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General POIS Discussions / Sexual preference in POIS
« Last post by kindalikeitnow on December 01, 2021, 12:26:01 PM »

A question. Does anyone here notice having issues with their sexual orientation when in POIS? I notice in myself that i start feeling like i could be bi instead of straight. This feeling goes away out of POIS.

I feel more insecure & anxious during this time too which may be related.
Quick update...

Still doing my deep breathing exercises and my symptoms are enormously improved. Sometimes I don't notice any symptoms at all except for the lung issues, but these lung issues are now more apparent because there aren't any stronger symptoms to cover it up.

I'm currently at the end of the third POIS day (my symptoms last 3 days, the third day usually being the worst), I've felt good all day until recently when my lungs felt like the inflammation spiked. I'm having frequent deep coughs like my lungs are desperately trying to get the air out, short quick breaths, and my chest feels like it wants to cave in. I got an blood oxygen saturation reader and put it on for a few minutes and it fluctuated a lot, mostly sitting around 95-97%, but at one point dipped as low as 89% (I did have to wait til I got home to get it and by that point felt like I was starting to improve).  Still not much symptoms other than the lung issues.  I'm starting to think it's prolonged oxygen issues that cause my problems since my symptoms don't come on right away.

I'll continue to update. I'd like to if anybody has tried the deep breathing exercises and what they did for you.
I would like to share my experience, after I come.  the pressure starts to drop, then sleep comes, but then the head starts to make a little pressure, the eyes hurt and I get discouraged for anything.  sometimes even the "explosive head" phenomenon occurs.  It's pretty awesome and I would like some help.
I would if I could, but I cant afford it myself and I still havnt found a doctor who wants to collaborate with me on POIS. Havn't tryed thiamin alone, just the B-complex.
POIS Research / Re: Testosterone-PPARs-PGC1a-Irisin axis
« Last post by Progecitor on November 30, 2021, 01:55:07 AM »
Associations with other diseases:
1. Myasthenia Gravis (MG)

Although I am not a case of myasthenia gravis (MG), but interestingly some common factors are possibly involved in both MG and my POIS subtype. At first I didn't think much of this, but then I noticed that MG has been already associated with POIS by members and there could be some comorbidity as well.

MG is more researched than POIS, so I thought it was worth quoting some information to give the issue some perspective.

Beta blockers (e.g. propranolol) can aggravate symptoms in myasthenia gravis or asthma.

Beta blockers and agonists possibly make up another division in POIS subtypes.

Beta 2 adrenergic agonists are beneficial in some cases of MG.
The diagnosis of myasthenia gravis (MG) was finally confirmed by direct measurement of diaphragmatic strength using magnetic nerve stimulation providing clear cut evidence of significant fatigable weakness and the demonstration of muscle-specific kinase (MuSK) serum antibodies using a novel cell-based assay. Review of the literature suggested a possible impairment of excitation–contraction coupling with malfunction of a signaling protein downstream to the AchR, without an accompanying impairment of electrical transmission. This postulated mechanism, resulting in a disturbance of calcium signaling, explained the unusual features in this patient's illness and led to treatment with salbutamol and ephedrine and to significant symptomatic improvement not achieved by any other treatment.

The same factors seem to be involved in my case!
Numerous reports demonstrate that the loss of PKA compartmentalization significantly disrupts PKA signaling and leads to many physiological dysfunctions, for example, in memory, immune response and cytoskeletal dynamics.
This study demonstrated that gravin undergoes subcellular redistribution following treatment with ionomycin or thapsigargin, both from extracellular Ca2+ influx and from intracellular store release. Although the mechanism behind calcium mediated redistribution of gravin has yet to be fully elucidated, previous work indicates the involvement of Ca2+/calmodulin.
Since gravin interacts with a diverse array of signaling molecules including PKA, PKC, PDE4, B2-adrenergic receptor (B2AR), cyclin D and others, subcellular translocation of this AKAP would likely affect signaling events involving these binding partners.
PKA, for instance, is known to require spatial compartmentalization by AKAPs. Thus, loss of cortically-localized gravin/PKA would likely affect PKA signaling by reducing activity at the plasma membrane or directing PKA signaling to another subcellular compartment. B2AR signaling is known to be regulated by gravin expression and redistribution in a variety of contexts and thus receptor mediated events leading to gravin redistribution would most certainly impact a wide range of B2AR dependent physiological activities known to be linked to gravin. Finally, reports that PDE4 binds to gravin and that this complex regulates cortical cAMP levels suggest that receptor mediated relocalization of gravin could impact cAMP dependent signaling broadly by altering dynamic control of [cAMP].
Our data supports the hypothesis that receptor mediated signaling events involving calcium and/or PKC can alter cAMP-dependent signaling through the spatial regulation of gravin and anchored PKA. This finding suggests that gravin facilitates a novel cross-talk mechanism in which cAMP-dependent signaling pathways are altered by calcium and PKC, and lays the groundwork for future studies of gravin spatiotemporal dynamics in regulating cAMP-dependent signaling events.
Ca2+ elevation and purinergic receptor activation induces gravin relocalization.

SIRT1 is downregulated in MG!
Myasthenia gravis (MG) is an autoimmune disease associated with autoantibody production that leads to skeletal muscle weakness. By integrating the datasets, we identified 143 hypermethylation-low expression genes and 91 hypomethylation-high expression genes. Then we constructed PPI network and ceRNA networks by these genes. Phosphatase and tensin homolog (PTEN) and Abelson tyrosine-protein kinase (ABL)1 were critical genes in both PPI networks and ceRNA networks. And potential MG associated lncRNAs were selected by comprehensive analysis of the critical genes and ceRNA networks. In the hypermethylation-low expression genes associated ceRNA network, sirtuin (SIRT)1 was the most important gene and the lncRNA HLA complex (HC) P5 had the highest connection degree. Meanwhile, PTEN was the most important gene and the lncRNA LINC00173 had the highest connection degree in the hypomethylation-high expression genes associated ceRNA network.
As an autoimmune disease, MG is caused by both genetic and external factors. Genetics can influence disease susceptibility, which can be modulated by external factors such as infection or diet that lead to chromatin modification. Infections can induce the production of antibodies that act as autoantibodies against AChR; in fact, exacerbation of MG is often associated with infection. Thus, aberrant antigen processing and presentation may contribute to the pathogenesis of MG. IFN-g level was shown to be elevated in MG patients.
The top 5 hub genes in the PPI network of hypermethylation-low expression genes were VHL, ZBTB16, WSB1, TRIM4, and RNF144b. ZBTB16, also known as promyelocytic leukemia zinc finger (PLZF), is a transcription factor that promotes the recruitment of effector T helper cells during the development of innate lymphocyte lineages and is also essential for the development of osteoblasts and spermatogonia. ZBTB16 may contribute to abnormal T cell development in MG, and ZBTB16 methylation is a potential mechanism of MG pathogenesis.
SIRT1 has been linked to immune-related diseases such as tumors and autoimmune diseases and was decreased in the PBMCs of multiple sclerosis patients during relapses. The lncRNAs HCP5, OIP5-AS1, and LINC00894 were the most important lncRNAs in the ceRNA network. HCP5 is associated with several autoimmune diseases including psoriatic arthritis, systemic lupus erythematosus, and Graves’ disease; and OIP5-AS1 was found to play a critical role in the ceRNA network of multiple sclerosis.

Irisin is elevated in MG!?
Serum irisin levels were significantly elevated in Myasthenia gravis (MG) patients compared with HCs. Furthermore, serum irisin levels were associated with the myasthenia gravis activities of daily living score in ocular myasthenia gravis (OMG) patients, but there was no relationship to be considered of any relevant value in generalized myasthenia gravis (GMG) patients. Acetylcholine receptor antibody–positive MG patients had higher serum irisin levels compared with HCs. Thymoma, endotracheal intubation, or intensive care unit treatments subsequently were not found to have effect on serum levels of irisin, but tendencies of increase were observed in negative ones.

Increasing PGC-1a is probably beneficial in MG.
These results implied that Qiangji Jianli Decoction may provide a potential therapeutic strategy through promoting mitochondrial biogenesis to alleviate myasthenia gravis via activating the AMPK/PGC-1a signaling pathway.

2. COVID-19

The same factors are also involved in COVID-19, so a comparison is in order.

Alpha adrenergic antagonists (blockers) are possibly beneficial in COVID-19 infection.
Here, we analyzed a large cohort of patients hospitalized at Veterans Health Administration (VA) hospitals, in whom a1-AR antagonists are commonly used to treat unrelated diseases such as benign prostatic hyperplasia (BPH), post-traumatic stress disorder (PTSD), or arterial hypertension.
Having an active prescription for any a1-AR antagonist (tamsulosin, silodosin, prazosin, terazosin, doxazosin, or alfuzosin) at the time of admission had a significant negative association with in-hospital mortality (relative risk reduction 18%) and death within 28 days of admission (relative risk reduction 17%). In a subset of patients on doxazosin specifically, an inhibitor of all three alpha-1 adrenergic receptors, we observed a relative risk reduction for death of 74% compared to matched controls not on any a1-AR antagonist at the time of admission. These findings suggest that use of a1-AR antagonists may reduce mortality in COVID-19.
While dexamethasone and other immunosuppressive strategies have shown some promise in improving outcomes in patients with severe COVID-19, they have not shown benefit (and may be detrimental) when given to patients with less advanced disease.
Catecholamines (adrenaline, noradrenaline, and dopamine) are monoamine hormones that signal through adrenergic receptors (ARs) expressed on tissues including cells of the immune system. Cells of the innate and adaptive immune system (phagocytes, lymphocytes) are capable of producing catecholamines de novo and signal in an autocrine/paracrine self-regulatory fashion. Beyond their well-established role in neurotransmission and physiological fight-or-flight responses, catecholamines have been shown to amplify immune responses and enhance acute inflammatory injury in vitro and in vivo by increasing cytokine production in immune cells (e.g., IL-6, TNF-a, MIP-2). In animal models of hyperinflammation, prophylactic treatment with an alpha-1 adrenergic receptor (a1-AR) antagonist that inhibits all three receptor subtypes (a1A-,a1D-, and a1B-AR) can prevent cytokine storm and death by blocking deleterious catecholamine signaling and immune responses.
Importantly, a1-AR antagonists are immunomodulatory, but not immunosuppressive drugs.

Beta adrenergic antagonists (blockers) are possibly beneficial in COVID-19 infection.
A combined Dutch/German study investigated 1134 patients recently hospitalised because of Covid-19 infection and extracted information from their electronic medical records.
Treatment with ACEIs or ARBs did not influence the major outcome, while beta-blocker treatment significantly reduced the risk of major outcome. In contrast, calcium channel blocker (CCB) treatment worsened the major outcomes. There was also a statistically non-significant trend for diuretic treatment to worsen the major outcomes. Hypertension was the most important comorbidity in the German part of the study.
A previous study suggested a modestly lower likelihood of a positive test for Covid-19 among patients taking beta-blockers. Another recent paper suggested that non-selective beta-blockers blunt the excessive inflammatory burst commonly reported in severe Covid-19 infected patients.

Table 1 lists the many beneficial effects of beta blockers in COVID-19.

Irisin is possibly beneficial in COVID-19, while SIRT1 is detrimental!?
The cell line showed the expression of multiple genes related to severe COVID-19, such as FURIN, ADAM10, TLR3, KDM5B, SIRT1 and TRIB3.
Our data showed that irisin treatment decreased the levels of FURIN, ADAM10, TLR3, KDM5B and SIRT1 mRNA expression, and increased the levels of TRIB3 transcript by 3-fold. These results come together with the beneficial results that irisin has shown in a recent study published by our group, in which irisin improved uncoupling protein 1 (UCP1) production, reduced lipid profile and oxidative stress, while not altering leptin, adiponectin, peroxisome proliferator-activated receptor gamma (PPARG) and FNDC5 levels.
FURIN cleaves SARS-CoV-2 spike (S) glycoprotein, the key protein used to infect mammal cells; ADAM10 is correlated with ACE2 cleavage regulation in human airway epithelia; TLR3 plays an important role in the innate response to SARS-CoV or MERS-CoV infection and regulates ACE2 cleavage; KDM5B regulates positively ACE2; in more than 57% addressed studies, researchers found that SIRT1 was upregulated in the lung of patients with severe COVID-19 comorbidities; all these genes favor the viral infection and can be potential targets for preventing SARS-CoV-2 spread. On the other hand, TRIB3 gene has been linked to fatty acid synthesis control and insulin resistance, in addition to regulating plasma levels of triglycerides and HDL cholesterol in humans and was previously reported to decrease virus infection and replication; so TRIB3 can be considered a therapeutic target for COVID-19.
Irisin is found in human blood at concentrations of 3–5 ng/ml; circulates at ~3.6 ng/ml in sedentary individuals; this level is increased to ~4.3 ng/ml in individuals undergoing aerobic interval training. The involvement of irisin in viral infection is poorly understood; however, a cross-sectional study of patients with HIV demonstrated that irisin levels correlated negatively with body fat and positively with fat-free mass and strength parameters. In another scenario, researchers verified that FNDC5 overexpression or irisin supplementation could preserve mitochondrial function and attenuate oxidative damage as well as cell apoptosis.
Although alveolar cells do not express irisin, previous studies using exogenous irisin indicated that these cells benefit from irisin in case the pulmonary tissue is damaged; the administration of irisin in mice subjected to ischemia demonstrated that inflammation in the lungs was reduced, there was evident tissue repair, and hypoxemia and proinflammatory cytokines were decreased.

PGC-1a increases TRIB3! This is also a very comprehensive study about PGC-1a.
Hence, in healthy individuals, in response to a high-fat diet, SIRT1 may stimulate FA oxidation through PPARA–PGC-1a–lipin-1.
In particular, the expression of Ucp2 and the prolactin receptor gene (Prlr), both of which significantly influence B-cell function, were downregulated by SIRT1 overexpression.
Overexpression of PGC-1a in cultures of primary rat skeletal muscle cells induces increased expression of the mammalian tribbles homolog TRIB3, an inhibitor of AKT signaling, highlighting the potential of PGC-1a to cause insulin resistance. Moreover, PGC-1?/? mice are protected against high-fat diet induced insulin resistance. Acute disruption of hepatic PGC-1 expression enhances insulin sensitivity, in part reflecting reduced expression of TRIB3. The observation that, in liver, TRIB3 is a target for PPARA and that knockdown of hepatic TRIB3 expression improves glucose tolerance, whereas hepatic overexpression of TRIB3 reverses the insulin-sensitive phenotype of PGC-1-deficient mice has led to the suggestion that TRIB3 inhibitors may have a potential role in the treatment of T2DM. However, more recently, chronic reduction of hepatic PGC-1a expression has been shown to impair hepatic insulin sensitivity.

Association between COVID-19, MG and supplements:

COVID-19 course in MG is rather unpredictable.
The risk of COVID-19 in MG patients seems to be no higher than that of the general population, regardless of immunosuppressive therapies. In our cohort, COVID-19 barely affected MG course.

Most patients with MG hospitalized for COVID-19 had severe courses of the disease: 87% were admitted in the intensive care unit, 73% needed mechanical ventilation, and 30% died. Immunoglobulin use and the plasma exchange procedure were safe. Immunosuppressive therapy seems to be associated with better outcomes, as it might play a protective role.

A total of 91 patients with myasthenia gravis were included at the time of interim analysis. Myasthenia gravis worsening or crisis requiring rescue therapy (eg, intravenous immunoglobulin, plasma exchange, or steroids) in the setting of COVID-19 was reported in 36 (40%) of 91 patients. Complete recovery or discharge to home was reported in 39 (43%) patients, whereas 22 (24%) patients died due to COVID-19.
Current data, which might be biased toward poor outcomes reporting, show that patients with myasthenia gravis who are infected with severe acute respiratory syndrome coronavirus 2 are frequently admitted to hospital, have disease exacerbations, and have a higher mortality than the general population with COVID-19.

Clinical responses of MG patients during SARS-CoV-2 infection are unpredictable and challenging for clinicians. From the pathogenetic point of view, it has been hypothesized that Treg/Th17 imbalance in the course of SARS-CoV-2 could amplify or trigger the excessive autoimmune response. Though there is no direct evidence for the involvement of proinflammatory cytokines and chemokines in lung pathology, the change of laboratory parameters, including elevated serum cytokine, chemokine level in infected patients correlating with the severity of the disease and adverse outcome, confirmed a possible role for hyper-inflammatory responses in COVID-19.

As the most important predictors of severe COVID-19 in MG patients we identified unsatisfied condition of MG with lower FVC, previous long-term corticosteroid treatment especially in higher doses, older age, the presence of cancer, and recent rituximab treatment.

NAC increases SIRT1 and B-adrenergic signaling, so does it adversely affect COVID-19 course, even though it proved beneficial in small cohort studies?!
The expressions of MnSOD, SIRT1, and FOXO3a were examined at both transcriptional and protein levels. The expression levels of MnSOD, SIRT1, and FOXO3a reduced significantly in the PM2.5 group as compared to the control group. However, their expression levels were increased after NAC intervention. These results suggested that SIRT1 exerted a protective effect against PM2.5-induced respiratory oxidative damage by regulating the expression of FOXO3a. NAC can activate SIRT1 and exert an anti-oxidative role in PM2.5-induced oxidative injury.

Conclusions: like pyruvate, the antioxidant NAC potentiated B-adrenergic inotropism of stunned myocardium. Unlike pyruvate, NAC did not increase cellular energy reserves, thus effectively limiting its potentiation of B-adrenergic stimulation. Thus, pyruvate's potentiation of B-adrenergic stimulation in stunned myocardium is most likely the result of the combined effects of its antioxidant and energetic properties.

Overall, our study demonstrated that NAC therapy provided a significant improvement in oxygenation parameters and reduction in CRP, NEWS2 scale, and length of hospitalization in hospitalized patients with COVID-19.

Melatonin may exacerbate MG.
The use of melatonin in patients with MG, whether ocular or generalized, may trigger exacerbations of the disease, probably due to an upregulation of adaptative immune response and an interaction with treatment involving corticosteroids and other immunosuppressants.

Melatonin is supposedly beneficial in COVID-19.
Compared with the control group, the clinical symptoms such as cough, dyspnea, and fatigue, as well as the level of CRP and the pulmonary involvement in the intervention group had significantly improved.
Adjuvant use of melatonin has a potential to improve clinical symptoms of COVID-19 patients and contribute to a faster return of patients to baseline health.

Recently, a randomized controlled study reported that low doses of melatonin significantly improved symptoms in hospitalized COVID-19 patients, leading to more rapid discharge with no side effects, while significantly decreasing levels of CRP, proinflammatory cytokines, and modulating dysregulated genes governing cellular and humoral immunity.

Melatonin mostly inhibits SIRT1, however in some cases it may actually increase it.
Additionally, melatonin treatment down-regulated SIRT1 and up-regulated acetylated-p53. Sirtinol (a known SIRT1 inhibitor) and SIRT1 siRNA further enhanced the antitumor activity of melatonin, while SRT1720 (a known SIRT1 activator) attenuated the antitumor activity of melatonin.

Here, we challenged our hypothesis that melatonin will impart antiproliferative response against prostate cancer (PCa) via inhibiting Sirt1. We demonstrated that melatonin significantly inhibited Sirt1 protein and activity in vitro in multiple human PCa cell lines, and melatonin-mediated Sirt1 inhibition was accompanied with a significant decrease in the proliferative potential of PCa cells, but not of normal cells. Our data identified melatonin as a novel inhibitor of Sirt1 and suggest that melatonin can inhibit PCa growth via Sirt1 inhibition.

Our results suggested that severe burns could induce acute kidney injury, which could be partially reversed by melatonin. Melatonin attenuated oxidative stress, inflammation and apoptosis accompanied by the increased expression of SIRT1. The protective effects of melatonin were abrogated by the inhibition of SIRT1. In conclusion, we demonstrate that melatonin improves severe burn-induced AKI via the activation of SIRT1 signaling.

These data indicate that melatonin per se is capable of relaxing vascular smooth muscle and that low doses of melatonin impair alpha-1 and alpha-2 adrenergic responses without changes in the beta adrenergic response of vascular smooth muscle.

The ratio of pAMPK to AMPK and the protein levels of SIRT1 and cytosolic PGC-1 in the diabetic control group group were declined compared to those in the NC group. These markers were significantly increased in the vitamin D3 group.

The mean expression of the PGC1-a gene was increased amongst the ulcerative colitis (UC) patients treated with Zinc (Zn) supplement. However, in the control group, no any changes have been recorded for this gene. The mean expression of the SIRT1 gene was increased amongst the UC patients treated with Zn supplement. However, in the control group, no any changes have been recorded for this gene. In cell culture experiments and colitis animal models, Zn administration improves intestinal barrier function and reduces expression of proinflammatory cytokines. The study findings revealed that the expression of both SIRT1 and PGC1-a genes were significantly increased after Zn supplementation.
In a similar survey, Khazdouz et al. reported that Selenium (Se) supplement caused some changes in the SIRT1 and PGC1-a genes in UC patients. They reported that the SIRT1 gene expression in the Se group was significantly increased compared to the placebo. An increase in the expression of the PGC-1a gene in the Se group was not statistically significant. It seems that Se supplementation caused a significant decrease in the inflammatory response of the colon by a significant increase in the expression of the SIRT1 gene. Researches established that SIRT1 can regulation of intestinal inflammation and tissue homeostasis in UC model.

Of course these facts don't make for an easy interpretation, but anyone with an active COVID-19 infection should be still careful with SIRT1 activators and beta adrenergic agonists even if they are potentially beneficial in some cases of POIS.
General Alternative Causes and Treatments of POIS / ninety percent recpvered from PIS
« Last post by helium on November 29, 2021, 11:15:23 PM »
lately, i have  stopped eating wheat products a half a day prior to SEX and a half a day afterwards and this seems to help so far.
please spread to any person you know who has POIS.
refuah sheleima
Re: Quantum’s recommended link to explain POIS to your DOCTORS

I recently asked Quantum to suggest a POIS link to show my cardiologist.

Quantum suggested this link:

And it worked!

Thank you, Quantum!

My increased dose of TRT-
for-POIS-onset has ALSO been approved - - today - - by my Endocrinologist, to whom I sent Quantum’s link.

Thanks again, Quantum!

I am glad that this review article had been positively perceived by your cardiologist, Demo !
Re: Quantum’s recommended link to explain POIS to your DOCTORS

I recently asked Quantum to suggest a POIS link to show my cardiologist.

Quantum suggested this link:

And it worked!

Thank you, Quantum!
My increased dose of TRT-for-POIS-onset has ALSO been approved - - today - - by my Endocrinologist, to whom I sent Quantum’s link.

Thanks again, Quantum!
Poll Center / Re: Opioids
« Last post by Limejuice on November 29, 2021, 06:02:38 PM »
Thank you for sharing this Hakira! Important information everyone needs to know.
POIS Research / Re: Cured POIS and possible CYP24A1 Connection
« Last post by Limejuice on November 29, 2021, 02:47:49 PM »
Mindlesstree, this is quite fascinating information.  I also take daily low dose vitamin D and C, which moderately helps with lingering symptoms. Please update us on your road to recovery!
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