD. Moreover, we find that the transcriptomic architecture of ASD interacts substantially with age, thus revealing windows of opportunity for treatments that target specific molecular pathology.
Abstract
Autism spectrum disorder (ASD) is a highly heterogeneous disorder, yet transcriptomic profiling of bulk brain tissue has identified substantial convergence among dysregulated genes and pathways in ASD. However, this approach lacks cell-specific resolution. We performed comprehensive transcriptomic analyses on bulk tissue and laser-capture microdissected (LCM) neurons from 59 postmortem human brains (27 ASD and 32 controls) in the superior temporal gyrus (STG) of individuals ranging from 2 to 73 years of age. In bulk tissue, synaptic signaling, heat shock protein-related pathways, and RNA splicing were significantly altered in ASD. There was age-dependent dysregulation of genes involved in gamma aminobutyric acid (GABA) (GAD1 and GAD2) and glutamate (SLC38A1) signaling pathways. In LCM neurons, AP-1-mediated neuroinflammation and insulin/IGF-1 signaling pathways were upregulated in ASD, while mitochondrial function, ribosome, and spliceosome components were downregulated. GABA synthesizing enzymes GAD1 and GAD2 were both downregulated in ASD neurons. Mechanistic modeling suggested a direct link between inflammation and ASD in neurons, and prioritized inflammation-associated genes for future study. Alterations in small nucleolar RNAs (snoRNAs) associated with splicing events suggested interplay between snoRNA dysregulation and splicing disruption in neurons of individuals with ASD. Our findings supported the fundamental hypothesis of altered neuronal communication in ASD, demonstrated that inflammation was elevated at least in part in ASD neurons, and may reveal windows of opportunity for biotherapeutics to target the trajectory of gene expression and clinical manifestation of ASD throughout the human lifespan....

Given mounting evidence suggesting potential mechanistic overlap between neurodevelopmental and neurodegenerative disorders, particularly with respect to genes involved in synapse and brain connectivity (24), we evaluated the overlap between our ASD findings with published results in Alzheimer’s disease (AD). Using results from Mount Sinai/JJ Peters VA Medical Center Brain Bank (MSBB) cohort (25), we demonstrated that the changes we detected in ASD were significantly overlapped with transcriptomic alterations observed in AD from the same brain region (Odds Ratio = 1.6, P = 1.9 × 10−8, SI Appendix, Fig. S8).

https://www.pnas.org/doi/10.1073/pnas.2206758120

This is also good.

Understanding Brain Diseases: From Receptor Dysregulation to Neurodegeneration, Neuroinflammation and Memory Impairment

file:///C:/Users/Nick/Downloads/002AC.pdf


Visitor IH

Last May I posted some the article "Recurrent UTIs linked to gut microbiome, chronic inflammation" and linked it. Here is a part of the article for the current purpose about butyrate and another article I am referencing about chronic fatigue. I have seen the linkage through my own study and wife's condition, but now it is being asserted by credentialed researchers. I had said my wife had chronic fatigue, leaky gut, and chronic urinary tract infections back in 96. These were a part of the picture.

Here is the piece I previously linked...
Recurrent UTIs linked to gut microbiome, chronic inflammation

"The real difference was in the makeup of their gut microbiomes. Patients with repeat infections showed decreased diversity of healthy gut microbial species, which could provide more opportunities for disease-causing species to gain a foothold and multiply. Notably, the microbiomes of women with recurrent UTIs were particularly scarce in bacteria that produce butyrate, a short-chain fatty acid with anti-inflammatory effects."

https://medicine.wustl.edu/news/recurrent-utis-linked-to-gut-microbiome-chronic-inflammation/

Now the one from the researcher I mentioned speaking about chronic fatigue and butyrate.

More Clues into ME/CFS Discovered in Gut Microbiome

"Of particular note, Williams team found that people with ME/CFS had abnormally low levels of several bacterial species, including Faecalibacterium prausnitzii (F. prausnitzii) and Eubacterium rectale. Both bacteria ferment non-digestible dietary fiber in the GI tract to produce a nutrient called butyrate. Intriguingly, Oh’s team also uncovered changes in several butyrate-producing microbial species, including F. prausnitzii.

Further detailed analyses in the Williams lab confirmed that the observed reduction in these bacteria was associated with reduced butyrate production in people with ME/CFS. That’s of special interest because butyrate serves as a primary energy source for cells that line the gut. Butyrate provides those cells with up to 70 percent of the energy they need, while supporting gut immunity.

Butyrate and other metabolites detected in the blood are important for regulating immune, metabolic, and endocrine functions throughout the body. That includes the amino acid tryptophan. The Oh team also found all ME/CFS participants had a reduction in gut microbes associated with breaking down tryptophan.

While butyrate-producing bacteria were found in smaller numbers, other microbes with links to autoimmune and inflammatory bowel diseases were increased. Williams’ group also reported an abundance of F. prausnitzii was inversely associated with fatigue severity in ME/CFS, further suggesting a possible link between changes in these gut bacteria and disease symptoms."

https://directorsblog.nih.gov/2023/02/14/more-clues-into-me-cfs-discovered-in-gut-microbiome/

One more for good measure.

9 Health Benefits Of Butyrate For Your Body And Gut

5. Plug a leaky gut

Your gut lining needs butyrate to stay healthy and function properly. It’s as simple as that.

The gut lining is an intestinal barrier. It selectively allows things like vitamins and minerals to leave the gut, enter the bloodstream, and travel to where they’re needed. Equally, it stops toxins, pathogens, and food compounds from entering the bloodstream and making you ill.

The process is called intestinal permeability by doctors and scientists. When the barrier is healthy, small holes called tight junctions relax, allowing water and nutrients to pass through.

Innocuous habits, like frequent snacking, stop these tight junctions from closing between meals, so bacteria and unwanted substances things can enter your bloodstream. This is leaky gut.photo_2019-05-13-15.17.17What is leaky gut and what’s my lifestyle got to do with it?
The butyrate produced by your gut microbes from the dietary fiber provides the fuel needed by the cells in your gut lining. By doing so, it preserves the integrity of your gut lining, preventing leaky gut from occurring.

https://atlasbiomed.com/blog/9-reasons-why-your-gut-needs-butyrate/

Visitor

I watched the half time show of the Supper Bowl last night and remembered 30 years ago when real talent was on stage, so sad.

Michael Jackson - Super Bowl XXVII 1993 Halftime Show

https://www.youtube.com/watch?v=EsopN7JKUVs

Visitor

As the shadow differs from the image the mind differs from the interpretation.

I think the following diagnosis and treatment came about in 2017 from the cited studies. it looks to some part to contain some fundamentals of the treatment I provided for my wife, but as I effected this treatment at 30 it was exponentially more difficult to understand and treat. It is such a blessing as she was caught so early in life. Nice to see professionals apply true treatment for some variations of this monstrous condition.

23-Month-Old Female with Regressive Autism

https://www.drkarafitzgerald.com/2017/08/30/23-month-old-female-with-regressive-autism/

I may have breeched my agreement as though two songs were linked, it was the same song. Have mercy please Kim. Bless you my sister. It will not happen again. Someone else is posting as "Visitor" at AoA as well. I have only posted twice since Christmas eve.

Intermezzo from Cavalleria Rusticana, Pietro Mascagni

https://www.youtube.com/watch?v=BIQ2D6AIys8

Visitor

Benedetta,

I have formulated some replies as to hypothalamic repair. I will say the wholistic approach in our case effected repair. I have found Doctors and researchers who give plausible pathology of repair, but I grow weary of speculation as an answer. I think of you regularly and will not respond to your query without a better grasp of the mechanism of repair. Though, a big step was taken when it was understood that certain neurons can be replaced or regenerated, which I felt had to be the case before it was accepted.

With the below I accentuate, feeling...or the lack thereof.

https://www.researchgate.net/figure/Non-conceptual-phenomenal-projection-The-sense-of-self-emerges-in-the-sphere-of-feeling_fig6_330320026#:~:text=The%20sense%20of%20self%20emerges%20in%20the%20sphere%20of%20feeling,Merleau%2DPonty%2C%201945).


Adele - Make You Feel My Love

https://www.youtube.com/watch?v=QVeubNxaBsg

... and the version I most appreciate.

Make You Feel My Love - Bob Dylan - Cover by Emily Linge

https://www.youtube.com/watch?v=qJu-_offsGI

Visitor

"Therefore let all the house of Israel know assuredly, that God hath made that same Jesus, whom ye have crucified, both Lord and Christ." Have mercy Lord.

God Bless us everyone. Merry Christmas

Benedetta

NAD+ supplements
That would be found in dairy, milk and fish and such.

That leads me back to diet. and it all keeps changing.
And fasting is coming into play. We have fasted before, as far back as the mid 90s.
He is convinced by the studies that there should be
No processed foods for sure, and no vegetable oils. they now know for a fact that it causes INFLAMATION,!

I am reading the "Obesity Code" written by some kidney doctor and he has tons of studies and making heads and tails out of them too. He said diabetes lead to kidney problems and insulin too much was leading to diabetes 2

That too much INSULIN and too much cortisone hormones cause inflammation too. Those two hormones.

He talks about the hypothalamus and how lesions can cause obesity. On and on.

That calories , and calories out do not explain obesity. I am surprised.

Vinegar to my surprise stops insulin spikes. Two teaspoons in a drink right before or while eating carbohydrates.

I might have made a mistake of giving up whole milk, but not low fat and skim milk. Whole milk, a steak and especially whey may still cause insulin spikes but they also causes the stomach to produce hormones that cause satiety. That is a nice word.
There are all kinds of great nuggets in the book.

Can hypothalamus if injured be repaired?

Visitor

(I Just) Died In Your Arms - Cutting Crew - Cover by Emily Linge

https://www.youtube.com/watch?v=lag6l-7S2GE

TRPM8 and body temperature effect neuron migration.

Visitor

Genomics and AI Spot Genetic Marker for Autism

"The Oak Ridge National Laboratory researchers discovered a significant site in the ACMSD (Aminocarboxymuconate Semialdehyde Decarboxylase) gene that is part of the kynurenine pathway and plays a role in the breakdown of tryptophan. According to the researchers, the ACMSD gene “lies at the nexus of numerous ASD-associated traits including neuroinflammation, sleep disorder, mitochondrial dysfunction, gastrointestinal abnormalities, and altered circadian rhythms.”

https://www.psychologytoday.com/us/blog/the-future-brain/202212/genomics-and-ai-spot-genetic-marker-autism

Not just in non verbal. Many conditions associated with ACMSD.

Structural variants identified using non-Mendelian inheritance patterns advance the mechanistic
understanding of autism spectrum disorder

We then identify an SV in the GRIK2 gene that alters RNA splicing and a regulatory region of the ACMSD gene in the kynurenine pathway as significantly associated with a non-verbal ASD phenotype, supporting our hypothesis that these currently excluded loci can provide a clearer mechanistic understanding of ASD. Finally, we use an explainable artificial intelligence approach to define subgroups demonstrating their use in the context of precision medicine.

https://reader.elsevier.com/reader/sd/pii/S2666247722000677?token=103E941B5E7D00B27468DC43BA274FF39AE8CE3D0F5E6042A601F142CD12F56DB89F2C87F7ADD70DE643AA1742C822C9&originRegion=us-east-1&originCreation=20221210161548

The Role of Kynurenine Pathway and NAD+ Metabolism in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious, complex, and highly debilitating long-term illness. People with ME/CFS are typically unable to carry out their routine activities. Key hallmarks of the disease are neurological and gastrointestinal impairments accompanied by pervasive malaise that is exacerbated after physical and/or mental activity. Currently, there is no validated cure of biomarker signature for this illness. Impaired tryptophan (TRYP) metabolism is thought to play significant role in the pathobiology of ME/CFS. TRYP is an important precursor for serotonin and the essential pyridine nucleotide nicotinamide adenine dinucleotide (NAD+). TRYP has been associated with the development of some parts of the brain responsible for behavioural functions. The main catabolic route for TRYP is the kynurenine pathway (KP). The KP produces NAD+ and several neuroactive metabolites with neuroprotective (i.e., kynurenic acid (KYNA)) and neurotoxic (i.e., quinolinic acid (QUIN)) activities. Hyperactivation of the KP, whether compensatory or a driving mechanism of degeneration can limit the availability of NAD+ and exacerbate the symptoms of ME/CFS. This review discusses the potential association of altered KP metabolism in ME/CFS. The review also evaluates the role of the patient’s gut microbiota on TRYP availability and KP activation. We propose that strategies aimed at raising the levels of NAD+ (e.g., using nicotinamide mononucleotide and nicotinamide riboside) may be a promising intervention to overcome symptoms of fatigue and to improve the quality of life in patients with ME/CFS. Future clinical trials should further assess the potential benefits of NAD+ supplements for reducing some of the clinical features of ME/CFS.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9116917/

Visitor

The glory of love and the gift of ignorance meet.

Sometimes When We Touch. This is my reality.

https://www.youtube.com/watch?v=NhzzDaUizas

Love making an effort.

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ETV4 promotes late development of prostatic intraepithelial neoplasia and cell proliferation through direct and p53-mediated downregulation of p21

https://jhoonline.biomedcentral.com/articles/10.1186/s13045-020-00943-w

I give up.

Visitor

I am deeply indebted to all the scientists who have taught me and helped me in my understanding. Equally, if not more so, are the musicians who interpreted spirit into being. God bless you all. The spirit end has led me.

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Broad transcriptomic dysregulation occurs across the cerebral cortex in ASD

"We find widespread transcriptomic changes across the cortex in ASD, exhibiting an anterior-to-posterior gradient, with the greatest differences in primary visual cortex, coincident with an attenuation of the typical transcriptomic differences between cortical regions."

"Notably, ETV4, which is known to have an important role in dendrite development, connectivity and plasticity and its expression—which is normally higher posteriorly (BA17) than anteriorly (BA4/6)—is significantly attenuated, diminishing this gradient in ASD16."

https://www.nature.com/articles/s41586-022-05377-7#Fig2

HIF dependent and independent transcriptional regulation of the human
PHD2 promoter

https://www.zora.uzh.ch/id/eprint/56116/1/Wollenick.pdf

Filmmaking and Cinematography Techniques: Blade Runner 2049

https://www.youtube.com/watch?v=lF5lmYgoYEM

Gata3 mir-155

Visitor

John Stone,

I have not been able to get up off the floor. If I can I will fight again. Blessings upon you.

Visitor

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The Lord God is my only hope.

Susan Ashton - Stand

https://www.youtube.com/watch?v=ElsOrzpD3mI

Visitor

The Legend of 1900 (1998) - 'Playing Love'

https://www.youtube.com/watch?v=MUIgReYNMac

Visitor

Frank Sinatra - Luck Be A Lady

https://youtu.be/X69P_Vce9vw

Visitor

I should give a disclaimer in part for my appreciation of Frank Sinatra. I played Nathan Detroit in our High School play. What a time.

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Many have called his the best American music ever sung and the best American voice that ever sang, echoing through the years.

As Frank Sinatra himself told it, it all began with a nickelodeon.

"My father had a piano that was a nickelodeon - put a nickel, and the roller would play," he told CBS News in 1985. "I was about 11 years old or so, and I remember the song was called Honest and Truly, and I had a voice that was like a siren - way up there. And some of the guys would pick me up and put me on the piano, and I would sing along with the piano, and they'd give me a dime, and I thought one day, 'What a great racket this is.'"

Richard Burton said at a tribute to Frank Sinatra: "This is a party for him as friend".

I don't know for sure Kim if this was part of your statement, but I endeavor to understand things. They sometimes are so close I understand them late. Thank you Kim. You are a strong, smart, and brave person.

Visitor

Integration of Transcriptome and Exome Genotyping Identifies Significant Variants with Autism Spectrum Disorder

"All the significantly upregulated and downregulated genes were searched for during the GO and pathway enrichment analysis. Significantly upregulated genes and their interactions (Figure 4) revealed highly significant protein–protein interactions based on the predictive model enrichment (p-value: <1.0 × 10−16). Downregulated genes (p-value < 0.001) and their interactions (Figure 4) demonstrated significant PPI enrichment with a p-value = 2.05 × 10−6. Pathway enrichment by the significantly upregulated and downregulated genes is presented in Table 5. Ribosome, oxidative phosphorylation, protein export, Parkinson’s disease, and Alzheimer’s disease-associated pathways were significantly enriched by the upregulated genes (Table 5). The impact on the genetic information processing and translation was significantly enriched by the 17 upregulated genes through the ribosome pathway. The HIF-1 signaling pathway, pyruvate metabolism, propanoate metabolism, metabolic pathways, the rap1 signaling pathway, the AMPK signaling pathway, the glucagon signaling pathway, proteoglycans in cancer, renal cell carcinoma, fatty acid biosynthesis, the insulin signaling pathway, and EGFR tyrosine kinase inhibitor resistance were significantly enriched by the downregulated genes (Table 5).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880056/

Potential Cross Talk between Autism Risk Genes and Neurovascular Molecules: A Pilot Study on Impact of Blood Brain Barrier Integrity

"Analyses of Human Genetic Risk Variants in Children with ASD
Multiple previous pathway analyses of ASD risk genes implied that immune and microglia signaling is important in ASD pathogenesis. These also suggested that neurovascular signaling is important, either causing or perhaps modifying ASD risk [34]. Weighted gene set enrichment analysis on the dataset of 2631 genes using the KEGG pathway database resulted in a network of 61 pathways at a significance level of 0.001. These pathways comprised a group of 659 distinct genes. The most prominent pathways featured in the subject database with respect to the largest number of genes were the mitogen-activated protein kinase (MAPK) and Rat sarcoma virus (RAS) signaling pathways, lysosome, long-term depression, GAP junction, and PI3K-Akt signaling pathway (Figure 1B).
A Weighted Panther Pathway enrichment analysis for protein–protein interactions (PPI) (Figure 2) on the dataset of 659 distinct genes resulted in a network of 12 signaling pathways at a significance FDR < 0.05. The most prominent pathways featured in the subject database with respect to the largest number of genes were the fibroblast growth factor (FGF), RAS, T and B cell activation, endothelin, integrin, transforming growth factor (TGF)-beta, angiogenesis, & Hedgehog signaling pathways (Figure 1B)."

"Panther pathways analyses identified 30+ genes which were expressed in neural circuits that are significantly associated with answers on the PCQ and Vineland (Figure 3 and Figure 4, Table 2 and Table 3). Signaling pathways included: (1) Hypoxia response via hypoxia-inducible factor 1 (HIF-1) activation (p = 0.0002); (2) Interleukin signaling (p = 0.0003); (3) p53 pathway (p = 0.005); (4) CHEK2 signaling (p = 0.006); (5) Insulin/IGF (insulin growth factor) pathway-protein kinase B signaling (p = 0.01); (6) PI3 kinase signaling (p = 0.02); (7) vascular endothelial growth factor (VEGF) signaling pathway; (p = 0.03); and (8) RAS pathway (p = 0.04) among the whole group comparison. In a whole group comparison, only the parent report of self-stimulatory behavior (PCQ12) on the PCQ demonstrated a significant difference between those with CNVs and those with normal microarrays (Table 2). The Vineland scales and other PCQ questions showed no significant findings between the two groups. However, when we divided the groups into ASD subjects with specific genetic variations among distinct RDoC neural circuits (Table 2 and Table 3), distinct findings were observed with questions related to anxiety on the PCQ and skills on the Vineland related to Activities of Daily Living (ADLs) and Motor function. Anxiety behaviors on the PCQ was significant (Figure 3) in the Positive Valence neural circuits with antenatal expression of two genes, each of which is involved in PI3K/Akt/mTOR-Vit D3 (p = 0.00009), Lipid metabolism (p = 0.0001), IL-11 (p = 0.0003), Amino acid metabolism (p = 0.001), androgen receptor (p = 0.001), and TGF beta (p = 0.003) signaling pathways, within related subcortical (Amy, STR) and limbic system (ACC) regions (Table 3). Cognitive control of anxiety is well known, and cognitive behavioral therapy is well established as a treatment for anxiety [35]. Similarly, anxiety behaviors on the PCQ were significantly associated with worse scores when nine genetic variants with antenatal expression were involved in Estrogen signaling (p = 0.000003), DNA IR-damage and cellular response via Ataxia telangiectasia (ATR) (p = 0.0001), tumor necrosis factor (TNF)alpha signaling (p = 0.0002), B Cell Receptor Pathway (p = 0.0003), PI3K/Akt/mTOR-Vit D3 signaling (p = 0.0004), and angiogenesis (p = 0.0004) in the Cognitive Systems brain regions (Figure 3, Table 3). Social communication is often linked to anxiety [36]. Anxiety PCQ behavioral scores from parents were significantly worse with antenatal expression of 11 gene variants involved with estrogen (p = 0.000005), leptin (p = 0.0002) and TNF alpha signaling (p = 0.0003)) within social communication regions (Figure 3, Table 3)."

https://www.mdpi.com/2073-4409/11/14/2211/htm

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Inflammation and Autophagy: A Convergent Point between Autism Spectrum Disorder (ASD)-Related Genetic and Environmental Factors: Focus on Aluminum Adjuvants

https://www.mdpi.com/2305-6304/10/9/518/htm

Visitor

Truth and attraction are incredibly powerful. Mixed with desire for learning and truth as in the below music video I see slight shades of my beloved.

Both Sides, Now - Joni Mitchell - Cover by Emily Linge

Visitor

The best Frank Sinatra story you will ever hear.

https://www.youtube.com/watch?v=-M8DH-YrmCg

Blade Runner 2049 / Frank Sinatra - One for my baby (and one more for the road)
A good bit of autism and virtual reality, at least for me.

https://www.youtube.com/watch?v=plSpRIC0ipA

Visitor

I could keep posting clear relevant scientific reports, but it seems it would matter little.

Here is a series of songs that speaks to mentally competent though imperfect people contrasted with neurodevelopmentally challenged people set to songs. Babies cry until there needs are met and that me be a challenge. Some cry in unusual ways throughout the years.

https://www.youtube.com/watch?v=SGyOaCXr8Lw

https://www.youtube.com/watch?v=tNdBLBleO90

https://www.youtube.com/watch?v=9iw_BE_X9sA

https://www.youtube.com/watch?v=5dBENngNDhs

https://www.youtube.com/watch?v=dmhtxLSUhYU

https://www.youtube.com/watch?v=zRZpaxBMJRU

One for me and my crybaby.

Left Banke - Walk Away Renee

https://www.youtube.com/watch?v=YbYZEQjTMMY

Visitor

Zac Brown Band - Colder Weather

I'm with your ghost again

https://www.youtube.com/watch?v=oouFE51HcqM

If I had mercy on me I would end this. They shoot horses don't they?

For the last post.

Ruby Tuesday

https://www.youtube.com/watch?v=VWJg6OTESns

I will be assimilated.

YES1

https://www.genecards.org/cgi-bin/carddisp.pl?gene=YES1

Co-Trimoxazole Allergy 64
Bactrim Allergy
Cotrimoxazol Allergy
Tmp/Smx Allergy
Trimethoprim/Sulfamethoxazole Allergy

https://www.malacards.org/card/co_trimoxazole_allergy

1 Innate Immune System 66Show member pathways 13.89 YES1 SYK STAT6 LYN LCK HLA-B
2 Disease 66Show member pathways 13.76 YES1 SYK LYN LCK KIT HLA-B
3 Signal Transduction 66 13.72 CXCL9 FRK FYN KIT LCK LYN
4 Class I MHC mediated antigen processing and presentation 66Show member pathways 13.46 YES1 SYK LYN LCK HLA-B FYN
5 Prolactin Signaling 64Show member pathways 13.41 SYK STAT6 PIK3C2A LYN LCK FYN
6 Response to elevated platelet cytosolic Ca2+ 66Show member pathways 13.23 YES1 SYK LYN LCK FYN FGR
7 Cytokine Signaling in Immune system 66Show member pathways 13.23 YES1 SYK STAT6 LYN LCK HLA-B
8 ADORA2B mediated anti-inflammatory cytokines production 66Show member pathways 13.09 YES1 SYK LYN HCK FYN FGR
9 TCR Signaling (Qiagen) 64Show member pathways 12.85 SYK STAT6 LYN LCK FYN
10 Signaling by Receptor Tyrosine Kinases 66 12.75 YES1 STAT6 LYN LCK KIT FYN

YAP1 Gene

https://www.genecards.org/cgi-bin/carddisp.pl?gene=YAP1

sex hormone-binding globulin measurement

polycystic ovary syndrome

migraine disorder, pulse pressure measurement

pulse pressure measurement

migraine disorder

Autism spectrum disorder: a neuro-immunometabolic hypothesis of the developmental
origins

"The proposed neuro-immunometabolic hypothesis can be used in future in vivo studies to
probe causally for the role of the immunometabolic gene and protein networks in ASD etiology, in
particular in the areas described as being the core of both the prediction processing network and
contextual fear memory, the anterior cingulate cortex.[57–59] Indeed, a recent study reported that
an immunometabolic dysregulation reduces the thickness of the anterior cingulate cortex, while
another study revealed 1,223 differentially methylated genes (5,018 Differentiated Methylated
Regions, DMRs) in this brain region 4 weeks after contextual fear conditioning.[60,61] In another
most recent study in a human cohort of stressed pregnant mothers and their newborns, we
identified novel associations between newborn epigenome-wide methylation status in saliva and
chronic stress suffered by the mother during pregnancy.[62] Among the positively associated
CpGs is the CpG annotated to YAP1 (Yes1 regulated transcription factor) whose deletion has
been related to reactive astrogliosis and astrocyte-driven microglial activation.[63] The protein of
another gene (CSMD1, CUB And Sushi Multiple Domains 1) associated to maternal cortisol,
CSMD1, seems to play a crucial role in regulating complement activation and inflammation in the
developing brain.[64,65] Two DMRs were also found annotated to DAXX (Death-associated
protein 6) and ARL4D (ADP- Ribosylation factor 4D), which together with CSMD1 have all been
directly or indirectly involved in neurodevelopmental disorders such as ASD, highlighting the
impact of prenatal stress on the epigenetic landscape of the newborn in genes associated to
neuroinflammation and ASD.[66–70]
Moreover, inflammatory priming in maternal immune activation (MIA) in general, can
substantially alter neurodevelopment.[71] Specifically, microglia as the key players in MIA can
modify neurogenesis, maturation of synapses and neural circuits. MIA due to various triggers,
bacterial/viral or autoimmune triggers, as reviewed extensively elsewhere,[71] can influence the
efficacy of microglia to sculpt neuronal connections. This can result in a dysfunctional
neurodevelopment culminating in ASD and other neurodevelopmental disorders in the offspring
such as attention-deficit/hyperactivity disorder and Tourette syndrome. Hence, inclusion of MIA
studies might lead to additional insights into the role of neuro-immunometabolic changes in
neurodevelopmental disorders such as ASD.
The therapeutic approaches may include prenatal and early neonatal screening using
early biomarkers of altered brain development due to intrauterine exposure to stress or
inflammation, followed by early postnatal reprogramming of these effects using behavioral (e.g.,
environmental enrichment) or bioelectronic tools to correct brain developmental trajectories at an
early stage.[2,72–74] "

https://arxiv.org/ftp/arxiv/papers/1909/1909.05198.pdf

Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome

Anaerobic threshold and recovery time after exercise depend on rates of lactate production and clearance. Lactate is made from pyruvate, mostly arising from glucose catabolism via the glycolytic pathway or from breakdown of certain amino acids. Under normal aerobic conditions, pyruvate is transported into mitochondria, where it is converted to acetyl-CoA by the pyruvate dehydrogenase (PDH) complex. In addition, acetyl-CoA is produced independently of PDH, via degradation of fatty acids and ketogenic amino acids. The acetyl-CoA formed in these processes is further oxidized in the TCA cycle and thereby serves to fuel mitochondrial respiration and adenosine triphosphate (ATP) production by oxidative phosphorylation. Under anaerobic conditions, when lack of oxygen prohibits mitochondrial respiration, pyruvate builds up in cytosol, which leads to increased production and cellular excretion of lactate. Mitochondrial dysfunction leads to both excessive lactate production and a deficient supply of ATP (16) and has been suggested to play a role in ME/CFS (17). PDH functions as a gateway in oxidative metabolism by coordinating the breakdown of 2- and 3-carbon energy substrates derived from carbohydrates, fats, and amino acids (18). A reduction in PDH enzymatic activity may lead to accumulation of pyruvate and thereby cause overproduction of lactate, even in the presence of adequate oxygen levels (16). In addition to allosteric regulation, PDH activity is controlled by PDH kinases (PDKs) that inhibit PDH enzyme activity by phosphorylation (19, 20) and PDH phosphatases that catalyze reciprocal dephosphorylation (18). Sirtuin 4 (SIRT4) was recently identified as a mitochondrial lipoamidase inhibiting PDH activity (21). PDK1–PDK4 are regulated at the transcriptional level via signaling cues involving factors such as AMP-dependent protein kinase (AMPK) (22), PPARs (23), and HIF1 (24). A possible role of impaired PDH function and abnormal AMPK activation in ME/CFS has been proposed (25).

https://insight.jci.org/articles/view/89376

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372702/

https://www.genecards.org/cgi-bin/carddisp.pl?gene=PDK1

Visitor

I have paid close attention, though I don't know when I have understood. I lack in everyway.

Ruby Tuesday
Song by The Rolling Stones

She would never say where she came from
Yesterday don't matter if it's gone
While the sun is bright
Or in the darkest night
No one knows, she comes and goes
Goodbye, Ruby Tuesday
Who could hang a name on you?
When you change with every new day
Still, I'm gonna miss you
Don't question why she needs to be so free
She'll tell you it's the only way to be
She just can't be chained
To a life where nothing's gained
And nothing's lost, at such a cost
Goodbye, Ruby Tuesday
Who could hang a name on you?
When you change with every new day
Still, I'm gonna miss you
"There's no time to lose, " I heard her say
Catch your dreams before they slip away
Dying all the time
Lose your dreams and you will lose your mind
Ain't life unkind?
Goodbye, Ruby Tuesday
Who could hang a name on you?
When you change with every new day
Still, I'm gonna miss you
Goodbye, Ruby Tuesday
Who could hang a name on you?
When you change with every new day
Still, I'm gonna miss you
Source: LyricFind
Songwriters: Keith Richards / Mick Jagger

Visitor

There are reasons to live I am sure.

"I'd rather live in his world" Maybe is the case..

Gladys Knight & The Pips - Midnight Train to Georgia

https://www.youtube.com/watch?v=A0F9lh8TiSM

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"There’s a dark secret in me." I reflected my fate.

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Listed this in 1996 about my wife.

"18. Menstrual cycles that were never timely and severe pms."

I have not see this association made anywhere until this posted recently in the following:

"Premenstrual Dysphoric Disorder (PMDD) is a hormonal health condition that causes clinically significant and impairing depression, anxiety, mood swings, and uncomfortable physical symptoms in the week leading up to menses, the onset of a period. PMDD symptoms improve following menses and are minimal, if not absent, in the weeks following. PMDD disproportionately affects people with autism and ADHD. Various medications can help control PMDD symptoms1."

https://www.additudemag.com/pmdd-autism-adhd/

My wife's condition leveled her mental function in many ways beyond the issues reflected in this PMS presentation, but this is a part.

Visitor

AC/DC - Back in Black (

https://www.youtube.com/watch?v=f2p0xrY4CMs

Visitor

"The hushed morbidity." Get a clue people.

ADHD & Symptom Tests Adult ADHD
ADHD IN WOMEN
PMDD, Autism, and ADHD: The Hushed Comorbidity

"Premenstrual dysphoric disorder (PMDD) is a hormonal health condition that causes severe mood and functioning issues, and disproportionately affects people with ADHD or autism. "

My statement in 1996, "18. Menstrual cycles that were never timely and severe pms."

I feel like I am in a mentally challenged world"

https://www.additudemag.com/pmdd-autism-adhd/

Visitor

Being Democrat now is about dividing and and gaining political advantage, not about truth. as one has said "Truth is not a left wing value." I have fought them over and over gain. Democrat = narcissist. I no longer make apologies for opposing Democrats. They are generally dirty little things,

https://www.youtube.com/watch?v=hD9C5I7-FoQ

https://www.youtube.com/watch?v=L-7V_f_XK6s

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iN 1996 BEFORE EANYONE MADE AN ASSOCIATION i SAID. " 18. "Menstrual cycles that were never timely and severe pms." tHE FACTS ARE SO INCREDIBLY DEEPER, BUT NO ONE CARES.

PMDD, Autism, and ADHD: The Hushed Comorbidity

https://www.additudemag.com/pmdd-autism-adhd/

Visitor

I appreciate about 25 percent of Democrats. The rest are Deplorables.

Visitor

Cold-inducible RNA-binding protein causes endothelial dysfunction via activation of Nlrp3 inflammasome

Haman understanding prohibits a strong appreciation for many reports.

Abstract
Cold-inducible RNA-binding protein (CIRP) is a damage-associated molecular pattern (DAMP) molecule which stimulates proinflammatory cytokine release in hemorrhage and sepsis. Under these medical conditions, disruption of endothelial homeostasis and barrier integrity, typically induced by proinflammatory cytokines, is an important factor contributing to morbidity and mortality. However, the role of CIRP in causing endothelial dysfunction has not been investigated. In this study, we show that intravenous injection of recombinant murine CIRP (rmCIRP) in C57BL/6 mice causes lung injury, evidenced by vascular leakage, edema, increased leukocyte infiltration and cytokine production in the lung tissue. The CIRP-induced lung damage is accompanied with endothelial cell (EC) activation marked by upregulation of cell-surface adhesion molecules E-selectin and ICAM-1. Using in vitro primary mouse lung vascular ECs (MLVECs), we demonstrate that rmCIRP treatment directly increases the ICAM-1 protein expression and activates NAD(P)H oxidase in MLVECs. Importantly, CIRP stimulates the assembly and activation of Nlrp3 inflammasome in MLVECs accompanied with caspase-1 activation, IL-1β release and induction of proinflammatory cell death pyroptosis. Finally, our study demonstrates CIRP-induced EC pyroptosis in the lungs of C57BL/6 mice for the first time. Taken together, the released CIRP in shock can directly activate ECs and induce EC pyroptosis to cause lung injury.

https://pubmed.ncbi.nlm.nih.gov/27217302/

Visitor

"But there has been some good articles written that addiction is also part of this mess."

I do not enter the arena of giving answers anymore. I see the outer elements, but no listens to me so I no longer offer insight. Beside this people conflate intentions with reaction. Bitter much? Yes. I tried stating truths more than 20 years ago n through recent times and no has listened.

Soundgarden - Spoonman

https://www.youtube.com/watch?v=T0_zzCLLRvE

Visitor

I don't believe in man's innate righteousness. But, honesty is very possible. I find this man, Jonathan Haidt, among the honest and insightful.

The moral roots of liberals and conservatives

https://www.youtube.com/watch?v=8SOQduoLgRw

Count Basie - Shout And Feel It (Swing Kids)

https://www.youtube.com/watch?v=bPuKXlDhxoY

Visitor

This is my theme song, no doubt. This is just ahead of "On the Street Where you Live " by Dean martin. They swatch at times, but this is the top because of personal reasons.

Ella Fitzgerald - It’s Only a Paper Moon

https://www.youtube.com/watch?v=2_uwE0WkM7Y

Visitor

If you knew what I understand you would not censor my posts.

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Couple of weeks ago went to the 3614 JACKSON HIGHWAY RECORDING STUDIO and the Fame Studio in the shoals area. Loved every minute of it. R e s p e c t. Aretha is gold. I recommend visiting theses studios. Than you Dr. Dre.

Visitor

A beautiful refrain.

https://www.youtube.com/watch?v=uNldXkeNQm8

Visitor

https://www.youtube.com/watch?v=z6mpWSMkkyI My appreciation of the Beatles and the Stones only grows.

https://www.youtube.com/watch?v=z6mpWSMkkyI

Visitor

Meaning is beyond me. feeling persists.
I love the Carpenters.
https://www.youtube.com/watch?v=evETS8_WFGE

Visitor

The metabolic roots of senescence: mechanisms and opportunities for intervention

https://www.nature.com/articles/s42255-021-00483-8

Metformin, Rapamycin, and Nad+

https://agelessrx.com/longevity-101-metformin-rapamycin-nad/

Visitor

I meant to add this to the last link. I had quit alcohol for 3 months and started again today.

Double edged swords are the rule it seems. I love everyone.

Recurrent UTIs linked to gut microbiome, chronic inflammation


https://medicine.wustl.edu/news/recurrent-utis-linked-to-gut-microbiome-chronic-inflammation/

Visitor

Oxytocin-Linked Signaling Provides Keys to Treating Social Disorders

In the more difficult cases the extremes aspects of microbiome disruption or dysbiosis are not linear and may effect individuals into adolescents and beyond. Our case is unusual.

"To confirm whether this mechanism is indeed pivotal in controlling social memory, the investigators blocked the phosphorylation of OXTR in the medial amygdala in normal wild-type rats using an interfering peptide and selectively mutated the PKD1 gene in the medial amygdala in mice. In both animal models, the retention of social memory was reduced. On the other hand, expressing a phosphomimetic mutant of OXTR—a mutant bearing an amino acid substitution that mimics phosphorylated OXTR—rescued social memory.

Their findings indicate a positive feedback loop between PKD1 and OXTR supports OXT activity. The ability of rats and mice to recognize their littermates depends on this mechanism since rodents that harbor a mutated oxytocin receptor forgot about familiar animals and treated them as strangers if separated for a day.

“Our findings describe a phosphoregulatory loop for OXTR and its critical role in social behavior that might be further explored in associated disorders,” the authors noted."

https://www.genengnews.com/topics/translational-medicine/oxytocin-linked-signaling-provides-keys-to-treating-social-disorders/

https://www.genecards.org/cgi-bin/carddisp.pl?gene=PKD1

Human Phenotype Ontology for PKD1 Gene

Recurrent urinary tract infections

My wife had these recurrent infections, though you can have them without Autism. Older folks have them often with mental disruption.

https://www.genecards.org/cgi-bin/carddisp.pl?gene=PKD1

Recurrent UTIs linked to gut microbiome, chronic inflammation

"A new study suggests that women who get recurrent UTIs may be caught in a vicious cycle in which antibiotics given to eradicate one infection predispose them to develop another. The study, by researchers at Washington University School of Medicine in St. Louis and the Broad Institute of MIT and Harvard, showed that a round of antibiotics eliminates disease-causing bacteria from the bladder but not from the intestines. Surviving bacteria in the gut can multiply and spread to the bladder again, causing another UTI.

At the same time, repeated cycles of antibiotics wreak havoc on the community of helpful bacteria that normally live in the intestines, the so-called gut microbiome. Similar to other disorders in which gut microbes and the immune system are linked, women with recurrent UTIs in the study had less diverse microbiomes that were deficient in an important group of bacteria that helps regulate inflammation, and a distinct immunological signature in their blood indicative of inflammation.

“It’s frustrating for women who are coming in to the doctor with recurrence after recurrence after recurrence, and the doctor, who’s typically male, gives them advice about hygiene,” said co-senior author Scott J. Hultgren, PhD, the Helen L. Stoever Professor of Molecular Microbiology at Washington University. “That’s not necessarily what the problem is. It’s not necessarily poor hygiene that’s causing this. The problem lies in the disease itself, in this connection between the gut and the bladder and levels of inflammation. Basically, physicians don’t know what to do with recurrent UTI. All they have is antibiotics, so they throw more antibiotics at the problem, which probably just makes things worse.”

Most UTIs are caused by Escherichia coli (E. coli) bacteria from the intestines that get into the urinary tract. To understand why some women get infection after infection and others get one or none, Hultgren teamed up with Broad Institute scientists Ashlee Earl, PhD, the senior group leader for the Bacterial Genomics Group at Broad and the paper’s co-senior author, and Colin Worby, PhD, a computational biologist and the paper’s lead author.

The researchers studied 15 women with histories of recurrent UTIs and 16 women without. All participants provided urine and blood samples at the start of the study and monthly stool samples. The team analyzed the bacterial composition in the stool samples, tested the urine for the presence of bacteria, and measured gene expression in blood samples.

Over the course of a year, 24 UTIs occurred, all in participants with histories of repeated UTIs. When participants were diagnosed with a UTI, the team took additional urine, blood and stool samples.

The difference between the women who got repeated UTIs and those who didn’t, surprisingly, didn’t come down to the kind of E. coli in their intestines or even the presence of E. coli in their bladders. Both groups carried E. coli strains in their guts capable of causing UTIs, and such strains occasionally spread to their bladders.

The real difference was in the makeup of their gut microbiomes. Patients with repeat infections showed decreased diversity of healthy gut microbial species, which could provide more opportunities for disease-causing species to gain a foothold and multiply. Notably, the microbiomes of women with recurrent UTIs were particularly scarce in bacteria that produce butyrate, a short-chain fatty acid with anti-inflammatory effects.

“We think that women in the control group were able to clear the bacteria from their bladders before they caused disease, and women with recurrent UTI were not, because of a distinct immune response to bacterial invasion of the bladder potentially mediated by the gut microbiome,” Worby

said.

The findings highlight the importance of finding alternatives to antibiotics for treating UTIs.

“Our study clearly demonstrates that antibiotics do not prevent future infections or clear UTI-causing strains from the gut, and they may even make recurrence more likely by keeping the microbiome in a disrupted state,” Worby said

Hultgren has long worked on finding innovative therapies to eradicate disease-causing strains of E. coli from the body while sparing the rest of the bacterial community. His research forms the basis of an experimental drug based on the sugar mannoside and an investigational vaccine, both of which are being tested in people. Another strategy would be to rebalance the microbiome through fecal transplants, probiotic foods or other means.

https://medicine.wustl.edu/news/recurrent-utis-linked-to-gut-microbiome-chronic-inflammation/

Urinary Recurrent Infection in Children with Autism Spectrum Disorder

https://www.researchgate.net/publication/331212344_Urinary_Recurrent_Infection_in_Children_with_Autism_Spectrum_Disorder#read

Benedetta

Nick;
Don't worry about that phrase.
I was surprised does not mean what you think it means.
It means something more profound.
I felt that it meant more than just not calling some out to do something bad to some one.

Mike Rowe pinpointed for me on an interview with Glen Beck. I wish I had been able to put it into words like Mike Rowe did. At last, I am not that good with thoughts and words.

MIke Rowe said that the phrase is really about; being lied to, even when we know it is a lie, and we are just suppose to accept it. . Yes, the journalist interviewing the race car winner Brandon was doing it to be nice - even though we all could hear what was really being said, but it is the prime example of the age we live in of lies.

Keeping with this inflammation highway theme - one thing for sure that we are seeing with the covid vaccine; it is causing blood clots or vascular disease by the spike protein messing with the ACE 2 receptor that is very rich in the lining of the blood vessels, and the response of the immune system it the blood vessels thus inflammation. So this whole article is holding up as truth as time goes forth. Any truth at this time is a real treasure.

Visitor

Darryl Worley - I Miss My Friend

https://www.youtube.com/watch?v=8zNf4sOO_mg
I would like to apologize to Our president Joe Biden. I mentioned "lets Go Brandon" in an earlier post and am ashamed of having posted that. I pray God's greatest blessing on our President and I also apologize for slandering the Guardian" publication. I don't grasp all that is happening, but I glorify God in the highest and turn from my error.

Visitor

Benedetta,

Thank you for your thoughtful words and sympathy. I really do appreciate your kindness and prayers. Bless you.

Benedetta

Visitor;
I am so sorry about your niece.

So very sad two little kids lost their mother and you another family member.

I could handle -- the I am coming home songs.

The Okay song had me in tears again.

I lift your family up in prayer.
That all I seem to do now a days.

I .

Visitor

Golden Buzzer: Nightbirde's Original Song Makes Simon Cowell Emotional - America's Got Talent 2021

God directed this posting.

https://www.youtube.com/watch?v=CZJvBfoHDk0

Visitor

Please just post this. I am sober. The truth is far Stanger than fiction. I intend to continue to learn for the sake of those at AoA and all those damaged. Music is my sustenance and in part my guidance.
This a song quite specials to me. I am trying to resume my progress instead of ending it.

Jenna Mammina - When I'm Called Home

https://www.youtube.com/watch?v=uNldXkeNQm8

Original

When I'm Called Home - Abbey Lincoln

https://www.youtube.com/watch?v=6UfJmuH2X3U

Visitor

The funeral for my niece was last Sunday. She was 36 years old with two children still at home. 3 or 4 weeks before her stroke she had a corvid shot and started having some headaches afterwards. She had an ischemic stoke that effected 3 main arteries effecting her brain and was dead within a day of the i initial stroke effect. There was no autopsy, so this is circumstantial in nature. A medical professional in our family has a "high suspicion" the vaccine precipitated the stroke. My niece was a nurse.

On another front I stand against Joni Mitchell and will sadly discard her music. I never cared much for Neil Young, so no loss there. If I could delink her from my postings I would. This is not a minor issue. I am not against any getting a corvid shot, but I detest the mandate and I also believe in free speech.

Covid-19 vaccine: Common stroke symptoms must be ‘urgently evaluated’

https://www.ucl.ac.uk/news/2021/may/covid-19-vaccine-common-stroke-symptoms-must-be-urgently-evaluated

Visitor

"ALl the way from Andrew Wakefield reporting that kids at the Royal hospital with autism had high build up of vitamin B 12 because they were not able to use it in their metabolism.
Then I read a book by some psychiatrist that had spent a life time treating mental disorders with different vit Bs and other things."

I marvel at the ignorance among the "learned''. Forces of conformity can blind anyone it seems. I have scores of clear clarities in biologicals pathways and effects I have thought to post here, but I have lost heart as it has not mattered thus far. I don't like this world.

Visitor

Sarah McLachlan -- River (

I was far ahead, now far behind.

https://www.youtube.com/watch?v=jiYYWDSI_oU

Visitor

"Life can only be understood backwards; but it must be lived forwards." Soren Kierkegaard

This is true for understanding complex disease as well.

Visitor

Nobody Does It Better

https://www.youtube.com/watch?v=uWWwKDttHnM

No one will unederstand.

Visitor

a-ha - Take On Me (Live From MTV Unplugged)

https://www.youtube.com/watch?v=-xKM3mGt2pE

benedetta Stilwell

Same here Nick.
It is pretty hard to take, and it stays with you.

If communisis is coming then so is poverty. Even if communism does not come, Poverty will probably still be here, just
because it just got a good foot hold

My 92 year old mother just lost her husband, so of course she is grieving. When she gets down in the dumps she starts talking about how bad she had it as a child.

Dad never talked like that. In spite of being poor, he had a good time with his cousins swimming in the creek - when he was not worked to death. But he wanted for Christmas really bad, gum boots to wade the branches and the snow, and of course never got them. All his life; all he ever asked for was some boots for Christmas. Every year. Until I realized that no matter how many boots he accumulated in a life time it would never make up for that one Christmas.

Visitor

I left Kentucky, but he understanding of those non partisan lovely people remains with me.
https://www.youtube.com/watch?v=-ew_bfFvros

The current Governor has a D beside his name. He has the sense of a true Kentuckian, but he fights it. Her is a triu Christian. I like him, but he is trying to please his masters. Please pray for him.

Visitor

Benedetta,
You said: "That old saying: I don't agree with what you said, but I will fight to the death for you to say it -- they really did not believe that. I have been amazed at what they really don't believe."

They haven't for a while that is one of the biggest things that have pushed me away from many of them. They once had great things to offer. Not so much these days. I retain that attitude of free speech. My own brother was in a hard way and I invited him to be with me often to support him. We talked some politics from time to time and once in my home we were discussing property rights and I defended the individuals right to their property and he said the state owned it all in the end. I pushed back and he shouted me down and said "you are not going to speak". Everytime I tried to respond he said "you're not going to speak, you're a Nazi". I fell silent, but had impulses to kick his butt out of my house. The irony of him forbidding me to speak while calling me a Nazi. It has tested my values of turning the other cheek. He was liberal, well he fancied himself one, but he was a modern leftist as he accused me of being what he was. I see these type everywhere today. Some on the news networks. Some networks clearly run by some of them. Give me Liberty.

Visitor

What A Beautiful Name

https://www.youtube.com/watch?v=tiIMtID54K8

\I do believe this my last post. I have so much to share, but it seems it makes no differnce.

Visitor

It is clearly coincidental, but my wife's middle name is Lee. I absolutely adore that name Lee. A pure and Godly name to me.

https://www.medecinesciences.org/en/articles/medsci/full_html/2021/08/msc200562/msc200562.html

Visitor

I grew up in the primordial. Liberals showed me the other side. I above them all found truth. Because one side elevates itself I extol the other. Bothe were superb teachers.

Home Free - Hillbilly Bone

https://www.youtube.com/watch?v=y_7_RTogRBw

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