Author Topic: POIS paper treatment summary  (Read 15502 times)

Muon

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Re: POIS paper treatment summary
« Reply #20 on: December 13, 2020, 10:21:58 AM »
Take a look at Goldstein's decision tree. Goldstein used Testosterone as ketamine antagonist and dopamine agonist. Suggestion: POISers could be categorized by profiling drugs in case of limbic deregulation. Limbic deregulation could be one cause among other causes. Diagnostic flow charts could be made alongside treatment flow charts. I've already seen some of the stuff being used on this forum back in this tree. His latest book is >600 pages. No point in reading when I don't have access to prescriptions.

Edit: Send me a personal message if you are interested in the book  ;)
« Last Edit: December 13, 2020, 03:35:27 PM by Muon »

Muon

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Re: POIS paper treatment summary
« Reply #21 on: December 13, 2020, 05:42:32 PM »
Will post some snippets from the book later. I already see a potential reason why some of the personal treatments here work like they do. POIS might be neurosomatic.

Edit: Some snippets about Testosterone:

Androgens such as testosterone increase the secretion of dopamine, probably by decreasing the activity of the dopamine transporter. Ritalin and cocaine also have this action. Androgens also increase DA by interacting with NO.

The amino acid taurine inhibits the dopamine transporter and maywork somewhat like Ritalin. Taurine is an agent I have tried on several of my patients. It did not enhance dopamine effects but may augment lamotrigine in some individuals.

In rats that are testosterone deficient, the density of tyrosine hydroxylase (TH)-immunopositive axons in the prefrontal cortex increases. Tyrosine hydroxylase converts tyrosine to dopa and is usually the ratelimiting enzyme in the biosynthesis of the catecholamines. The dysregulation of TH is attenuated by supplementing rats with testosterone. The effect is mainly on dopamine and not norepinephrine. Testosterone depletion produces a dopamine hyperinnervation in the prefrontal cortex in an attempt to compensate for decreased production of dopamine.

I have stopped using nitroglycerin as much. Too many patients have migraine headaches, and nitric oxide has been found to cause this disorder. With no history of severe headaches, I can opt to try it (one-half of a 0.3 mg tablet). It either works or not. It sometimes acts as an NMDA agonist since it is a retrograde messenger. Those that respond to nitroglycerin will often benefit from testosterone, oxytocin, and agonists of DA, NE, and glutamate, all of which act in the MPOA to produce arousal and orgasm.

I start testosterone gel at 10 mg/ml, particularly in women with decreased libido if they fail on transdermal estrogen. Their testosterone levels are usually very low.

Perhaps the most relevant aspect of the neuroregulatory aspects of gonadal steroids in neurosomatic disorers is that “estradiol enhances and testosterone attenuates novelty stress-stimulated increases in c-Fos mRNA in the hippocampus, with presumed consequent alterations in the transcription regulatory effects of c-Fos” (Roca CA et al., 1999). Until recently, I have been reluctant to use antiestrogen therapy in women except in treatment-refractory bipolar disorder (Goldstein JA, 1986). I have used testosterone only in men who respond to nitroglycerin, since NO increases DA in the medial preoptic area of the brain. I may be liberalizing its use in transdermal treatment trials, however. When effective, it markedly increases alertness.

When men have a good response to nitroglycerin, I try transdermal testosterone, which has an effect in 30 to 60 minutes or less. If it works, they feel much more energetic. Testosterone induces the secretion of NO, which in turn increases DA in the medial preoptic area (Du J, Hull EM, 1999), which is the area of the brain that determines an individual’s response to sexual stimuli. I shall discuss the sexual response in neurosomatic disorders in the section on oxytocin. A much lower dose of transdermal testosterone can have a similar effect on women.

The situation in which synaptic fatigue is most obvious is that of sexual arousal and ejaculation in the male with a neurosomatic disorder. Some males relapse after ejaculation. A few relapse, but in a different, milder way, after sexual arousal. Arousal seems to depend on activation of the medial preoptic area by testosterone, which facilitates NO synthase. NO increases the secretion of DA in the POA, which, as has been seen, is associated with anticipation of reward. Arousal can be augmented by dextroamphetamine, which also increases DA, particularly in the NAc. Lesions of the MPOA in animals decrease sexual behavior. Sexual arousal, causing increased DA secretion, can cause relapse. Ejaculation is related to the actions of NE and oxytocin.

If the patient is hypertensive, anxious, has ADHD, or experiences nightmares, guanfacine would be a good choice. If perimenopausal or low in testosterone, hormonal therapy would be helpful. Such patients usually have a good response to nitroglycerin, the active form of which is nitric oxide. Orgasm centrally requires estrogen or testosterone, NO, OXT, and norepinephrine, plus a little dopamine acting atD1 receptors. Arousal requiresDA, OXT, testosterone, and NO. Testosterone induces NO synthesis, which then stimulates DA release in the medial preoptic nucleus, which facilitates arousal and penile erection. Oxytocin is required for penile erection.

Some articles posted earlier on the website regarding PE, NO, DA and Testosterone:

Stimulation of dopamine autoreceptors elicits “premature ejaculation” in rats

Relevance of serum nitric oxide levels and the efficacy of selective serotonin reuptake inhibitors treatment on premature ejaculation: decreased nitric oxide is associated with premature ejaculation

Testosterone Induces Molecular Changes in Dopamine Signaling Pathway Molecules in the Adolescent Male Rat Nigrostriatal Pathway
« Last Edit: December 14, 2020, 11:48:45 AM by Muon »


Muon

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Re: POIS paper treatment summary
« Reply #23 on: December 17, 2020, 01:59:16 PM »
Muon:

"Hello Dr. Rubin,

 A while ago you mentioned that you had treated 2 POIS patients. Are you going to report this eventually in literature? If not, could you share what you have given to these men? Drug name, dose, duration and the subjective amount of relief these men got as a result? And what other meds you have tried in these men which were unsuccessful. I could add that info to this thread:
"

 https://poiscenter.com/forums/index.php?topic=3551.0

Dr. Rachel S. Rubin MD, IF:

"Thank you for reaching out!

See our abstract attached that we presented to the SMSNA this year
":

Introduction: Postorgasmic illness syndrome (POIS) is a condition that is not well described in the literature. Waldinger and Schweitzer were the first to elaborate on the symptoms, of which the main ones are severe fatigue, intense warmth, and a transient flu-like state. These symptoms have a rapid onset and can last between 2-7 days. The two leading hypotheses regarding the pathophysiology of this condition include immunogenic reactivity to autologous semen leading to a hypersensitivity reaction and a proposition that this is a disorder of the endogenous opioid system. POIS is classified as a rare disorder by the NIH Office of Rare Disease Research, with ~50 cases recorded in the literature over the last 10 years. Historically, patients have been treated with SSRIs, benzodiazepines, and/or antihistamines, but there is no standardized treatment for this condition.

Objective: We describe two patients affected by POIS, their symptomatology, and the treatment methods that were successful in alleviating their symptoms.

Methods: Patient A is a 24 year old male who started having symptoms at age 14. His main symptoms included feeling drained post-orgasm, conjunctivitis, as well as sinus pain, headache, and stomach pains. Patient B is a 32 year old male whose symptoms included post-orgasm fatigue, somnolence, and cold-like symptoms, but the most bothersome was the deep internal fatigue. Both men reported that symptoms persisted weeks after orgasm. Both patients had no significant past medical history, normal genitourinary physical exams, and normal laboratory workups. Patient A was trialed on a combination of pseudoephedrine and hydroxyzine, which led to a marked improvement in his symptoms. He was advised to take 50 mg hydroxyzine nightly and pseudoephedrine 1 hour before orgasm. Patient B was trialed on 25mg tramadol, which he took immediately post orgasm. The tramadol led to a significant improvement of his symptoms, most significantly, the fatigue. Both men were also enrolled in sex therapy as part of their treatment.

Results: We found that the treatment methods used with these two patients support the two leading theories about the etiology of POIS, namely the disorder of the opioid system and the immune system hypersensitivity theory. Jiang et al posited that orgasm consumes large amounts of u-opioids, and in these patients, leads to symptoms similar to those of opioid withdrawal (flu-like symptoms, anxiety, fatigue). Tramadol, a u-opioid agonist, might allow for the repletion of the u-opioids in this specific subset of patients. In a hypersensitivity reaction, the body releases large amounts of histamine, therefore, it is likely that an antihistamine, such as hydroxyzine, would alleviate the associated symptoms. In patient A, who had many allergy-like symptoms, it was logical to trial pseudoephedrine and hydroxyzine.
 
Conclusions: POIS is a rare disorder that requires more research. POIS is likely underrecognized and underreported in the general population and may have more than one etiology. It is important to consider a multi-dimensional approach to treatment, take note of each patient's specific symptoms, and recognize different options of pharmaceutical treatment.
« Last Edit: December 17, 2020, 03:30:03 PM by Muon »

Muon

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Re: POIS paper treatment summary
« Reply #24 on: December 21, 2020, 12:45:15 PM »
"It should be obvious why neurosomatic male patients, who have NE-dependent ejaculation-related processes, commonly relapse for up to a week after having sex. Because DA is depleted after ejaculation, there is a marked increase in central prolactin concentration, thought to account for the refractory period after orgasm in men (Exton MS et al., 2001). Large volumes of NE are secreted in several areas, including the hypothalamus, thoracolumbar cord, and during intromission and ejaculation (Meston CM, Frohlich PF, 2000)."

Mushnikk

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Re: POIS paper treatment summary
« Reply #25 on: December 22, 2020, 10:47:43 AM »
"It should be obvious why neurosomatic male patients, who have NE-dependent ejaculation-related processes, commonly relapse for up to a week after having sex. Because DA is depleted after ejaculation, there is a marked increase in central prolactin concentration, thought to account for the refractory period after orgasm in men (Exton MS et al., 2001). Large volumes of NE are secreted in several areas, including the hypothalamus, thoracolumbar cord, and during intromission and ejaculation (Meston CM, Frohlich PF, 2000)."

Explain the abbreviations, thank you!

Muon

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Re: POIS paper treatment summary
« Reply #26 on: December 22, 2020, 12:14:46 PM »

Muon

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Re: POIS paper treatment summary
« Reply #27 on: December 27, 2020, 09:54:50 AM »
If you encounter POISers who have tried methods for their symptoms with a certain degree of succes and who aren't listed yet on the first page, then dump a link to that thread or post here so I or can incorporate them into the list. It's easier for everyone to get a proper overview this way. Thank you.

Muon

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Re: POIS paper treatment summary
« Reply #28 on: December 29, 2020, 01:06:03 PM »
There is too much information on all POIS forums combined. I don't have the energy to go through all of it. People on these forums did such a poor job collecting relevant information and centralize it. Spending time on endless fruitless discussions while most clues are being left in the dust, unbelievable. Almost zero documentation. Healthcare is a similar mess. Doctors not exchanging information about POISers with eachother or centralize this to a database. You don't even need extra money, restructering the healthcare system helps a lot to boost efficiency. Rant out.

Muon

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Re: POIS paper treatment summary
« Reply #29 on: December 29, 2020, 10:46:02 PM »
Massive paper about CBD:
Immune Responses Regulated by Cannabidiol (2020)

Some folks can resolve their POIS completely with CBD oil, like Vandemolen. Aside from mast cell stabilisation via CB1/2, it can act through other receptors; "These studies show that CBD acts through the adenosine A2A receptor, especially in microglial cells." Milnacipran in the case of hurray could also act on microglia.

CBD could be inducing Tregs just like TRT, see this post and articles below:

Cannabidiol (CBD) induces functional Tregs in response to low-level T cell activation (2017)

Cannabidiol (CBD) induces functional CD4+ CD25+ FOXP3+ Tregs (2016)

Response to CBD could differ depending on the level of T cell activation.
« Last Edit: December 30, 2020, 10:55:12 AM by Muon »

Muon

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Re: POIS paper treatment summary
« Reply #30 on: January 01, 2021, 02:42:06 PM »
Interesting. If I take anti-histamines with pseudoephedrine they are more effective than anti-histamines alone (ie Allegra-D). Pseudoephedrine is a norepinephrine releasing agent.

"Pseudoephedrine acts on alpha- and beta2-adrenergic receptors" Ref

Activation of beta2-adrenergic receptors on mast cells is the primary pathway for adrenergic agents to inhibit mast cells.

Table 1 and chapter 5: Neuroendocrinology of mast cells: Challenges and controversies.

Quote from: Dr. Rubin
Patient A was trialed on a combination of pseudoephedrine and hydroxyzine, which led to a marked improvement in his symptoms.

And/or pseudoephedrine counters vasodilation which is induced by histamine:

https://en.wikipedia.org/wiki/Histamine#Vasodilation_and_fall_in_blood_pressure

Vasodilation and fall in blood pressure
"It has been known for more than one hundred years that an intravenous injection of histamine causes a fall in the blood pressure.[18] The underlying mechanism concerns both vascular hyperpermeability and vasodilation. Histamine binding to endothelial cells causes them to contract, thus increasing vascular leak. It also stimulates synthesis and release of various vascular smooth muscle cell relaxants, such as nitric oxide, endothelium-derived hyperpolarizing factors and other compounds, resulting in blood vessel dilation.[19] These two mechanisms play a key role in the pathophysiology of anaphylaxis. "

https://en.wikipedia.org/wiki/Pseudoephedrine#Mechanism_of_action

"Pseudoephedrine is a sympathomimetic amine. Its principal mechanism of action relies on its direct action on the adrenergic receptor system.[15][16] The vasoconstriction that pseudoephedrine produces is believed to be principally an alpha-adrenergic receptor response."
« Last Edit: January 01, 2021, 03:36:18 PM by Muon »

Vandemolen

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Re: POIS paper treatment summary
« Reply #31 on: January 02, 2021, 09:12:51 PM »
Massive paper about CBD:
Immune Responses Regulated by Cannabidiol (2020)

Some folks can resolve their POIS completely with CBD oil, like Vandemolen. Aside from mast cell stabilisation via CB1/2, it can act through other receptors; "These studies show that CBD acts through the adenosine A2A receptor, especially in microglial cells." Milnacipran in the case of hurray could also act on microglia.

CBD could be inducing Tregs just like TRT, see this post and articles below:

Cannabidiol (CBD) induces functional Tregs in response to low-level T cell activation (2017)

Cannabidiol (CBD) induces functional CD4+ CD25+ FOXP3+ Tregs (2016)

Response to CBD could differ depending on the level of T cell activation.
Too bad for me that cbd does not work for me anymore. I think I am allergic for things that go with the cbd. I am also allergic for vitamin D.
POIS since 2000. Very bad since 2008. I knew that I have POIS since June 2010. Desensitization since March 2011. I stopped with desens in July 2016. I have 50% less POIS. And only 1 day of POIS. Purified CBD works for me, but I am allergic for CBD.

Muon

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Re: POIS paper treatment summary
« Reply #32 on: January 06, 2021, 12:46:20 PM »
Dumping some half baked info here, will maybe take a look at it later. Could a subgroup of POISers be categorized as certain responders based on this diagram?

https://forums.phoenixrising.me/threads/dr-jay-goldsteins-rapid-remission-me-cfs-treatments.34516/page-6#post-582561

Lot of stuff in the diagram is used by POISers.
Quote from: Nas
I was looking at Goldstein diagram earlier. And it seems that Nicotine (dopamine agonist) gives me a bad reaction And Coffee (an Adenosine receptor stimulant) slightly improves my symptoms. So I don't know what's xxxxxx up, my dopamine receptors or Benzodiazepine receptors.
I think you meant to say that it increases adenosine, It's an antagonizer: Caffeine and adenosine. https://thebrain.mcgill.ca/flash/i/i_03/i_03_m/i_03_m_par/i_03_m_par_cafeine.html#drogues. Is a weak non-selective PDE inhibitor. Also got acetylcholinesterase inhibition properties.

Mestinon had no effect on Nas. Cigarette smoke induced symptoms in him (discussed this is endothelial dysfuncton thread). "Nicotine and cigarette smoke both induce the expression of liver enzymes (e.g., certain cytochrome P450 proteins) which metabolize drugs, leading to the potential for alterations in drug metabolism" https://en.wikipedia.org/wiki/Nicotine#Drug_interactions
I'm not interested to dive into this p450 rabbit hole: https://en.wikipedia.org/wiki/Cytochrome_P450#Other_specific_CYP_functions
But it could mess up hormone metabolism, already discussed in the case of Heather in the women's thread. And fatty acids and eicosanoids metabolism which is involved in PLA2/AA cascade inflammation.

Coffee dose dependent is benificial to HOD as benzodiazepines.

Takedrugstoletgo had succes with dextroamphetamine.

Benzo's and nootropics had some effect on my brother's symptoms.

Heather and demo felt awful on progesterone/norethisterone but good on testosterone (they aren't ketamine responders, rather the opposite, and/or dopamine responders).

A few individuals used viagra and PDE4.

Some do improve on mestinon (pyridostigmine)

So far the pyridostigmine (mestinon) isn't doing anything yet in my case. Mestinon increases acetylcholine availability. I feel bad on alcohol, a NMDA receptor blocker, it also blocks or activates nAChRs depending on subtype I believe.

Aren't the selective alpha1 blockers used in Reisman's paper also PDE5 inhibitors? These folks may feel worse on naphazoline. There are PDE inhibitors in the diagram.

I've also read that Midodrine is used for peripheral denervation in dysautonomia.

Me and Ironfeather could be trembling after exercise, isn't this effect also seen in alcohol abusers?
« Last Edit: January 06, 2021, 01:27:21 PM by demografx »

Iwillbeatthis

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Re: POIS paper treatment summary
« Reply #33 on: January 06, 2021, 01:25:03 PM »
I found nicotine gives me brain fog when taken normally, but when I was at a party and having a bad reaction to alcohol, a cigarette seemed to fix things, I also remember at a football game I watched I was feeling foggy and bad then tried nicotine gum and it helped my symptoms again.

Muon

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Re: POIS paper treatment summary
« Reply #34 on: January 06, 2021, 04:07:43 PM »
Agmatine sulfate increases BDNF and eNOS, I ordered some and it came today so I will test it out

Any result?

Iwillbeatthis

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Re: POIS paper treatment summary
« Reply #35 on: January 06, 2021, 06:56:35 PM »
Agmatine sulfate increases BDNF and eNOS, I ordered some and it came today so I will test it out

Any result?

Nope, I tried inside POIS it did nothing, then tried outside of POIS when I was feeling foggy and tired, it did clear the brain fog and give me energy but every time it wears off it induces a headache and I feel strange. So I'm not gonna use it anymore and its probably a bad idea for me to take arginine related things as they may feed viruses + increase spermidine production. The guy who used the agmatine for his autistic kid combined it with MCT oil though.

I got Sulforaphane from the same company so will try that next, I got them both for really cheap.

Muon

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Re: POIS paper treatment summary
« Reply #36 on: January 07, 2021, 12:06:14 PM »
Hello, I have started taking Zinc Picolinate 40mg and I have noticed a slight improvement in my POIS symptoms (a bit more alert and my psoriasis is not so bad).

Could this mean that my POIS is hormone-related given Zinc is linked to testosterone, etc? Is there anything else I should try alongside Zinc given I have seen some improvements with Zinc?

Simultaneous measurement of multiple Th1 and Th2 serum cytokines in psoriasis and correlation with disease severity

"We observed that IFN-g and IL-8 cytokines were elevated in psoriatics and correlated with parameters of disease severity while IL-10 and IL-12 were decreased."

Susceptibility-associated genetic variation at IL12B enhances Th1 polarization in psoriasis

Tuning the brain:
"If NGF levels are too high, a phenomenon called apoptosis occurs. Apoptosis is associated with cell death. Using zinc in fairly
physiologic concentrations attenuates the apoptosis induced by NGF.

Zinc can block NMDA receptors acutely and can also induce a Src family-mediated (tyrosine kinase) up-regulation of NMDA-receptor
function.

The NMDA receptor has numerous modulatory sites. These include those for ketamine, polyamines, zinc, magnesium, pH, redox, glycosylation,
glycine, heparin, dextromethorphan, and dynorphin.
"

...Sounds like an 'abnormal' endogenous process due to orgasm that can be triggered by an exogenous substance, in this case semen...

...From second paper:
"Human seminal plasma contains very high concentrations of prostaglandins when compared to other bodily secretions. It is now apparent that PGE2, 19-hydroxyprostaglandin E1 and 19-hydroxyprostaglandin E2 are the three major prostaglandins in human seminal plasma, each being present in millimolar concentrations..."
I think it's the prostaglandins in the semen that cause this. Or it could be caused by the polyamines (spermine, spermidine).

"Spermine is a nociceptive substance. Its algogenic effect may possibly be antagonized by Ca2+-channel blockers, SAMe, morphine, and various NMDA antagonists, especially those acting at the polyamine site.

Spermine stimulates Casein Kinase II (CKII) and up-regulates NMDA-channel activity, probably through coupling to the spermine modulatory site on the receptor.
"

Several agents block the spermine site:

Nylidrin, isoxsuprine, acamprosate, ifenprodil, eliprodil, and haloperidol.
« Last Edit: January 07, 2021, 12:34:33 PM by Muon »

Muon

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Re: POIS paper treatment summary
« Reply #37 on: January 07, 2021, 01:55:30 PM »
From tuning the brain (Dr. J. Goldstein):
The situation in which synaptic fatigue is most obvious is that of sexual arousal and ejaculation in the male with a neurosomatic disorder. Some males relapse after ejaculation. A few relapse, but in a different, milder way, after sexual arousal.

SYNAPTIC FATIGUE

Synaptic fatigue is a term that used to make me think an axon terminal had been repetitively stimulated so frequently that its supply of transmittercontaining vesicles in the appropriate position at the membrane to be released ("docked") could not keep up with the demand. Such a process is termed "frequency-dependent depression." It occurs over minutes of repetitive firing and recovers slowly, eventually reaching an equilibrium with transmitter packaging into recycled vesicles. In the case of the catecholamines, using this scenario, there could also be

  • decreased precursor (phenylalanine and tyrosine--even L-dopa);
  • insufficient activity of tyrosine hydroxylase, the rate-limiting enzyme for catecholamine biosynthesis;
  • low levels of the various cofactors for the enzyme chain DA and NE;
  • impaired axonal transport to the terminal;
  • impaired manufacture, transport, and reuptake of DA and NE vesicles at the terminal;
  • problems with the Ca2+ channels (which open to initiate vesicle release); and
  • dysregulation of communication in the postsynaptic neuron
« Last Edit: April 13, 2021, 05:36:05 AM by Muon »

Muon

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Re: POIS paper treatment summary
« Reply #38 on: January 10, 2021, 11:35:19 PM »
Too bad for me that cbd does not work for me anymore. I think I am allergic for things that go with the cbd. I am also allergic for vitamin D.

Why did it work for you in the first place? Why don't doctors try to figure this out? I gave you a book. Open it and search (CTRL-F) for 'canna'. It affects so many things. Increases serotonin, inhibits adenylyl cyclase, affects opioids, dopamine, and the list goes on. You need other substances to test potential mechanisms of CBD one by one.

berlin1984

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Re: POIS paper treatment summary
« Reply #39 on: January 12, 2021, 12:10:07 AM »
Method of POIS relief central hub

Wow, great compilation..