"In sickness and in health"

Clint Black - When I Said I Do

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

Gordon Lightfoot - Wreck Of The Edmund Fitzgerald

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

The angels among us shining.

Collin Raye - She's With Me

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

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

Al Green - Let's Stay Together

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

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/

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

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

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

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

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

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

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?

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/

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.

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

The Lord God is my only hope.

Susan Ashton - Stand

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

Frank Sinatra - Luck Be A Lady

https://youtu.be/X69P_Vce9vw

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.

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

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

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

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

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.

"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/

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/

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/

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

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

A beautiful refrain.

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

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

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/

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.

Benedetta,

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

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

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

Sarah McLachlan -- River (

I was far ahead, now far behind.

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

Nobody Does It Better

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

No one will unederstand.

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.

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.

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

God loves us all.

Voices of Lee // Oh How He Loves You and Me

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

What passes for liberals these days are narrow minded asshole censors. Whatever remains of real Democrats please cleanse yourselves of this evil.
The left are just malicious authoritarian power mongers. People who truly value truth and freedom will always be attacker by this scum. They care not one whit what he said about his vaccination experience. The left are legalist pre and simple. Thay abhor free speech. they are the true Nazis! My own brother called me a Nazi for believing In private property rights. I was dumbfounded. He would trash all of our relationship so he could look down on me and control me in his mind. What I realized was he was like all leftist , a control freak. I join the chorus; "let's Go Brandon"!

Don McLean was right about the Rolling Stone culture.

Rolling Stone Is Trying to Cancel Eric Clapton

https://pjmedia.com/news-and-politics/matt-margolis/2021/10/11/rolling-stone-is-trying-to-cancel-eric-clapton-n1523029

The leftist puttied mass forced me to this position. It is war.

I agree about the importance of music Benedetta. Smile

They say Eric Clapton is not God aftercall. I never gave him that place. But he is the greatest guitarist ever. The words have the power, Superman more powerful than a locomotive. I look forward to your concert Eric Clapton.

Song by Johnny Cash

I Hear The Train A-Comin'; It's Rollin' 'Round The Bend,
And I Ain't Seen The Sunshine Since I Don't Know When,
I'm Stuck At Folsom Prison And Time Keeps Draggin' On.
But That Train Keeps A-Rollin'
On Down To San Antone.
When I Was Just A Baby, My Mama Told Me. Son,
Always Be A Good Boy; Don't Ever Play With Guns.
But I Shot A Man In Reno Just To Watch Him Die.
When I Hear That Whistle Blowin'
I Hang My Head And Cry.
I Bet There's Rich Folks Eatin' In A Fancy Dining Car.
They're Prob'ly Drinkin' Coffee And Smokin' Big Cigars,
But I Know I Had It Comin', I Know I Can't Be Free,
But Those People Keep A-Movin',
And That's What Tortures Me.
Well, If They Freed Me From This
Prison, If That Railroad Train Was Mine,
I Bet I'd Move On Over A Little Farther Down The Line,
Far From Folsom Prison, That's Where I Want To Stay,
And I'd Let That Lonesome Whistle
Blow My Blues Away.

Confusion has its's costs. Understatement. Universal understatement.

Turns out is is a heart by design. I became curious and found this which confirms Joni painted it this way. for a Valentines day association..

"Brian Blade, said, "oh, I like that picture. "I was in my early 30s. And I looked at it and the fold of the sleeve had a heart in it. The way it -- I went, heart on the sleeve, that's romantic, that'll do!"

https://jonimitchell.com/paintings/view.cfm?id=194

I always loved that song.

Taurine there was an article on that in the Epoch health section.

So many studies about sooooo many problems with the metabolism that it takes my breath away.

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.

Way back at the beginning of the 19th century after they took the part of the corn that had niacin ?B3 in it - to make corn meal there was an on going epidemic of pellagra,.
I thought it was an accident, until some one said better be more suspicious than that.

I've been drivin' all night, my hands wet on the wheel
And there's a voice in my head that drives my heel
It's my baby callin', sayin' I need you here
And it's a half past four and I'm shiftin' gear
When she is lonely and the longing gets too much
She sends a cable coming in from above
Don't need no phone at all
We've got a thing that's called radar love
We've got a wave in the air
Radar love
The radio's playin' some forgotten song
Brenda Lee's "Coming On Strong"
The road has got me hypnotized
And I'm speedin' into a nude sunrise
When I get lonely and I'm sure I've had enough
She sends her comfort coming in from above
We don't need no letter at all
We've got a thing that's called radar love
We've got a line in the sky
No more speed, I'm almost there
Gotta keep cool now, gotta take care
Last car to pass, here I go
And the line of cars go down real slow-woah
And the radio played that forgotten song
Brenda Lee's "Coming On Strong"
And the newsman sang his same song
Oh, one more radar lover gone
When I get lonely and I'm sure I've had enough
She sends her comfort coming in from above
We don't need no letter at all
We've got a thing that's called radar love
We've got a line in the sky
We've got a thing that's called radar love
We've got a thing that's called
Radar love

Kynurenine Pathway in Autism Spectrum Disorders in Children

Abstract
Background: There is increasing evidence that altered immune responses play a role in the pathogenesis of autism spectrum disorders (ASD), together with dysfunction of the serotonergic and glutamatergic systems. Since the kynurenine (KYN) pathway that degrades tryptophan (TRP) is activated in various neuroinflammatory states, we aimed to determine whether this pathway is activated in ASD.

Methods: Sixty-five pediatric ASD patients (including 52 boys) were enrolled from an epidemiological survey covering 2 counties in Norway; 30 (46.5%) of these patients were diagnosed with childhood autism, 16 (24.6%) with Asperger syndrome, 12 (18.5%) with atypical autism, 1 (1.5%) with Rett syndrome, and 6 (9.2%) with other ASD. The serum levels of the following markers were measured in the children with ASD and compared to those in 30 healthy children: TRP, KYN, kynurenic acid (KA), 3-hydroxykynurenine, and quinolinic acid.

Results: The mean serum level of KA was significantly lower in the ASD group than in the healthy controls (28.97 vs. 34.44 nM, p = 0.040), while the KYN/KA ratio was significantly higher in the ASD group (61.12 vs. 50.39, p = 0.006). The same relative values were found when comparing the childhood autism subgroup with the controls. Also, the mean serum level of TRP was significantly lower in children with a subdiagnosis of childhood autism than in those with Asperger syndrome (67.26 vs. 77.79 μM, p = 0.020).

Conclusion: Our study indicates that there is an increased neurotoxic potential and also a possible lower KYN aminotransferase activity in ASD.

https://pubmed.ncbi.nlm.nih.gov/29694960/