The Rhyothemis princeps Brain Externalization Project

Journal articles: Association of sleep duration in middle and old age with incidence of dementia (2021) https://www.nature.com/articles/s41467-021-22354-2 - an epidemiological study followed people for 25 years and found those who reported sleeping 6 hours or less per night had 30% higher risk of dementia relative to those who reported sleeping at least 7 hours, on average Sleep arousal burden is associated with long-term all-cause and cardiovascular mortality in 8001 community-dwelling older men and women (2021) https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehab151/6239256 - a polysomnography study found higher all-cause and cardiovascular disease associated with higher arousal burden (a measure of unconscious wakefulness) for women, associations were less strong for men; potential for arousal burden as a biomarker & modifiable risk factor News articles: Sleeping Too Little in Middle Age May Increase Dementia Risk, Study Finds (2021) https://www.nytime...

 Lemon balm ( Melissa officinalis ) was found to improve sleep in a fly model of Alzheimer's disease. Screening of sleep assisting drug candidates with a Drosophila model (2020) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390450/   "Overall, female flies were more vulnerable to DD stimulation considering total sleep time, but not in the sleep frequency. Therefore, female flies were chosen for the following drug screening study. ... the administration of melatonin shortened sleep latency but did not increase the total sleep time during sleep deprivation ( Fig 4A, 4B and 4F ), indicating that melatonin may only induce flies to sleep faster but not longer. Such results are consistent with human clinical trials that have reported that the prescription of melatonin helps induce sleep but does not enhance total sleep time [ 4 ]. Moreover, the activity index shows no change after melatonin treatment ( Fig 4G ), suggesting that melatonin has a limited effect on activity during wake...

Notes on: Histidine in Health and Disease: Metabolism, Physiological Importance, and Use as a Supplement  (2020) https://www.mdpi.com/2072-6643/12/3/848 "According to several studies, dietary [histidine] HIS affects histamine concentrations in immune cells, the stomach, and the brain [ 58 , 59 , 60 , 61 ]. Altered function of the immune system, allergic reactions, and/or peptic ulcers have not been reported after HIS administration. ... In the skin, filaggrin, a skin barrier protein with high HIS content, is the main HIS source for histidase to generate ammonia and urocanate [40]. Because most of the ammonia produced in the splanchnic region is detoxified to urea in the liver, the skin should be considered a significant source of blood ammonia in the systemic circulation. ... Although HIS is a precursor of histamine, allergic reactions or peptic ulcers caused by increased gastric acid secretion have not been reported. Practically important might be reduced folate status [ 45 ,...

  https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awab054/6242260  "Animal studies suggest that noradrenergic fibres from the locus coeruleus play a key role in providing trophic support for both astrocytes and neurons, and in suppressing inflammation and oxidative stress. 19 Control of microvascular flow by the noradrenergic locus coeruleus might provide part of this trophic support by helping to match oxygen availability to cellular oxidative phosphorylation in brain tissue."   https://pubmed.ncbi.nlm.nih.gov/23426667/ "Our data demonstrate that stimulation of the LC activates a broad network of cortical pyramidal cells and interneurons and concomitantly increases cortical perfusion. The hyperemic response virtually disappeared after selective lesioning of the LC–NA system and required activation of α- and β-adrenoreceptors. In addition, the evoked CBF response to the LC–NA system required the release of glutamate and GABA likely from the...

Someone on a forum asked why iNOS inhibitors (e.g., agmatine, anatabine) would be beneficial and my reply follows: Too much NO generates peroxyynitrite and can cause nitrosative and oxidative stress, causing production of nitrated/oxidized alpha synuclein and oxidized dopamine. NO generated by iNOS in glial cells is particularly problematic for neurons. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3408780/ This is in contrast with NO generated by the endothelium during exercise, which acts on the endothelium (autocrine signalling) which in turn produces good things like BDNF (the vascular endothelium can be thought of as an endocrine organ). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2791344/ https://youtu.be/lhZZS6_-Cg4 There are lots of studies on iNOS inhibitors in models of Parkinson's and other neurodegenerative disease. https://pubmed.ncbi.nlm.nih.gov/31192483/ Tobacco use and Solanaceae vegetable consumption are associated with reduced risk of PD. If causal, the relations...

Hydrogen sulfide (H2S) signalling is involved in the central regulation of breathing / ventilatory response. If the enzyme that makes H2S, cystathionine beta synthase, (CBS) is blocked, the neural network that controls breathing in the brain  breaks down and gasping results.  https://www.nature.com/articles/s42003-020-01312-6 Dopamine and serotonin upregulate CBS activity. CBS has a heme moiety and needs vitamin B6 as a cofactor. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0022568 "Cystathionine-β-synthase (CBS) is the most likely endogenous candidate enzyme to increase H 2 S production. Endogenous H 2 S is mainly synthesized by CBS and cystathionine-γ-lyase [8] , [9] . Both enzymes depend on pyridoxal 5′-phosphate (PLP) as a cofactor [10] . However, only CBS contains a heme moiety, which may bind oxygen and make the enzyme function dependent on oxygen levels, as demonstrated in recombinant human CBS [11] . In addition, a range of biogenic amines, in...

  Dr. Crystal Ripplinger 5:40 nerve:myocyte ratio similar to capillary myocyte ratio; all myocytes in ventricular myocardium are in contact with at least one neuronal process     6:27 more nerves at base of heart than apex, more sympathetic in epicardium, more parasympathetic in endocardium   11:15 how sympathetic nerve loss contributes to arrhythmia post-myocardial infarction (heart attack) 12:52 heterogeneity in innervation can be arrhythmogenic   13:02 nerve loss, lack of norepinephrine can lead to beta adrenergic receptor hypersenstitivity & supersensitive response to neurotransmitters     14:03 Chondroitin sulfate proteoglycans (CSPGs) inhibit sympathetic regeneration after infarction, also prevent spinal cord regeneration   20:22 localized lesioning with anti-DBH-saporin; anti-dopamine beta hydroxylase antibody conjugated to toxin that gets into cell via synaptic vesicle   28:30 differences between larger animals (rabbi...

The eat 'five a day' (referring to servings of fruits and vegetables) recommendation of the World Health Organization and many national health agencies has new support based on findings by Wang et al. (2021) from the Nurses' Health Study and the Health Professionals Follow-up Study.   - link to open access article: https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.048996 The study found a reduction in all-cause mortality as well as reductions in mortality due to respiratory diseases, cardiovascular disease and cancer. The thresholds for reductions in mortality were achieved at two servings of fruit and three servings of vegetables per day. No additional benefit was seen for over five servings. Sadly, there was no significant reduction found for neurodegenerative diseases (but see the Michley et al. (2017, open access) study on Parkinson disease re: fresh vs. canned/frozen). Wang et al. (2021) Above is Figure 1 from Wang et al. (2021); it is quite small and th...

 Another reason why infants are prone to methemoglobinemia is that fetal hemoglobin is more easily oxidized.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1071541/ "Methemoglobinemia has been reported in young infants (<6 months) in whom severe metabolic acidosis develops from diarrhea and dehydration. 7 Young infants may be particularly susceptible to this complication because of their low stomach acid production, large number of nitrite-reducing bacteria, and the relatively easy oxidation of fetal hemoglobin. Small infants have lower erythrocyte levels of cytochrome b reductase. 8 Higher intestinal pH of infants may promote the growth of gram-negative organisms that convert dietary nitrates to nitrites." ~ I was reminded of  fetal hemoglobin when I watched a video recently where persistence of fetal hemoglobin as a rescue mutation for thalassemia was discussed; here's my comment on it: https://youtu.be/ml1svbRo7Lg?t=990  Great interview. I'm sure this w...

https://www.justintimemedicine.com/CurriculumContent/p/4954 "This basolateral secretion of HCO 3 − into the bloodstream is sometimes called the “alkaline tide” which normally accompanies gastric acid secretion with eating. The metabolic alkalosis of vomiting is essentially an exaggeration of this response; HCl is lost from the stomach so more is made to replace it, causing even more bicarb to be secreted "out the back end" of the parietal cell and into the bloodstream."   from Wikipedia: "Alkaline tide refers to a condition, normally encountered after eating a meal, where during the production of hydrochloric acid by parietal cells in the stomach, the parietal cells secrete bicarbonate ions across their basolateral membranes and into the blood, causing a temporary increase in pH . [1] "   ~ PPIs can cause metabolic acidosis; can be prescribed to prevent metabolic alkalosis from vomiting.

Lemon balm ( Melissa officinalis ) methanolic extract was shown to have antiviral activity in vitro against enterovirus 71 - attributed to the antioxidant constituent rosmarinic acid. https://www.nature.com/articles/s41598-017-12388-2 "Several lines of evidence support the notion that the redox status of host affects viral pathogenesis 26 . We have previously shown that EV71 infection induces oxidative stress, which in turn promotes viral replication 27 , 28 . Treatment with antioxidants, such as N-acetylcysteine (NAC) or mito-Tempo, suppresses EV71 replication 27 , 28 , 29 . Natural antioxidants, epigallocatechin gallate (EGCG) and gallocatechin gallate (GCG), in green tea have antiviral activity, which correlates well with their antioxidant capacity 30 . It is probable that the antiviral activities of natural products may be partly attributed to their antioxidative activities." Review article on redox biology of respiratory viral infections: https://pubmed.ncbi.nlm.nih....

Videos on methemoglobinemia: https://youtu.be/2RFcH_nlR84 Regular pulse oximeter will read normal in cases of methemoglobinemia. Signs include central cyanosis - blue lips, tongue (as opposed to perhipheral). Deficiencies in glucose-6-phosphate dehydrogenase or NADH cytochrome b5 reductase (CYB5R ; aka methemoglobin reductase) are risk factors. Excessive nitrite or nitrate consumption can cause MetHb; infants are at higher risk since they produce less CYB5R. Methemoglobinemia can be a side effect of dopamine antagonists such as metocloparmide (Reglan). Methemoglobinemia from metoclopramide more often occurs in infants, cases in adults are rare but can occur: https://europepmc.org/article/med/10870338 Elevated methemoglobin is among the plasma biomarkers of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) - as is elevated alpha ketoglutarate: https://pubmed.ncbi.nlm.nih.gov/30563204/ Interesting abstract: https://2018.febscongress.org/abstract_preview.aspx?idAbstractEnc=442...