Paradoxical cns
Closer Examination of GHB Theory
2024.05.30 19:26 Defying_Gravitas Closer Examination of GHB Theory
(x-post from other sub where it was wildly unpopular. I've seen others here with similar theories so hopefully we can have a more productive convo here)
OPINION: Anecdotally, people generally have a "preferred" beer. Why would OJO have two brands? Option 1: He bought a beer for someone else. Option 2: The Miller Lite was a draft and/or tasted weird (skunky, or?) so maybe he switched to a bottle of something else. Sometimes the draft lines haven't been cleaned in awhile... but sometimes the taste of bar drinks can be impacted by GHB... This may be important later. [4]
FACT 2: Witnesses indicate Karen was drinking a clear liquid from a clear glass. She and John are also described as overtly affectionate.
FACT 3: CCTV shows John taking a swallow of a clear liquid from a clear glass and exiting the bar with glass in hand.
FACT 4: Karen drove her vehicle, a dark Lexus SUV, while John rode in the front passenger seat.
OPINION: Someone who is particular about people cutting through their lawn and particular about the kids' breakfasts is unlikely to be okay with drinking and driving. Option 1: John believed Karen was not impaired. Option 2: John's own judgment was impaired and therefore he didn't realize she was impaired.
FACT 5: Witness Heather Maxon believes she saw two occupants, one male, in the dark SUV that ultimately pulled up in front of 34 Fairview.
FACT 6: Witness Ryan Nagel believes he saw an SUV not in park, with in-tact tail lights and without rear damage, containing only a female driver facing forward with hands on the wheel. Neither Maxon nor Nagel saw John O'Keefe in or outside of the vehicle as they were leaving.
FACT 7: Karen awoke from John's couch after 4am. She could not find him and had no memory of what had happened 4 hours earlier. She was immediately frantic and distraught about his absence. She believed she'd last seen John at the Waterfall. Her behavior does not seem consistent with a traditional hangover.
Ask yourself this: who would benefit from 2 to 4 hours of Karen's and John's memory loss? What could be done to them while they were impaired? Why was Jen McCabe so insistent about them attending the "after-party"? What, if any, was the "surprise" Jen had for Karen? Did she want to see them make fools of themselves or be made fun of? Did she want a front-row seat to watch the entertainment portion of a prank?
If both Karen and John were drugged/impaired without their knowledge, and both attended, the possibilities range from relatively harmless silly photos or an intent to embarrass Karen and John to more nefarious plans, like SA to Karen or maybe roughing up John. He could be a human punching bag and then wake up on the lawn and have no idea where he was or how he got banged up. Unless someone accidentally took it too far and caused the injury to the back of his head.
There'd be no memory of anything that happened. There'd be no evidence of a drug in their systems. Rumors have indicated Karen didn't stay at the Alberts' house because she didn't feel well and was confused about if they were welcome. By the time her blood was drawn at the hospital, it was well after the 4 hours that GHB can be detected in the bloodstream.
Look at the list of effects and side-effects again.
submitted by Defying_Gravitas to justiceforKarenRead [link] [comments]
BACKGROUND
GHB is a party drug that produces feelings of euphoria, confidence, relaxation and sociability. Smaller doses can be more stimulating and larger doses can be more sedative.[1]TIME [2, 3]
- GHB takes effect in 15 to 30 minutes
- Effects last 3 to 6 hours
- Detected in blood ≤ 4 hours
- Detected in urine ≤ 12 hours
CENTRAL NERVOUS SYSTEM EFFECTS [3]
- euphoria
- drowsiness
- decreased anxiety
- confusion
- memory impairment
- visual hallucinations
- paradoxically, excited and aggressive behavior
- GHB greatly increases the CNS depressant effects of alcohol and other depressants.
EFFECTS [3]
- Low doses of GHB produce nausea
- High doses of GHB can result in:
- Unconsciousness
- Seizures
- Slowed heart rate
- Greatly slowed breathing
- Lower body temperature
- Vomiting
- Nausea
- Coma
- Death
SOURCES
- [SOURCE 1]
- [SOURCE 2]
- [SOURCE 3]
- [SOURCE 4] Waterfall Bar Menu indicates 3 brands on tap but indicates others are available. Publication date is unclear.
FACTS AND OPINION
FACT 1: The 11:58pm Waterfall receipt indicates John O'Keefe paid for 3 drinks: Bud Lite Bottle, Miller Lite Lager, Tito's. They are listed alphabetically, not in order of purchase.OPINION: Anecdotally, people generally have a "preferred" beer. Why would OJO have two brands? Option 1: He bought a beer for someone else. Option 2: The Miller Lite was a draft and/or tasted weird (skunky, or?) so maybe he switched to a bottle of something else. Sometimes the draft lines haven't been cleaned in awhile... but sometimes the taste of bar drinks can be impacted by GHB... This may be important later. [4]
FACT 2: Witnesses indicate Karen was drinking a clear liquid from a clear glass. She and John are also described as overtly affectionate.
FACT 3: CCTV shows John taking a swallow of a clear liquid from a clear glass and exiting the bar with glass in hand.
FACT 4: Karen drove her vehicle, a dark Lexus SUV, while John rode in the front passenger seat.
OPINION: Someone who is particular about people cutting through their lawn and particular about the kids' breakfasts is unlikely to be okay with drinking and driving. Option 1: John believed Karen was not impaired. Option 2: John's own judgment was impaired and therefore he didn't realize she was impaired.
FACT 5: Witness Heather Maxon believes she saw two occupants, one male, in the dark SUV that ultimately pulled up in front of 34 Fairview.
FACT 6: Witness Ryan Nagel believes he saw an SUV not in park, with in-tact tail lights and without rear damage, containing only a female driver facing forward with hands on the wheel. Neither Maxon nor Nagel saw John O'Keefe in or outside of the vehicle as they were leaving.
FACT 7: Karen awoke from John's couch after 4am. She could not find him and had no memory of what had happened 4 hours earlier. She was immediately frantic and distraught about his absence. She believed she'd last seen John at the Waterfall. Her behavior does not seem consistent with a traditional hangover.
THEORY
What if someone in this already-established collection of pranksters/roughhousers (including at least one potentially jilted paramour) slipped something into their drinks? Option 1: Someone slipped something into Karen's drink, and John is accidentally also drugged when he drinks from her glass. Option 2: Someone slipped something into BOTH Karen's drink and John's drink. John is accidentally dosed a second time when he drinks from Karen's cup.Ask yourself this: who would benefit from 2 to 4 hours of Karen's and John's memory loss? What could be done to them while they were impaired? Why was Jen McCabe so insistent about them attending the "after-party"? What, if any, was the "surprise" Jen had for Karen? Did she want to see them make fools of themselves or be made fun of? Did she want a front-row seat to watch the entertainment portion of a prank?
If both Karen and John were drugged/impaired without their knowledge, and both attended, the possibilities range from relatively harmless silly photos or an intent to embarrass Karen and John to more nefarious plans, like SA to Karen or maybe roughing up John. He could be a human punching bag and then wake up on the lawn and have no idea where he was or how he got banged up. Unless someone accidentally took it too far and caused the injury to the back of his head.
There'd be no memory of anything that happened. There'd be no evidence of a drug in their systems. Rumors have indicated Karen didn't stay at the Alberts' house because she didn't feel well and was confused about if they were welcome. By the time her blood was drawn at the hospital, it was well after the 4 hours that GHB can be detected in the bloodstream.
Look at the list of effects and side-effects again.
- euphoria
- drowsiness
- decreased anxiety
- confusion
- memory impairment
- visual hallucinations
- paradoxically, excited and aggressive behavior
- nausea and vomiting
- unconsciousness
2024.05.18 07:45 cath_wou Challenging interesting time sensitive case! Help please :)
Cate, Yellowknife, Canada 33yo Female 5’6'', 118-120 pounds Meds (went from none to): Propranolol 20 to 40mg/day Ketotifen (1-4mg/day) Rupall (20-40mg/day) Very new since yesterday: Amitriptyline 10mg As needed now (hate them but was told to take to avoid CNS and ANS and PNS attacks): Valium 5-10mg as needed (I don’t take it everyday at all and just started taking it AFTER my venous gases were taken so they didn’t do what you will read about)
Supplements: Curcumin LongVida Quercetin Resveratrol Benfothiamine L-Carnitine Ubiquinol NAC NADH
Hi!
My name is Cate. I am 33yo and I am from Canada. Just to give a little bit of a background, I was always an extremely active person. I have a dog I used to walk and hike with hours a day. I would happily trade a party with friends just to go walk with my dog. I always was a highly sensitive person nervous system wise. When I was young, I would tell my mom to 'turn off the sun' (lol). I lived well with it though. I became a social worker. Worked crazy hours. I’ve had insomnia for years since a first nervous injury after getting EBV. I recovered though. I moved to a very small town 7 years ago and I live with my dog. I love Life and the outdoor. The only health issue I had was a sensitive nervous system and some rosacea. I also know now that I was prone to dysautonomia but I was extremely active so having low BP and athletic HR (50bpm) wasn’t unusual. I would sometimes get dizzy when standing but not always and never had tachycardia or palpitations from it. I also had slightly stretchy skin so was prone to EDS. I know now, you’ll soon understand why. Back in 2018, I took Accutane and burnt in the sun. I developed mild SFN but it went away with time and my life was normal. More than normal. It was great! :)
In December 2023 I was prescribed Doxy for my Rosacea. I took it once and had to stop as I felt warm patches of skin on my body. It reminded me of the SFN. So I didn’t take a chance. However, I noticed in the weeks after that I had developed a weird anxiety and some insomnia (nervous system injury #1). A few weeks later, I was told to try Metronidazole. I used it for about 2 weeks. All hell broke loose. It started with pins and needles in hands and feet. Never had that before so I didn’t think much of it. Then I became very dizzy. And my mood changed. I was crying for no reason, historically. And I started having burning skin on my limbs. I stopped the meds. But it was too late. I had developed palpitations, lower voice, weak legs, etc. I had a neurotoxicity. (Nervous system injury #2) My doctor didn’t want to believe it was that but was thinking GBS. I was however hyoerreflexive so it wasn’t GBS. But he prescribed some Ativan. I took it but quickly it wasn’t doing what it was supposed to do. After even just a few days I could feel more anxiety. It was awful. So I stopped taking them after about 10 days. Things went from bad to worse: terrible panic attacks, flashes of light and stroboscopic type of images when closing my eyes, insomnia but to the point of not sleeping for a month, pelvic floor pain, myoclonus jerks, full body internal vibration, sensitivity to sound, it was scary. (Nervous system injury #3). I forgot to say but my periods also never came.
I was sent for an MRI and obviously my MRI was ok. But things were NOT normal. My palpitations were so bad, my heart would skip beats, I was so dehydrated cause I became hyperadrenergic. I also started to have anhedonia and my GI motility stopped. I could not feel hunger anymore. It was weird. But I wasn’t short of breath. Just had palpitations. Doctors told me I have FND, but it was not FND. FND doesn’t stop your periods, doesn’t mess with your hormones, doesn’t give you continuous insomnia for a month. And I never had a limb not functioning or had a seizure. Therefore. I left to find more and better answers. I knew it as the nervous system but I am not a doctor so had to rely on them for help.
I went back to my home town. I was a mess but physically I was fine. I was eating, digesting, but I had become more short fuse, still having the myoclonus, and all the other weird symptoms with some derealization and sound sensitivity. But I could still laugh etc. I went to see a doctor and he thought maybe it was a bad withdrawal so I was put on a high dose of Valium. Obviously all of my symptoms vanished but others showed up: I started having hand tremors and benzos would act very paradoxically on me. It was increasing my BP and HR, made me cry all the time and become aggressive. I had to come off then. I stayed on them for 6 weeks from 40mg (that’s crazy, I was taking 1mg of Ativan..) to 25mg and was then switched to Gabapentin. The hospital who did that however decided after a few days that I didn’t need the Gabapentin anymore and removed it. I thought I was gonna die. I started having tremors on my face and even to my tongue. I started being very agitated (obviously, I was going through a terrible withdrawal!) and was told they would inject me with antipsychotic. I honestly have never been this traumatized in my life. I restarted the Gabapentin and took it for a month. Hated it too cause ai was super paradoxical to it as well. Most people feel calm on Gabapentin. I felt so agitated and developed weird body movements like my head would twist involuntarily and my fingers were moving from left to right, especially on my left hand.
I stopped the Gabapentin after tapering. In a few days, I was back to normal. I was so happy. Could walk my dog daily, drive, go to the grocery store, I had found myself again. Until I went on a hike. It wasn’t a long hike but it was more demanding than the walks I was doing on flat ground daily. I would walk for several hours but never to the point of being anaerobic. On that hike I did though.
After the hike, I started feeling jittery. My nervous system didn’t like that at all. I went to bed, put on a meditation and fell asleep. That night is still traumatic lol. I felt electric zaps all in my body and spine. I sweat so much. I woke up drenched and with pain everywhere but mostly, every joint in my body cracked. Every single one. I had never been in pain like that in my life. But also, the palpitations were back but much much worse. And also high BP, which I never had even during the beginning after the neurotoxicity started. I wasn’t able to function anymore. I saw my GP and he didn’t like what he saw. I was completely dehydrated, muscles and joints were all painful, crazy palpitations, high blood pressure that I never had before, could hardly walk. He sent me to the hospital. He also confirmed this isn’t FND for the same reasons I mentioned before, and he knows me very well. All my muscles literally melted almost overnight. Like literally melted. And my skin had become stretchy as if all my connective tissues broke down (EDS flared up but like literally overnight).
Once at the hospital, they finally took things more seriously. I was started on on IV fluid for low potassium (very weird cause I make my electrolytes every day and never had an issue with that. You’ll see, it’s relevant). I also had elevated proteins in my body. Very weird too cause I wasn’t eating more proteins than I used to. I also had low WBC. My hormones were obviously all over the place. I was actually due to start my period and it never came. I stopped pooing again and stopped digesting my food. I know that’s dysautonomia. I had started to feel slightly better after a few days and walked a bit in the hallway. That night.. other ‘attack’. I don’t know how to call them. A few days after that, I still had pain in my muscles and was scared I was denervated (Metronidazole does that), so I though I would speed up the process by giving myself a full body deep tissue massage….. worse mistake of my life. Worse attack that night and the next day I had burning pain all over. Worse palpitations. All over. I also am now in a wheelchair because if I walk even a few minutes, I get an attack that night and wake up with even more weird stuff.
Fast forward to now. I am in Vancouver, Canada. As there isn’t many specialists in my small town (there isn’t any lol). I am worse than ever. My bloodwork look horrendous. My venous gases show I am in acidosis. I cannot breathe if I sit up or stand so I am laying down. My fasting glucose is at 6. I wore a CGM for months and I had perfect blood sugar and was never insulin resistant. I have low MPVs. Low potassium always despite eating bananas and drinking electrolytes all the time. My skin is completely dehydrated and flaking. I get palpitations even laying down.
I had a nerve conduction test and so far so good, I still have nerves. This is not just dysautonomia. Even at my worse, I didn’t have palpitations laying down in bed. And never to that extend. I have developed every problems of the Pentad like it is called: EDS, Dysautonomia, MCAS, Autoimmunity and I don’t remember the last one but I have it too.
I know this is an over reactive/over sensitive nervous system. That’s quite obvious. I have been running on NS injuries after NS injuries for almost 5 months. Also, my breath smells like ketones now I was told. I eat normally.
However, there is more. I forgot to say, on top of that, I have a pituitary tumour (but we know it’s not that causing the issues as when I was on benzos, my periods came back!), I have a thyroid nodula but it’s non-secreting (have had it over 10 years now) and I have a history of hypothyroidism for which I took meds for two months and then I never had an issue with it again. They tested it at the hospital and it’s ok. There is some auto-immunity in my family. My sister had a bout of RA after she gave birth, my mom has EDS for sure and also had Endometriosis, she also has orthostatic intolerance which is the very beginning stage of dysautonomia, she has rosacea prone skin too. Etc.
I know this cascade triggered viral infections and auto-immunity, but what do I do? These things are understood by only a small minority of doctors and I don’t know where to start. I think I will never get better if we don’t figure out the cause of my problems with the insulin and mostly why I have respiratory acidosis!
I don’t have ANA activated so far in my bloodwork for the main stuff but clearly I know what’s up..! I know EDS is considered a genetic condition but I strongly think as many doctors that they are auto-immune related. Never had any problems with that until my nervous system broke down which also activated inflammation and my immune system to start having real troubles.
Let me know where to start please, I am scared of dying in the hotel room. I am tired of being in bed but I know I am making things worse when I walk. I am developing ME/CFS, I know it, but it still won’t say why I am hypoventilating 24/7 with low potassium and low MPV and low WBC with high proteins. I am freaking out that my life and health are literally going to hell because of an antibiotic..! For a perioral dermatitis 😂..! I am remaining calm but.. not gonna lie.. it’s no fun.
Thanks for your help!!!
Cate xx
submitted by cath_wou to AskDocs [link] [comments]
Supplements: Curcumin LongVida Quercetin Resveratrol Benfothiamine L-Carnitine Ubiquinol NAC NADH
Hi!
My name is Cate. I am 33yo and I am from Canada. Just to give a little bit of a background, I was always an extremely active person. I have a dog I used to walk and hike with hours a day. I would happily trade a party with friends just to go walk with my dog. I always was a highly sensitive person nervous system wise. When I was young, I would tell my mom to 'turn off the sun' (lol). I lived well with it though. I became a social worker. Worked crazy hours. I’ve had insomnia for years since a first nervous injury after getting EBV. I recovered though. I moved to a very small town 7 years ago and I live with my dog. I love Life and the outdoor. The only health issue I had was a sensitive nervous system and some rosacea. I also know now that I was prone to dysautonomia but I was extremely active so having low BP and athletic HR (50bpm) wasn’t unusual. I would sometimes get dizzy when standing but not always and never had tachycardia or palpitations from it. I also had slightly stretchy skin so was prone to EDS. I know now, you’ll soon understand why. Back in 2018, I took Accutane and burnt in the sun. I developed mild SFN but it went away with time and my life was normal. More than normal. It was great! :)
In December 2023 I was prescribed Doxy for my Rosacea. I took it once and had to stop as I felt warm patches of skin on my body. It reminded me of the SFN. So I didn’t take a chance. However, I noticed in the weeks after that I had developed a weird anxiety and some insomnia (nervous system injury #1). A few weeks later, I was told to try Metronidazole. I used it for about 2 weeks. All hell broke loose. It started with pins and needles in hands and feet. Never had that before so I didn’t think much of it. Then I became very dizzy. And my mood changed. I was crying for no reason, historically. And I started having burning skin on my limbs. I stopped the meds. But it was too late. I had developed palpitations, lower voice, weak legs, etc. I had a neurotoxicity. (Nervous system injury #2) My doctor didn’t want to believe it was that but was thinking GBS. I was however hyoerreflexive so it wasn’t GBS. But he prescribed some Ativan. I took it but quickly it wasn’t doing what it was supposed to do. After even just a few days I could feel more anxiety. It was awful. So I stopped taking them after about 10 days. Things went from bad to worse: terrible panic attacks, flashes of light and stroboscopic type of images when closing my eyes, insomnia but to the point of not sleeping for a month, pelvic floor pain, myoclonus jerks, full body internal vibration, sensitivity to sound, it was scary. (Nervous system injury #3). I forgot to say but my periods also never came.
I was sent for an MRI and obviously my MRI was ok. But things were NOT normal. My palpitations were so bad, my heart would skip beats, I was so dehydrated cause I became hyperadrenergic. I also started to have anhedonia and my GI motility stopped. I could not feel hunger anymore. It was weird. But I wasn’t short of breath. Just had palpitations. Doctors told me I have FND, but it was not FND. FND doesn’t stop your periods, doesn’t mess with your hormones, doesn’t give you continuous insomnia for a month. And I never had a limb not functioning or had a seizure. Therefore. I left to find more and better answers. I knew it as the nervous system but I am not a doctor so had to rely on them for help.
I went back to my home town. I was a mess but physically I was fine. I was eating, digesting, but I had become more short fuse, still having the myoclonus, and all the other weird symptoms with some derealization and sound sensitivity. But I could still laugh etc. I went to see a doctor and he thought maybe it was a bad withdrawal so I was put on a high dose of Valium. Obviously all of my symptoms vanished but others showed up: I started having hand tremors and benzos would act very paradoxically on me. It was increasing my BP and HR, made me cry all the time and become aggressive. I had to come off then. I stayed on them for 6 weeks from 40mg (that’s crazy, I was taking 1mg of Ativan..) to 25mg and was then switched to Gabapentin. The hospital who did that however decided after a few days that I didn’t need the Gabapentin anymore and removed it. I thought I was gonna die. I started having tremors on my face and even to my tongue. I started being very agitated (obviously, I was going through a terrible withdrawal!) and was told they would inject me with antipsychotic. I honestly have never been this traumatized in my life. I restarted the Gabapentin and took it for a month. Hated it too cause ai was super paradoxical to it as well. Most people feel calm on Gabapentin. I felt so agitated and developed weird body movements like my head would twist involuntarily and my fingers were moving from left to right, especially on my left hand.
I stopped the Gabapentin after tapering. In a few days, I was back to normal. I was so happy. Could walk my dog daily, drive, go to the grocery store, I had found myself again. Until I went on a hike. It wasn’t a long hike but it was more demanding than the walks I was doing on flat ground daily. I would walk for several hours but never to the point of being anaerobic. On that hike I did though.
After the hike, I started feeling jittery. My nervous system didn’t like that at all. I went to bed, put on a meditation and fell asleep. That night is still traumatic lol. I felt electric zaps all in my body and spine. I sweat so much. I woke up drenched and with pain everywhere but mostly, every joint in my body cracked. Every single one. I had never been in pain like that in my life. But also, the palpitations were back but much much worse. And also high BP, which I never had even during the beginning after the neurotoxicity started. I wasn’t able to function anymore. I saw my GP and he didn’t like what he saw. I was completely dehydrated, muscles and joints were all painful, crazy palpitations, high blood pressure that I never had before, could hardly walk. He sent me to the hospital. He also confirmed this isn’t FND for the same reasons I mentioned before, and he knows me very well. All my muscles literally melted almost overnight. Like literally melted. And my skin had become stretchy as if all my connective tissues broke down (EDS flared up but like literally overnight).
Once at the hospital, they finally took things more seriously. I was started on on IV fluid for low potassium (very weird cause I make my electrolytes every day and never had an issue with that. You’ll see, it’s relevant). I also had elevated proteins in my body. Very weird too cause I wasn’t eating more proteins than I used to. I also had low WBC. My hormones were obviously all over the place. I was actually due to start my period and it never came. I stopped pooing again and stopped digesting my food. I know that’s dysautonomia. I had started to feel slightly better after a few days and walked a bit in the hallway. That night.. other ‘attack’. I don’t know how to call them. A few days after that, I still had pain in my muscles and was scared I was denervated (Metronidazole does that), so I though I would speed up the process by giving myself a full body deep tissue massage….. worse mistake of my life. Worse attack that night and the next day I had burning pain all over. Worse palpitations. All over. I also am now in a wheelchair because if I walk even a few minutes, I get an attack that night and wake up with even more weird stuff.
Fast forward to now. I am in Vancouver, Canada. As there isn’t many specialists in my small town (there isn’t any lol). I am worse than ever. My bloodwork look horrendous. My venous gases show I am in acidosis. I cannot breathe if I sit up or stand so I am laying down. My fasting glucose is at 6. I wore a CGM for months and I had perfect blood sugar and was never insulin resistant. I have low MPVs. Low potassium always despite eating bananas and drinking electrolytes all the time. My skin is completely dehydrated and flaking. I get palpitations even laying down.
I had a nerve conduction test and so far so good, I still have nerves. This is not just dysautonomia. Even at my worse, I didn’t have palpitations laying down in bed. And never to that extend. I have developed every problems of the Pentad like it is called: EDS, Dysautonomia, MCAS, Autoimmunity and I don’t remember the last one but I have it too.
I know this is an over reactive/over sensitive nervous system. That’s quite obvious. I have been running on NS injuries after NS injuries for almost 5 months. Also, my breath smells like ketones now I was told. I eat normally.
However, there is more. I forgot to say, on top of that, I have a pituitary tumour (but we know it’s not that causing the issues as when I was on benzos, my periods came back!), I have a thyroid nodula but it’s non-secreting (have had it over 10 years now) and I have a history of hypothyroidism for which I took meds for two months and then I never had an issue with it again. They tested it at the hospital and it’s ok. There is some auto-immunity in my family. My sister had a bout of RA after she gave birth, my mom has EDS for sure and also had Endometriosis, she also has orthostatic intolerance which is the very beginning stage of dysautonomia, she has rosacea prone skin too. Etc.
I know this cascade triggered viral infections and auto-immunity, but what do I do? These things are understood by only a small minority of doctors and I don’t know where to start. I think I will never get better if we don’t figure out the cause of my problems with the insulin and mostly why I have respiratory acidosis!
I don’t have ANA activated so far in my bloodwork for the main stuff but clearly I know what’s up..! I know EDS is considered a genetic condition but I strongly think as many doctors that they are auto-immune related. Never had any problems with that until my nervous system broke down which also activated inflammation and my immune system to start having real troubles.
Let me know where to start please, I am scared of dying in the hotel room. I am tired of being in bed but I know I am making things worse when I walk. I am developing ME/CFS, I know it, but it still won’t say why I am hypoventilating 24/7 with low potassium and low MPV and low WBC with high proteins. I am freaking out that my life and health are literally going to hell because of an antibiotic..! For a perioral dermatitis 😂..! I am remaining calm but.. not gonna lie.. it’s no fun.
Thanks for your help!!!
Cate xx
2024.05.17 05:05 Defying_Gravitas Closer Examination of the GHB Theory
BACKGROUND
GHB is a party drug that produces feelings of euphoria, confidence, relaxation and sociability. Smaller doses can be more stimulating and larger doses can be more sedative.[1]TIME [2, 3]
- GHB takes effect in 15 to 30 minutes
- Effects last 3 to 6 hours
- Detected in blood ≤ 4 hours
- Detected in urine ≤ 12 hours
CENTRAL NERVOUS SYSTEM EFFECTS [3]
- euphoria
- drowsiness
- decreased anxiety
- confusion
- memory impairment
- visual hallucinations
- paradoxically, excited and aggressive behavior
- GHB greatly increases the CNS depressant effects of alcohol and other depressants.
EFFECTS [3]
- Low doses of GHB produce nausea
- High doses of GHB can result in:
- Unconsciousness
- Seizures
- Slowed heart rate
- Greatly slowed breathing
- Lower body temperature
- Vomiting
- Nausea
- Coma
- Death
SOURCES
- [SOURCE 1]
- [SOURCE 2]
- [SOURCE 3]
- [SOURCE 4] Waterfall Bar Menu indicates 3 brands on tap but indicates others are available. Publication date is unclear.
FACTS AND OPINION
FACT 1: The 11:58pm Waterfall receipt indicates John O'Keefe paid for 3 drinks: Bud Lite Bottle, Miller Lite Lager, Tito's. They are listed alphabetically, not in order of purchase.OPINION: Anecdotally, people generally have a "preferred" beer. Why would OJO have two brands? Option 1: He bought a beer for someone else. Option 2: The Miller Lite was a draft and/or tasted weird (skunky, or?) so maybe he switched to a bottle of something else. Sometimes the draft lines haven't been cleaned in awhile... but sometimes the taste of bar drinks can be impacted by GHB... This may be important later. [4]
FACT 2: Witnesses indicate Karen was drinking a clear liquid from a clear glass. She and John are also described as overtly affectionate.
FACT 3: CCTV shows John taking a swallow of a clear liquid from a clear glass and exiting the bar with glass in hand.
FACT 4: Karen drove her vehicle, a dark Lexus SUV, while John rode in the front passenger seat.
OPINION: Someone who is particular about people cutting through their lawn and particular about the kids' breakfasts is unlikely to be okay with drinking and driving. Option 1: John believed Karen was not impaired. Option 2: John's own judgment was impaired and therefore he didn't realize she was impaired.
FACT 5: Witness Heather Maxon believes she saw two occupants, one male, in the dark SUV that ultimately pulled up in front of 34 Fairview.
FACT 6: Witness Ryan Nagel believes he saw an SUV not in park, with in-tact tail lights and without rear damage, containing only a female driver facing forward with hands on the wheel. Neither Maxon nor Nagel saw John O'Keefe in or outside of the vehicle as they were leaving.
FACT 7: Karen awoke from John's couch after 4am. She could not find him and had no memory of what had happened 4 hours earlier. She was immediately frantic and distraught about his absence. She believed she'd last seen John at the Waterfall. Her behavior does not seem consistent with a traditional hangover.
THEORY
What if someone in this already-established collection of pranksters/roughhousers (including at least one potentially jilted paramour) slipped something into their drinks? Option 1: Someone slipped something into Karen's drink, and John is accidentally also drugged when he drinks from her glass. Option 2: Someone slipped something into BOTH Karen's drink and John's drink. John is accidentally dosed a second time when he drinks from Karen's cup.Ask yourself this: who would benefit from 2 to 4 hours of Karen's and John's memory loss? What could be done to them while they were impaired? Why was Jen McCabe so insistent about them attending the "after-party"? What, if any, was the "surprise" Jen had for Karen? Did she want to see them make fools of themselves or be made fun of? Did she want a front-row seat to watch the entertainment portion of a prank?
If both Karen and John were drugged/impaired without their knowledge, and both attended, the possibilities range from relatively harmless silly photos or an intent to embarrass Karen and John to more nefarious plans, like SA to Karen or maybe roughing up John. He could be a human punching bag and then wake up on the lawn and have no idea where he was or how he got banged up. Unless someone accidentally took it too far and caused the injury to the back of his head.
There'd be no memory of anything that happened. There'd be no evidence of a drug in their systems. Rumors have indicated Karen didn't stay at the Alberts' house because she didn't feel well and was confused about if they were welcome. By the time her blood was drawn at the hospital, it was well after the 4 hours that GHB can be detected in the bloodstream.
Look at the list of effects and side-effects again.
- euphoria
- drowsiness
- decreased anxiety
- confusion
- memory impairment
- visual hallucinations
- paradoxically, excited and aggressive behavior
- nausea and vomiting
- unconsciousness
2024.04.24 07:39 blazingdragon09 [CA-ON] [H] Lots of cards from SM to SV, Lots of Slabs, and Plenty of Hits! [W] PayPal
Hi all, I'm finally going through the arduous process of getting rid of a lot of the random cards that I've acquired over the last year or so. I tune in to a lot of Pokemon streamers so I end up getting random cards here and there but I've sorted them out to make it easier for you guys to look through the binders. Additionally, I have a spread sheet that's mostly up to date on all of these cards so if you're looking for specific cards, I can share that with you. Prices for everything will be based on Ebay last sold listings. The only items here over $100 is the Penny SAR slab as well as the Dragonite V and Galarian Moltres V singles. The prices for those are added to their respective pictures in the Imgur post. Lastly, I'm happy to ship internationally and I'm happy to provide estimates if you reach out. I am local to Toronto so local pickup is an option, too!
Slabs
Top Loaders
Sun & Moon - Base Set
Sun & Moon - Burning Shadows
Sun & Moon - Forbidden Light
Sun & Moon - Unified Minds
Sun & Moon - Cosmic Eclipse
Sun & Moon - Remix Bout (JP)
Sword & Shield - Rebel Clash
Sword & Shield - Darkness Ablaze
Sword & Shield - Champion's Path
Sword & Shield - Vivid Voltage
Sword & Shield - Shining Fates
Sword & Shield - Battle Styles
Sword & Shield - Chilling Reign
Sword & Shield - Evolving Skies
Sword & Shield - Celebrations
Sword & Shield - Fusion Strike
Sword & Shield - Brilliant Stars
Sword & Shield - Astral Radiance
Sword & Shield - Pokemon GO
Sword & Shield - Lost Origin
Sword & Shield - Silver Tempest
Sword & Shield - Crown Zenith
Sword & Shield - Eevee Heroes (KR)
Sword & Shield - Star Birth (KR)
Sword & Shield - VStar Universe (JP)
Scarlet & Violet - Base Set
Scarlet & Violet - Paldea Evolved
Scarlet & Violet - Obsidian Flames
Scarlet & Violet - 151
Scarlet & Violet - Paradox Rift
Scarlet & Violet - Paldean Fates
Scarlet & Violet - Ruler of the Black Flame (JP)
Scarlet & Violet - Raging Surf (JP)
Scarlet & Violet - Future Flash (JP)
submitted by blazingdragon09 to pkmntcgtrades [link] [comments]
Slabs
Top Loaders
Sun & Moon - Base Set
Sun & Moon - Burning Shadows
Sun & Moon - Forbidden Light
Sun & Moon - Unified Minds
Sun & Moon - Cosmic Eclipse
Sun & Moon - Remix Bout (JP)
Sword & Shield - Rebel Clash
Sword & Shield - Darkness Ablaze
Sword & Shield - Champion's Path
Sword & Shield - Vivid Voltage
Sword & Shield - Shining Fates
Sword & Shield - Battle Styles
Sword & Shield - Chilling Reign
Sword & Shield - Evolving Skies
Sword & Shield - Celebrations
Sword & Shield - Fusion Strike
Sword & Shield - Brilliant Stars
Sword & Shield - Astral Radiance
Sword & Shield - Pokemon GO
Sword & Shield - Lost Origin
Sword & Shield - Silver Tempest
Sword & Shield - Crown Zenith
Sword & Shield - Eevee Heroes (KR)
Sword & Shield - Star Birth (KR)
Sword & Shield - VStar Universe (JP)
Scarlet & Violet - Base Set
Scarlet & Violet - Paldea Evolved
Scarlet & Violet - Obsidian Flames
Scarlet & Violet - 151
Scarlet & Violet - Paradox Rift
Scarlet & Violet - Paldean Fates
Scarlet & Violet - Ruler of the Black Flame (JP)
Scarlet & Violet - Raging Surf (JP)
Scarlet & Violet - Future Flash (JP)
2024.03.26 16:50 gzcl Five Years Without a Rest Day
Hello, gzcl here with another post about training without rest days. I recently crossed the five-year mark of training without rest days, so I figured it warranted an update.
Here is the update from last year. Many other details about my training, including videos of PR lifts, can be found in my post history, Instagram, YouTube, and blog. Each is linked throughout this post.
Before we get into the post, I want to be clear that I am not saying that everyone should train without rest days, or that nobody needs them, or that I’m better than anyone because I have not taken rest days, or that rest days are inherently useless or bad, or that not taking rest days always produce better results or training like this makes me a hard-core tough guy type. So, please, do not read into this post such contrivances.
Again, this post is not telling you that you absolutely do not need rest days, no matter what. This post is critical of rest days because it has been my experience that rest days are often taken for granted and are therefore abused; something which may inhibit training rather than aid it.
Now, I would like to address some basic facts of who I am and what my situation is. These things will provide insight into why I chose to train without rest days, how I am able to do it, and why I am here encouraging you to consider whether rest days are necessary, based on your circumstances, abilities, and goals.
About me:
Age: 38
Years Training: 15+
Bodyweight: 205 to 210, daily average. (Up from 158 on day 31 of training without rest days)
Height: 5’5”
Recent 1-Rep Maxes: 525 squat, 340 bench, 600 deadlift (no belt), 250 strict press.
All these lifts were performed within the last year of training without rest days. The only lift that is not an all-time PR 1RM is the bench. That is because the bench press messes with my shoulder, a longstanding injury that I am always training around as best as I can; my lifetime 1RM bench PR is 380 pounds. While 635 pounds is my best deadlift, it was with a belt, so the above linked deadlift is a PR of significant variation.
Training Environment: Home gym for the first three-ish years of training without rest days, then I opened my own gym. I train at very high elevation (over 10,000 feet) in a well-outfitted commercial facility.
Health: No chronic illnesses or diseases. I very rarely get sick. In these five years there was only one time where I had very bad congestion. I still trained. I opted to do a conditioning workout of KB swings and push-ups. It was a great choice at the time because I felt much better the next day. The worst are migraines I get somewhat frequently. When this happens, I will just go lighter or change the plan of the day to doing arms, as those workouts are less stressful in general. If I am even feeling a bit under the weather, I train with reduced volume, intensity, or both, depending on the day and my assessment of where I am then standing recovery wise.
Injuries: No serious recent injuries, mostly just training around or in consideration of preexisting injuries (sustained before training without rest days). This has limited the frequency of very heavy lifting, so I’ve opted for more of a volume, and therefore, lighter weight approach in general. That said, I’ve still hit 1RM personal records in these five years. I’m just not lifting heavy each week because when I do I increase my chances of aggravating an old injury.
Drug Use: No, I am not using steroids, testosterone, SARMS, or other such chemicals, peptides, hormones, etc. I do have low test and nearly a decade ago I tried TRT for a year. It did not help me. I do not claim to be a “lifetime natural.” These five years of training without rest days was not benefitted by using such performance enhancements.
Diet: Whatever my wife makes, or wherever we go out to eat (which is mostly Mexican food). I do not adhere to a strict diet. I eat a lot of breakfast burritos which have plenty of eggs and meat. Most of my diet is based around red meat, especially dinner. Lately, my household has been having a lot of hot pot, which is a copious amount of thin sliced meat, golden radishes, various noodles, and rice cakes. For the last five years I have been rotating different lengths of bulk and cut cycles. I have gained about 50 pounds in this period.
Supplements: I try to take creatine and vitamin D consistently. Sometimes I miss days. Same goes for electrolytes. I may incorporate other supplements from time to time, such as fish oil, but have found much of that to have no clear benefit to performance. Not that I doubt those things. It just isn’t a priority for me.
Sleep: Average around 6 to 8 hours per night. Sometimes I get less, as I do suffer from sleepless nights occasionally. These may be just 2 to 4 hours of sleep. Still in such cases I will train, adjusting the goal of the session as needed. I do try to have a relatively strict bedtime.
Why do I train daily?
The overwhelming majority of my workouts are based on my General Gainz training framework. You can read more about programs and constructing workouts with GG on my blog. A very detailed description of GG and a progression constructed from that framework can be read in my blog “General Gainz Body Building.” Searching “General Gainz” on reddit will provide many reviews as well as examples of programs others have created with the framework or adapted existing programs to their needs and goals.
In a nutshell, nearly all my workouts are based around using weights. When on vacation I’ve had to do a few bodyweight workouts. Those would typically be done for reps against the clock, so a conditioning session. That said, I estimate that 99% of my workouts these last five years used weights of some kind (bars, dumbbells, kettlebells, cables). Most of my workouts in these five years have consisted of adding reps until I reach a determined volume threshold, then adding weight (this is called accumulation). By training in this way I have managed to set many rep max PR’s. This is especially true for the squat because last year PR’d rep maxes from 1RM (525LB) to 100RM (135LB).
None of my workouts these last five years have consisted of only doing stretching or yoga, or going for a walk, hike, cardio only, or other such activities. I do not call shoveling snow a workout, nor chopping wood. As I live at over 10,000 feet elevation, my winters have plenty of those things which I just call “living.” Some days I’ll shovel snow for a few hours, then workout. That’s just how it is. In general, my training resembles those common traits of strength and conditioning and/or bodybuilding training.
Because consistency is my primary goal, I am not stuck to a certain split or weekly training schedule. I have a loosely planned schedule and shift days as needed, based on how I assess my recovery. If I planned to squat but my legs are still very sore from a few days before, I will push that a day or two later, instead opting to do something like press. I have found that while I have successfully trained full body for many weeks on end, it does become tiresome, so when it does, I’ll shift to a movement or body part split.
There have been several periods of time in these five years where I have trained the same lift every day for many weeks. I have done this for squat, press, and most recently, the deadlift. Such periods were great for developing those lifts. In each time I was able to reach goals, setting new personal records. Just last week I hit a 600-pound beltless conventional deadlift, a lifetime 1RM PR (the most I’ve ever deadlifted without a belt). That came on the heels of training the deadlift for ten weeks, every day (at submax weights and submax volume). Before testing that 1RM I did take two days off from deadlifting (training shoulders and triceps respectively). For context, in October 2023 I barely completed a 545-pound deadlift while wearing a belt (and with the hype of doing that lift at my gym’s deadlift party).
Most of my workouts are an hour or less. If I do a conditioning workout, I try to keep those around 20 to 30 minutes. If you want to see more specific examples of workouts or lifts I’ve done, you can see those on my Instagram, YouTube, blog, and previous posts here on reddit.
The goals of this post are to prove that:
1. Rest days are just another training variable that can be manipulated to benefit training.
Rest days are like the weight on the bar, the number of reps, total volume, variety of exercises, rest times, lift frequency, and so many other variables when it comes to training. There is no optimal frequency of training that applies to everyone. Likewise, there is no optimal frequency of rest days that applies to everyone. Such is the nature of individual differences. When not taking rest days, other variables need to be adjusted to account for training the next day.
Does this mean you probably cannot train every day to complete exhaustion, taking every lift to absolute failure? Yes. However, because training frequency is higher without rest days, that means skill development can be emphasized. This means greater efficiency and lower risk of injury, thereby improving work capacity and recovery potential. Over time these improve how well you can recover from heavier and/or higher volume workouts. So, as work capacity and skill increases, your ability to perform and recover from tougher workouts more frequently will likewise improve.
2. Excluding rest days does not necessarily inhibit progress to either size or strength.
Before these five years I trained with rest days. I had competed in powerlifting for several years. During that period I won best lifter at a state championship as well as competing several times at the USPA American Cup and the IPL World Championships, often placing first in my weight class. I was decently strong for a lightweight powerlifter who moved up from the 148 class to the 181 class over four years.
I am now bigger than I’ve ever been, both in terms of overall bodyweight and the measurements across my shoulders, chest, legs, and arms. I recently achieved 18” arms for the first time in my life; a goal I had set a few years ago. I also set all-time personal records in many lifts, despite not training how powerlifters usually do.
Not only that, but I have trained several clients who also no longer take rest days. Each of them improving their own size and/or strength. So, not only have I grown bigger and stronger without rest days compared to those times when I was taking rest days, I have also witnessed others do the same. I credit this largely to increased training frequency and finally prioritizing more impactful recovery habits (sleep, nutrition, hydration, and de-stressing). When it comes to recovering from training, those practices matter a whole lot more than days of inactivity (AKA “Rest Days”).
3. Excluding rest days is a great catalyst for improving training consistency.
When taking rest days it was easy for me to justify going too hard because “tomorrow is a rest day.” This would frequently result in going too hard, thereby necessitating unaccounted for deloads and rest days (at the time I thought rest days were a make-or-break recovery factor). Such training is akin to two steps forward one step back, and sometimes, many steps back. That kind of regression can be demotivating, which may result in a period of not training at all. While I didn’t have many of those periods, and was consistent before training without rest days, now my training is far more consistent. Not only in terms of frequency, but also in terms of intensity, volume, and effort.
Without rest days I have learned how to better dial in my training, resulting in more effective workouts. Such compounding results add up! Training without rest days is now one step forward, followed by another, and countless others. Because my training is better regulated without rest days, I have not sustained a major injury that resulted in significant setbacks. Lastly, I don’t have to drag myself into the gym anymore. It is now just something I do, and I am nearly every day looking forward to my workout (some workouts I know will be grueling, and I do not look forward to those as much). This is because nearly every workout produces results, albeit small; they are frequent and just as rewarding.
4. Excluding rest days can improve training knowledge (knowing how to train).
Because I am not taking rest days I must account for the other variables when it comes to my training and align those in such a way that both produces results while at the same time allowing for training again tomorrow. This means that I am more aware of my effort, volume, and intensity. Without rest days, learning how to train happens faster, resulting in better progress sooner. I am now better at choosing exercises that benefit me and the way in which I execute those movements. For example, I am no longer benching as often because I feel I should, or simply that it is “in my program, so I must do it.” Rather, I limit that as needed while being more aggressive with other upper body pressing movements.
Similarly, I am better at constructing and executing fruitful workouts, compared to times past, when I would frequently go off plan and do more than needed, at the time believing that pushing myself to complete exhaustion and nearly always taking sets to failure was necessary to progress. That is not the case for me, or anyone. While I do believe that minimal is not optimal, the idea that more is always better is also not true. When it comes to training, as much as you can recover from is best. The only way to know that limit is to train enough to learn what that limit is and the various ways in which that limit can be reached; all while understanding that your limit will increase over time, and when it does, so too must your training.
5. Rest days are not the make-or-break factor when it comes to recovering from workouts.
As I’ve said many times these last five years, the recovery habits that matter most are sleep, nutrition, hydration, and de-stressing. Rest days, meaning days of inactivity, are at best the worst form of recovery. Recovery depends on your work capacity. If you can only do little, you can recover from little. Gradually improving your work capacity through training increases your ability to recover. That process requires the all-important factors of sleep, nutrition, hydration, and limiting non-training related stress, not sedentary days.
Days of inactivity are counterproductive most of the time. Such days would be better spent doing low-impact training like pushing a sled, or cardio, thereby improving your work capacity and therefore your ability to recover from future workouts. If rest days were necessary, then I would not have grown as big and as strong as I have in these last five years. I’ve seen many people online say that not taking rest days produces negative results, guaranteed injury, burnout, and other such undesirable outcomes. The opposite is true, that is, if you learn how to train without rest days, something which necessitates prioritizing genuine recovery habits.
Common Objections
In previous posts here on reddit, or as I’ve experienced on social media, people have said a few things about my not taking rest days. Here I will address these common objections and criticisms to training daily.
1. “But you cannot train hard” or “You’re not training hard enough” by not taking rest days.
Response: In these last five years I have grown bigger and stronger than I’ve ever been. My training is effective. With it I have achieved many goals. Whether you call it “hard” means nothing in the face of my results. Hard training, while important, is not the harbinger of results. Consistency, effort, and patience are. Daily training bolsters those three all-important factors.
The definition of “training hard” is individually dependent. Some will say that all sets must be taken to failure, or very close, to train hard. Others will say that massive amounts of volume are needed to train hard. Still more will say other things about what it means to train hard; drop sets, limited rest, supersets, no machines, “functional training” only, etc. In every case the assumption is that training hard, every workout, is necessary to progress in the gym. The reality is that our definition of hard is only as hard as we’ve ever pushed ourselves. Your hard may be my easy, or vice versa.
That “training hard” is necessary to progress is a false premise often made by those whose egos are built on how hard they proclaim their training to be. The fact is, my training is as hard as it needs to be, based on the session’s goal and how I determine my recovery to be. I have done many of the hardest workouts of my life in these last five years. But many are not nearly so difficult. Not every session needs to be as tough as the one before it. This truth is obvious when comparing leg workouts to arm workouts. Leg days are a meme for hardship whereas arm days are often believed to be easy – because it is true! Even the hardest arms workout pales in comparison to the hardest legs workout. I will always do an arm workout when I am not feeling well because they are the easiest workouts to do with a high degree of focus, quality effort, reps, and volume.
Training consistency and recovery from that training matters far more than proximity to failure, or the volume of a single session, or other such minutia of which so many overemphasize so that they can deem their training “hard” (and therefore, themselves). For me personally, I find lifting near max weights to be a whole lot harder than doing near max volume. It is tougher for me to recover from. Therefore, I do a lot more volume-based training. Does that mean my training is always easy because I prefer it? I guess in some way, yes. But I do not train so that I can feel hard or say that I do hard things. I train, firstly because I enjoy the process, and secondly, so that I can achieve goals.
Is that process sometimes difficult? Yes. Does progress depend on training always being difficult? No. Sometimes one more rep or one more pound comes easily, and those are just two forms of many kinds of progress to be made in the gym.
2. “Training every day doesn’t make you more hard-core” and “Hard-core lifters cannot train daily” (therefore, I am not hard-core, as such accusers themselves identify).
Response: I agree with this. I am not hard-core for training daily. Furthermore, manufactured hardship, as weight training necessarily is, is something I do not see has being inherently or distinctly “hard.” There is nothing “hard-core” about the gym. It is quite a comfortable hobby, even when it is difficult. Even when there is pain, or, paradoxically, discomfort, the act of weight training is safe, nearly always indoors in climate-controlled gyms, with purpose-built equipment, done for self-improvement via sustained incremental progress. It costs money and time. It is firstly, a selfish act. It is, therefore, not a practice through which one experiences genuine hardship and thereby becomes hard themselves. Lifting weights is a luxury, a pleasure, and therefore, not hard-core. I don’t pretend it is and hope more begin to see it my way.
3. Training every day is not optimal.
Response: This argument is often paired alongside the idea that training hard is required to progress. Thus, rationally (though incorrect), if training hard then rest days are necessary because if you are not taking rest days then you cannot be training hard. Superficially, this makes sense. However, after a moment of deeper consideration, even the meatiest head will see that it is possible to train hard one way and the next day train something else just as hard. Such is possible when employing any kind of split, whether that be by movement, or body part, or other variables such as volume, intensity, or density.
As touched on in the previous section, sometimes progress comes easily. It has been my experience that with a sensible structure and methodical progression, bolstered by keen autoregulation practices, that adding another rep or putting on five more pounds is less daunting compared to those times when I was always grinding myself into dust trying to eek out every pound, every rep, at every opportunity – at the cost of pain, which I conflated with progress; a common outlook regarding training. Such a mindset about training is based on the fear of missing out (FOMO), which from my experience, produces short lived results, injuries, and dwindling enthusiasm in the gym.
There is no standard of “optimal” that applies to everyone. The most recoverable work is optimal. That depends on the individual. That said, there is truth in the importance of frequency, volume, intensity (meaning load respective of 1RM), and effort. None of those things can be eschewed completely. Each is a variable that must be deliberately adjusted based on the individual’s goals and abilities. The first among those variables is frequency, something which rest days inherently limits. Higher training frequency means more opportunities to reach the limit of recoverable work, which is always the most optimal way to train. Frequency is king among variables (Mentzer cultists in shambles).
4. “But you would be bigger and stronger if you were taking rest days.”
Response: Such hackneyed remarks are made by those trying to ignite FOMO within me without considering my training history. For a decade I took rest days and “trained hard” (as I understood it then). I was strong then. But now, I am both bigger and stronger – without taking rest days.
This bromide idea is held by those say, “Rest days produce results, not the training” in one breath and in the next say, “I train harder than you, so I need rest days.” So, which is it? If the first, then training hard does not matter, only the rest days. If the second, then the training matters more than the rest days. The third position is that both matter equally, then necessitating equal rest days to training days, something not seen amongst the biggest and strongest lifters who often promote training up to 6x a week and sometimes multiple times per day.
This statement placates the accuser who themselves has FOMO about their training and their recovery, believing that without rest days they would be missing out on gains. I would bet the opposite because I’ve experienced it myself. Rest days limited my progress because I trained less and my training was less recoverable because I over emphasized the importance of inactivity, placing it above better means of recovery.
Rest days improving recovery is not a guarantee for everyone, because as I said above, rest days are merely another variable. They are not a fixed need and are the lowest tier of importance when it comes to recovering from workouts. Do some people need rest days, yes. Might they see better results without them? Perhaps. That is only knowable if one attempts to train without rest days, adjusting other variables as needed, including prioritizing the more important aspects of recovery (sleep, nutrition, hydration, and de-stressing).
5. “The science shows that rest days are needed to progress.”
Response: This is a false claim made by those appealing to an authority which they have no meaningful connection to or understanding of. There is not a single study that unequivocally proves that regardless of how one trains that rest days are required to get bigger and stronger. Such claims are often paired with remarks about “CNS burnout” or “systemic fatigue” which is also false. Lifting weights is remarkably easier to recover from than other activities, in particular running, which people do daily for years on end without objection. How? By adjusting the many variables we have at our disposal to increase our training frequency.
Though some authorities on training may claim rest days are needed, they lack practical experience training without them while at the same time carrying a bias due to their investment in particular methods of training and the brand in which their status rests upon. Might rest days be needed because of the way they train and their recovery habits? Sure. That, however, does not prove that progress cannot be made unless rest days are taken. One such figure is Mike Israetel, PhD., who made a video on this topic, which I responded to here. Though highly credentialed and regarded in the training community, his take is remarkably bad, irrational, and contradicts his own material.
Conclusion
Rest days, commonly practiced as day of low activity or inactivity, encourage doing too much in the gym in a single workout than one can recover from while at the same time limiting training frequency and therefore slow the improvement of work capacity and skill development. That was the case when I was taking rest days during the first decade of my training and I am sure it is for many of you. Therefore, I argue that rest days can inhibit progress rather than help it, as they did my own. As a result of my experience, I encourage you to see if increasing your training frequency (with a likewise increase in your recovery habits; sleep, nutrition, hydration, and de-stressing) will increase your results.
Consider whether rest days are something that inhibits you or benefits you. Are rest days when you backslide, eat poorly, sleep little, and stress over other parts of your life? Are they days you take because you find yourself going too hard in the gym and frequently grinding yourself into the dirt and potentially causing injury? Or might rest days be days you need because you simply do not like training? Think about your rest days and why you take them, and how you can make them better – perhaps including not taking them and training instead. Decreasing days of inactivity might not mean lifting weights more often, but perhaps doing more cardio, or some other form of physical exercise that you enjoy. Training without rest days for you does not have to look how it does for me. Find the appropriate level of activity for you, and should you find that to be lacking, strive to gradually do more.
submitted by gzcl to Fitness [link] [comments]
Here is the update from last year. Many other details about my training, including videos of PR lifts, can be found in my post history, Instagram, YouTube, and blog. Each is linked throughout this post.
Before we get into the post, I want to be clear that I am not saying that everyone should train without rest days, or that nobody needs them, or that I’m better than anyone because I have not taken rest days, or that rest days are inherently useless or bad, or that not taking rest days always produce better results or training like this makes me a hard-core tough guy type. So, please, do not read into this post such contrivances.
Again, this post is not telling you that you absolutely do not need rest days, no matter what. This post is critical of rest days because it has been my experience that rest days are often taken for granted and are therefore abused; something which may inhibit training rather than aid it.
Now, I would like to address some basic facts of who I am and what my situation is. These things will provide insight into why I chose to train without rest days, how I am able to do it, and why I am here encouraging you to consider whether rest days are necessary, based on your circumstances, abilities, and goals.
About me:
Age: 38
Years Training: 15+
Bodyweight: 205 to 210, daily average. (Up from 158 on day 31 of training without rest days)
Height: 5’5”
Recent 1-Rep Maxes: 525 squat, 340 bench, 600 deadlift (no belt), 250 strict press.
All these lifts were performed within the last year of training without rest days. The only lift that is not an all-time PR 1RM is the bench. That is because the bench press messes with my shoulder, a longstanding injury that I am always training around as best as I can; my lifetime 1RM bench PR is 380 pounds. While 635 pounds is my best deadlift, it was with a belt, so the above linked deadlift is a PR of significant variation.
Training Environment: Home gym for the first three-ish years of training without rest days, then I opened my own gym. I train at very high elevation (over 10,000 feet) in a well-outfitted commercial facility.
Health: No chronic illnesses or diseases. I very rarely get sick. In these five years there was only one time where I had very bad congestion. I still trained. I opted to do a conditioning workout of KB swings and push-ups. It was a great choice at the time because I felt much better the next day. The worst are migraines I get somewhat frequently. When this happens, I will just go lighter or change the plan of the day to doing arms, as those workouts are less stressful in general. If I am even feeling a bit under the weather, I train with reduced volume, intensity, or both, depending on the day and my assessment of where I am then standing recovery wise.
Injuries: No serious recent injuries, mostly just training around or in consideration of preexisting injuries (sustained before training without rest days). This has limited the frequency of very heavy lifting, so I’ve opted for more of a volume, and therefore, lighter weight approach in general. That said, I’ve still hit 1RM personal records in these five years. I’m just not lifting heavy each week because when I do I increase my chances of aggravating an old injury.
Drug Use: No, I am not using steroids, testosterone, SARMS, or other such chemicals, peptides, hormones, etc. I do have low test and nearly a decade ago I tried TRT for a year. It did not help me. I do not claim to be a “lifetime natural.” These five years of training without rest days was not benefitted by using such performance enhancements.
Diet: Whatever my wife makes, or wherever we go out to eat (which is mostly Mexican food). I do not adhere to a strict diet. I eat a lot of breakfast burritos which have plenty of eggs and meat. Most of my diet is based around red meat, especially dinner. Lately, my household has been having a lot of hot pot, which is a copious amount of thin sliced meat, golden radishes, various noodles, and rice cakes. For the last five years I have been rotating different lengths of bulk and cut cycles. I have gained about 50 pounds in this period.
Supplements: I try to take creatine and vitamin D consistently. Sometimes I miss days. Same goes for electrolytes. I may incorporate other supplements from time to time, such as fish oil, but have found much of that to have no clear benefit to performance. Not that I doubt those things. It just isn’t a priority for me.
Sleep: Average around 6 to 8 hours per night. Sometimes I get less, as I do suffer from sleepless nights occasionally. These may be just 2 to 4 hours of sleep. Still in such cases I will train, adjusting the goal of the session as needed. I do try to have a relatively strict bedtime.
Why do I train daily?
- To see if I can.
- Because I enjoy the process (despite some torturous individual sessions).
- It improves my mood and general outlook on life while at the same time improving my quality of life by making everyday tasks easier (shoveling snow in particular) by limiting the impact of old injuries.
- It keeps my efforts in the gym better regulated so that I do not go overboard in a single session (“because tomorrow is a rest day”) and risk injuring myself, as I’ve done many times in the past when I was taking rest days.
The overwhelming majority of my workouts are based on my General Gainz training framework. You can read more about programs and constructing workouts with GG on my blog. A very detailed description of GG and a progression constructed from that framework can be read in my blog “General Gainz Body Building.” Searching “General Gainz” on reddit will provide many reviews as well as examples of programs others have created with the framework or adapted existing programs to their needs and goals.
In a nutshell, nearly all my workouts are based around using weights. When on vacation I’ve had to do a few bodyweight workouts. Those would typically be done for reps against the clock, so a conditioning session. That said, I estimate that 99% of my workouts these last five years used weights of some kind (bars, dumbbells, kettlebells, cables). Most of my workouts in these five years have consisted of adding reps until I reach a determined volume threshold, then adding weight (this is called accumulation). By training in this way I have managed to set many rep max PR’s. This is especially true for the squat because last year PR’d rep maxes from 1RM (525LB) to 100RM (135LB).
None of my workouts these last five years have consisted of only doing stretching or yoga, or going for a walk, hike, cardio only, or other such activities. I do not call shoveling snow a workout, nor chopping wood. As I live at over 10,000 feet elevation, my winters have plenty of those things which I just call “living.” Some days I’ll shovel snow for a few hours, then workout. That’s just how it is. In general, my training resembles those common traits of strength and conditioning and/or bodybuilding training.
Because consistency is my primary goal, I am not stuck to a certain split or weekly training schedule. I have a loosely planned schedule and shift days as needed, based on how I assess my recovery. If I planned to squat but my legs are still very sore from a few days before, I will push that a day or two later, instead opting to do something like press. I have found that while I have successfully trained full body for many weeks on end, it does become tiresome, so when it does, I’ll shift to a movement or body part split.
There have been several periods of time in these five years where I have trained the same lift every day for many weeks. I have done this for squat, press, and most recently, the deadlift. Such periods were great for developing those lifts. In each time I was able to reach goals, setting new personal records. Just last week I hit a 600-pound beltless conventional deadlift, a lifetime 1RM PR (the most I’ve ever deadlifted without a belt). That came on the heels of training the deadlift for ten weeks, every day (at submax weights and submax volume). Before testing that 1RM I did take two days off from deadlifting (training shoulders and triceps respectively). For context, in October 2023 I barely completed a 545-pound deadlift while wearing a belt (and with the hype of doing that lift at my gym’s deadlift party).
Most of my workouts are an hour or less. If I do a conditioning workout, I try to keep those around 20 to 30 minutes. If you want to see more specific examples of workouts or lifts I’ve done, you can see those on my Instagram, YouTube, blog, and previous posts here on reddit.
The goals of this post are to prove that:
1. Rest days are just another training variable that can be manipulated to benefit training.
Rest days are like the weight on the bar, the number of reps, total volume, variety of exercises, rest times, lift frequency, and so many other variables when it comes to training. There is no optimal frequency of training that applies to everyone. Likewise, there is no optimal frequency of rest days that applies to everyone. Such is the nature of individual differences. When not taking rest days, other variables need to be adjusted to account for training the next day.
Does this mean you probably cannot train every day to complete exhaustion, taking every lift to absolute failure? Yes. However, because training frequency is higher without rest days, that means skill development can be emphasized. This means greater efficiency and lower risk of injury, thereby improving work capacity and recovery potential. Over time these improve how well you can recover from heavier and/or higher volume workouts. So, as work capacity and skill increases, your ability to perform and recover from tougher workouts more frequently will likewise improve.
2. Excluding rest days does not necessarily inhibit progress to either size or strength.
Before these five years I trained with rest days. I had competed in powerlifting for several years. During that period I won best lifter at a state championship as well as competing several times at the USPA American Cup and the IPL World Championships, often placing first in my weight class. I was decently strong for a lightweight powerlifter who moved up from the 148 class to the 181 class over four years.
I am now bigger than I’ve ever been, both in terms of overall bodyweight and the measurements across my shoulders, chest, legs, and arms. I recently achieved 18” arms for the first time in my life; a goal I had set a few years ago. I also set all-time personal records in many lifts, despite not training how powerlifters usually do.
Not only that, but I have trained several clients who also no longer take rest days. Each of them improving their own size and/or strength. So, not only have I grown bigger and stronger without rest days compared to those times when I was taking rest days, I have also witnessed others do the same. I credit this largely to increased training frequency and finally prioritizing more impactful recovery habits (sleep, nutrition, hydration, and de-stressing). When it comes to recovering from training, those practices matter a whole lot more than days of inactivity (AKA “Rest Days”).
3. Excluding rest days is a great catalyst for improving training consistency.
When taking rest days it was easy for me to justify going too hard because “tomorrow is a rest day.” This would frequently result in going too hard, thereby necessitating unaccounted for deloads and rest days (at the time I thought rest days were a make-or-break recovery factor). Such training is akin to two steps forward one step back, and sometimes, many steps back. That kind of regression can be demotivating, which may result in a period of not training at all. While I didn’t have many of those periods, and was consistent before training without rest days, now my training is far more consistent. Not only in terms of frequency, but also in terms of intensity, volume, and effort.
Without rest days I have learned how to better dial in my training, resulting in more effective workouts. Such compounding results add up! Training without rest days is now one step forward, followed by another, and countless others. Because my training is better regulated without rest days, I have not sustained a major injury that resulted in significant setbacks. Lastly, I don’t have to drag myself into the gym anymore. It is now just something I do, and I am nearly every day looking forward to my workout (some workouts I know will be grueling, and I do not look forward to those as much). This is because nearly every workout produces results, albeit small; they are frequent and just as rewarding.
4. Excluding rest days can improve training knowledge (knowing how to train).
Because I am not taking rest days I must account for the other variables when it comes to my training and align those in such a way that both produces results while at the same time allowing for training again tomorrow. This means that I am more aware of my effort, volume, and intensity. Without rest days, learning how to train happens faster, resulting in better progress sooner. I am now better at choosing exercises that benefit me and the way in which I execute those movements. For example, I am no longer benching as often because I feel I should, or simply that it is “in my program, so I must do it.” Rather, I limit that as needed while being more aggressive with other upper body pressing movements.
Similarly, I am better at constructing and executing fruitful workouts, compared to times past, when I would frequently go off plan and do more than needed, at the time believing that pushing myself to complete exhaustion and nearly always taking sets to failure was necessary to progress. That is not the case for me, or anyone. While I do believe that minimal is not optimal, the idea that more is always better is also not true. When it comes to training, as much as you can recover from is best. The only way to know that limit is to train enough to learn what that limit is and the various ways in which that limit can be reached; all while understanding that your limit will increase over time, and when it does, so too must your training.
5. Rest days are not the make-or-break factor when it comes to recovering from workouts.
As I’ve said many times these last five years, the recovery habits that matter most are sleep, nutrition, hydration, and de-stressing. Rest days, meaning days of inactivity, are at best the worst form of recovery. Recovery depends on your work capacity. If you can only do little, you can recover from little. Gradually improving your work capacity through training increases your ability to recover. That process requires the all-important factors of sleep, nutrition, hydration, and limiting non-training related stress, not sedentary days.
Days of inactivity are counterproductive most of the time. Such days would be better spent doing low-impact training like pushing a sled, or cardio, thereby improving your work capacity and therefore your ability to recover from future workouts. If rest days were necessary, then I would not have grown as big and as strong as I have in these last five years. I’ve seen many people online say that not taking rest days produces negative results, guaranteed injury, burnout, and other such undesirable outcomes. The opposite is true, that is, if you learn how to train without rest days, something which necessitates prioritizing genuine recovery habits.
Common Objections
In previous posts here on reddit, or as I’ve experienced on social media, people have said a few things about my not taking rest days. Here I will address these common objections and criticisms to training daily.
1. “But you cannot train hard” or “You’re not training hard enough” by not taking rest days.
Response: In these last five years I have grown bigger and stronger than I’ve ever been. My training is effective. With it I have achieved many goals. Whether you call it “hard” means nothing in the face of my results. Hard training, while important, is not the harbinger of results. Consistency, effort, and patience are. Daily training bolsters those three all-important factors.
The definition of “training hard” is individually dependent. Some will say that all sets must be taken to failure, or very close, to train hard. Others will say that massive amounts of volume are needed to train hard. Still more will say other things about what it means to train hard; drop sets, limited rest, supersets, no machines, “functional training” only, etc. In every case the assumption is that training hard, every workout, is necessary to progress in the gym. The reality is that our definition of hard is only as hard as we’ve ever pushed ourselves. Your hard may be my easy, or vice versa.
That “training hard” is necessary to progress is a false premise often made by those whose egos are built on how hard they proclaim their training to be. The fact is, my training is as hard as it needs to be, based on the session’s goal and how I determine my recovery to be. I have done many of the hardest workouts of my life in these last five years. But many are not nearly so difficult. Not every session needs to be as tough as the one before it. This truth is obvious when comparing leg workouts to arm workouts. Leg days are a meme for hardship whereas arm days are often believed to be easy – because it is true! Even the hardest arms workout pales in comparison to the hardest legs workout. I will always do an arm workout when I am not feeling well because they are the easiest workouts to do with a high degree of focus, quality effort, reps, and volume.
Training consistency and recovery from that training matters far more than proximity to failure, or the volume of a single session, or other such minutia of which so many overemphasize so that they can deem their training “hard” (and therefore, themselves). For me personally, I find lifting near max weights to be a whole lot harder than doing near max volume. It is tougher for me to recover from. Therefore, I do a lot more volume-based training. Does that mean my training is always easy because I prefer it? I guess in some way, yes. But I do not train so that I can feel hard or say that I do hard things. I train, firstly because I enjoy the process, and secondly, so that I can achieve goals.
Is that process sometimes difficult? Yes. Does progress depend on training always being difficult? No. Sometimes one more rep or one more pound comes easily, and those are just two forms of many kinds of progress to be made in the gym.
2. “Training every day doesn’t make you more hard-core” and “Hard-core lifters cannot train daily” (therefore, I am not hard-core, as such accusers themselves identify).
Response: I agree with this. I am not hard-core for training daily. Furthermore, manufactured hardship, as weight training necessarily is, is something I do not see has being inherently or distinctly “hard.” There is nothing “hard-core” about the gym. It is quite a comfortable hobby, even when it is difficult. Even when there is pain, or, paradoxically, discomfort, the act of weight training is safe, nearly always indoors in climate-controlled gyms, with purpose-built equipment, done for self-improvement via sustained incremental progress. It costs money and time. It is firstly, a selfish act. It is, therefore, not a practice through which one experiences genuine hardship and thereby becomes hard themselves. Lifting weights is a luxury, a pleasure, and therefore, not hard-core. I don’t pretend it is and hope more begin to see it my way.
3. Training every day is not optimal.
Response: This argument is often paired alongside the idea that training hard is required to progress. Thus, rationally (though incorrect), if training hard then rest days are necessary because if you are not taking rest days then you cannot be training hard. Superficially, this makes sense. However, after a moment of deeper consideration, even the meatiest head will see that it is possible to train hard one way and the next day train something else just as hard. Such is possible when employing any kind of split, whether that be by movement, or body part, or other variables such as volume, intensity, or density.
As touched on in the previous section, sometimes progress comes easily. It has been my experience that with a sensible structure and methodical progression, bolstered by keen autoregulation practices, that adding another rep or putting on five more pounds is less daunting compared to those times when I was always grinding myself into dust trying to eek out every pound, every rep, at every opportunity – at the cost of pain, which I conflated with progress; a common outlook regarding training. Such a mindset about training is based on the fear of missing out (FOMO), which from my experience, produces short lived results, injuries, and dwindling enthusiasm in the gym.
There is no standard of “optimal” that applies to everyone. The most recoverable work is optimal. That depends on the individual. That said, there is truth in the importance of frequency, volume, intensity (meaning load respective of 1RM), and effort. None of those things can be eschewed completely. Each is a variable that must be deliberately adjusted based on the individual’s goals and abilities. The first among those variables is frequency, something which rest days inherently limits. Higher training frequency means more opportunities to reach the limit of recoverable work, which is always the most optimal way to train. Frequency is king among variables (Mentzer cultists in shambles).
4. “But you would be bigger and stronger if you were taking rest days.”
Response: Such hackneyed remarks are made by those trying to ignite FOMO within me without considering my training history. For a decade I took rest days and “trained hard” (as I understood it then). I was strong then. But now, I am both bigger and stronger – without taking rest days.
This bromide idea is held by those say, “Rest days produce results, not the training” in one breath and in the next say, “I train harder than you, so I need rest days.” So, which is it? If the first, then training hard does not matter, only the rest days. If the second, then the training matters more than the rest days. The third position is that both matter equally, then necessitating equal rest days to training days, something not seen amongst the biggest and strongest lifters who often promote training up to 6x a week and sometimes multiple times per day.
This statement placates the accuser who themselves has FOMO about their training and their recovery, believing that without rest days they would be missing out on gains. I would bet the opposite because I’ve experienced it myself. Rest days limited my progress because I trained less and my training was less recoverable because I over emphasized the importance of inactivity, placing it above better means of recovery.
Rest days improving recovery is not a guarantee for everyone, because as I said above, rest days are merely another variable. They are not a fixed need and are the lowest tier of importance when it comes to recovering from workouts. Do some people need rest days, yes. Might they see better results without them? Perhaps. That is only knowable if one attempts to train without rest days, adjusting other variables as needed, including prioritizing the more important aspects of recovery (sleep, nutrition, hydration, and de-stressing).
5. “The science shows that rest days are needed to progress.”
Response: This is a false claim made by those appealing to an authority which they have no meaningful connection to or understanding of. There is not a single study that unequivocally proves that regardless of how one trains that rest days are required to get bigger and stronger. Such claims are often paired with remarks about “CNS burnout” or “systemic fatigue” which is also false. Lifting weights is remarkably easier to recover from than other activities, in particular running, which people do daily for years on end without objection. How? By adjusting the many variables we have at our disposal to increase our training frequency.
Though some authorities on training may claim rest days are needed, they lack practical experience training without them while at the same time carrying a bias due to their investment in particular methods of training and the brand in which their status rests upon. Might rest days be needed because of the way they train and their recovery habits? Sure. That, however, does not prove that progress cannot be made unless rest days are taken. One such figure is Mike Israetel, PhD., who made a video on this topic, which I responded to here. Though highly credentialed and regarded in the training community, his take is remarkably bad, irrational, and contradicts his own material.
Conclusion
Rest days, commonly practiced as day of low activity or inactivity, encourage doing too much in the gym in a single workout than one can recover from while at the same time limiting training frequency and therefore slow the improvement of work capacity and skill development. That was the case when I was taking rest days during the first decade of my training and I am sure it is for many of you. Therefore, I argue that rest days can inhibit progress rather than help it, as they did my own. As a result of my experience, I encourage you to see if increasing your training frequency (with a likewise increase in your recovery habits; sleep, nutrition, hydration, and de-stressing) will increase your results.
Consider whether rest days are something that inhibits you or benefits you. Are rest days when you backslide, eat poorly, sleep little, and stress over other parts of your life? Are they days you take because you find yourself going too hard in the gym and frequently grinding yourself into the dirt and potentially causing injury? Or might rest days be days you need because you simply do not like training? Think about your rest days and why you take them, and how you can make them better – perhaps including not taking them and training instead. Decreasing days of inactivity might not mean lifting weights more often, but perhaps doing more cardio, or some other form of physical exercise that you enjoy. Training without rest days for you does not have to look how it does for me. Find the appropriate level of activity for you, and should you find that to be lacking, strive to gradually do more.
2024.03.24 06:55 Brief-Bother1125 Paradoxical Reactions To All Medication
I have severe MCAS and am unable to tolerate ANY medication or supplement as I have paradoxical reactions to all of them. I don’t get typical MCAS reactions (from what I’ve read about MCAS) that include anaphylaxis or allergy-like symptoms. I experience pain on an 100/10 pain scale (most days I just lay in bed and scream), tremors, muscle spasms, headaches, low blood pressure and feeling like I’m being electrocuted and burned. Pain is predominantly in my spine but throughout my whole body. I can only suspect that the mast cells around my spine have caused inflammation?
And these paradoxical reactions are with any medication or supplement, or when trying to change the dose of a medication. Earlier on, meds would help for 2-3 days and then turn on me around day 3-4. Now, I can’t even take a med for one day without my body freaking out. I’m unable to take any H1 or H2 antihistamine or mast cell stabilizer without the above mentioned reactions.
I thought some of this could due to overactive CNS and was desperate enough to get a stellate ganglion block at the advice of my MCAS doctor but I react to that too and it’s put me in an even worse state. And I can’t take anything else to calm the CNS either, of course. I meditate, tried brain retraining, do cold showers, etc. None of this helps.
I’ve done the gene panel and there were no clear indicators. I can’t afford to get my medications compounded anyway and my insurance (Medicare) would never help with that. I’ve asked.
I’ve lost 70 pounds in 8 months and am down to 4 safe foods. At this rate I’ll starve to death. I can’t even look in the mirror as I have extreme muscle wasting and loose skin - I’m a shell of my former self.
Does anyone else experience this to this severe of a degree? If so, does anything help at all or am I just going to die a slow painful death because I can’t take the medications that are supposed to help and can’t eat more than 4 foods? I’m terrified and can’t go on like this anymore. I can’t live a med-free life with these symptoms, they’re debilitating.
If anyone has experienced this and had a doctor or clinic actually believe them, care and help them, I’d love that information.
Thanks so much in advance for any helpful advice or info. Reading success stories for being able to get on meds that helped you and could in return save my life is appreciated.
submitted by Brief-Bother1125 to MCAS [link] [comments]
And these paradoxical reactions are with any medication or supplement, or when trying to change the dose of a medication. Earlier on, meds would help for 2-3 days and then turn on me around day 3-4. Now, I can’t even take a med for one day without my body freaking out. I’m unable to take any H1 or H2 antihistamine or mast cell stabilizer without the above mentioned reactions.
I thought some of this could due to overactive CNS and was desperate enough to get a stellate ganglion block at the advice of my MCAS doctor but I react to that too and it’s put me in an even worse state. And I can’t take anything else to calm the CNS either, of course. I meditate, tried brain retraining, do cold showers, etc. None of this helps.
I’ve done the gene panel and there were no clear indicators. I can’t afford to get my medications compounded anyway and my insurance (Medicare) would never help with that. I’ve asked.
I’ve lost 70 pounds in 8 months and am down to 4 safe foods. At this rate I’ll starve to death. I can’t even look in the mirror as I have extreme muscle wasting and loose skin - I’m a shell of my former self.
Does anyone else experience this to this severe of a degree? If so, does anything help at all or am I just going to die a slow painful death because I can’t take the medications that are supposed to help and can’t eat more than 4 foods? I’m terrified and can’t go on like this anymore. I can’t live a med-free life with these symptoms, they’re debilitating.
If anyone has experienced this and had a doctor or clinic actually believe them, care and help them, I’d love that information.
Thanks so much in advance for any helpful advice or info. Reading success stories for being able to get on meds that helped you and could in return save my life is appreciated.
2024.02.16 20:52 ThatsRightlSaidlt Got inspired to build a pothead deck since this version of [[Fblthp, the lost]] is numbered 420. Any suggestions?
![Got inspired to build a pothead deck since this version of [[Fblthp, the lost]] is numbered 420. Any suggestions?](https://b.thumbs.redditmedia.com/XeWLVpY4g1f6n3RiBlqiEWKeUONVla39ar4ev2j8qMk.jpg "Got inspired to build a pothead deck since this version of [[Fblthp, the lost]] is numbered 420. Any suggestions?") | Theme is pothead/drug cultured theme deck. I got inspired when I saw this version of Fblthp and how it’s numbered 420. I’m looking for ANY card(s) in magic history to use in a standard commander deck {from text, subtext, images, etc} that are drug or weed related. It’s not limited to drug related cards, helper cards to make the deck viable is okay too, but I need help finding these cards. The sceenshots of card images is what I have so far, here’s the list: submitted by ThatsRightlSaidlt to magicTCG [link] [comments] 1 Fblthp, the Lost (RVR) 420 1 Ith, High Arcanist (TSR) 255 1 High Priest of Penance (CLB) 848 1 Urza, Lord High Artificer (CMM) 130 1 High Tide (DMR) 54 1 High Alert (RNA) 182 1 Paliano, the High City (CNS) 65 1 Highway Robber (DDM) 61 1 High Market (AFC) 246 1 Zopandrel, Hunger Dominus (ONE) 195 1 Vorinclex, Voice of Hunger (MUL) 29 1 Hungering Hydra (C20) 177 1 He Who Hungers (CHK) 114 1 Unnatural Hunger (MMQ) 169 1 Cosmic Hunger (MOM) 182 1 Vicious Hunger (GVL) 50 1 Cabal Ritual (TOR) 51 1 Dark Ritual (SLP) 16 F 1 Desperate Ritual (UMA) 127 1 Forbidden Ritual (VIS) 60 1 Ritual of the Machine (ALL) 59 1 Increasing Confusion (DKA) 41 1 Daze (NEM) 30 1 Mindbreak Trap (ZEN) 57 1 Rushwood Herbalist (MMQ) 265 1 Grasslands (CMM) 1002 1 False Cure (ONS) 146 1 Healing Leaves (PLC) 150 1 Eladamri, Lord of Leaves (TMP) 224 1 Paradox Haze (TSP) 71 1 Cauldron Haze (EVE) 84 1 Obscuring Haze (CMM) 308 1 Ethereal Haze (CHK) 9 1 Haze Frog (ROE) 187 1 Haze of Pollen (AKR) 193 1 Smokestack (SLC) 1998 1 Smoke (5ED) 268 1 Aisha of Sparks and Smoke (SLX) 12 1 Smoke Spirits' Aid (NEC) 22 1 Smoke Shroud (MH1) 69 1 Azra Smokeshaper (MH1) 79 1 Swiftfoot Boots (LCC) 314 1 Propaganda (WHO) 219 1 Lightning Greaves (WHO) 243 1 Talisman of Creativity (WHO) 248 1 Adrix and Nev, Twincasters (SLD) 1544 1 Krark, the Thumbless (SLD) 1543 1 Sakashima of a Thousand Faces (SLD) 1541 1 Yargle, Glutton of Urborg (SLD) 1542 1 Ulamog, the Ceaseless Hunger (SLD) 1122 1 Etali, Primal Storm (SLD) 1123 1 Ghalta, Primal Hunger (SLD) 1124 1 Black Market Connections (CLB) 620 1 Black Market (CLB) 739 1 Azusa, Lost but Seeking (CMM) 679 1 Well of Lost Dreams (BRR) 62 1 Lost in the Maze (MKM) 64 1 Lost in the Woods (DKA) 123 1 Pair o' Dice Lost (UNF) 149 1 Super-Duper Lost (UNF) 59 1 Totally Lost (RVR) 64 1 Lost to Legend (LTR) 22 |
2024.02.03 21:52 RainbowButtMonkeyz Deck advice
 | I Have been playing around with this deck for current qeek. Seems to hold up well. Looking for advice on card substitutes for the 9 space card, etc submitted by RainbowButtMonkeyz to cuecardgameAvid [link] [comments] |
2024.01.15 18:41 LinguisticsTurtle There's a 2017 paper that puts forward a hypothesis that ADHD has to do with "bottom-up" signals. But what post-2017 papers shed light on how likely this hypothesis is to be accurate?
The 2017 paper was 6 years ago. I wonder what's happened research-wise since that 2017 paper came out. To be clear, it's just a hypothesis; it's not like I (or any of the researchers who think it's a good hypothesis) assert that it's true. Evidence is still being collected. The data will reveal whether this hypothesis should be abandoned or whether it makes sense. See below an excerpt from the 2017 paper:
https://www.sciencedirect.com/science/article/abs/pii/S0306987717312306
https://www.sciencedirect.com/science/article/abs/pii/S0306987717312306
submitted by LinguisticsTurtle to ADHDers [link] [comments]
https://www.sciencedirect.com/science/article/abs/pii/S0306987717312306
Meta-analysis of adoption and twin-studies has suggested that genetics may explain as much as 71% and 73% of the variance in ADHD core symptoms inattentiveness and/or hyperactivity-impulsivity, with larger dominant genetic effects on inattention and larger additive effects on hyperactivity (7). There is though strong evidence that these symptoms are extremes of continuously varying population traits (8, 9), and not categorical in character. Intriguing epigenetic research is also beginning to nuance the picture of ADHD as being mainly a genetic condition (10-13). Despite this development GxE models and integrative approaches in studies addressing ADHD pathophysiology seem spare, and focus of research interest appears skewed towards CNS and behavioral outcomes. Given the neurobiological conceptualization above these outcomes can though be expected to interact with peripheral nervous system function; i.e. bottom-up processing. Although substantial evidence indicates tonic dysregulation (14-16) or altered autonomic reactivity (14, 17) in ADHD, the roots and consequences of autonomic imbalance on symptomatology of the disorder remains largely unproblematized in literature, and few studies to date have addressed the role of the third autonomic branch, the enteric nervous system (ENS). While the microbiome-gut-brain axis in ADHD is so far mainly unexplored, a paradigm transition in GxE psychopathology research and Neuroscience is expected (6, 18), that hold potential of altering the conceptualization of controlling mechanisms for the disorder.And here are more excerpts:
https://www.sciencedirect.com/science/article/abs/pii/S0306987717312306
The enteric nervous system is connected to the sympathetic as well as the parasympathetic nervous system (83), and mainly communicates with the brain through the vagus nerve (cranial nerve X) and spinal cord pathways (84). Also, 75% of the parasympathetic nervous system consists of the vagus nerve (85), with a ratio of 9:1 for afferent versus efferent vagal fibres in peripheral nerve bundles (86). An autonomic dysregulation model of ADHD that involves enteric imbalance thus implies vagus nerve dysregulation. Several studies have reported altered activity and/or reactivity of the parasympathetic nervous system in ADHD (15-17, 87, 88), but findings are inconsistent (see overview in (15)). It is also unclear how cortical activation and peripheral arousal in ADHD are related, although preliminary data has suggested a possible inverse correlation (89)....
Afferent vagus nerve stimulation may have effects comparable to elevated afferent vagal activity caused by enhanced enteric signaling, and can therefore be used as a model for evaluation of presumptive physiological CNS consequences. Afferent vagus nerve signaling stimulates the HPA-axis releasing glucocorticoid hormones (90). Also, animal studies have indicated that stimulation of vagal afferents inhibits parasympathetic efferent signaling to the heart, and thus reduces cardiac vagal tone (91, 92). In rodent studies, vagus nerve stimulation towards the nucleus of the solitary tract (i.e. afferent vagal activation), increased the firing rate of norepinephrine releasing neurons of the locus coeruleus and subsequent serotonin releasing neurons of the dorsal raphe nucleus (93). This indicates that vagus nerve stimulation support the excitatory pathway to the locus coeruleus more than the parallel inhibitory GABAergic pathway (93). A rodent study has also shown that chronic peripheral vagus nerve impairment caused by unilateral microchip low-frequency vagus stimulation lead to dopamine system inhibition in different brain structures (especially mesolimbic and mesocortical systems) (94). Additionally, electrical stimulation of the peripheral vagus nerve has resulted in significant alterations of physiologically important nutritional macro- and trace elements in dopamine related brain structures (substantia nigra and corpus striatum) of rodents (95). This indicates that enhanced afferent enteric signaling, as hypothesized here, may compromise metabolic homeostasis in vagus nerve related CNS regions. Metabolic alterations linked to vagus nerve activity have been found also in a clinical cohort study, showing that vagus nerve stimulation significantly increased energy expenditure (96), which has been reported elevated in ADHD subjects (28, 29). It is worth noticing that experimental overstimulation of a nerve is known to result in reduced transmission of stimuli due to lack of neurotransmitter substance (94). This can be relevant to severe ADHD symptoms, if viewed as continuous traits, and entail paradoxical effects that may cause equivocal findings. Neuro-immune modulatory interactions are often non-linear. It therefore seems reasonable to assume that vagus nerve dysregulation due to reduced but also enhanced enteric signaling may compromize homeostasis of immune system function and inflammatory regulation, and increase tryptophan metabolism along the kynurenine pathway. Vagus nerve stimulation in conditions with vagal underactivity (97- 99) may thus show positive efficacy outcomes that seem contradictory to our hypothesis if they are interpreted as linear interactions. It may equally be important whether efferent or afferent vagal stimulation is applied (90). Several studies have indicated altered immunological markers and tryptophan metabolism in ADHD (46, 75, 76, 100), which support our hypothesis of enteric dysregulation.
Inattention, with difficulty organizing and sustaining in activities or tasks, distractibility and frequent failure to attend details etc. are core symptoms in ADHD diagnostic criteria. These attention deficits have been suggested to reflect a low arousal level that secondary impair executive and endogenous (but not exogenous) attention orienting (101). Also, an integrative theoretical model has suggested that dysregulation between tonic and phasic activity of the locus coeruelus norepinephrine arousal system compromises attentional performance in ADHD and predispose to impulsive behaviors (102). Can ADHD attention symptoms be secondary to increased vagal afferent signaling that bias information processing towards bottom-up exogenous attention orienting?
Afferent vagus nerve fibers project sensory information to the locus coeruleus via the nucleus of the solitary tract (93). Evidence has indicated that activation of the locus coeruleus is triggered by environmental sensory cues that provoke interruption of ongoing behavior in order to reorientate and facilitate an adaptive behavior response (103). Norepinephrine from the locus coeruleus neurons is the only known source of this neurotransmitter for a majority of the forebrain (103). Like dopamine, norepinephrine has a U-shaped influence on prefrontal cortex cognitive abilities and physiology (104). This means that both too high levels (as in acute uncontrollable stress) and too low levels (as in fatigue and plausibly hypoarousal) impairs prefrontal cortex function (104). Low tonic arousal in normal subjects has been associated with asymmetric visuo-spatial attention, favoring stimuli from the right side (105). In the opposite direction, an experimental human study has shown that chronic psychosocial stress (i.e. elevated sympathetic activation) increased couplings between dorsolateral prefrontal cortex and temporal lobe areas that are involved in visual processing, which may have the short-term benefits of favoring a single, salient stimulus (106). Also, lower resting heart rate variability has been linked to a more exogenous attention orienting, which may impede effective emotion regulation (107). An ERP-study (scalp-recorded Event-Related brain Potential) has shown reduced automatic attention to salient sound stimuli in young adults (age 18-23) with ADHD (n=21) versus controls (n=18) (108). The results indicated that the attention problem in ADHD originates at a lower processing level, where inhibition is irrelevant. Authors suggested the locus coeruleus as the most likely site of deficit, due to its role in arousal and in regulating amplification of incoming (i.e. bottom-up) information (108). These results are supported by EEG recordings of evoked Gamma-Band Response (GBR) activity, which indicated increased distractibility in ADHD at an early level of perception (109). Importantly, no deviation was found during working memory encoding and retrieval, suggesting that the attention deficit in ADHD is specific to interference susceptibility (109).
2024.01.15 13:17 VictorEden16 Highly possible cause for non-sexual PSSD/PFS symptoms is literally written on Wikipedia
You will need to read 2 articles : 1) https://en.m.wikipedia.org/wiki/Neurosteroid 2) https://en.wikipedia.org/wiki/GABAA_receptor
Gaba-a receptors are vital for our CNS. They are affected by neurosteroids and alcohol, among other things, and in rare cases are subject to epigenetic changes, which cause emotional disregulation and various responses to drugs/alcohol.
It’s specifically written in the neurosteroid article that neurosteroids are affected by SSRI , especially fluvoxamine, which caused me PSSD.
What probably happened is in some genetically predisposed people altered levels of neurosteroids epigenetically changed gaba-a receptors which caused anhedonia,emotional blunting and no response to alcohol. Such symptoms can also happen without SSRI due to stress.
Read this quote specifically: There are multiple indications that paradoxical reactions upon – for example – benzodiazepines, barbiturates, inhalational anesthetics, propofol, neurosteroids, and alcohol are associated with structural deviations of GABAA receptors. The combination of the five subunits of the receptor (see images above) can be altered in such a way that for example the receptor's response to GABA remains unchanged but the response to one of the named substances is dramatically different from the normal one.
There are estimates that about 2–3 % of the general population may suffer from serious emotional disorders due to such receptor deviations, with up to 20% suffering from moderate disorders of this kind. It is generally assumed that the receptor alterations are, at least partly, due to genetic and also epigenetic deviations. There are indication that the latter may be triggered by, among other factors, social stress or occupational burnout.
I will add that i never liked alcohol even before PSSD and had emotional disorders , this can’t be a coincidence.
submitted by VictorEden16 to PSSD [link] [comments]
Gaba-a receptors are vital for our CNS. They are affected by neurosteroids and alcohol, among other things, and in rare cases are subject to epigenetic changes, which cause emotional disregulation and various responses to drugs/alcohol.
It’s specifically written in the neurosteroid article that neurosteroids are affected by SSRI , especially fluvoxamine, which caused me PSSD.
What probably happened is in some genetically predisposed people altered levels of neurosteroids epigenetically changed gaba-a receptors which caused anhedonia,emotional blunting and no response to alcohol. Such symptoms can also happen without SSRI due to stress.
Read this quote specifically: There are multiple indications that paradoxical reactions upon – for example – benzodiazepines, barbiturates, inhalational anesthetics, propofol, neurosteroids, and alcohol are associated with structural deviations of GABAA receptors. The combination of the five subunits of the receptor (see images above) can be altered in such a way that for example the receptor's response to GABA remains unchanged but the response to one of the named substances is dramatically different from the normal one.
There are estimates that about 2–3 % of the general population may suffer from serious emotional disorders due to such receptor deviations, with up to 20% suffering from moderate disorders of this kind. It is generally assumed that the receptor alterations are, at least partly, due to genetic and also epigenetic deviations. There are indication that the latter may be triggered by, among other factors, social stress or occupational burnout.
I will add that i never liked alcohol even before PSSD and had emotional disorders , this can’t be a coincidence.
2024.01.09 01:15 wernostrangerstoluv Writing new season plots because why not
Ok so:
S6:
Everyone is now Guardian of their own Miraculous, but LB has to shepherd them. This once again hurts CN but now, instead of giving up his Miraculous he has a heart to heart with LB where they talk about what they want. This shows Adrien's emotional intelligence because he was born from an emotion while also giving us cute Ladynoir stuff. Ignore my awful writing this is not a script its basic talking points that happen over a much longer period of time):"mlady i dont understand. why are you pushing me away? have i not shown that im capable? have i not shown that im responsible?"
"yes kitty but...i just"
"you dont have to do this alone"
"I just don't know if i can trus-"
"mlady i will always be by your side. ive shown that already. obviously this fear isnt from me. You dont have to say what caused this or what you are thinking, but you do have to put faith in me, as i do you"
After this he becomes a bigger leader of the team. He also taps in further to his power of Bad Luck (to balance out lbs power), which allows him to bring bad luck upon a person he chooses. he learns all the holders identities and teaches them the same way LB does. He grows in power. Meanwhile, we see Adrien struggling as an orphan because of his mixed feelings abt his father. Then, LB works up the courage to tell him the truth abt Monarchs identity. Adrien makes up a story about how he found out and throws away the rings, leading him to learning the truth about his existence from Natalie. Feeling lied to, he isolates himself from Natalie and turns to Mari for support, but she always seems preoccupied. This leads to them breaking up. We get to see both LB and CN just be incredibly depressed and try to comfort eachother (Ladynoir and sad Adrienette). Lila slowly uses her miraculous, but her secret is 75% through the season.
Tensions rise as Lila becomes a bigger and bigger threat. Realizing they cannot defeat her, LB and CN head into the past to the Agreste Manor to take the jewel before Lila can get to it. A very young Bunnix helps them. Paris is safe in the hands of the rest of the team. In the process, ladybug is injured and chat noir has to leave her outside while he goes in. He sees the final battle and in an attempt to get the broach he is spotted by Gabe and BugNoire. BN is so shocked that she misses a beat and is knocked unconscious. Meanwhile, LB can't stay put and limps her way to the battle to protect CN. CN and Gabe battle which leads Gabe learning CN's identity + an emotional scene. Gabe still wins, taking both his sons miraculous and the earrings off of an unconscious BN. LB sees Adrien. Gabe begins to make his wish. Meanwhile, Adrien is gets his miraculous from BN and sees her identity while LB manages to grab the butterfly miraculous. CN and LB look at each other with shock due to all the new knowledge. In the rain begins to play. Record scratch. In between them emerges a distraught adult Bunnix.
"Mini Bug, WHAT DID YOU DO." Fade to black.
(So we got our reveal but there is still interest being held for the next season.)
Season 7
So the drastic change in events prevents the s6 chain of event from ever occurring. Events are disintegrating rapidly, and so are our heroes. Because Lila didn't get the miraculous, they never had to go back in time. Thus, LB and CN are disintegrating rapidly too. An unknown force has been chasing Bunnix and it is after our two heroes. The only way to fix this is to set it back to how it was originally, which means the two would lose to Lila. Its a lose-lose situation. While they try to figure out what to do, they must hop times to protect themselves. The love square is closed once and for all as the two know each other's identities. However, after all the hurt these two have endured they switched to your stereotypical slow burn romance. They battle and repair their relationships. They watch how silly they used to be. We get a bit of meta humor. They start to disintegrate and ladybug keeps using her power to re-create them, which is drawing essential energy from her. As they hop through time, they manage to fly under the radar all but once. When was that time? Cat Blanc. They do something (idk what thats up to you writers) that makes Marinette write her name, which was not in the original timeline. (This fixes the bunnix caused her own existence paradox; see artistic aloubell.) CN finds out about ChatBlanc and we get a ton of angst and healing and trauma for both Characters. Tensions continue to rise and as both get more powerful they also get more self-centered. Ya'll write the rest I have no idea how this should end.
submitted by wernostrangerstoluv to MiraculousFanfiction [link] [comments]
S6:
Everyone is now Guardian of their own Miraculous, but LB has to shepherd them. This once again hurts CN but now, instead of giving up his Miraculous he has a heart to heart with LB where they talk about what they want. This shows Adrien's emotional intelligence because he was born from an emotion while also giving us cute Ladynoir stuff. Ignore my awful writing this is not a script its basic talking points that happen over a much longer period of time):"mlady i dont understand. why are you pushing me away? have i not shown that im capable? have i not shown that im responsible?"
"yes kitty but...i just"
"you dont have to do this alone"
"I just don't know if i can trus-"
"mlady i will always be by your side. ive shown that already. obviously this fear isnt from me. You dont have to say what caused this or what you are thinking, but you do have to put faith in me, as i do you"
After this he becomes a bigger leader of the team. He also taps in further to his power of Bad Luck (to balance out lbs power), which allows him to bring bad luck upon a person he chooses. he learns all the holders identities and teaches them the same way LB does. He grows in power. Meanwhile, we see Adrien struggling as an orphan because of his mixed feelings abt his father. Then, LB works up the courage to tell him the truth abt Monarchs identity. Adrien makes up a story about how he found out and throws away the rings, leading him to learning the truth about his existence from Natalie. Feeling lied to, he isolates himself from Natalie and turns to Mari for support, but she always seems preoccupied. This leads to them breaking up. We get to see both LB and CN just be incredibly depressed and try to comfort eachother (Ladynoir and sad Adrienette). Lila slowly uses her miraculous, but her secret is 75% through the season.
Tensions rise as Lila becomes a bigger and bigger threat. Realizing they cannot defeat her, LB and CN head into the past to the Agreste Manor to take the jewel before Lila can get to it. A very young Bunnix helps them. Paris is safe in the hands of the rest of the team. In the process, ladybug is injured and chat noir has to leave her outside while he goes in. He sees the final battle and in an attempt to get the broach he is spotted by Gabe and BugNoire. BN is so shocked that she misses a beat and is knocked unconscious. Meanwhile, LB can't stay put and limps her way to the battle to protect CN. CN and Gabe battle which leads Gabe learning CN's identity + an emotional scene. Gabe still wins, taking both his sons miraculous and the earrings off of an unconscious BN. LB sees Adrien. Gabe begins to make his wish. Meanwhile, Adrien is gets his miraculous from BN and sees her identity while LB manages to grab the butterfly miraculous. CN and LB look at each other with shock due to all the new knowledge. In the rain begins to play. Record scratch. In between them emerges a distraught adult Bunnix.
"Mini Bug, WHAT DID YOU DO." Fade to black.
(So we got our reveal but there is still interest being held for the next season.)
Season 7
So the drastic change in events prevents the s6 chain of event from ever occurring. Events are disintegrating rapidly, and so are our heroes. Because Lila didn't get the miraculous, they never had to go back in time. Thus, LB and CN are disintegrating rapidly too. An unknown force has been chasing Bunnix and it is after our two heroes. The only way to fix this is to set it back to how it was originally, which means the two would lose to Lila. Its a lose-lose situation. While they try to figure out what to do, they must hop times to protect themselves. The love square is closed once and for all as the two know each other's identities. However, after all the hurt these two have endured they switched to your stereotypical slow burn romance. They battle and repair their relationships. They watch how silly they used to be. We get a bit of meta humor. They start to disintegrate and ladybug keeps using her power to re-create them, which is drawing essential energy from her. As they hop through time, they manage to fly under the radar all but once. When was that time? Cat Blanc. They do something (idk what thats up to you writers) that makes Marinette write her name, which was not in the original timeline. (This fixes the bunnix caused her own existence paradox; see artistic aloubell.) CN finds out about ChatBlanc and we get a ton of angst and healing and trauma for both Characters. Tensions continue to rise and as both get more powerful they also get more self-centered. Ya'll write the rest I have no idea how this should end.
2024.01.08 22:56 wernostrangerstoluv Writing the new season plots because why not
Ok so:
S6:
Everyone is now Guardian of their own Miraculous, but LB has to shepherd them. This once again hurts CN but now, instead of giving up his Miraculous he has a heart to heart with LB where they talk about what they want. This shows Adrien's emotional intelligence because he was born from an emotion while also giving us cute Ladynoir stuff. Ignore my awful writing this is not a script its basic talking points that happen over a much longer period of time): "mlady i dont understand. why are you pushing me away? have i not shown that im capable? have i not shown that im responsible?"
"yes kitty but...i just"
"you dont have to do this alone"
"I just don't know if i can trus-"
"mlady i will always be by your side. ive shown that already. obviously this fear isnt from me. You dont have to say what caused this or what you are thinking, but you do have to put faith in me, as i do you"
After this he becomes more powerful and a bigger leader of the team. he learns all the holders identities and teaches them the same way LB does. He grows in power. Meanwhile, we see Adrien struggling as an orphan because of his mixed feelings abt his father. Then, LB works up the courage to tell him the truth abt Monarchs identity. Adrien makes up a story about how he found out and throws away the rings, leading him to learning the truth about his existence from Natalie. Feeling lied to, he isolates himself from Natalie and turns to Mari for support, but she always seems preoccupied. This leads to them breaking up. We get to see both LB and CN just be incredibly depressed and try to comfort eachother (Ladynoir and sad Adrienette). Lila slowly uses her miraculous, but her secret is 75% through the season.
Tensions rise as Lila becomes a bigger and bigger threat. Realizing they cannot defeat her, LB and CN head into the past to the Agreste Manor to take the jewel before Lila can get to it. A very young Bunnix helps them. Paris is safe in the hands of the rest of the team. In the process, ladybug is injured and chat noir has to leave her outside while he goes in. He sees the final battle and in an attempt to get the broach he is spotted by Gabe and BugNoire. BN is so shocked that she misses a beat and is knocked unconscious. Meanwhile, LB can't stay put and limps her way to the battle to protect CN. CN and Gabe battle which leads Gabe learning CN's identity + an emotional scene. Gabe still wins, taking both his sons miraculous and the earrings off of an unconscious BN. LB sees Adrien. Gabe begins to make his wish. Meanwhile, Adrien is gets his miraculous from BN and sees her identity while LB manages to grab the butterfly miraculous. CN and LB look at each other with shock due to all the new knowledge. In the rain begins to play. Record scratch. In between them emerges a distraught adult Bunnix.
"Mini Bug, WHAT DID YOU DO." Fade to black.
(So we got our reveal but there is still interest being held for the next season.)
Season 7
So the drastic change in events prevents the s6 chain of event from ever occurring. Events are disintegrating rapidly, and so are our heroes. Because Lila didn't get the miraculous, they never had to go back in time. Thus, LB and CN are disintegrating rapidly too. An unknown force has been chasing Bunnix and it is after our two heroes. The only way to fix this is to set it back to how it was originally, which means the two would lose to Lila. Its a lose-lose situation. While they try to figure out what to do, they must hop times to protect themselves. The love square is closed once and for all as the two know each other's identities. However, after all the hurt these two have endured they switched to your stereotypical slow burn romance. They battle and repair their relationships. They watch how silly they used to be. We get a bit of meta humor. They start to disintegrate and ladybug keeps using her power to re-create them, which is drawing essential energy from her. As they hop through time, they manage to fly under the radar all but once. When was that time? Cat Blanc. They do something (idk what thats up to you writers) that makes Marinette write her name, which was not in the original timeline. (This fixes the bunnix caused her own existence paradox; see artistic aloubell.) CN finds out about ChatBlanc and we get a ton of angst and healing and trauma for both Characters. Tensions continue to rise and as both get more powerful they also get more self-centered. Ya'll write the rest I have no idea how this should end.
submitted by wernostrangerstoluv to miraculousladybug [link] [comments]
S6:
Everyone is now Guardian of their own Miraculous, but LB has to shepherd them. This once again hurts CN but now, instead of giving up his Miraculous he has a heart to heart with LB where they talk about what they want. This shows Adrien's emotional intelligence because he was born from an emotion while also giving us cute Ladynoir stuff. Ignore my awful writing this is not a script its basic talking points that happen over a much longer period of time): "mlady i dont understand. why are you pushing me away? have i not shown that im capable? have i not shown that im responsible?"
"yes kitty but...i just"
"you dont have to do this alone"
"I just don't know if i can trus-"
"mlady i will always be by your side. ive shown that already. obviously this fear isnt from me. You dont have to say what caused this or what you are thinking, but you do have to put faith in me, as i do you"
After this he becomes more powerful and a bigger leader of the team. he learns all the holders identities and teaches them the same way LB does. He grows in power. Meanwhile, we see Adrien struggling as an orphan because of his mixed feelings abt his father. Then, LB works up the courage to tell him the truth abt Monarchs identity. Adrien makes up a story about how he found out and throws away the rings, leading him to learning the truth about his existence from Natalie. Feeling lied to, he isolates himself from Natalie and turns to Mari for support, but she always seems preoccupied. This leads to them breaking up. We get to see both LB and CN just be incredibly depressed and try to comfort eachother (Ladynoir and sad Adrienette). Lila slowly uses her miraculous, but her secret is 75% through the season.
Tensions rise as Lila becomes a bigger and bigger threat. Realizing they cannot defeat her, LB and CN head into the past to the Agreste Manor to take the jewel before Lila can get to it. A very young Bunnix helps them. Paris is safe in the hands of the rest of the team. In the process, ladybug is injured and chat noir has to leave her outside while he goes in. He sees the final battle and in an attempt to get the broach he is spotted by Gabe and BugNoire. BN is so shocked that she misses a beat and is knocked unconscious. Meanwhile, LB can't stay put and limps her way to the battle to protect CN. CN and Gabe battle which leads Gabe learning CN's identity + an emotional scene. Gabe still wins, taking both his sons miraculous and the earrings off of an unconscious BN. LB sees Adrien. Gabe begins to make his wish. Meanwhile, Adrien is gets his miraculous from BN and sees her identity while LB manages to grab the butterfly miraculous. CN and LB look at each other with shock due to all the new knowledge. In the rain begins to play. Record scratch. In between them emerges a distraught adult Bunnix.
"Mini Bug, WHAT DID YOU DO." Fade to black.
(So we got our reveal but there is still interest being held for the next season.)
Season 7
So the drastic change in events prevents the s6 chain of event from ever occurring. Events are disintegrating rapidly, and so are our heroes. Because Lila didn't get the miraculous, they never had to go back in time. Thus, LB and CN are disintegrating rapidly too. An unknown force has been chasing Bunnix and it is after our two heroes. The only way to fix this is to set it back to how it was originally, which means the two would lose to Lila. Its a lose-lose situation. While they try to figure out what to do, they must hop times to protect themselves. The love square is closed once and for all as the two know each other's identities. However, after all the hurt these two have endured they switched to your stereotypical slow burn romance. They battle and repair their relationships. They watch how silly they used to be. We get a bit of meta humor. They start to disintegrate and ladybug keeps using her power to re-create them, which is drawing essential energy from her. As they hop through time, they manage to fly under the radar all but once. When was that time? Cat Blanc. They do something (idk what thats up to you writers) that makes Marinette write her name, which was not in the original timeline. (This fixes the bunnix caused her own existence paradox; see artistic aloubell.) CN finds out about ChatBlanc and we get a ton of angst and healing and trauma for both Characters. Tensions continue to rise and as both get more powerful they also get more self-centered. Ya'll write the rest I have no idea how this should end.
2023.11.18 23:07 WishboneFar4739 Cerebrolysin after benzo injury
I used a benzo ( zopiclone) which turned paradoxal quite fast. Severe akathasia , dystonia , weight gain, blood pooling - cns damage.
I was taken off cold turkey and than hell broke lose. Reinstated the already paradoxal med and tapered off.
My posture is TERRIBLE ever since :
Severe lordosis in back, and a huge hump of bones in my upper spine creating an exaggerateds shape in my body .
I found out my daughter has this in a mild form , she of course never used a benzo so I think it’s genetic and the zopiclone just destroyed all the dopa and GABA I had left in my brain.
Can anyone recommend me a peptide to help me fix the spine as I am sure it’s only from the muscle changes / Cns changes which are a result from brain issue.
Also I wonder if the extreme weight gain can be reversed with a peptide or Cerebrolysin.
No diet helps , tried carnivore low carb zero carb vegan Mediterranean it’s my profession to work with nutrition this ain’t going to do a thing,
Please anyone who has any insight how the hell can I fix my poor posture from brain changes while I am not even able to STAND from pain and weakness and muscles tight
submitted by WishboneFar4739 to Cerebrolysin [link] [comments]
I was taken off cold turkey and than hell broke lose. Reinstated the already paradoxal med and tapered off.
My posture is TERRIBLE ever since :
Severe lordosis in back, and a huge hump of bones in my upper spine creating an exaggerateds shape in my body .
I found out my daughter has this in a mild form , she of course never used a benzo so I think it’s genetic and the zopiclone just destroyed all the dopa and GABA I had left in my brain.
Can anyone recommend me a peptide to help me fix the spine as I am sure it’s only from the muscle changes / Cns changes which are a result from brain issue.
Also I wonder if the extreme weight gain can be reversed with a peptide or Cerebrolysin.
No diet helps , tried carnivore low carb zero carb vegan Mediterranean it’s my profession to work with nutrition this ain’t going to do a thing,
Please anyone who has any insight how the hell can I fix my poor posture from brain changes while I am not even able to STAND from pain and weakness and muscles tight
2023.11.02 00:29 WoogieSolo Hydrocort and BP drop?
Hi everyone. Currently involved in the care of a very sad case. A young patient in their 20's with severe and diffuse brain damage, microthrombi and infarct, secondary to fat emboli. Day 10 ventilated etc, BP currently unsupported. No significant medical background.
My question is, regarding Hydrocort. Twice when giving IV Hydrocort, 100mg push, the patient has had a near immediate drop in their MAP, 75>55ISh, which self resolved in approx 2 mins.
Is this an odd paradoxical effect? Or could this perhaps be informing us of compromised CNS function? Thanks very much for any help.
submitted by WoogieSolo to IntensiveCare [link] [comments]
My question is, regarding Hydrocort. Twice when giving IV Hydrocort, 100mg push, the patient has had a near immediate drop in their MAP, 75>55ISh, which self resolved in approx 2 mins.
Is this an odd paradoxical effect? Or could this perhaps be informing us of compromised CNS function? Thanks very much for any help.
2023.07.20 01:41 Viviiddly Collection
 | My collection so far. What y’all think? submitted by Viviiddly to 4kbluray [link] [comments] |
2023.07.06 16:36 NoEstablishment5984 alien
It seems like all my comments are being deleted. I will post answer at the end of the message.
From the late 2000s to the mid-2010s, I worked as a molecular biologist for a national security contractor in a program to study Exo-Biospheric-Organisms (EBO). The aim of the program was to elucidate the genome and proteome basis of these organisms. Although the study of OBCs has been going on for decades in other programs, the new high-throughput DNA sequencing technologies of the late 90s unblocked stagnant research in this area. Since then, several breakthroughs have led to significant advances in our understanding of the genome and proteome of these beings. What we've learned so far has enabled us to outline some disconcerting perspectives about our place in this universe. Briefly, we've discovered that the EBO genome is a chimera of genomes from our biosphere and from an unknown one. They are artificial, ephemeral and disposable organisms created for a purpose that still partially eludes us. I'll be substantiating my statements after a brief introduction.
The reason for disclosing these secrets is quite simple. I believe that every human being has the right to know the truth, and that to progress, humanity needs to divest itself of certain institutions and organizations that will probably not survive these revelations in the long term. I'm aware that I'll have very little impact in this regard, but I still believe that small leaks are necessary to break the dam of misinformation on this subject. When the governments will eventually reveal these secrets, there will undoubtedly be a societal upheaval, but in my opinion, the longer we wait, the worse it will be. I choose to divulge what I know anonymously out of selfishness for the well-being of myself and my family. I'm aware that this diminishes the reach and credibility of my message, but it's the furthest I am willing to go. I chose this forum because it offers a good compromise between anonymity and popularity. In order to protect my anonymity, I will be purposely vague or even contradictory about any information that could identify me (date, education, role etc.). I'll even introduce red herrings in this respect. I want to make it clear that any information related to the subject of the research will not be treated in this way.
Before going any further, please excuse me if you find it difficult to understand what I'm explaining. Some parts of my text are very technical. It's difficult to find the right balance between vulgarization and scientific explanation. I'll continue by talking about myself. What's the point of talking about me knowing that the information will necessarily be misleading? I simply want to introduce a perspective on the type of people who work there, normal scientists. I have a Ph.D. in molecular biology. I didn't actively seek to be part of this program, rather it was a stroke of luck that introduced me to one of the senior scientists. I met this person at a conference where I was presenting a poster on my Ph.D. research. When I think back, I don't believe he was impressed by what I was presenting, because it was quite frankly a project that wasn't going anywhere. I think it was rather the most important aspect of a professional life: the attitude and the ease with which you make connections. Shortly afterwards, I graduated and received a call from this person offering me a position. At the time, everything pointed to me working in a regular laboratory.
I did a series of three increasingly suspicious interviews, each in a different location, where my scientific background and knowledge became less and less relevant. The first was with two of the senior scientists, the second and third with people I've never seen again and who were obviously not interested in science. Sometime after the interview, I was asked to go to a fourth location where what seemed like a corporate lawyer presented me with an NDA. He made sure not only to explain every detail, but also that I understood the consequence of not respecting it.
The first Employment weeks were by far the most memorable, although I spent most of that time in a depressing archive room. It consists almost exclusively of reading about the subject of study and to get us up to speed. There's no secret Wikipedia or even a reference book to guide us. There are only dry reports, memos, presentations, procedures and SOPs. These documents are almost exclusively about the biology of EBOs, but there are also a few that deal with other subjects such as their food, religion or culture. There were no documents on their technology.
As mentioned above, the aim of the project is to gain a better understanding of the EBO genome and proteome. To achieve this, a team of around twenty scientists, four senior scientists and a director was involved. The scientists, like myself, had as their main responsibility to carry out the technical work. As each scientist had to my knowledge a Ph.D., we were all somewhat overqualified for what is ultimately a technician's job. The senior scientists, who make full use of their diplomas, had the task of designing the assays and had a supervisory responsibility. They were also in charge of training new employees, and sometimes even came in to do technical work. The director, of course, was the person in charge who dictated priorities to the senior scientists. He was rarely on site, and the few times he was, it was to attend meetings. Other than the scientific staff, there were security guards working for one subcontractor or another. There were no support staff such as janitors or maintenance workers. Scientists were responsible for this kind of work. In addition, logistical constraints ensure that every scientist is capable of carrying out any technical activity.
The laboratory itself is located in Fort Detrick, Maryland, in a building used for legitimate biomedical research. The clandestine operations are carried out in a restricted part of the basement, out of sight from regular workers. Contrary to what one might imagine, the biosafety level is not maximal for this type of research. Indeed, the lab containing EBO samples or derived cell cultures is BSL3, while the lab where assays are conducted are only BSL2. The BSL3 area of the facility includes a freezer room and a cell culture lab and is only accessible through an antechamber from the BSL2 section. EBO carcasses are preserved in horizontal freezers at a temperature of -80°C nominal. To maximize the preservation of these carcasses, they are preserved in vacuum bags and the air in the room is controlled to minimize humidity. There are only four bodies and none of them are complete. It's obvious that these creatures have died as a result of major trauma. I've never witnessed a motorcycle accident fatality, but it probably looks similar to this. It is acknowledged that there are more EBOs caracasses at other locations. The cell culture laboratory, as its name suggests, is where cell lines derived from EBOs are grown and related activities are performed. I'll talk in more detail about these specific cell lines later on. The BSL2 part is mainly used for assays, immunohistochemistry, genetic engineering, immunocytochemistry, storage etc. There's also a cell culture lab, but this is used for more traditional cell lines. Other than the labs, there are all the amenities you could find in an office. Note that the internet access is limited to senior staff and up. There is, however, an intranet for bioinformatics needs.
On the subject of the biology of these beings, I'll start by discussing genetics, then their gross anatomy and finally their biological systems. For the sake of clarity, the information that I provide here is an aggregation of what I have observed and what I have read. I will make many comparisons with human anatomy because it is the most logical reference.
Genetics:
First, I'd like to discuss their genetics. Their genetics are like ours, based on DNA. This fact was very puzzling for me when I first learned about it. We imagine that beings from an alternate biosphere would have genetics based on a completely foreign biochemical system and surprisingly, this is not the case. Several conclusions can be drawn from this surprising revelation. The one that immediately comes to mind is that our biosphere and theirs share a common ancestry. They're eukaryotes, which means their cells have nuclei containing genetic material. Which suggests that their biosphere would have been separated from ours sometime after the appearance of this type of organism. The term Exo-Biospheric-Organism is actually a misnomer, but as it's a historical term, it's still used. Their genetics are not only based on the same genetic system, but they’re also even compatible with our own cellular machinery. This means that you can take a human gene and insert it into an EBO cell, and that gene will be translated into protein, and this of course works in reverse with a human gene inserted into an EBO cell. There are important differences in post-translational modifications that will make the final protein non-functional, but I'll discuss these later. Their genome consists of 16 circular chromosomes.
You're probably familiar with the concept of intergenic region or "junk DNA". These are basically DNA sequences that don't code for proteins. These are evolutionary residues, transposons, inactivated genes and so on. To give you an idea, in humans, intergenic regions represent approximately 99% of our genome. I'm aware that these sequences aren't completely useless, they can be used as histone anchors, as buffers to protect coding DNA from radiation or even as alternative open reading frames, but that's rather peripheral.
What's particularly striking about the EBO genome is the uniformity of these intergenic regions. We see the same sequences repeated everywhere, and the distance in bp between the genes is virtually the same throughout their genome. The result is a minimalist, highly condensed genome. In fact, it's much smaller than ours. Moreover, the quantity of protein-coding genes is even significantly lower than ours, probably due to genetic refinement but also to biological processes that are absent in EBO. The uniformity of these sequences is a major indication of the artificiality of these beings. There is no complex organism on earth that has such elegance in its sequences. There is no evolutionary pressure that can lead to this kind of characteristic other than genetic engineering.
Speaking of genetic engineering, following sequencing of their genomes, we noticed a troubling and universal characteristic in the 5' of the regulatory sequence of each gene which we call the Tri-Palindromic Region. The TPR are 134bp sequences containing, as its name suggests, 3 palindromes. In genetics, a palindrome is a DNA sequence that when read in the same direction, gives the same sequence on both DNA strands. They serve both as a flag and as a binding site for proteins. The three palindromes in the TPR are distinct from one another and have been poetically named "5'P TPR", "M TPR" and "3' TPR". The TPR is composed (in 5' - 3' order) of 5'P TPR, 12bp spacer, Chromosomal address, 12bp spacer, M TPR, 12bp spacer, Gene address, 12pb spacer and 3' TPR. The chromosomal address is composed of 4 bp and is identical in each TPR of the same chromosome, but distinct between each of the 16 chromosomes of the genome. The Gene address is a 64bp sequence that is unique for each gene in the whole genome. It's therefore understandable that the TPR serves as a unique address not only for numerically identifying a gene, but also for identifying its chromosomal location. For those with only a basic knowledge of genetics, this is completely unheard of. No living thing in our biosphere has this kind of precise address in its genome. Once again, the presence of TPR cannot be explained by evolutionary pressure but only by genetic engineering on a genomic scale.
TPR opens the door to several possibilities. One of them suggests that EBO geneticists can insert or remove a gene from a cell in a way that is far more targeted and efficient than our technology allows. No proteins have been identified in the EBO genome that interacts with TPR. Rather, we believe that these proteins are exclusively targeted by external genetic engineering tools, probably used at the zygotic stage of embryonic development. The nature of these tools is unclear, but we definitely don't have anything like them. The probable absence of these proteins from the genome is a further indication of their artificiality. Given the high probability of artificiality of their genome and the apparent ease of modifying it with biomolecular tools, it's not out of the question that there could be polymorphism between individuals depending on their role and function. In other words, an individual could be genetically designed to have characteristics that give it an advantage in performing a given task, like soldier ants and worker ants in an anthill. Note that these previous statements are speculation. To my knowledge only one individual genome has been sequenced, I can't make a definitive statement on genetic variation between individuals.
I've talked a lot about intergenic regions, now I'll briefly discuss intragenic sequences. Briefly, because there's not a lot less to say despite its obvious importance. Much like ours, their genes have silencers, enhancers, promoters, 5'UTRs, exons, introns, 3' UTRs etc. There are many genes analogous to ours, which is not surprising given the compatibility of our cellular machinery. What's disturbing is that some genes correspond directly, nucleotide by nucleotide, with known human genes or even some animal genes. For these genes, there doesn't seem to be any artificial refinement but rather a crude copying and pasting. Why they do it is nebulous and still subject to conjecture. There are also many genes which are not found in our biosphere whose role has not been identified. Finding the purpose of these novel genes is one of the aims of the program. I'd like to note before going any further that this heterogeneity of genes of known and unknown origin is an undeniable proof of the artificiality of EBOs.
To conclude with genetics, the mitochondrial genome, at the time I was working there, had not yet been sequenced. It's safe to assume that this genome would also be streamlined and possibly has some version of TPR.
Transcription and translation and protein expression.
I briefly introduced the differences in post-translational modifications between human and EBO. This is hardly a surprise, as we often see the same thing between different terrestrial species. Obtaining a viable protein from a DNA sequence is a complex process involving hundreds of protein intermediates, each with a precise and essential role. A minor variation in this assembly line can lead to functional irregularities in the final product. So, it's no surprise that there are setbacks along the way when the first EBO gene transfection attempts failed to produce the desired functional protein in human cell lines. Fortunately for us, the work of what I imagine to be another team at another site has led to the development of an EBO cell line named EPI-G11 derived from epithelial tissues. With this tool in our hands, we were able to transfect and overexpress proteins of interest in order to eventually purify and study them. For your information, we use a biological ballistics delivery system (AKA gene gun) for our transfection needs because other methods are not very effective with cells of this line. For example, the viral vectors tested cannot be internalized by EPI-G11 and lipofection is too lethal. EPI-G11, like most eukaryotic cell lines, enters a phase of exponential growth when exposed to Fetal Bovine Serum. It's only half surprising that a cell line from such an exotic source should be sensitive to the growth factors present in FBS. In my opinion, this can be explained by the addition of animal genes to the genome, such as growth receptors.
Gross anatomy:
They are morphologically very similar to the grey aliens that are part of modern folklore. Their height is about 150cm, they have two arms, two legs and a head. Still, there are some notable differences.
Skin: The grey skin that is often described in folklore is in fact a biosynthetic film which, likely, serves to protect the EBO from a hostile environment. It doesn't provide effective protection against temperature changes, but it does offer adequate protection against the passage of liquids. It's possible that this film confers other advantages but my knowledge on the subject is limited. Under the grey film, the epidermis is rather white, and the texture is very regular and without any hair. We do not see any defect other than the folds near the joints. It's described as greasy in one report, but that's not something I've observed. The same report states that a strong, lingering smell of burnt hair and ammonia is present when the film is removed. There are a lot of pores on the skin, crossing from the epidermis to a gland in the hypodermis. These glands and pores are the terminal part of the excretory-sudoriferous system, which could explain the previously mentioned smell.
Head: The head contains two large, oversized eyes, two nostrils without protuberance, a narrow mouth without lips and two ear canals without auricles. There is a mandible, but the musculature is vestigial. There are no teeth or tongue in the oral cavity. The nasal cavity where the nostrils meet is compact and does not rise cranially but extends axially. There appears to be no equivalent to the olfactory bulb in the nasal cavity. The mouth leads directly to the esophagus and the nasal cavity to the trachea. The trachea and esophagus do not communicate.
Eye: Like the skin, the eyes are covered with a semi-transparent biosynthetic film that offers the same environmental protection, while providing protection against certain wavelengths and light intensity. When the film is removed, a more traditional eye is revealed. It's about three times larger than a human eye and there are no eyelids. The size of their eyes suggests they have excellent night vision. It seems paradoxical to cover them with a semi-opaque film. Perhaps they only need to wear it in a bright environment. Their sclera is the same color as their skin, the iris is pale grey, and the pupil is black and oversized. The lens is rounder than a human, and the musculature used to adjust focus is more developed. On the retina, there are at least 6 types of cone cells. The responsiveness of each of these 6 types of cone is specific to a wavelength band, with a minimum of overlap between each other. The result is a broader visible spectrum.
Ear: As mentioned, the outer ear has no auricle and the ear canal is unremarkable. The inner ear has all the characteristics of a typical vestibular and cochlear system, although the curvature of the cochlea is more pronounced than a human. This probably results in greater hearing acuity for low frequencies.
Brain: The brain is tetraspheric, i.e. composed of four major sections. The sections are separated by transverse and longitudinal fissures and are connected to the central lobe, which acts as brainstem and cerebellum. The volume of the brain is around 20% superior to that of a man of the same height. It has a much more pronounced level of gyrication than an average human. Moreover, the ratio of glial cells to neurons is also slightly higher than in humans. It is important to mention the presence of nodules on the central lobe. Histological analysis of these structures reveals a kind of intricate biological circuitry. It is speculated that these nodules are essential to interact with their technology. Consequently, determining the proteome of these structures is an absolute priority for the program.
Neck: The neck is proportionally longer than that of a human, and at the same time relatively thin. As mentioned, the esophagus and trachea are separate. There are no vocal cords in this region.
Thorax: The musculature of the thorax is underdeveloped. Muscles equivalent to the pectoralis major can be seen. We can also see the trapezius and deltoid muscles. The sternocleidomastoids are well defined. The ribs and sternum are clearly visible. There are no nipples.
Abdomen: The abdomen is wider than the thorax and bulges slightly forward. There is no navel.
Pelvis: The pelvic bones are apparent. There are no genitals or anus.
Hands and feets: Their hands have four digits, including an opposable thumb on the medial side. They have no nails, and the texture of their fingerprints is composed of concentric circles. Fingers are proportionally much longer than in humans. Unlike humans, finger musculature is entirely intrinsic to the hand. In other words, the muscles used to move the fingers are not in the forearms but entirely located in the hands. At first glance, the feet consist of just two digits, but a necropsy soon determined that each toe was made of two fused digits. The medial toe is marginally longer than the distal toe. The feet are relatively longer and narrower than in a human. Their musculature, however, is vestigial.
The EBOs endoskeleton is very similar to ours, at least in terms of composition. There's collagen, hydroxyapatite but also copper oxide crystals where marrow would normally be found. The role of these crystals has not been established, but it is not a crystalopathic condition. The blood cells of the myeloid lineage (or the equivalent for these creatures) therefore mature in a different location than in humans i.e. in the thymus like organ. A transverse section of the bone reveals osteon and osteocytes. There appear to be few osteoblasts and no osteoclasts. This indicates that the bones are no longer growing and cannot absorb the minerals present or adapt mechanically to changes in posture.
Biological system:
Respiratory system: Their cellular respiration is equivalent to ours, i.e. they need to oxidize organic components to produce energy. Their lungs have no reciprocating action, but rather have a unidirectional flow of air, similar to those seen in birds, which is more efficient than ours. It is speculated that this is in response to the brain's elevated metabolic needs. Vocalization is produced by vibration of the wall membrane at the junction between the two air sacs.
The Circulatory system of EBOs is rather analogous to ours. The heart is located in the mediastanum, but in a more medial position, directly beneath the sternum. The heart has two ventricles and two atria. There is an aorta, a pulmonary vein, a pulmonary artery and a vena cava. Blood flowing to the pulmonary capillaries via the pulmonary artery is pumped against the flow of air, maximizing gas exchange efficiency. The blood gas barrier is relatively narrow in these capillaries, at least compared to a human. Then oxygen-rich blood is returned to the heart and then expelled into the aorta and the rest of the body. Before returning to the heart, the blood will pass through the hepatorenal organ which, among other things, filters and controls osmotic pressure of the blood.
The blood itself is also analogous to that of a human. However, the proportion of plasma is much higher, albumin is in similar proportion ,hormone levels are much lower, metal ion levels are much higher (particularly copper) and glucose levels are significantly higher. The color of the blood is brownish, given the higher proportion of plasma and concentration of metal ions. On the cellular side, there are erythrocytes which, in addition to hemoglobin for binding oxygen, display several complexes capable of binding copper ions. It's not clear what role these copper ions play but we believe it neutralizes blood ammonia, among other things. Several cell types with leukocyte characteristics have been observed, but no comprehensive knowledge of them exists. Platelets are present, but in smaller proportions than in humans.
Excreto-sudoriferous system: This system is completely different from what I've seen. As mentioned earlier, there is no large orifice, like an anus or urethra, to get rid of biological waste. Instead, there are countless small pores on the surface of the skin. There's a large medial organ called the hepatorenal organ, which acts as both kidney and liver and is central to maintaining homeostasis. This organ is highly vascularized and the blood must pass through it before returning to the heart. Its role is, among other things, to purify the blood of metabolic waste. Waste is excreted into the equivalent of a ureter, which branches out into four. Each branch flows towards one of the four limbs and in turn these branches divide until they end up as thousands of excretory pores. The motility of this excretory system is mediated by a weak peristalsis at the proximal level and on the four main branches. Peristalsis ceases around the first distal junction. As there is no urea cycle, the ammonia concentration at the exit of the hepatorenal organ is very high. This ammonia is carried to the pores and gives the distinct odor I mentioned earlier. The rationale behind this unusual excretory system is directly related to this excreted ammonia, which enables thermoregulation by evaporating on the skin's surface. The greater the physical effort, the greater the metabolism. This in turn leads to a rise in temperature, and a corresponding increase in metabolic waste via amino acid catabolism. This leads to an increase in filtration and ammonia excretion, which ultimately lowers body temperature.
Digestive system: The digestive system is extremely underdeveloped. There's no there is no stomach in the familiar sense. However, there is a pseudo-stomach located at the transition between the thoracic and abdominal cavities. This organ is not involved in digestion, but only serves as a reservoir. A sphincter controls the flow of food into the intestine. The intestine is limited to the equivalent of our small intestine, i.e. it only serves to absorb liquids and nutrients and acts as the main digestion site. It has villi and microvilli like ours. The intestine ends in the hepato-renal organ, where non-digested matter is transported to the ureter and excretory system. Residues are dissolved in the ammonia of metabolic waste for excretion. There's an organ near the pseudostomachal sphincter that secretes digestive enzymes directly into the intestine. This organ is inspirationally called the digestive organ. It secretes mainly proteolytic enzymes and glycoside hydrolases.
Given the absence of teeth, the narrowness and rigidity of the esophagus, the absence of a true stomach and the absence of defecation, it is strongly believed that EBOs can only consume food in liquid form. It is assumed that, given the high metabolic needs of their brains, this food would have a high carbohydrate concentration. In order to meet other metabolic needs, there must also be a high protein content in the food consumed. These two statements are supported by the type of enzyme secreted by the digestive organ. It is therefore speculated that the food consumed is a sort of broth rich in sugar and protein, which probably also has a high copper content. Given the strict limitations on the type of food that they can consume, it's unlikely that this type of creature could survive in our biosphere without technological support.
Endocrine system: Knowledge of the endocrine system is minimal. We know that cells are receptive to bovine growth hormones, so it's assumed that certain functions are regulated by such a system. Endocrine mechanisms are very complex, and it goes without saying that they are best studied on living subjects.
Immune system: The immune system is another unknown. There seems to be an innate immune system but there doesn't seem to be any adaptive immunity, at least not similar to what is known. There's a thymus-like organ near the heart that's proportionally larger than in humans. This organ seems to be where all blood cells mature. Some cells have leukocyte characteristics such as granularity. The immune cells that germinate here have a high copper concentration. The surface receptors of innate immune cells have not yet been characterized, so we might as well say that all the work remains to be done.
Nervous system: The nervous system is also relatively similar. The spinal cord begins at the base of the central lobe of the brain and propagates down the vertebral column. In the vertebrae there are ganglia made of afferent and efferent neurons. In short, other than the CNS, there is nothing out of the ordinary.
Musculoskeletal system: The musculoskeletal system is very ordinary, albeit underdeveloped. Most of the human skeletal muscles have an equivalent. Only the hands, feet and forearms are different. It should be noted that the proportion of type 1 and type 2 muscle fibers is different from that in a human. Indeed, type 1 outnumbers type 2 by about a factor of 10.
Artificial system: We speculate that artificial molecular machines may be present in the body, and that copper, if present, would be essential to their function or assembly. Importantly, no AMMs have been observed.
Question 1: Amazing story. Have you shared this with the Senate Select Commission on Intelligence or with AARO and do you have evidence to back this up?
Thank you, no I haven't and no I won't. It sounds like a honey trap to me. I will not place my life in the hands of politicians. I have no proof other than this message. I know it's not much but it's what I'm prepared to offer
Question 2: Well that was a read ... So they are bio engineered worker bees... Any elemental components that are unutributal to our biome ?
Yes, knowing that they're disposable, unable to live independently without technological support, and that they're ephemeral. The only suitable hypothesis is that they are alive only to accomplish their task. Can you clarify your question about elemental components?
Question 3: I havent read everything in detail but can you expend on the document on their religion?
EBOs believe that the soul is not an extension of the individual, but rather a fundamental characteristic of nature that expresses itself as a field, not unlike gravity. In the presence of life, this field acquires complexity, resulting in negative entropy if that makes sense. This gain in complexity is directly correlated with the concentration of living organisms in a given location. With time, and with the right conditions, life in turn becomes more complex until the appearance of sentient life. After reaching this threshold, the field begins to express itself through these sentient beings, forming what we call the soul. Through their life experiences, sentient beings will in turn influence the field in a sort of positive feedback loop. This in turn further accelerates the complexity of the field. Eventually, when the field reaches a "critical mass", there will be a sort of apotheosis. It's not clear what this means in practical terms, but this quest for apotheosis seems to be the EBOs main motivation.
The author of the document added his reflections and interpretations as an appendix. He specified that, for them, the soul field is not a belief but an obvious truth. He also argues that the soul loses its individuality after death, but that memory and experience persist as part of the field. This fact would influence the philosophy and culture of EBOs, resulting in a society that doesn't fear death but which places no importance or reverence on individuality. This "belief" compels them to seed life, shape it, nurture it, monitor it and influence it for the ultimate purpose of creating this apotheosis. Paradoxically, they have little or no respect for an individual's well-being.
Please be advised that I'm speaking from memory of something I read more than 10 years ago, so take the following with a grain of salt. Also, I'm not a philosopher or an artist, so please excuse my struggle to properly formulate the concepts and my dry terminology. Finally, note that this information comes from a document whose author was directly interacting with an EBO. It is not specified whether it was an ambassador, a crash survivor, a prisoner. The means of communication were not specified either.
Question 4: Wtf he dropped the location of the lab
Battelle National Biodefense Institute. It is on google map
submitted by NoEstablishment5984 to LandoranEmpire [link] [comments]
From the late 2000s to the mid-2010s, I worked as a molecular biologist for a national security contractor in a program to study Exo-Biospheric-Organisms (EBO). The aim of the program was to elucidate the genome and proteome basis of these organisms. Although the study of OBCs has been going on for decades in other programs, the new high-throughput DNA sequencing technologies of the late 90s unblocked stagnant research in this area. Since then, several breakthroughs have led to significant advances in our understanding of the genome and proteome of these beings. What we've learned so far has enabled us to outline some disconcerting perspectives about our place in this universe. Briefly, we've discovered that the EBO genome is a chimera of genomes from our biosphere and from an unknown one. They are artificial, ephemeral and disposable organisms created for a purpose that still partially eludes us. I'll be substantiating my statements after a brief introduction.
The reason for disclosing these secrets is quite simple. I believe that every human being has the right to know the truth, and that to progress, humanity needs to divest itself of certain institutions and organizations that will probably not survive these revelations in the long term. I'm aware that I'll have very little impact in this regard, but I still believe that small leaks are necessary to break the dam of misinformation on this subject. When the governments will eventually reveal these secrets, there will undoubtedly be a societal upheaval, but in my opinion, the longer we wait, the worse it will be. I choose to divulge what I know anonymously out of selfishness for the well-being of myself and my family. I'm aware that this diminishes the reach and credibility of my message, but it's the furthest I am willing to go. I chose this forum because it offers a good compromise between anonymity and popularity. In order to protect my anonymity, I will be purposely vague or even contradictory about any information that could identify me (date, education, role etc.). I'll even introduce red herrings in this respect. I want to make it clear that any information related to the subject of the research will not be treated in this way.
Before going any further, please excuse me if you find it difficult to understand what I'm explaining. Some parts of my text are very technical. It's difficult to find the right balance between vulgarization and scientific explanation. I'll continue by talking about myself. What's the point of talking about me knowing that the information will necessarily be misleading? I simply want to introduce a perspective on the type of people who work there, normal scientists. I have a Ph.D. in molecular biology. I didn't actively seek to be part of this program, rather it was a stroke of luck that introduced me to one of the senior scientists. I met this person at a conference where I was presenting a poster on my Ph.D. research. When I think back, I don't believe he was impressed by what I was presenting, because it was quite frankly a project that wasn't going anywhere. I think it was rather the most important aspect of a professional life: the attitude and the ease with which you make connections. Shortly afterwards, I graduated and received a call from this person offering me a position. At the time, everything pointed to me working in a regular laboratory.
I did a series of three increasingly suspicious interviews, each in a different location, where my scientific background and knowledge became less and less relevant. The first was with two of the senior scientists, the second and third with people I've never seen again and who were obviously not interested in science. Sometime after the interview, I was asked to go to a fourth location where what seemed like a corporate lawyer presented me with an NDA. He made sure not only to explain every detail, but also that I understood the consequence of not respecting it.
The first Employment weeks were by far the most memorable, although I spent most of that time in a depressing archive room. It consists almost exclusively of reading about the subject of study and to get us up to speed. There's no secret Wikipedia or even a reference book to guide us. There are only dry reports, memos, presentations, procedures and SOPs. These documents are almost exclusively about the biology of EBOs, but there are also a few that deal with other subjects such as their food, religion or culture. There were no documents on their technology.
As mentioned above, the aim of the project is to gain a better understanding of the EBO genome and proteome. To achieve this, a team of around twenty scientists, four senior scientists and a director was involved. The scientists, like myself, had as their main responsibility to carry out the technical work. As each scientist had to my knowledge a Ph.D., we were all somewhat overqualified for what is ultimately a technician's job. The senior scientists, who make full use of their diplomas, had the task of designing the assays and had a supervisory responsibility. They were also in charge of training new employees, and sometimes even came in to do technical work. The director, of course, was the person in charge who dictated priorities to the senior scientists. He was rarely on site, and the few times he was, it was to attend meetings. Other than the scientific staff, there were security guards working for one subcontractor or another. There were no support staff such as janitors or maintenance workers. Scientists were responsible for this kind of work. In addition, logistical constraints ensure that every scientist is capable of carrying out any technical activity.
The laboratory itself is located in Fort Detrick, Maryland, in a building used for legitimate biomedical research. The clandestine operations are carried out in a restricted part of the basement, out of sight from regular workers. Contrary to what one might imagine, the biosafety level is not maximal for this type of research. Indeed, the lab containing EBO samples or derived cell cultures is BSL3, while the lab where assays are conducted are only BSL2. The BSL3 area of the facility includes a freezer room and a cell culture lab and is only accessible through an antechamber from the BSL2 section. EBO carcasses are preserved in horizontal freezers at a temperature of -80°C nominal. To maximize the preservation of these carcasses, they are preserved in vacuum bags and the air in the room is controlled to minimize humidity. There are only four bodies and none of them are complete. It's obvious that these creatures have died as a result of major trauma. I've never witnessed a motorcycle accident fatality, but it probably looks similar to this. It is acknowledged that there are more EBOs caracasses at other locations. The cell culture laboratory, as its name suggests, is where cell lines derived from EBOs are grown and related activities are performed. I'll talk in more detail about these specific cell lines later on. The BSL2 part is mainly used for assays, immunohistochemistry, genetic engineering, immunocytochemistry, storage etc. There's also a cell culture lab, but this is used for more traditional cell lines. Other than the labs, there are all the amenities you could find in an office. Note that the internet access is limited to senior staff and up. There is, however, an intranet for bioinformatics needs.
On the subject of the biology of these beings, I'll start by discussing genetics, then their gross anatomy and finally their biological systems. For the sake of clarity, the information that I provide here is an aggregation of what I have observed and what I have read. I will make many comparisons with human anatomy because it is the most logical reference.
Genetics:
First, I'd like to discuss their genetics. Their genetics are like ours, based on DNA. This fact was very puzzling for me when I first learned about it. We imagine that beings from an alternate biosphere would have genetics based on a completely foreign biochemical system and surprisingly, this is not the case. Several conclusions can be drawn from this surprising revelation. The one that immediately comes to mind is that our biosphere and theirs share a common ancestry. They're eukaryotes, which means their cells have nuclei containing genetic material. Which suggests that their biosphere would have been separated from ours sometime after the appearance of this type of organism. The term Exo-Biospheric-Organism is actually a misnomer, but as it's a historical term, it's still used. Their genetics are not only based on the same genetic system, but they’re also even compatible with our own cellular machinery. This means that you can take a human gene and insert it into an EBO cell, and that gene will be translated into protein, and this of course works in reverse with a human gene inserted into an EBO cell. There are important differences in post-translational modifications that will make the final protein non-functional, but I'll discuss these later. Their genome consists of 16 circular chromosomes.
You're probably familiar with the concept of intergenic region or "junk DNA". These are basically DNA sequences that don't code for proteins. These are evolutionary residues, transposons, inactivated genes and so on. To give you an idea, in humans, intergenic regions represent approximately 99% of our genome. I'm aware that these sequences aren't completely useless, they can be used as histone anchors, as buffers to protect coding DNA from radiation or even as alternative open reading frames, but that's rather peripheral.
What's particularly striking about the EBO genome is the uniformity of these intergenic regions. We see the same sequences repeated everywhere, and the distance in bp between the genes is virtually the same throughout their genome. The result is a minimalist, highly condensed genome. In fact, it's much smaller than ours. Moreover, the quantity of protein-coding genes is even significantly lower than ours, probably due to genetic refinement but also to biological processes that are absent in EBO. The uniformity of these sequences is a major indication of the artificiality of these beings. There is no complex organism on earth that has such elegance in its sequences. There is no evolutionary pressure that can lead to this kind of characteristic other than genetic engineering.
Speaking of genetic engineering, following sequencing of their genomes, we noticed a troubling and universal characteristic in the 5' of the regulatory sequence of each gene which we call the Tri-Palindromic Region. The TPR are 134bp sequences containing, as its name suggests, 3 palindromes. In genetics, a palindrome is a DNA sequence that when read in the same direction, gives the same sequence on both DNA strands. They serve both as a flag and as a binding site for proteins. The three palindromes in the TPR are distinct from one another and have been poetically named "5'P TPR", "M TPR" and "3' TPR". The TPR is composed (in 5' - 3' order) of 5'P TPR, 12bp spacer, Chromosomal address, 12bp spacer, M TPR, 12bp spacer, Gene address, 12pb spacer and 3' TPR. The chromosomal address is composed of 4 bp and is identical in each TPR of the same chromosome, but distinct between each of the 16 chromosomes of the genome. The Gene address is a 64bp sequence that is unique for each gene in the whole genome. It's therefore understandable that the TPR serves as a unique address not only for numerically identifying a gene, but also for identifying its chromosomal location. For those with only a basic knowledge of genetics, this is completely unheard of. No living thing in our biosphere has this kind of precise address in its genome. Once again, the presence of TPR cannot be explained by evolutionary pressure but only by genetic engineering on a genomic scale.
TPR opens the door to several possibilities. One of them suggests that EBO geneticists can insert or remove a gene from a cell in a way that is far more targeted and efficient than our technology allows. No proteins have been identified in the EBO genome that interacts with TPR. Rather, we believe that these proteins are exclusively targeted by external genetic engineering tools, probably used at the zygotic stage of embryonic development. The nature of these tools is unclear, but we definitely don't have anything like them. The probable absence of these proteins from the genome is a further indication of their artificiality. Given the high probability of artificiality of their genome and the apparent ease of modifying it with biomolecular tools, it's not out of the question that there could be polymorphism between individuals depending on their role and function. In other words, an individual could be genetically designed to have characteristics that give it an advantage in performing a given task, like soldier ants and worker ants in an anthill. Note that these previous statements are speculation. To my knowledge only one individual genome has been sequenced, I can't make a definitive statement on genetic variation between individuals.
I've talked a lot about intergenic regions, now I'll briefly discuss intragenic sequences. Briefly, because there's not a lot less to say despite its obvious importance. Much like ours, their genes have silencers, enhancers, promoters, 5'UTRs, exons, introns, 3' UTRs etc. There are many genes analogous to ours, which is not surprising given the compatibility of our cellular machinery. What's disturbing is that some genes correspond directly, nucleotide by nucleotide, with known human genes or even some animal genes. For these genes, there doesn't seem to be any artificial refinement but rather a crude copying and pasting. Why they do it is nebulous and still subject to conjecture. There are also many genes which are not found in our biosphere whose role has not been identified. Finding the purpose of these novel genes is one of the aims of the program. I'd like to note before going any further that this heterogeneity of genes of known and unknown origin is an undeniable proof of the artificiality of EBOs.
To conclude with genetics, the mitochondrial genome, at the time I was working there, had not yet been sequenced. It's safe to assume that this genome would also be streamlined and possibly has some version of TPR.
Transcription and translation and protein expression.
I briefly introduced the differences in post-translational modifications between human and EBO. This is hardly a surprise, as we often see the same thing between different terrestrial species. Obtaining a viable protein from a DNA sequence is a complex process involving hundreds of protein intermediates, each with a precise and essential role. A minor variation in this assembly line can lead to functional irregularities in the final product. So, it's no surprise that there are setbacks along the way when the first EBO gene transfection attempts failed to produce the desired functional protein in human cell lines. Fortunately for us, the work of what I imagine to be another team at another site has led to the development of an EBO cell line named EPI-G11 derived from epithelial tissues. With this tool in our hands, we were able to transfect and overexpress proteins of interest in order to eventually purify and study them. For your information, we use a biological ballistics delivery system (AKA gene gun) for our transfection needs because other methods are not very effective with cells of this line. For example, the viral vectors tested cannot be internalized by EPI-G11 and lipofection is too lethal. EPI-G11, like most eukaryotic cell lines, enters a phase of exponential growth when exposed to Fetal Bovine Serum. It's only half surprising that a cell line from such an exotic source should be sensitive to the growth factors present in FBS. In my opinion, this can be explained by the addition of animal genes to the genome, such as growth receptors.
Gross anatomy:
They are morphologically very similar to the grey aliens that are part of modern folklore. Their height is about 150cm, they have two arms, two legs and a head. Still, there are some notable differences.
Skin: The grey skin that is often described in folklore is in fact a biosynthetic film which, likely, serves to protect the EBO from a hostile environment. It doesn't provide effective protection against temperature changes, but it does offer adequate protection against the passage of liquids. It's possible that this film confers other advantages but my knowledge on the subject is limited. Under the grey film, the epidermis is rather white, and the texture is very regular and without any hair. We do not see any defect other than the folds near the joints. It's described as greasy in one report, but that's not something I've observed. The same report states that a strong, lingering smell of burnt hair and ammonia is present when the film is removed. There are a lot of pores on the skin, crossing from the epidermis to a gland in the hypodermis. These glands and pores are the terminal part of the excretory-sudoriferous system, which could explain the previously mentioned smell.
Head: The head contains two large, oversized eyes, two nostrils without protuberance, a narrow mouth without lips and two ear canals without auricles. There is a mandible, but the musculature is vestigial. There are no teeth or tongue in the oral cavity. The nasal cavity where the nostrils meet is compact and does not rise cranially but extends axially. There appears to be no equivalent to the olfactory bulb in the nasal cavity. The mouth leads directly to the esophagus and the nasal cavity to the trachea. The trachea and esophagus do not communicate.
Eye: Like the skin, the eyes are covered with a semi-transparent biosynthetic film that offers the same environmental protection, while providing protection against certain wavelengths and light intensity. When the film is removed, a more traditional eye is revealed. It's about three times larger than a human eye and there are no eyelids. The size of their eyes suggests they have excellent night vision. It seems paradoxical to cover them with a semi-opaque film. Perhaps they only need to wear it in a bright environment. Their sclera is the same color as their skin, the iris is pale grey, and the pupil is black and oversized. The lens is rounder than a human, and the musculature used to adjust focus is more developed. On the retina, there are at least 6 types of cone cells. The responsiveness of each of these 6 types of cone is specific to a wavelength band, with a minimum of overlap between each other. The result is a broader visible spectrum.
Ear: As mentioned, the outer ear has no auricle and the ear canal is unremarkable. The inner ear has all the characteristics of a typical vestibular and cochlear system, although the curvature of the cochlea is more pronounced than a human. This probably results in greater hearing acuity for low frequencies.
Brain: The brain is tetraspheric, i.e. composed of four major sections. The sections are separated by transverse and longitudinal fissures and are connected to the central lobe, which acts as brainstem and cerebellum. The volume of the brain is around 20% superior to that of a man of the same height. It has a much more pronounced level of gyrication than an average human. Moreover, the ratio of glial cells to neurons is also slightly higher than in humans. It is important to mention the presence of nodules on the central lobe. Histological analysis of these structures reveals a kind of intricate biological circuitry. It is speculated that these nodules are essential to interact with their technology. Consequently, determining the proteome of these structures is an absolute priority for the program.
Neck: The neck is proportionally longer than that of a human, and at the same time relatively thin. As mentioned, the esophagus and trachea are separate. There are no vocal cords in this region.
Thorax: The musculature of the thorax is underdeveloped. Muscles equivalent to the pectoralis major can be seen. We can also see the trapezius and deltoid muscles. The sternocleidomastoids are well defined. The ribs and sternum are clearly visible. There are no nipples.
Abdomen: The abdomen is wider than the thorax and bulges slightly forward. There is no navel.
Pelvis: The pelvic bones are apparent. There are no genitals or anus.
Hands and feets: Their hands have four digits, including an opposable thumb on the medial side. They have no nails, and the texture of their fingerprints is composed of concentric circles. Fingers are proportionally much longer than in humans. Unlike humans, finger musculature is entirely intrinsic to the hand. In other words, the muscles used to move the fingers are not in the forearms but entirely located in the hands. At first glance, the feet consist of just two digits, but a necropsy soon determined that each toe was made of two fused digits. The medial toe is marginally longer than the distal toe. The feet are relatively longer and narrower than in a human. Their musculature, however, is vestigial.
The EBOs endoskeleton is very similar to ours, at least in terms of composition. There's collagen, hydroxyapatite but also copper oxide crystals where marrow would normally be found. The role of these crystals has not been established, but it is not a crystalopathic condition. The blood cells of the myeloid lineage (or the equivalent for these creatures) therefore mature in a different location than in humans i.e. in the thymus like organ. A transverse section of the bone reveals osteon and osteocytes. There appear to be few osteoblasts and no osteoclasts. This indicates that the bones are no longer growing and cannot absorb the minerals present or adapt mechanically to changes in posture.
Biological system:
Respiratory system: Their cellular respiration is equivalent to ours, i.e. they need to oxidize organic components to produce energy. Their lungs have no reciprocating action, but rather have a unidirectional flow of air, similar to those seen in birds, which is more efficient than ours. It is speculated that this is in response to the brain's elevated metabolic needs. Vocalization is produced by vibration of the wall membrane at the junction between the two air sacs.
The Circulatory system of EBOs is rather analogous to ours. The heart is located in the mediastanum, but in a more medial position, directly beneath the sternum. The heart has two ventricles and two atria. There is an aorta, a pulmonary vein, a pulmonary artery and a vena cava. Blood flowing to the pulmonary capillaries via the pulmonary artery is pumped against the flow of air, maximizing gas exchange efficiency. The blood gas barrier is relatively narrow in these capillaries, at least compared to a human. Then oxygen-rich blood is returned to the heart and then expelled into the aorta and the rest of the body. Before returning to the heart, the blood will pass through the hepatorenal organ which, among other things, filters and controls osmotic pressure of the blood.
The blood itself is also analogous to that of a human. However, the proportion of plasma is much higher, albumin is in similar proportion ,hormone levels are much lower, metal ion levels are much higher (particularly copper) and glucose levels are significantly higher. The color of the blood is brownish, given the higher proportion of plasma and concentration of metal ions. On the cellular side, there are erythrocytes which, in addition to hemoglobin for binding oxygen, display several complexes capable of binding copper ions. It's not clear what role these copper ions play but we believe it neutralizes blood ammonia, among other things. Several cell types with leukocyte characteristics have been observed, but no comprehensive knowledge of them exists. Platelets are present, but in smaller proportions than in humans.
Excreto-sudoriferous system: This system is completely different from what I've seen. As mentioned earlier, there is no large orifice, like an anus or urethra, to get rid of biological waste. Instead, there are countless small pores on the surface of the skin. There's a large medial organ called the hepatorenal organ, which acts as both kidney and liver and is central to maintaining homeostasis. This organ is highly vascularized and the blood must pass through it before returning to the heart. Its role is, among other things, to purify the blood of metabolic waste. Waste is excreted into the equivalent of a ureter, which branches out into four. Each branch flows towards one of the four limbs and in turn these branches divide until they end up as thousands of excretory pores. The motility of this excretory system is mediated by a weak peristalsis at the proximal level and on the four main branches. Peristalsis ceases around the first distal junction. As there is no urea cycle, the ammonia concentration at the exit of the hepatorenal organ is very high. This ammonia is carried to the pores and gives the distinct odor I mentioned earlier. The rationale behind this unusual excretory system is directly related to this excreted ammonia, which enables thermoregulation by evaporating on the skin's surface. The greater the physical effort, the greater the metabolism. This in turn leads to a rise in temperature, and a corresponding increase in metabolic waste via amino acid catabolism. This leads to an increase in filtration and ammonia excretion, which ultimately lowers body temperature.
Digestive system: The digestive system is extremely underdeveloped. There's no there is no stomach in the familiar sense. However, there is a pseudo-stomach located at the transition between the thoracic and abdominal cavities. This organ is not involved in digestion, but only serves as a reservoir. A sphincter controls the flow of food into the intestine. The intestine is limited to the equivalent of our small intestine, i.e. it only serves to absorb liquids and nutrients and acts as the main digestion site. It has villi and microvilli like ours. The intestine ends in the hepato-renal organ, where non-digested matter is transported to the ureter and excretory system. Residues are dissolved in the ammonia of metabolic waste for excretion. There's an organ near the pseudostomachal sphincter that secretes digestive enzymes directly into the intestine. This organ is inspirationally called the digestive organ. It secretes mainly proteolytic enzymes and glycoside hydrolases.
Given the absence of teeth, the narrowness and rigidity of the esophagus, the absence of a true stomach and the absence of defecation, it is strongly believed that EBOs can only consume food in liquid form. It is assumed that, given the high metabolic needs of their brains, this food would have a high carbohydrate concentration. In order to meet other metabolic needs, there must also be a high protein content in the food consumed. These two statements are supported by the type of enzyme secreted by the digestive organ. It is therefore speculated that the food consumed is a sort of broth rich in sugar and protein, which probably also has a high copper content. Given the strict limitations on the type of food that they can consume, it's unlikely that this type of creature could survive in our biosphere without technological support.
Endocrine system: Knowledge of the endocrine system is minimal. We know that cells are receptive to bovine growth hormones, so it's assumed that certain functions are regulated by such a system. Endocrine mechanisms are very complex, and it goes without saying that they are best studied on living subjects.
Immune system: The immune system is another unknown. There seems to be an innate immune system but there doesn't seem to be any adaptive immunity, at least not similar to what is known. There's a thymus-like organ near the heart that's proportionally larger than in humans. This organ seems to be where all blood cells mature. Some cells have leukocyte characteristics such as granularity. The immune cells that germinate here have a high copper concentration. The surface receptors of innate immune cells have not yet been characterized, so we might as well say that all the work remains to be done.
Nervous system: The nervous system is also relatively similar. The spinal cord begins at the base of the central lobe of the brain and propagates down the vertebral column. In the vertebrae there are ganglia made of afferent and efferent neurons. In short, other than the CNS, there is nothing out of the ordinary.
Musculoskeletal system: The musculoskeletal system is very ordinary, albeit underdeveloped. Most of the human skeletal muscles have an equivalent. Only the hands, feet and forearms are different. It should be noted that the proportion of type 1 and type 2 muscle fibers is different from that in a human. Indeed, type 1 outnumbers type 2 by about a factor of 10.
Artificial system: We speculate that artificial molecular machines may be present in the body, and that copper, if present, would be essential to their function or assembly. Importantly, no AMMs have been observed.
Question 1: Amazing story. Have you shared this with the Senate Select Commission on Intelligence or with AARO and do you have evidence to back this up?
Thank you, no I haven't and no I won't. It sounds like a honey trap to me. I will not place my life in the hands of politicians. I have no proof other than this message. I know it's not much but it's what I'm prepared to offer
Question 2: Well that was a read ... So they are bio engineered worker bees... Any elemental components that are unutributal to our biome ?
Yes, knowing that they're disposable, unable to live independently without technological support, and that they're ephemeral. The only suitable hypothesis is that they are alive only to accomplish their task. Can you clarify your question about elemental components?
Question 3: I havent read everything in detail but can you expend on the document on their religion?
EBOs believe that the soul is not an extension of the individual, but rather a fundamental characteristic of nature that expresses itself as a field, not unlike gravity. In the presence of life, this field acquires complexity, resulting in negative entropy if that makes sense. This gain in complexity is directly correlated with the concentration of living organisms in a given location. With time, and with the right conditions, life in turn becomes more complex until the appearance of sentient life. After reaching this threshold, the field begins to express itself through these sentient beings, forming what we call the soul. Through their life experiences, sentient beings will in turn influence the field in a sort of positive feedback loop. This in turn further accelerates the complexity of the field. Eventually, when the field reaches a "critical mass", there will be a sort of apotheosis. It's not clear what this means in practical terms, but this quest for apotheosis seems to be the EBOs main motivation.
The author of the document added his reflections and interpretations as an appendix. He specified that, for them, the soul field is not a belief but an obvious truth. He also argues that the soul loses its individuality after death, but that memory and experience persist as part of the field. This fact would influence the philosophy and culture of EBOs, resulting in a society that doesn't fear death but which places no importance or reverence on individuality. This "belief" compels them to seed life, shape it, nurture it, monitor it and influence it for the ultimate purpose of creating this apotheosis. Paradoxically, they have little or no respect for an individual's well-being.
Please be advised that I'm speaking from memory of something I read more than 10 years ago, so take the following with a grain of salt. Also, I'm not a philosopher or an artist, so please excuse my struggle to properly formulate the concepts and my dry terminology. Finally, note that this information comes from a document whose author was directly interacting with an EBO. It is not specified whether it was an ambassador, a crash survivor, a prisoner. The means of communication were not specified either.
Question 4: Wtf he dropped the location of the lab
Battelle National Biodefense Institute. It is on google map
2023.07.06 14:27 MartianXAshATwelve [REPOST From r/Aliens] From the late 2000s to the mid-2010s, I worked as a molecular biologist for a national security contractor in a program to study Exo-Biospheric-Organisms (EBO). I will share with you a lot of information on this subject. Feel free to ask questions or ask for clarification
****Note*** This post was published on aliens But the user who posted it has now been suspended from the reddit. I am posting it on StrangeEarth so that we can have it in bulk. aliens mod cannot confirm the user identity but they are trying to contact him. I cannot post all the comments but leaving the link to original post so that you can check it.https://www.reddit.com/aliens/comments/14rp7w9/from_the_late_2000s_to_the_mid2010s_i_worked_as_a/
submitted by MartianXAshATwelve to StrangeEarth [link] [comments]
It seems like all my comments are being deleted. I will post answer at the end of the message.
From the late 2000s to the mid-2010s, I worked as a molecular biologist for a national security contractor in a program to study Exo-Biospheric-Organisms (EBO). The aim of the program was to elucidate the genome and proteome basis of these organisms. Although the study of OBCs has been going on for decades in other programs, the new high-throughput DNA sequencing technologies of the late 90s unblocked stagnant research in this area. Since then, several breakthroughs have led to significant advances in our understanding of the genome and proteome of these beings. What we've learned so far has enabled us to outline some disconcerting perspectives about our place in this universe. Briefly, we've discovered that the EBO genome is a chimera of genomes from our biosphere and from an unknown one. They are artificial, ephemeral and disposable organisms created for a purpose that still partially eludes us. I'll be substantiating my statements after a brief introduction.
The reason for disclosing these secrets is quite simple. I believe that every human being has the right to know the truth, and that to progress, humanity needs to divest itself of certain institutions and organizations that will probably not survive these revelations in the long term. I'm aware that I'll have very little impact in this regard, but I still believe that small leaks are necessary to break the dam of misinformation on this subject. When the governments will eventually reveal these secrets, there will undoubtedly be a societal upheaval, but in my opinion, the longer we wait, the worse it will be. I choose to divulge what I know anonymously out of selfishness for the well-being of myself and my family. I'm aware that this diminishes the reach and credibility of my message, but it's the furthest I am willing to go. I chose this forum because it offers a good compromise between anonymity and popularity. In order to protect my anonymity, I will be purposely vague or even contradictory about any information that could identify me (date, education, role etc.). I'll even introduce red herrings in this respect. I want to make it clear that any information related to the subject of the research will not be treated in this way.
Before going any further, please excuse me if you find it difficult to understand what I'm explaining. Some parts of my text are very technical. It's difficult to find the right balance between vulgarization and scientific explanation. I'll continue by talking about myself. What's the point of talking about me knowing that the information will necessarily be misleading? I simply want to introduce a perspective on the type of people who work there, normal scientists. I have a Ph.D. in molecular biology. I didn't actively seek to be part of this program, rather it was a stroke of luck that introduced me to one of the senior scientists. I met this person at a conference where I was presenting a poster on my Ph.D. research. When I think back, I don't believe he was impressed by what I was presenting, because it was quite frankly a project that wasn't going anywhere. I think it was rather the most important aspect of a professional life: the attitude and the ease with which you make connections. Shortly afterwards, I graduated and received a call from this person offering me a position. At the time, everything pointed to me working in a regular laboratory.
I did a series of three increasingly suspicious interviews, each in a different location, where my scientific background and knowledge became less and less relevant. The first was with two of the senior scientists, the second and third with people I've never seen again and who were obviously not interested in science. Sometime after the interview, I was asked to go to a fourth location where what seemed like a corporate lawyer presented me with an NDA. He made sure not only to explain every detail, but also that I understood the consequence of not respecting it.
The first Employment weeks were by far the most memorable, although I spent most of that time in a depressing archive room. It consists almost exclusively of reading about the subject of study and to get us up to speed. There's no secret Wikipedia or even a reference book to guide us. There are only dry reports, memos, presentations, procedures and SOPs. These documents are almost exclusively about the biology of EBOs, but there are also a few that deal with other subjects such as their food, religion or culture. There were no documents on their technology.
As mentioned above, the aim of the project is to gain a better understanding of the EBO genome and proteome. To achieve this, a team of around twenty scientists, four senior scientists and a director was involved. The scientists, like myself, had as their main responsibility to carry out the technical work. As each scientist had to my knowledge a Ph.D., we were all somewhat overqualified for what is ultimately a technician's job. The senior scientists, who make full use of their diplomas, had the task of designing the assays and had a supervisory responsibility. They were also in charge of training new employees, and sometimes even came in to do technical work. The director, of course, was the person in charge who dictated priorities to the senior scientists. He was rarely on site, and the few times he was, it was to attend meetings. Other than the scientific staff, there were security guards working for one subcontractor or another. There were no support staff such as janitors or maintenance workers. Scientists were responsible for this kind of work. In addition, logistical constraints ensure that every scientist is capable of carrying out any technical activity.
The laboratory itself is located in Fort Detrick, Maryland, in a building used for legitimate biomedical research. The clandestine operations are carried out in a restricted part of the basement, out of sight from regular workers. Contrary to what one might imagine, the biosafety level is not maximal for this type of research. Indeed, the lab containing EBO samples or derived cell cultures is BSL3, while the lab where assays are conducted are only BSL2. The BSL3 area of the facility includes a freezer room and a cell culture lab and is only accessible through an antechamber from the BSL2 section. EBO carcasses are preserved in horizontal freezers at a temperature of -80°C nominal. To maximize the preservation of these carcasses, they are preserved in vacuum bags and the air in the room is controlled to minimize humidity. There are only four bodies and none of them are complete. It's obvious that these creatures have died as a result of major trauma. I've never witnessed a motorcycle accident fatality, but it probably looks similar to this. It is acknowledged that there are more EBOs caracasses at other locations. The cell culture laboratory, as its name suggests, is where cell lines derived from EBOs are grown and related activities are performed. I'll talk in more detail about these specific cell lines later on. The BSL2 part is mainly used for assays, immunohistochemistry, genetic engineering, immunocytochemistry, storage etc. There's also a cell culture lab, but this is used for more traditional cell lines. Other than the labs, there are all the amenities you could find in an office. Note that the internet access is limited to senior staff and up. There is, however, an intranet for bioinformatics needs.
On the subject of the biology of these beings, I'll start by discussing genetics, then their gross anatomy and finally their biological systems. For the sake of clarity, the information that I provide here is an aggregation of what I have observed and what I have read. I will make many comparisons with human anatomy because it is the most logical reference.
Genetics:
First, I'd like to discuss their genetics. Their genetics are like ours, based on DNA. This fact was very puzzling for me when I first learned about it. We imagine that beings from an alternate biosphere would have genetics based on a completely foreign biochemical system and surprisingly, this is not the case. Several conclusions can be drawn from this surprising revelation. The one that immediately comes to mind is that our biosphere and theirs share a common ancestry. They're eukaryotes, which means their cells have nuclei containing genetic material. Which suggests that their biosphere would have been separated from ours sometime after the appearance of this type of organism. The term Exo-Biospheric-Organism is actually a misnomer, but as it's a historical term, it's still used. Their genetics are not only based on the same genetic system, but they’re also even compatible with our own cellular machinery. This means that you can take a human gene and insert it into an EBO cell, and that gene will be translated into protein, and this of course works in reverse with a human gene inserted into an EBO cell. There are important differences in post-translational modifications that will make the final protein non-functional, but I'll discuss these later. Their genome consists of 16 circular chromosomes.
You're probably familiar with the concept of intergenic region or "junk DNA". These are basically DNA sequences that don't code for proteins. These are evolutionary residues, transposons, inactivated genes and so on. To give you an idea, in humans, intergenic regions represent approximately 99% of our genome. I'm aware that these sequences aren't completely useless, they can be used as histone anchors, as buffers to protect coding DNA from radiation or even as alternative open reading frames, but that's rather peripheral.
What's particularly striking about the EBO genome is the uniformity of these intergenic regions. We see the same sequences repeated everywhere, and the distance in bp between the genes is virtually the same throughout their genome. The result is a minimalist, highly condensed genome. In fact, it's much smaller than ours. Moreover, the quantity of protein-coding genes is even significantly lower than ours, probably due to genetic refinement but also to biological processes that are absent in EBO. The uniformity of these sequences is a major indication of the artificiality of these beings. There is no complex organism on earth that has such elegance in its sequences. There is no evolutionary pressure that can lead to this kind of characteristic other than genetic engineering.
Speaking of genetic engineering, following sequencing of their genomes, we noticed a troubling and universal characteristic in the 5' of the regulatory sequence of each gene which we call the Tri-Palindromic Region. The TPR are 134bp sequences containing, as its name suggests, 3 palindromes. In genetics, a palindrome is a DNA sequence that when read in the same direction, gives the same sequence on both DNA strands. They serve both as a flag and as a binding site for proteins. The three palindromes in the TPR are distinct from one another and have been poetically named "5'P TPR", "M TPR" and "3' TPR". The TPR is composed (in 5' - 3' order) of 5'P TPR, 12bp spacer, Chromosomal address, 12bp spacer, M TPR, 12bp spacer, Gene address, 12pb spacer and 3' TPR. The chromosomal address is composed of 4 bp and is identical in each TPR of the same chromosome, but distinct between each of the 16 chromosomes of the genome. The Gene address is a 64bp sequence that is unique for each gene in the whole genome. It's therefore understandable that the TPR serves as a unique address not only for numerically identifying a gene, but also for identifying its chromosomal location. For those with only a basic knowledge of genetics, this is completely unheard of. No living thing in our biosphere has this kind of precise address in its genome. Once again, the presence of TPR cannot be explained by evolutionary pressure but only by genetic engineering on a genomic scale.
TPR opens the door to several possibilities. One of them suggests that EBO geneticists can insert or remove a gene from a cell in a way that is far more targeted and efficient than our technology allows. No proteins have been identified in the EBO genome that interacts with TPR. Rather, we believe that these proteins are exclusively targeted by external genetic engineering tools, probably used at the zygotic stage of embryonic development. The nature of these tools is unclear, but we definitely don't have anything like them. The probable absence of these proteins from the genome is a further indication of their artificiality. Given the high probability of artificiality of their genome and the apparent ease of modifying it with biomolecular tools, it's not out of the question that there could be polymorphism between individuals depending on their role and function. In other words, an individual could be genetically designed to have characteristics that give it an advantage in performing a given task, like soldier ants and worker ants in an anthill. Note that these previous statements are speculation. To my knowledge only one individual genome has been sequenced, I can't make a definitive statement on genetic variation between individuals.
I've talked a lot about intergenic regions, now I'll briefly discuss intragenic sequences. Briefly, because there's not a lot less to say despite its obvious importance. Much like ours, their genes have silencers, enhancers, promoters, 5'UTRs, exons, introns, 3' UTRs etc. There are many genes analogous to ours, which is not surprising given the compatibility of our cellular machinery. What's disturbing is that some genes correspond directly, nucleotide by nucleotide, with known human genes or even some animal genes. For these genes, there doesn't seem to be any artificial refinement but rather a crude copying and pasting. Why they do it is nebulous and still subject to conjecture. There are also many genes which are not found in our biosphere whose role has not been identified. Finding the purpose of these novel genes is one of the aims of the program. I'd like to note before going any further that this heterogeneity of genes of known and unknown origin is an undeniable proof of the artificiality of EBOs.
To conclude with genetics, the mitochondrial genome, at the time I was working there, had not yet been sequenced. It's safe to assume that this genome would also be streamlined and possibly has some version of TPR.
Transcription and translation and protein expression.
I briefly introduced the differences in post-translational modifications between human and EBO. This is hardly a surprise, as we often see the same thing between different terrestrial species. Obtaining a viable protein from a DNA sequence is a complex process involving hundreds of protein intermediates, each with a precise and essential role. A minor variation in this assembly line can lead to functional irregularities in the final product. So, it's no surprise that there are setbacks along the way when the first EBO gene transfection attempts failed to produce the desired functional protein in human cell lines. Fortunately for us, the work of what I imagine to be another team at another site has led to the development of an EBO cell line named EPI-G11 derived from epithelial tissues. With this tool in our hands, we were able to transfect and overexpress proteins of interest in order to eventually purify and study them. For your information, we use a biological ballistics delivery system (AKA gene gun) for our transfection needs because other methods are not very effective with cells of this line. For example, the viral vectors tested cannot be internalized by EPI-G11 and lipofection is too lethal. EPI-G11, like most eukaryotic cell lines, enters a phase of exponential growth when exposed to Fetal Bovine Serum. It's only half surprising that a cell line from such an exotic source should be sensitive to the growth factors present in FBS. In my opinion, this can be explained by the addition of animal genes to the genome, such as growth receptors.
Gross anatomy:
They are morphologically very similar to the grey aliens that are part of modern folklore. Their height is about 150cm, they have two arms, two legs and a head. Still, there are some notable differences.
Skin: The grey skin that is often described in folklore is in fact a biosynthetic film which, likely, serves to protect the EBO from a hostile environment. It doesn't provide effective protection against temperature changes, but it does offer adequate protection against the passage of liquids. It's possible that this film confers other advantages but my knowledge on the subject is limited. Under the grey film, the epidermis is rather white, and the texture is very regular and without any hair. We do not see any defect other than the folds near the joints. It's described as greasy in one report, but that's not something I've observed. The same report states that a strong, lingering smell of burnt hair and ammonia is present when the film is removed. There are a lot of pores on the skin, crossing from the epidermis to a gland in the hypodermis. These glands and pores are the terminal part of the excretory-sudoriferous system, which could explain the previously mentioned smell.
Head: The head contains two large, oversized eyes, two nostrils without protuberance, a narrow mouth without lips and two ear canals without auricles. There is a mandible, but the musculature is vestigial. There are no teeth or tongue in the oral cavity. The nasal cavity where the nostrils meet is compact and does not rise cranially but extends axially. There appears to be no equivalent to the olfactory bulb in the nasal cavity. The mouth leads directly to the esophagus and the nasal cavity to the trachea. The trachea and esophagus do not communicate.
Eye: Like the skin, the eyes are covered with a semi-transparent biosynthetic film that offers the same environmental protection, while providing protection against certain wavelengths and light intensity. When the film is removed, a more traditional eye is revealed. It's about three times larger than a human eye and there are no eyelids. The size of their eyes suggests they have excellent night vision. It seems paradoxical to cover them with a semi-opaque film. Perhaps they only need to wear it in a bright environment. Their sclera is the same color as their skin, the iris is pale grey, and the pupil is black and oversized. The lens is rounder than a human, and the musculature used to adjust focus is more developed. On the retina, there are at least 6 types of cone cells. The responsiveness of each of these 6 types of cone is specific to a wavelength band, with a minimum of overlap between each other. The result is a broader visible spectrum.
Ear: As mentioned, the outer ear has no auricle and the ear canal is unremarkable. The inner ear has all the characteristics of a typical vestibular and cochlear system, although the curvature of the cochlea is more pronounced than a human. This probably results in greater hearing acuity for low frequencies.
Brain: The brain is tetraspheric, i.e. composed of four major sections. The sections are separated by transverse and longitudinal fissures and are connected to the central lobe, which acts as brainstem and cerebellum. The volume of the brain is around 20% superior to that of a man of the same height. It has a much more pronounced level of gyrication than an average human. Moreover, the ratio of glial cells to neurons is also slightly higher than in humans. It is important to mention the presence of nodules on the central lobe. Histological analysis of these structures reveals a kind of intricate biological circuitry. It is speculated that these nodules are essential to interact with their technology. Consequently, determining the proteome of these structures is an absolute priority for the program.
Neck: The neck is proportionally longer than that of a human, and at the same time relatively thin. As mentioned, the esophagus and trachea are separate. There are no vocal cords in this region.
Thorax: The musculature of the thorax is underdeveloped. Muscles equivalent to the pectoralis major can be seen. We can also see the trapezius and deltoid muscles. The sternocleidomastoids are well defined. The ribs and sternum are clearly visible. There are no nipples.
Abdomen: The abdomen is wider than the thorax and bulges slightly forward. There is no navel.
Pelvis: The pelvic bones are apparent. There are no genitals or anus.
Hands and feets: Their hands have four digits, including an opposable thumb on the medial side. They have no nails, and the texture of their fingerprints is composed of concentric circles. Fingers are proportionally much longer than in humans. Unlike humans, finger musculature is entirely intrinsic to the hand. In other words, the muscles used to move the fingers are not in the forearms but entirely located in the hands. At first glance, the feet consist of just two digits, but a necropsy soon determined that each toe was made of two fused digits. The medial toe is marginally longer than the distal toe. The feet are relatively longer and narrower than in a human. Their musculature, however, is vestigial.
The EBOs endoskeleton is very similar to ours, at least in terms of composition. There's collagen, hydroxyapatite but also copper oxide crystals where marrow would normally be found. The role of these crystals has not been established, but it is not a crystalopathic condition. The blood cells of the myeloid lineage (or the equivalent for these creatures) therefore mature in a different location than in humans i.e. in the thymus like organ. A transverse section of the bone reveals osteon and osteocytes. There appear to be few osteoblasts and no osteoclasts. This indicates that the bones are no longer growing and cannot absorb the minerals present or adapt mechanically to changes in posture.
Biological system:
Respiratory system: Their cellular respiration is equivalent to ours, i.e. they need to oxidize organic components to produce energy. Their lungs have no reciprocating action, but rather have a unidirectional flow of air, similar to those seen in birds, which is more efficient than ours. It is speculated that this is in response to the brain's elevated metabolic needs. Vocalization is produced by vibration of the wall membrane at the junction between the two air sacs.
The Circulatory system of EBOs is rather analogous to ours. The heart is located in the mediastanum, but in a more medial position, directly beneath the sternum. The heart has two ventricles and two atria. There is an aorta, a pulmonary vein, a pulmonary artery and a vena cava. Blood flowing to the pulmonary capillaries via the pulmonary artery is pumped against the flow of air, maximizing gas exchange efficiency. The blood gas barrier is relatively narrow in these capillaries, at least compared to a human. Then oxygen-rich blood is returned to the heart and then expelled into the aorta and the rest of the body. Before returning to the heart, the blood will pass through the hepatorenal organ which, among other things, filters and controls osmotic pressure of the blood.
The blood itself is also analogous to that of a human. However, the proportion of plasma is much higher, albumin is in similar proportion ,hormone levels are much lower, metal ion levels are much higher (particularly copper) and glucose levels are significantly higher. The color of the blood is brownish, given the higher proportion of plasma and concentration of metal ions. On the cellular side, there are erythrocytes which, in addition to hemoglobin for binding oxygen, display several complexes capable of binding copper ions. It's not clear what role these copper ions play but we believe it neutralizes blood ammonia, among other things. Several cell types with leukocyte characteristics have been observed, but no comprehensive knowledge of them exists. Platelets are present, but in smaller proportions than in humans.
Excreto-sudoriferous system: This system is completely different from what I've seen. As mentioned earlier, there is no large orifice, like an anus or urethra, to get rid of biological waste. Instead, there are countless small pores on the surface of the skin. There's a large medial organ called the hepatorenal organ, which acts as both kidney and liver and is central to maintaining homeostasis. This organ is highly vascularized and the blood must pass through it before returning to the heart. Its role is, among other things, to purify the blood of metabolic waste. Waste is excreted into the equivalent of a ureter, which branches out into four. Each branch flows towards one of the four limbs and in turn these branches divide until they end up as thousands of excretory pores. The motility of this excretory system is mediated by a weak peristalsis at the proximal level and on the four main branches. Peristalsis ceases around the first distal junction. As there is no urea cycle, the ammonia concentration at the exit of the hepatorenal organ is very high. This ammonia is carried to the pores and gives the distinct odor I mentioned earlier. The rationale behind this unusual excretory system is directly related to this excreted ammonia, which enables thermoregulation by evaporating on the skin's surface. The greater the physical effort, the greater the metabolism. This in turn leads to a rise in temperature, and a corresponding increase in metabolic waste via amino acid catabolism. This leads to an increase in filtration and ammonia excretion, which ultimately lowers body temperature.
Digestive system: The digestive system is extremely underdeveloped. There's no there is no stomach in the familiar sense. However, there is a pseudo-stomach located at the transition between the thoracic and abdominal cavities. This organ is not involved in digestion, but only serves as a reservoir. A sphincter controls the flow of food into the intestine. The intestine is limited to the equivalent of our small intestine, i.e. it only serves to absorb liquids and nutrients and acts as the main digestion site. It has villi and microvilli like ours. The intestine ends in the hepato-renal organ, where non-digested matter is transported to the ureter and excretory system. Residues are dissolved in the ammonia of metabolic waste for excretion. There's an organ near the pseudostomachal sphincter that secretes digestive enzymes directly into the intestine. This organ is inspirationally called the digestive organ. It secretes mainly proteolytic enzymes and glycoside hydrolases.
Given the absence of teeth, the narrowness and rigidity of the esophagus, the absence of a true stomach and the absence of defecation, it is strongly believed that EBOs can only consume food in liquid form. It is assumed that, given the high metabolic needs of their brains, this food would have a high carbohydrate concentration. In order to meet other metabolic needs, there must also be a high protein content in the food consumed. These two statements are supported by the type of enzyme secreted by the digestive organ. It is therefore speculated that the food consumed is a sort of broth rich in sugar and protein, which probably also has a high copper content. Given the strict limitations on the type of food that they can consume, it's unlikely that this type of creature could survive in our biosphere without technological support.
Endocrine system: Knowledge of the endocrine system is minimal. We know that cells are receptive to bovine growth hormones, so it's assumed that certain functions are regulated by such a system. Endocrine mechanisms are very complex, and it goes without saying that they are best studied on living subjects.
Immune system: The immune system is another unknown. There seems to be an innate immune system but there doesn't seem to be any adaptive immunity, at least not similar to what is known. There's a thymus-like organ near the heart that's proportionally larger than in humans. This organ seems to be where all blood cells mature. Some cells have leukocyte characteristics such as granularity. The immune cells that germinate here have a high copper concentration. The surface receptors of innate immune cells have not yet been characterized, so we might as well say that all the work remains to be done.
Nervous system: The nervous system is also relatively similar. The spinal cord begins at the base of the central lobe of the brain and propagates down the vertebral column. In the vertebrae there are ganglia made of afferent and efferent neurons. In short, other than the CNS, there is nothing out of the ordinary.
Musculoskeletal system: The musculoskeletal system is very ordinary, albeit underdeveloped. Most of the human skeletal muscles have an equivalent. Only the hands, feet and forearms are different. It should be noted that the proportion of type 1 and type 2 muscle fibers is different from that in a human. Indeed, type 1 outnumbers type 2 by about a factor of 10.
Artificial system: We speculate that artificial molecular machines may be present in the body, and that copper, if present, would be essential to their function or assembly. Importantly, no AMMs have been observed.
Question 1: Amazing story. Have you shared this with the Senate Select Commission on Intelligence or with AARO and do you have evidence to back this up?
Thank you, no I haven't and no I won't. It sounds like a honey trap to me. I will not place my life in the hands of politicians. I have no proof other than this message. I know it's not much but it's what I'm prepared to offer
Question 2: Well that was a read ... So they are bio engineered worker bees... Any elemental components that are unutributal to our biome ?
Yes, knowing that they're disposable, unable to live independently without technological support, and that they're ephemeral. The only suitable hypothesis is that they are alive only to accomplish their task. Can you clarify your question about elemental components?
Question 3: I havent read everything in detail but can you expend on the document on their religion?
EBOs believe that the soul is not an extension of the individual, but rather a fundamental characteristic of nature that expresses itself as a field, not unlike gravity. In the presence of life, this field acquires complexity, resulting in negative entropy if that makes sense. This gain in complexity is directly correlated with the concentration of living organisms in a given location. With time, and with the right conditions, life in turn becomes more complex until the appearance of sentient life. After reaching this threshold, the field begins to express itself through these sentient beings, forming what we call the soul. Through their life experiences, sentient beings will in turn influence the field in a sort of positive feedback loop. This in turn further accelerates the complexity of the field. Eventually, when the field reaches a "critical mass", there will be a sort of apotheosis. It's not clear what this means in practical terms, but this quest for apotheosis seems to be the EBOs main motivation.
The author of the document added his reflections and interpretations as an appendix. He specified that, for them, the soul field is not a belief but an obvious truth. He also argues that the soul loses its individuality after death, but that memory and experience persist as part of the field. This fact would influence the philosophy and culture of EBOs, resulting in a society that doesn't fear death but which places no importance or reverence on individuality. This "belief" compels them to seed life, shape it, nurture it, monitor it and influence it for the ultimate purpose of creating this apotheosis. Paradoxically, they have little or no respect for an individual's well-being.
Please be advised that I'm speaking from memory of something I read more than 10 years ago, so take the following with a grain of salt. Also, I'm not a philosopher or an artist, so please excuse my struggle to properly formulate the concepts and my dry terminology. Finally, note that this information comes from a document whose author was directly interacting with an EBO. It is not specified whether it was an ambassador, a crash survivor, a prisoner. The means of communication were not specified either.
Question 4: Wtf he dropped the location of the lab
Battelle National Biodefense Institute. It is on google map
2023.06.26 23:20 UsualAnnual9945 I'm Brazilian, and it seems that it was Doctor Italo Venturelli who operated on the creature. He uses metaphors...
At the end of the video, the doctor tells that he created a popular tale, called the universal, here it is:
link to the video: https://www.youtube.com/watch?v=CgzVQ4AEezY
link to Dr ítalo venturelli tale: https://www.ovnihoje.com/2023/06/26/um-jogo-de-xadrez-com-um-extraterrestre/
The Universal
Well, I'll start by saying that this short story is just a "fiction", based on a montage of reports and facts, about a chess game very different from the usual ones. I hesitated for many years to write this story.
There are some chess games with memorable titles, such as “Sempre Viva”, “Imortal”, so I decided to write “A Universal”.
Legend has it that back in the 90s, we had an unusual visit here in the city of Varginha. Suddenly, out of nowhere, two creatures appeared that were spotted by three city girls. After that there is a series of facts and reports, but for those of us who play and love the game of chess, I transformed all of that into what could have been the most extraordinary fact that ever happened to humanity.
From the already known… So I believe that the apparently oldest of the three had some kind of problem, let's say with his GPS. From what everything indicates and from the clinical examination, there was what we call, here in the medical field: signs of intracranial hypertension.
As its skull was larger than a human's, and practically translucent, a certain dilation of some structures was noted, which in certain aspects, resembled human ones.
The unbelievable thing is that even without speaking with the voice, the “conversation” was practically logical.
Another interesting feature was the fact that in humans, we have so-called lateral ventricles. We have two, which are located one on each side of the brain.” In it” we notice three, one being the larger of the two. From this larger ventricle, three types of canaliculi emerged, which led to the convexity, and which stood out in the frontal region, like horns to which some referred. To me they looked like sensitive receptors that communicated with your entire CNS.
I expose all this, so that from now on, we can talk about the relationship of this “fiction” with the game of chess.
As we are in the interior of Minas Gerais, and given the repercussions that this fact would bring, soon after carrying out the correction, a doubt arose: How to know if we have resolved the issue. We had the other 2, but one was very young, very small, and the other, quieter and barely moving, as if it had not adapted to our size.
Well then, due to the resources we had at the time, we decided to test it. But how to test something we don't know about. Ask you a question? Ridiculous; Even starting from the point of view that these Messrs. they know the human race well, having been around for a long time. We concluded testing it in a very simple way; How about a game of chess?
We know that to play chess you need a good memory, attention, reasoning, good nerves, in short, a good test would give you an idea if we could discharge you so that you could return. Well the question arises: Mr E, in question, did not know the rules.
We took Mr E to our chess club, which has existed here in the city since 1948, and which is located next to a replica of the spaceship, so that E would feel more at home.
Quiet, pleasant place where we could spend some time alone.
I had the privilege of explaining in detail what we were doing there.
Our fellow chess players were there to witness this historical fact, including my teacher Gerson Peres Batista, and friends: Carlos Alberto Rezende, Hugo Sérgio, Breim, Antonino, Rogério, Rita, Marco Salles, Zezo, Italinho, Leka, Divi, Jé , Lâ, Cabé, André, José Pedacinho do Céu, Ré, Regina, Sil, Miguel Giudicissi, my cousin Tito, Cesar das Combinations, Edson Kalaf, my father Mr Italo Venturelli, who taught me how to play, my uncle Ângelo, who taught me the sheikh in the open, whose board was the lid of the kitchen cupboard door, and who once took my beautiful Lady.
Our champion Adriano Caldeira was there, who encouraged me to write this text, and who, during the game, guided us on the nuances that appeared in this magical game.
Well, the “conversation” with E was interesting, because unlike us humans, who need, during speech, the movement of action and retroaction, to understand what was said, with him it seemed that when I said a word, he understood the meaning. close, literally as if there was an understanding on his part, of the word, even before it was sounded by me. For a moment I thought about not even talking, and just thinking, but as we were in more people and ES in the room, I decided to start talking.
Understood. Forward.
Between us, a true journey. Me playing white, and E black, after all he already knew my first move. So we went to the situation in which I inform the location of the pieces in their incredible and surprising ending.
White position: Kc3, B a6, Bb6, Nf4, Ng4, a7, h6
Black: Ka1, a2, h2
White plays Rc2, threatening mate with Be5++; Mr E played h1 pawn promotion being on the eighth square; Here Mr E requests: black king!! Well this is impossible, the pawn when it reaches its eighth square, it can be any piece, except the king, let alone a black king, I said.
Mr E- Well that's not what I understood; I did everything to have the strongest piece in the game, which is a king!
I thought with such an illustrious visitor as this one, I could not disagree, hence the question became very difficult, due to a paradox that could exist in our chess dimension. How to mate a king, if there was still another one in playable condition on the board.
Well, let's move on, after all, all this is already crazy.
Well, if I mate with Be5 I'll create a big problem, because I mate one and drown the other. Hence a draw? Or half a win? Is there half a win?
If Bb7, with mate in H, it drowns Ra1!
Well just imagined here. I followed A8 (I asked for another black king). What the hell is this now said Mr E, you humans are smart. Can this?
With the new rules, which are emerging now, this is possible, and even quite logical!
That leaves E, King b8. Single move for Black. Follows h7; Black's king goes again to a8, unique; Last and fantastic move, pawn h8 =White Queen, checkingmate the three black kings at the same time. Can this, asks E.
Under the new rules, yes, and we can see from your question, that Mr E can now move on, knowing that even reading our thoughts, he will never be able to predict our creativity.
Go with God Mr E. He promised he'd be back but saying he never was, just, just.
Don't ask me anymore, because it doesn't exist anymore; just the just. Incredible; and because for me; just at the time and place of need; fair. Like this.
submitted by UsualAnnual9945 to UFOs [link] [comments]
link to the video: https://www.youtube.com/watch?v=CgzVQ4AEezY
link to Dr ítalo venturelli tale: https://www.ovnihoje.com/2023/06/26/um-jogo-de-xadrez-com-um-extraterrestre/
The Universal
Well, I'll start by saying that this short story is just a "fiction", based on a montage of reports and facts, about a chess game very different from the usual ones. I hesitated for many years to write this story.
There are some chess games with memorable titles, such as “Sempre Viva”, “Imortal”, so I decided to write “A Universal”.
Legend has it that back in the 90s, we had an unusual visit here in the city of Varginha. Suddenly, out of nowhere, two creatures appeared that were spotted by three city girls. After that there is a series of facts and reports, but for those of us who play and love the game of chess, I transformed all of that into what could have been the most extraordinary fact that ever happened to humanity.
From the already known… So I believe that the apparently oldest of the three had some kind of problem, let's say with his GPS. From what everything indicates and from the clinical examination, there was what we call, here in the medical field: signs of intracranial hypertension.
As its skull was larger than a human's, and practically translucent, a certain dilation of some structures was noted, which in certain aspects, resembled human ones.
The unbelievable thing is that even without speaking with the voice, the “conversation” was practically logical.
Another interesting feature was the fact that in humans, we have so-called lateral ventricles. We have two, which are located one on each side of the brain.” In it” we notice three, one being the larger of the two. From this larger ventricle, three types of canaliculi emerged, which led to the convexity, and which stood out in the frontal region, like horns to which some referred. To me they looked like sensitive receptors that communicated with your entire CNS.
I expose all this, so that from now on, we can talk about the relationship of this “fiction” with the game of chess.
As we are in the interior of Minas Gerais, and given the repercussions that this fact would bring, soon after carrying out the correction, a doubt arose: How to know if we have resolved the issue. We had the other 2, but one was very young, very small, and the other, quieter and barely moving, as if it had not adapted to our size.
Well then, due to the resources we had at the time, we decided to test it. But how to test something we don't know about. Ask you a question? Ridiculous; Even starting from the point of view that these Messrs. they know the human race well, having been around for a long time. We concluded testing it in a very simple way; How about a game of chess?
We know that to play chess you need a good memory, attention, reasoning, good nerves, in short, a good test would give you an idea if we could discharge you so that you could return. Well the question arises: Mr E, in question, did not know the rules.
We took Mr E to our chess club, which has existed here in the city since 1948, and which is located next to a replica of the spaceship, so that E would feel more at home.
Quiet, pleasant place where we could spend some time alone.
I had the privilege of explaining in detail what we were doing there.
Our fellow chess players were there to witness this historical fact, including my teacher Gerson Peres Batista, and friends: Carlos Alberto Rezende, Hugo Sérgio, Breim, Antonino, Rogério, Rita, Marco Salles, Zezo, Italinho, Leka, Divi, Jé , Lâ, Cabé, André, José Pedacinho do Céu, Ré, Regina, Sil, Miguel Giudicissi, my cousin Tito, Cesar das Combinations, Edson Kalaf, my father Mr Italo Venturelli, who taught me how to play, my uncle Ângelo, who taught me the sheikh in the open, whose board was the lid of the kitchen cupboard door, and who once took my beautiful Lady.
Our champion Adriano Caldeira was there, who encouraged me to write this text, and who, during the game, guided us on the nuances that appeared in this magical game.
Well, the “conversation” with E was interesting, because unlike us humans, who need, during speech, the movement of action and retroaction, to understand what was said, with him it seemed that when I said a word, he understood the meaning. close, literally as if there was an understanding on his part, of the word, even before it was sounded by me. For a moment I thought about not even talking, and just thinking, but as we were in more people and ES in the room, I decided to start talking.
Understood. Forward.
Between us, a true journey. Me playing white, and E black, after all he already knew my first move. So we went to the situation in which I inform the location of the pieces in their incredible and surprising ending.
White position: Kc3, B a6, Bb6, Nf4, Ng4, a7, h6
Black: Ka1, a2, h2
White plays Rc2, threatening mate with Be5++; Mr E played h1 pawn promotion being on the eighth square; Here Mr E requests: black king!! Well this is impossible, the pawn when it reaches its eighth square, it can be any piece, except the king, let alone a black king, I said.
Mr E- Well that's not what I understood; I did everything to have the strongest piece in the game, which is a king!
I thought with such an illustrious visitor as this one, I could not disagree, hence the question became very difficult, due to a paradox that could exist in our chess dimension. How to mate a king, if there was still another one in playable condition on the board.
Well, let's move on, after all, all this is already crazy.
Well, if I mate with Be5 I'll create a big problem, because I mate one and drown the other. Hence a draw? Or half a win? Is there half a win?
If Bb7, with mate in H, it drowns Ra1!
Well just imagined here. I followed A8 (I asked for another black king). What the hell is this now said Mr E, you humans are smart. Can this?
With the new rules, which are emerging now, this is possible, and even quite logical!
That leaves E, King b8. Single move for Black. Follows h7; Black's king goes again to a8, unique; Last and fantastic move, pawn h8 =White Queen, checkingmate the three black kings at the same time. Can this, asks E.
Under the new rules, yes, and we can see from your question, that Mr E can now move on, knowing that even reading our thoughts, he will never be able to predict our creativity.
Go with God Mr E. He promised he'd be back but saying he never was, just, just.
Don't ask me anymore, because it doesn't exist anymore; just the just. Incredible; and because for me; just at the time and place of need; fair. Like this.
2023.05.21 08:35 FirefighterOk3804 Overexpression of the Androgen Receptor in the Brain leads to low distribution of DHT to peripheral tissues, and low expression of 5ar2 in periiheral tissues
We have 3 main 5ar enzymes in our bodies, 5ar1, 5ar2 and 5ar3. 5ar2 is predominantly expressed in the prostate, seminal vesicles, epididymis. In women its expressed predominantly in the fallopian, tubes, vagina and cervix. 5ar2 is the predominant enzyme for converting testosterone into DHT, especially within these tissues. Meaning it converts a lot of T into DHT within these tissues. In the prostate the 5ar2 enzyme is under the positive control of The androgen receptor (AR) meaning the more AR signalling the higher the expression of 5ar2 there.
Now if you look at the other isoenzymes 5ar1 and 3 it turns out depending on which tissues theyre in they are negatively regulated by testosterone and AR signalling. Especially in NEURAL tissue. Meaning the more testosterone and AR levels the lower the levels of the 5ar1 and 5ar3 enzymes. 5ar1 and 5ar3 are expressed almost ubiquitously throughout the body. And are highly expressed in the brain/CNS. What i think happens when you take an SSRI or go on a 5ar2 inhibitor you deplete androgen dependent tissues of DHT decreasing AR signalling in key tissues (I.e prostate). What this does is decrease the EXPRESSION of 5ar2 decreasing testosterone metabolism by 5ar2 in these key tissues. What i think happens then is that testosterone accumulates in other tissues ESPECIALLY in the Brain/CNS causing androgen receptor expression to be OVEREXPRESSED in neural tissue (the AR is positively regulated by androgens in neural tissue). What this does is it causes a profound decrease in the expression of the 5ar1 and/or the 5ar3 enzymes within the Brain. This has a dramatic effect for the rest of the body aswell. For example proper AR signalling within the brain has been shown in mice to be important for the myelination of nerves not only in the brain but in the peripheral nervous system aswell. It is has also been found that AR signalling in the brain increases muscle mass and strength in mice.
I have the speculation that the CNS/PNS plays a primary role in the distribution of DHT to peripheral tissues like muscle and especially androgen dependent tissues like the prostate/genitals. Where circulating T/DHT plays only a minor role in providing tissues with androgens. It may even be the case that the primary functioning of circulating testosterone, is to allow the CNS to convert T into DHT and distribute DHT throughout the body via proper functioning of 5ar within the CNS.
I think this distribution function via the CNS allows DHT to be delivered to androgen dependent tissues and help to MAINTAIN 5ar2 expression within these tissues. I speculate 5ar2 levels are very low within the genitals/prostate as a result of the low distribution of DHT to them via the nervous system. testosterone is 5-10 times higher in the brains of pfs victims vs controls. I think this is a sign of testosterone accumulating in the CNS unable to be converted to DHT and be delivered to peripheral tissues (especially the genitals and prostate) via the nervous system.
Its like 5ar in the brain is like a ‘tap’ which delivers dht to our tissues, and that ‘tap’ has been turned off.
As to why anti androgens crash us. I think when you take an anti A, you are decreasing AR signalling within key tissues such as the prostate or the fallopian tubes decreasing 5ar2 expression causing testosterone to accumulate within the brain which can trigger a crash or worsening of symptoms.
Anyway these are my thoughts. Its not complete but i think it can make sense of the strangeness of pfs/pssd, and the paradoxes of the condition.
Josh
submitted by FirefighterOk3804 to postfinasteridetheory [link] [comments]
Now if you look at the other isoenzymes 5ar1 and 3 it turns out depending on which tissues theyre in they are negatively regulated by testosterone and AR signalling. Especially in NEURAL tissue. Meaning the more testosterone and AR levels the lower the levels of the 5ar1 and 5ar3 enzymes. 5ar1 and 5ar3 are expressed almost ubiquitously throughout the body. And are highly expressed in the brain/CNS. What i think happens when you take an SSRI or go on a 5ar2 inhibitor you deplete androgen dependent tissues of DHT decreasing AR signalling in key tissues (I.e prostate). What this does is decrease the EXPRESSION of 5ar2 decreasing testosterone metabolism by 5ar2 in these key tissues. What i think happens then is that testosterone accumulates in other tissues ESPECIALLY in the Brain/CNS causing androgen receptor expression to be OVEREXPRESSED in neural tissue (the AR is positively regulated by androgens in neural tissue). What this does is it causes a profound decrease in the expression of the 5ar1 and/or the 5ar3 enzymes within the Brain. This has a dramatic effect for the rest of the body aswell. For example proper AR signalling within the brain has been shown in mice to be important for the myelination of nerves not only in the brain but in the peripheral nervous system aswell. It is has also been found that AR signalling in the brain increases muscle mass and strength in mice.
I have the speculation that the CNS/PNS plays a primary role in the distribution of DHT to peripheral tissues like muscle and especially androgen dependent tissues like the prostate/genitals. Where circulating T/DHT plays only a minor role in providing tissues with androgens. It may even be the case that the primary functioning of circulating testosterone, is to allow the CNS to convert T into DHT and distribute DHT throughout the body via proper functioning of 5ar within the CNS.
I think this distribution function via the CNS allows DHT to be delivered to androgen dependent tissues and help to MAINTAIN 5ar2 expression within these tissues. I speculate 5ar2 levels are very low within the genitals/prostate as a result of the low distribution of DHT to them via the nervous system. testosterone is 5-10 times higher in the brains of pfs victims vs controls. I think this is a sign of testosterone accumulating in the CNS unable to be converted to DHT and be delivered to peripheral tissues (especially the genitals and prostate) via the nervous system.
Its like 5ar in the brain is like a ‘tap’ which delivers dht to our tissues, and that ‘tap’ has been turned off.
As to why anti androgens crash us. I think when you take an anti A, you are decreasing AR signalling within key tissues such as the prostate or the fallopian tubes decreasing 5ar2 expression causing testosterone to accumulate within the brain which can trigger a crash or worsening of symptoms.
Anyway these are my thoughts. Its not complete but i think it can make sense of the strangeness of pfs/pssd, and the paradoxes of the condition.
Josh
2023.05.01 01:55 the_shek How do you differentiate between Cerebral Wasting Syndrome and Mineralocorticoid Deficiency?
Both are hypovolemic, hyponatremic, and hypotonic conditions.
Cerebral Wasting Syndrome is associated paradoxical polyuria and with CNS injuries including NSGY
Mineralocorticoid Deficiency has hyperkalemia (though I guess assume CWS would too?) and Non-Anion Gap Metabolic Acidosis (though I guess assume CWS would too?)
Is there any other way to think about this?
submitted by the_shek to Step2 [link] [comments]
Cerebral Wasting Syndrome is associated paradoxical polyuria and with CNS injuries including NSGY
Mineralocorticoid Deficiency has hyperkalemia (though I guess assume CWS would too?) and Non-Anion Gap Metabolic Acidosis (though I guess assume CWS would too?)
Is there any other way to think about this?
2023.03.13 16:45 Apart-Reference6751 Which Junji Ito book is your favorite?
 | submitted by Apart-Reference6751 to manga [link] [comments] |
2023.02.20 20:34 continentalgrip Within 30 minutes, balance improved and I was able to lift my essentially immobilized right arm straight up above my head for the first time in several years
(Edit: AH well here's the paper as opposed to copy paste. https://www.researchgate.net/publication/319094478_The_cause_of_multiple_sclerosis_is_autoimmune_attack_of_adenosyltransferase_thereby_limiting_adenosylcobalamin_production )
Paywall. Sorry about formatting. Guy says he sort of cured MS with adenosylcobalamin injections.
https://pubmed.ncbi.nlm.nih.gov/29150289/#:~:text=limiting%20adenosylcobalamin%20production-,The%20cause%20of%20multiple%20sclerosis%20is%20autoimmune%20attack%20of%20adenosyltransferase,Med%20Hypotheses.
abstract The pathogenesis of multiple sclerosis (MS) begins with an infection by a bacterium from the class of bacteria that produce and utilize adenosylcobalamin (AdoCbl) and possess an adenosyl transferase enzyme (ATR); these bacteria are the exogenous antigens that cause MS. Human ATR is homologous to bacterial ATR and B cells produce anti-ATR antibodies as an autoimmune response thereby reducing the concentration of ATR and thus limiting production of AdoCbl, one of the two bioactive forms of vitamin B12. The next step in MS pathogenesis is a period of subclinical AdoCbl deficiency over a period of many years resulting in production of odd-carbon-number fatty acids that are incorporated into myelin rendering it antigenic. The next step in MS pathogenesis is breach of the blood brain barrier thereby introducing leukocytes into the brain’s blood supply resulting in T cell attack of antigenic myelin. All epidemiological clusters are regions wherein the major agricultural products are legumes that produce a high percentage of odd-carbon-number fatty acids and contain symbiotic rhizobia type bacteria in root nodules and in the soil. This novel etiological hypothesis is called ‘‘multiple sclerosis due to adenosylcobalamin deficiency” (MS-AdoCbl). Creation of realistic animal models based on the MS-AdoCbl hypothesis is presented. Methods for testing predictions made by the MS-AdoCbl hypothesis are described.
Introduction Multiple sclerosis (MS) is a disease of the central nervous system (CNS), and the peripheral nervous system (PNS), (though difficult to distinguish from CNS causation), characterized by demyelination, formation of plaque lesions, damage to mitochondria with reduction of the ATP concentration, axonal degeneration, and with different forms or stages of MS defined by apparent clinical signs; the history of multiple sclerosis (MS) has been presented in introductory chapters of recent texts; Jean-Martin Charcot published the first comprehensive discussion in 1865 L’ Union Med 25:451–457, 467–472 (over 150 years ago) [1,2]. Attention to mitochondrial damage and its effects are more recent [3]. There has been much speculation on its etiology, thus books and journal articles typically state that the molecular events underlying MS are not known. Nevertheless, discussions on the possible etiology of MS and in depth speculation of its causes are available [4,5]. The MS-AdoCbl hypothesis The MS-AdoCbl hypothesis advocates that multiple sclerosis (MS) is caused by autoimmune attack of ATP:cob(I)alamin adenosyltransferase (referred to as adenosyltransferase or ATR) that converts cobalamins to the bioactive form 50 -deoxy-50 -adenosyl cobamide (adenosylcobalamin, Coenzyme B12 or AdoCbl). When the concentration of ATR is reduced the production of AdoCbl is limited resulting in metabolic changes that are pathological to the nervous system by causing myelin to become antigenic and this pathogenesis requires many years to develop. Introduction of leukocytes into the brain by breach of the blood brain barrier (or by other means) initiates immune attack of myelin causing the clinical signs of MS to manifest. Aspects of MS pathogenesis are related to deficiency of AdoCbl. The development of the MS-AdoCbl hypothesis Consideration of the similarity between subacute combined degeneration (SCD) and MS was instrumental in development of the MS-AdoCbl hypothesis and the existence of epidemiological hotspots argued for an exogenous antigen responsible for the development of MS. Bacteria that produce AdoCbl have ATR enzymes that are homologous to human ATR and thus infection https://doi.org/10.1016/j.mehy.2017.08.011 0306-9877/ 2017 The Author. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). ⇑ Corresponding author. E-mail address: boucher@cdsrllc.com URL: http://cdsrllc.com Medical Hypotheses 109 (2017) 29–37 Contents lists available at ScienceDirect Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy with such bacteria and immune response to them is the reason for MS being an autoimmune disease. The primary autoimmune attack is attack of ATR, located in mitochondria, resulting in production of odd-carbon-number compounds that are incorporated into myelin causing it to become antigenic; this would result from subclinical AdoCbl deficiency, extended over many years and accompanied by myelin turnover resulting in incorporation of antigenic compounds into myelin. Subsequently, a secondary immune attack of myelin occurs. The MS-AdoCbl hypothesis presents a new perspective for the etiology of MS since current views focus on attack of myelin as the primary immune response responsible for MS. This novel etiological hypothesis shall subsequently be referred to as the ‘‘multiple sclerosis due to adenosylcobalamin deficiency” (MS-AdoCbl) hypothesis, and was first published in the specification of US Patent Application No. 12/460,946 on Jan. 27, 2011. US Patent 8,691,790 (Patent790) describing therapy of MS issued April 8, 2014. The MS-AdoCbl hypothesis is the medical hypothesis and thesis of this article. A test of MS-AdoCbl hypothesis was therapy of MS with AdoCbl and success of the scoping experiments in therapy was the stimulus for writing a patent. This testing has been conducted on one MS patient for over ten years strongly supporting the hypothesis by providing substantial recovery from CNS symptoms of MS. AdoCbl therapy benefits PNS functions though not providing complete recovery nor does it provide recovery from mitochondrial damage and reduced ATP production.
Personal testing of the MS-AdoCbl hypothesis with AdoCbl therapy I was diagnosed with relapsing remitting multiple sclerosis (RRMS) in 1992 by Dr. J.S. Wolinsky who discussed MS with me regarding SCD presenting clinical signs and magnetic resonance imaging (MRI) similar to MS, although only SCD is responsive to B12 therapy. By 1997 stage change to secondary progressive multiple sclerosis (SPMS) was apparent. CNS and PNS symptoms progressed to include failure of working memory (with retention of less than five seconds) impaired cognition, slow processing, scanning speech, dystonia, paroxysmal spasms, gait disturbance, spasticity, dysarthria, loss of balance with frequent falls, heat stress, and other effects typical of MS [6]. As a clinically definite MS patient it was possible to test therapeutic methods on myself. Evaluation of therapy was a direct test of the proposed medical hypothesis. On 15 August 2006 I determined to pursue MS research myself and began to study the literature for MS. On 26 December 2006 I conceived an etiological hypothesis involving adenosyltransferase enzyme which converts cyanocobalamin (CNCbl) to AdoCbl, one of two bioactive forms of B12. I posited that the concentration of the adenosyltransferase enzyme (ATR) becomes reduced following autoimmune attack, thereby limiting production of AdoCbl, and leading to metabolic changes that are the initial pathogenesis of MS. It is worth noting that I found it necessary at that time to write on a notepad whatever was being considered, because my shortterm recall was so short. Given the etiological hypothesis that AdoCbl deficiency causes MS, a test of the hypothesis was evaluation of therapeutic benefit from AdoCbl parenterally administered, i.e., bypassing the need for the ATR enzyme. I determined to test my hypothesis by self-administration of AdoCbl. No U.S. Pharmacopeia (USP) grade, FDA approved injectable AdoCbl exists, though multiple sources of 97% AdoCbl were available for research purposes in vitro or with animals. A 3 mg/ml solution of AdoCbl in lactated Ringer’s solution was prepared and 1 ml was self-injected subcutaneously (sc) in the thigh 28 January 2007. The effects were pronounced and rapid. Within 5 min, recovery of memory and other improved cognitive abilities were apparent and my speech went from slow and labored to normal. Within 30 min, balance improved and I was able to lift my essentially immobilized right arm straight up above my head for the first time in several years. These effects, occurring mere minutes after injection, could only have resulted from direct action on nerves and not by means of anti-immune effects or myelin repair. Significantly, the effects described here of a single AdoCbl injection seemed to support the etiological hypothesis; the partial recovery from MS symptoms ostensibly resulted from neuroenhancement. No report of experimental AdoCbl therapy with humans for any reason was found. The patent literature showed that AdoCbl therapy had never been used and this led to the patent application and prosecution. For over 11 years, I carried out literature and laboratory research on my hypothesis, including regular injections (3–10 mg 5 weekly) of AdoCbl totaling ca. 9 g in 11 years. The results of this work show that AdoCbl therapy is effective, even life-changing, for treatment of a SPMS patient with therapy rationally based on the MSAdoCbl hypothesis. Epidemiology of MS In any study of the cause of a disease, it is important to assess common factors in identified clusters or ‘hotspots.’ Islands in the North Atlantic, including Iceland, Faroe, Orkney, and Shetland Islands constitute such epidemiological hotspots. Orkney Islands, had, in epidemiological studies conducted in 1974–1977, 309 cases of MS per 100,000 persons; in the Shetland Islands there were 184 cases of MS per 100,000 in 1974–1977; Orkney and Shetland islands represent the highest incidence rates for MS anywhere in the world and they also have the most cases of optic neuritis presenting as the initial symptom subsequently diagnosed as MS [7]. The agricultural products on these islands are pea, faba bean, lintil, grass pea, and chickpea all of which are legumes with rhizobia class bacteria in root nodules. [8] This is exceptional and may be the only location in the world having five or more major agricultural products that are legumes. These legumes form the staple diet of the islands and are predicted to contain a high percentage of odd-carbon-number fatty acids; this has not been specifically researched due to time constraints and could provide support for the MS-AdoCbl hypothesis once investigated. There is need for creation of a table of foods with percent odd-carbon-number fatty acids ranked from high to low content. The MS-AdoCbl hypothesis includes the concept that exogenous antigens responsible for eliciting the autoimmunogenic process producing MS are ATR-like enzymes contained in cobalamin- producing bacteria. In ‘‘Status of Cereal Cultivation in the North Atlantic Region” a map appears (page 12 of said article) showing these islands and describing cool weather legume cereal grains (likely containing odd-carbon-number fatty acids, etc.) as their principal agricultural products [9]. Another epidemiological hotspot, Olmstead County, Minnesota, with 160 cases per 100,000 is 2–3 times higher than the average in locations at that latitude [10]. Soybeans are the major agricultural product in Olmstead County with about 72,000 harvested acres of soybean [11]. Soybeans are legumes and Bradyrhizobium japonicum is the most common symbiotic bacteria [12]. The combination of local food rich in odd-carbon-number fatty acids that are legumes are predicted by the MS-AdoCbl hypothesis as factors producing epidemiological hotspots; the lowered AdoCbl concentration produces antigenic myelin from oddcarbon-number fatty acids. A bacterial PduO enzyme, homologous to human ATR, should produce a pronounced autoimmune response. Rhizobium and other bacteria found in legumes are predicted by (instrumental in the development of) the MS-AdoCbl hypothesis and contain conserved bacterial ATRs. Any cobalamin producing bacteria can be the exogenous antigen causing MS
although some bacteria are more efficient at causing MS. This multiplicity of exogenous antigens makes it difficult to identify a single bacterium as a highly significant exogenous antigen. Rhizobia bacteria have many ATP-binding cassette (ABC) transporters, e.g. Rhizobium leguminosarum has 183 ABC operons [13]. A study of bacterial genomes for bacteria found in legumes contains a phylogenetic tree of Rhizobial (and related bacteria) is presented (Fig. 1, pg. 616) in a study by Maclean et al. [14]. Nodule-producing bacteria are present in the soil even when crops other than legumes are grown in rotation. A person incurring a cut in such a field would be infected with bacteria common to legumes. There are many such bacteria possessing ATR-like enzymes, and each enzyme might be antigenic producing an immune response and antibodies that are cross-reactive to human ATR. Homology between a bacterial and a human ATR produces a stronger autoimmune response. Any bacterial IgG might or might not bind ATR strongly though a collection of IgGs have a cumulative effect and might bind ATR at different locations. Soil introduced into a cut will contain many different bacteria, not a single bacterium. The cumulative effect of infection with multiple cobalamin producing bacteria makes it difficult to identify a single exogenous antigen responsible for the development of MS. What is known, though, is that the ATR-like enzymes are from the class of bacteria producing AdoCbl. The higher risk in colder climates may be related to cobalamin metabolism and trafficking or differences in mitochondria since ATR is located within the inner membranes of mitochondria. Hypothetically a change in cobalamin metabolism (especially related to mitochondria) and trafficking occurs at puberty. These changes would be present in all persons as a function of average ambient temperatures and not MS patients alone. Possibly, the lower risk of MS in tropical regions is related to mitochondrial membrane thickness and mitochondrial membrane permeability investigations are needed. Another critical requirement in MS is BBB breach, which allows leukocytes with immune memory into the CNS blood system. No study of the BBB in relation to cobalamin trafficking proteins has yet appeared. Such a study, particularly one regarding populations residing at different latitudes, is obviously needed. Etiology of MS The MS-AdoCbl hypothesis describes a completely new understanding of the fundamental cause of MS. Rather than the current theories positing a generalized autoimmune assault on myelin brought on by some unknown immune-provoking event, the MSAdoCbl hypothesis cites autoimmune attack of ATR, reducing its concentration, and causing deficiency of AdoCbl as the main culprit initiating MS pathogenesis. The two bioactive forms of B12 are AdoCbl and methylcobalamin (MeCbl). MS pathogenesis follows AdoCbl deficiency which induces a cascade of metabolic changes wherein myelin becomes antigenic following metabolic turnover with antigenic structures incorporated into myelin. Metabolic turnover of polyphosphoinositides in myelin was studied by Eichberg and Dawson [15]. Davison and Gregson reported that turnover of a small fraction of myelin is rapid and the remaining fraction of myelin is metabolically stable with slow turnover [16]. Optic neuritis is a common presenting symptom and optic nerves likely have a rapid turnover rate; turnover could be studied with carbon-13 enriched foods followed by serial MRI. Development of antigenic myelin may take years to occur during which time the changes are subclinical. At some point the BBB happens to be breached allowing leukocytes to enter the blood supply in the brain and introducing leukocytes as markers in the CSF; the BBB breach may be the major immune provoking event. Normally, ATR with an adenosyl group from ATP converts B12 into AdoCbl. B12 deficiency can produce neurologic symptoms in SCD, similar to the symptoms of RRMS [17]. Left untreated, progressive spastic paraparesis and CNS impairments develop, with reversibility dependent upon the time elapsed before intervention with B12 [18]. Multiple sclerosis and B12 deficiency share many symptoms, including vision loss, muscle weakness, gait disturbances and cognitive impairment. Cobalamins are involved in myelin formation and repair while exerting immunomodulatory and neurotrophic effects. MRI studies of MS and SCD patients show striking similarities. B12 deficiency causes reduction of both bioactive forms, AdoCbl and MeCbl [19]. The MS-AdoCbl hypothesis predicts that the clinical signs of SCD and MS will be largely identical, having AdoCbl insufficiency as the basis for each. Aspects of MS are also indicative of a disturbance of MeCbl metabolism in the CNS, affecting anabolism, though slower to manifest clinical signs than AdoCbl deficiency and affecting protein synthesis and red blood cell maturation. This, according to MS-AdoCbl hypothesis, is because they both result from AdoCbl deficiency. If a SCD patient remains deficient in B12, the symptoms that manifest become similar to those of RRMS, again, for the simple reason that SCD and MS both result from an identical cause, deficiency of AdoCbl. If a SCD patient were not treated with B12 for years, the symptoms that would manifest are similar to symptoms of progressive MS; the reason SCD and progressive MS symptoms are similar is due to the cause for each being identical, deficiency of AdoCbl for an extended period of time. RRMS typically becomes SPMS and thus the two disease states are linked. Events precipitating AdoCbl deficiency in MS and SCD differ however, as shown in Fig. 1. In MS, autoimmune attack reduces the concentration of ATR and consequently AdoCbl. Because the clinical signs of SCD are easily recognized, laboratory tests are ordered without a long delay, revealing the underlying B12 deficiency, for which B12 is administered as a 1 mg intramuscular (im) injection [20]. This avenue of delivery has historically been preferred, possibly in order to take advantage of muscle tissue that provides a kind of timed release of the vitamin. From the perspective of MS-AdoCbl hypothesis and experimental MS therapy a sc injection between 4 mg and 8 mg AdoCbl might be preferred to rapidly supply AdoCbl to mitochondria and nerves. This also addresses the parallel requirement to replenish depleted cobalamin stores; no article discussing the importance of replenishing cobalamin stores in the liver or other tissues has been identified. The MS-AdoCbl hypothesis predicts depletion of stored AdoCbl, e.g., in the liver, a finding that awaits assessment in necroscopy liver samples from healthy individuals and MS patients, a key point. Paradoxically, administration of B12 is not helpful for a MS patient although SCD produces a similar MRI, since ATR deficiency prevents production of bioactive AdoCbl regardless of the concentration of B12 present. In therapy of SCD with B12, a common clinical mistake is to co-administer folic acid, which while lessening anemia, causes spinal cord lesions [21]. Administration
of folic acid further decreases the AdoCbl concentration by directing B12 along the pathway to MeCbl, rather than along the pathway to AdoCbl. Schubert and Hill published the crystal structure of ATP-bound human ATP:cob(I)alamin adenosyltransferase (ATR) along with bacterial PduO ATR enzymes showing its conserved AdoCbl binding sites and extensive homology, as shown in Fig. 2, and including an ATP binding site [22]. (This was isoform 239 K having lysine at position 239.) There are three types of adenosyltransferases (i.e. Cob-A-type, EuT-type, and PduO-type) based on structural similarity within a type; PduO is the most widely distributed and includes human, mammalian, and many bacterial ATRs. All have a common rotary mechanism of action [23]. Diverse ATRs are antigenic when crossing species by infection and therefore create an autoimmune response in the infected person (or animal). Autoimmune attack of ATR would be B-cell mediated, with exogenous antigens being ATR- like enzymes from the class of bacteria producing AdoCbl. Because the exogenous antigens are from any bacteria the class of AdoCbl producing bacteria, a 1:1 correspondence of MS with a single bacterium does not exist. Reduced AdoCbl concentration produces a cascade of events in the pathogenesis of MS including reduced production of cytokines, which require cobalamins for their [anabolic] production. AdoCbl is a cofactor for catabolism of odd-carbon-number fatty acids, branched chain fatty acids, and odd-carbon-number amino acids, via the methylmalonyl-CoA mutase (MCM) reaction that occurs in the mitochondrial matrix [24]. The term ‘‘vitamin B12” confounds identity of the four major cobalamin compounds in humans. The Cobalt +z (i.e., upper) ligand determines the biological activity for cobalamins, and the use of their specific names, cyanocobalamin (CNCbl), hydroxocobalamin (HOCbl), methylcobalamin (MeCbl), and adenosylcobalamin (AdoCbl) provide specificity to the individual cobalamin compounds. Today, radioimmunoassay (RIA) of cobalamins is the most common method in use [25]. RIA is stated to be specific, however it actually detects the corrin macrocycle and therefore measures combined corrin compounds, i.e., CNCbl, HOCbl, MeCbl, and AdoCbl rather than any one specifically, and cannot measure their individual concentrations, since each is masked by the other corrin
compounds. All studies attempting to correlate B12 concentrations and MS are flawed. Analysis with high performance liquid chroma tography-radioimmunoassay (HPLC-RIA) of the orphan stomach peptide, ghrelin, conducted after separation of proghrelins by HPLC, collection of fractions, and assessment of individual fractions by RIA has been reported [26]. To date, this tandem HPLC-RIA method has not been applied to individually quantify the four major cobalamins in humans. The MS-AdoCbl hypothesis predicts a low concentration of AdoCbl in the mitochondrial matrix (not analytically accessible), in serum and urine from MS patients compared to controls and this prediction can be tested after an analytical method with specificity and sufficient sensitivity is developed (potentially, cadaver mitochondria could be studied for AdoCbl content semiquantitatively). Serum analysis by RIA of B12 has a reference range for males of 200–1100 pg/ml (Quest Diagnostics, Irving, Texas), but as mentioned above, this represents the summation of all corrin compounds present. For example, RIA analysis of serum from a MS patient might show 1,000 pg/ml B12, while HPLC-RIA analysis of the same sample might show [CNCbl = 600 pg/ml + HOCbl = 100 pg/ml + MeCbl = 285 pg/ml + AdoCbl = 15 pg/ml] indicating a probable deficiency in AdoCbl; a normal AdoCbl serum concentration needs to be established. Current RIA protocols for cobalamin compound analyses are incapable of revealing AdoCbl deficiency. There is an acute need, therefore, for development of an accurate and precise HPLC-RIA protocol for the four major cobalamins in serum and urine in attogram/ml up to 1 mg/ml quantities to test for AdoCbl deficiency predicted by the MS-AdoCbl hypothesis. Also, the concentration of AdoCbl bound to transcobalamin2 (TC2) and other cobalamin binding proteins should be studied by HPLC-RIA after a test method is developed. Previous studies have demonstrated that RIA measurements of B12 concentrations do not correlate with MS [27,28]. The MS-AdoCbl hypothesis predicts that only abnormally low AdoCbl concentrations would correlate with MS. ATR concentrations and activity have been established for controls and are consistent with the typical 1 umol (or less) physiological concentrations of AdoCbl; the two known isoforms of ATR are 239 K, with a specific activity of 220 nmol min1 mg1 , and 239 M with a specific activity of 190 nmol min1 mg1 . These values are similar to bacterial ATRs, many of which have been characterized [29]. The typical ATR concentration for MS patients versus controls has not been reported; determination of ATR concentration would be a direct test of MS-AdoCbl hypothesis. Demonstration of antiATR antibodies would be a direct test of MS-AdoCbl hypothesis. Serum and mitochondrial ATR concentrations have not been compared for control individuals living at different latitudes or MS patients in various stages of MS and this should be accomplished semiquantitatively by a proposed extraction of mitochondria from cadavers, lyse mitochondria, polyacrylamide gel electrophoresis, stain, and use protein assay reagent. It is not possible to produce a massive dose of AdoCbl using a high concentration of cyanocobalamin or hydroxocobalamin since the ATR concentration is not sufficient even in control individuals. A study by Kira et al. [30] of therapy of 24 MS patients featuring massive doses (60 mg daily for 6 months) reported minor improvements in visual and auditory evoked potentials [30]. The finding was not corroborated; possibly the large concentration of MeCbl used served as a substrate for the low concentration of ATR and which produced, in turn, a small amount of AdoCbl. It was this AdoCbl that was responsible for whatever minor beneficial effects were observed. AdoCbl is water soluble and does not cause vitaminosis. The simplest heuristic is the trial-and-error method. Kira et al. used MeCbl as a therapeutic agent for treatment of MS and failed to produce significant results. The use of 60 mg daily MeCbl supports the idea that 10 mg daily AdoCbl would not pose a health risk. Pathogenesis of MS There six stages in the pathogenesis of MS. Stage I is the autoimmune attack by B cells of ATR after immune response to bacterial ATRs (found in bacteria that synthesize cobalamins) reducing its concentration and potentially eliminating it from many mitochondria throughout the body. Stage II is the resulting deficiency of AdoCbl causing failure of MCM catabolism of odd-carbon-number substrates throughout the body that may be referred to as subclinical AdoCbl deficiency. Sage III is the production of odd-carbonnumber fatty acids and other components that are incorporated into myelin rendering it antigenic and this stage might take years or even decades. Stage IV is a breach of BBB introducing immune system B and T cells into the brain that continue attack of ATR by B cells and initiate attack of antigenic myelin by T cells as well as any ATR enzymes or structures containing sequences similar to ATR. Stage V is attack of mitochondria, especially complex I, and any structural components having the epitope found in ATR. Stage VI is reduction of ATP production resulting from increased permeability of mitochondrial membranes thereby decoupling ATP production driven by the proton gradient across the inner mitochondrial membrane; many MS symptoms derive from ATP deficiency. The multiple stages are occurring somewhat simultaneously though manifesting different clinical signs. The clinical sign of demyelination results from R cell attack of myelin; the fatigue, muscle weakness, heat stress, and neuromuscular deficit result from attack of mitochondria reducing bioavailable ATP to cells. Symptoms such as fatigue, muscle weakness, or heat stress result from deficient ATP. Immune attack of PNS myelin is likely to be significant though really poorly understood. Damage to mitochondria and the PNS are extensive in MS. The immune response foundational to MS-AdoCbl hypothesis also damages mitochondria The amino acid sequence found in ATR also occurs in mitochondria and thus mitochondria are under immune attack limiting production of ATP. This is likely to be B cell mediated. Reduction of ATP availability attenuates the nerve pulse. Longer nerve tracts have more mitochondria in total than shorter nerve tracts and are affected first manifesting gait disturbance in the legs, then arms become weaker, and ultimately cranial nerves are affected resulting in Charcot’s triad (the near terminal stage: nystagmus, tremor, and scanning speech) described by Charcot in 1865. This attenuation effect is proportional to the length of the nerve tract and the total number of mitochondria involved. It is likely that greatly reduced ATP production causes plaque lesions characteristic of SCD or MS; no references were identified demonstrating reduced ATP concentration causing lesions and this should be investigated with spinal cord nerve cell cultures [31]. ATR requires ATP to produce AdoCbl, thus reduced ATP availability will also inhibit AdoCbl production. Optic neuritis as a presenting symptom of MS correlates with plaque lesions observable with MRI and this is often an early stage of RRMS. There are three pathogenic processes in MS, those being attack of ATR, demyelination, and mitochondrial damage reducing ATP production. The antigenic myelin (either conformational or having odd-carbon-number constituents) is produced from defective components created as a result subclinical cobalamin deficiency. RRMS has a stage change to SPMS when most antigenic myelin has been eliminated. Progressive forms have damage to mitochondria as the major pathogenic process. Patent790 claims the amino acid sequence RAVCRRAER forming the binding site for the corrin macrocycle prior to the production of AdoCbl (Patent790 claims other sequences as well). This sequence or a variant is likely
present in transport proteins or on mitochondrial membranes. There is need identify anti-ATR antibodies and to prepare fluorescent antibodies from them to label channels on mitochondria or other membrane structural features of mitochondrial membranes; it is beyond the scope of this article as it goes beyond proposing and testing the MS-AdoCbl hypothesis. In the specification of Patent790 an immunomodulator is described with ATR peptide sequences that are claimed, but financial limitations prevented its synthesis. It is vitally important to identify the presence of anti-ATR antibodies that are predicted by MS-AdoCbl theory. Studies show that when ATP production is significantly reduced from mitochondria within nerve cells axonal death results, though the details of how axonal death occurs in PPMS or SPMS are not known [32]. This would indicate that ATP is neuroprotective. Mao and Reddy [33] provide extensive discussion of MS as a neurodegenerative disease due to mitochondrial dysfunction and emphasize importance of mitochondrial DNA (mtDNA) [33]. In essence, this article advocates that progressive forms of MS are fundamentally a mitochondrial disease with the autoimmune target being mitochondrial complexes located inside the mitochondrial matrix. Mitochondrial damage results in decreased ATP production and many symptoms of MS result from deficiency of ATP in addition to demyelination. Much evidence is coming forth that mitochondrial dysfunction occurs in MS patients, mtDNA mutation, mitochondrial structural changes, and abnormal mitochondrial enzyme activities have been observed; impaired mitochondrial energy metabolism is important in the pathology of Alzheimer’s disease, Parkinson’s disease, and MS hence therapy targeting mitochondrial dysfunction has great potential [33]. Adenosine A2A receptors are increased in SPMS [34]. Studies confirm that mitochondria play a significant role in MS pathogenesis. Membranes with the respiratory chain composed of 5 enzyme complexes is located inside the inner membrane is controlled by both nuclear DNA and mtDNA; Rezaee et al. proposed that genetic factors in nuclear DNA and mtDNA contributed to Complex I anomalies in MS [35]. Kumleh et al. reported complex I activity was greatly decreased in MS patients although genetic mutations were not discovered [36]. It is proposed here that mitochondria and complex I are relentlessly under autoimmune attack (not primarily a genetic mutation) progressively at a slow pace since complex I is inside the inner mitochondrial membrane. Human complex I is responsible for electron transport and creating the proton gradient across the inner mitochondrial membrane creating the driving force for ATP production (other complexes are also involved). Human complex I consists of 14 subunits homologous to bacterial subunits [37]. Antibodies to complex 1 are proposed as potentially fundamental to progressive forms of MS possibly even initiating the attack of myelin in RRMS; there is need to investigate occurrence of these antibodies in MS patients. ATP binding cassette transporters (ABC transporters) are ubiquitous in living organisms, have highly conserved ATPase core structures in two highly conserved motifs: Walker A and Walker B; there are species specific regions as well as conserved regions and ABC transporters have been considered as targets for development of therapeutic agents [38]. There is need for investigation of antiABC transporter antibodies present in progressive MS patients, especially those originating in response to infection by Rhizobia bacteria. The reduction in AdoCbl is caused by autoimmune attack of ATR with the same peptide sequences likely present in the mitochondrion. Mayo reviews papers on the question if MS is a mitochondrial disease [33]. Mitochondria in nerve cells produce ATP utilized within the cell; the Enliten ATP Assay System (Promega) measures 1011 to 1016 moles of ATP and many solvent systems have been described with trichloroacetic acid being the best extractant for tissues. Studies are needed to compare ATP concentrations of MS patients (as a marker), nerve cell cultures, (or animal models) to controls and whether or not large dose AdoCbl therapy increases ATP production. In vitro studies of MS using cell culture where prepared nerve tracts could be utilized for MS studies with assay of ATP. Animal model studies in MS research While widely used and routinely cited as an animal model for MS, EAE is a poor approximation of the disease [39]. SCD resulting from cobalamin deficiency (actually AdoCbl deficiency) produces a realistic animal model; the totally gastrectomized (GTX) rat reproduces key morphological features of SCD and this is deemed as a good model of MS [40]. However, the GTX rat model is extreme by eliminating both AdoCbl and MeCbl completely and not separating those two variables. To extend this model to the proposed bacterial infection, a test animal would be inoculated with human ATR and bacterial PduO enzymes (or killed bacteria e.g. Rhizobia) triggering immune response to both the human and the test animal’s own ATR. The folate pathway for production of MeCbl would be active. Inclusion of folic acid in the diet will shunt cobalamins along the pathway to MeCbl. In this animal model the immune response to ATR would be B-cell mediated. Development of MS has an extended period of subclinical AdoCbl deficiency that produces antigenic myelin; Carmel indicates subclinical cobalamin deficiency is more common than generally recognized though the health impact is unclear [41]. Attack of antigenic myelin is likely T-cell mediated (based on EAE studies) [42]. An extended period of ATR and AdoCbl depletion prevents repair of myelin and introduces antigenicity in myelin. With an animal model it should be possible to accelerate induction of myelin antigenicity by providing a diet rich in odd-carbon-number fatty acids with minimal AdoCbl present (simulating subclinical cobalamin deficiency). The initial autoimmune target is ATR and the secondary immune system target is antigenic myelin. Potentially, AdoCbl is necessary for maintenance of BBB integrity. BBB breach allows white blood cells (WBCs) and other blood constituents (e.g. fibrinogen) to enter the brain crossing the BBB, activating the coagulation cascade, and recruiting T-cells and macrophages to cause CNS autoimmunity in the EAE animal model and potentially MS [43]. The proposed MS-AdoCbl animal model creates a more realistic MS model by depleting ATR and AdoCbl and then would introduce isolated WBCs into the brain’s blood system. Complete blood count (CBC) methods use filtration to separate individual types of leukocytes. Clonal expansion of human leukocytes is accomplished by cell culture with interleukins, with B Cell Receptor (BCR), with T Cell Receptor (TCR) and potentially other means that are not referenced here; the concept presented herein is to obtain leukocytes from buffy coats (WBCs) obtained by centrifugation followed by stimulation for clonal expansion of leukocytes; appropriate interleukins, BCR, or TCR may not be available for the test animal. Cross species experiments are advocated here i.e. attempting to utilize human interleukins for clonal expansion of leukocytes from test animals such as rat, mouse, or guinea pig. No references are provided since no such experiments were identified in the literature. If clonal expansion of leukocytes from a test animal were accomplished then filtration methods common to CBC could achieve separation of cell types. The final step in creating a realistic animal model of MS would be injecting individual cell types into the brains of test animals simulating BBB breach and observing the response. Progression of CNS demyelination in the test animal should be followed by MRI [44]. Traumatic brain injury has been studied in rats by MRI [45]. Creating a lab chow with only some MeCbl to prevent megaloblastic anemia and a large concentration of folic acid would ensure minimal AdoCbl is formed. Odd-carbonnumber fatty acids (FA) could be included in the lab chow diet.
(Continued in comments)
submitted by continentalgrip to B12_Deficiency [link] [comments]
Paywall. Sorry about formatting. Guy says he sort of cured MS with adenosylcobalamin injections.
https://pubmed.ncbi.nlm.nih.gov/29150289/#:~:text=limiting%20adenosylcobalamin%20production-,The%20cause%20of%20multiple%20sclerosis%20is%20autoimmune%20attack%20of%20adenosyltransferase,Med%20Hypotheses.
abstract The pathogenesis of multiple sclerosis (MS) begins with an infection by a bacterium from the class of bacteria that produce and utilize adenosylcobalamin (AdoCbl) and possess an adenosyl transferase enzyme (ATR); these bacteria are the exogenous antigens that cause MS. Human ATR is homologous to bacterial ATR and B cells produce anti-ATR antibodies as an autoimmune response thereby reducing the concentration of ATR and thus limiting production of AdoCbl, one of the two bioactive forms of vitamin B12. The next step in MS pathogenesis is a period of subclinical AdoCbl deficiency over a period of many years resulting in production of odd-carbon-number fatty acids that are incorporated into myelin rendering it antigenic. The next step in MS pathogenesis is breach of the blood brain barrier thereby introducing leukocytes into the brain’s blood supply resulting in T cell attack of antigenic myelin. All epidemiological clusters are regions wherein the major agricultural products are legumes that produce a high percentage of odd-carbon-number fatty acids and contain symbiotic rhizobia type bacteria in root nodules and in the soil. This novel etiological hypothesis is called ‘‘multiple sclerosis due to adenosylcobalamin deficiency” (MS-AdoCbl). Creation of realistic animal models based on the MS-AdoCbl hypothesis is presented. Methods for testing predictions made by the MS-AdoCbl hypothesis are described.
Introduction Multiple sclerosis (MS) is a disease of the central nervous system (CNS), and the peripheral nervous system (PNS), (though difficult to distinguish from CNS causation), characterized by demyelination, formation of plaque lesions, damage to mitochondria with reduction of the ATP concentration, axonal degeneration, and with different forms or stages of MS defined by apparent clinical signs; the history of multiple sclerosis (MS) has been presented in introductory chapters of recent texts; Jean-Martin Charcot published the first comprehensive discussion in 1865 L’ Union Med 25:451–457, 467–472 (over 150 years ago) [1,2]. Attention to mitochondrial damage and its effects are more recent [3]. There has been much speculation on its etiology, thus books and journal articles typically state that the molecular events underlying MS are not known. Nevertheless, discussions on the possible etiology of MS and in depth speculation of its causes are available [4,5]. The MS-AdoCbl hypothesis The MS-AdoCbl hypothesis advocates that multiple sclerosis (MS) is caused by autoimmune attack of ATP:cob(I)alamin adenosyltransferase (referred to as adenosyltransferase or ATR) that converts cobalamins to the bioactive form 50 -deoxy-50 -adenosyl cobamide (adenosylcobalamin, Coenzyme B12 or AdoCbl). When the concentration of ATR is reduced the production of AdoCbl is limited resulting in metabolic changes that are pathological to the nervous system by causing myelin to become antigenic and this pathogenesis requires many years to develop. Introduction of leukocytes into the brain by breach of the blood brain barrier (or by other means) initiates immune attack of myelin causing the clinical signs of MS to manifest. Aspects of MS pathogenesis are related to deficiency of AdoCbl. The development of the MS-AdoCbl hypothesis Consideration of the similarity between subacute combined degeneration (SCD) and MS was instrumental in development of the MS-AdoCbl hypothesis and the existence of epidemiological hotspots argued for an exogenous antigen responsible for the development of MS. Bacteria that produce AdoCbl have ATR enzymes that are homologous to human ATR and thus infection https://doi.org/10.1016/j.mehy.2017.08.011 0306-9877/ 2017 The Author. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). ⇑ Corresponding author. E-mail address: boucher@cdsrllc.com URL: http://cdsrllc.com Medical Hypotheses 109 (2017) 29–37 Contents lists available at ScienceDirect Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy with such bacteria and immune response to them is the reason for MS being an autoimmune disease. The primary autoimmune attack is attack of ATR, located in mitochondria, resulting in production of odd-carbon-number compounds that are incorporated into myelin causing it to become antigenic; this would result from subclinical AdoCbl deficiency, extended over many years and accompanied by myelin turnover resulting in incorporation of antigenic compounds into myelin. Subsequently, a secondary immune attack of myelin occurs. The MS-AdoCbl hypothesis presents a new perspective for the etiology of MS since current views focus on attack of myelin as the primary immune response responsible for MS. This novel etiological hypothesis shall subsequently be referred to as the ‘‘multiple sclerosis due to adenosylcobalamin deficiency” (MS-AdoCbl) hypothesis, and was first published in the specification of US Patent Application No. 12/460,946 on Jan. 27, 2011. US Patent 8,691,790 (Patent790) describing therapy of MS issued April 8, 2014. The MS-AdoCbl hypothesis is the medical hypothesis and thesis of this article. A test of MS-AdoCbl hypothesis was therapy of MS with AdoCbl and success of the scoping experiments in therapy was the stimulus for writing a patent. This testing has been conducted on one MS patient for over ten years strongly supporting the hypothesis by providing substantial recovery from CNS symptoms of MS. AdoCbl therapy benefits PNS functions though not providing complete recovery nor does it provide recovery from mitochondrial damage and reduced ATP production.
Personal testing of the MS-AdoCbl hypothesis with AdoCbl therapy I was diagnosed with relapsing remitting multiple sclerosis (RRMS) in 1992 by Dr. J.S. Wolinsky who discussed MS with me regarding SCD presenting clinical signs and magnetic resonance imaging (MRI) similar to MS, although only SCD is responsive to B12 therapy. By 1997 stage change to secondary progressive multiple sclerosis (SPMS) was apparent. CNS and PNS symptoms progressed to include failure of working memory (with retention of less than five seconds) impaired cognition, slow processing, scanning speech, dystonia, paroxysmal spasms, gait disturbance, spasticity, dysarthria, loss of balance with frequent falls, heat stress, and other effects typical of MS [6]. As a clinically definite MS patient it was possible to test therapeutic methods on myself. Evaluation of therapy was a direct test of the proposed medical hypothesis. On 15 August 2006 I determined to pursue MS research myself and began to study the literature for MS. On 26 December 2006 I conceived an etiological hypothesis involving adenosyltransferase enzyme which converts cyanocobalamin (CNCbl) to AdoCbl, one of two bioactive forms of B12. I posited that the concentration of the adenosyltransferase enzyme (ATR) becomes reduced following autoimmune attack, thereby limiting production of AdoCbl, and leading to metabolic changes that are the initial pathogenesis of MS. It is worth noting that I found it necessary at that time to write on a notepad whatever was being considered, because my shortterm recall was so short. Given the etiological hypothesis that AdoCbl deficiency causes MS, a test of the hypothesis was evaluation of therapeutic benefit from AdoCbl parenterally administered, i.e., bypassing the need for the ATR enzyme. I determined to test my hypothesis by self-administration of AdoCbl. No U.S. Pharmacopeia (USP) grade, FDA approved injectable AdoCbl exists, though multiple sources of 97% AdoCbl were available for research purposes in vitro or with animals. A 3 mg/ml solution of AdoCbl in lactated Ringer’s solution was prepared and 1 ml was self-injected subcutaneously (sc) in the thigh 28 January 2007. The effects were pronounced and rapid. Within 5 min, recovery of memory and other improved cognitive abilities were apparent and my speech went from slow and labored to normal. Within 30 min, balance improved and I was able to lift my essentially immobilized right arm straight up above my head for the first time in several years. These effects, occurring mere minutes after injection, could only have resulted from direct action on nerves and not by means of anti-immune effects or myelin repair. Significantly, the effects described here of a single AdoCbl injection seemed to support the etiological hypothesis; the partial recovery from MS symptoms ostensibly resulted from neuroenhancement. No report of experimental AdoCbl therapy with humans for any reason was found. The patent literature showed that AdoCbl therapy had never been used and this led to the patent application and prosecution. For over 11 years, I carried out literature and laboratory research on my hypothesis, including regular injections (3–10 mg 5 weekly) of AdoCbl totaling ca. 9 g in 11 years. The results of this work show that AdoCbl therapy is effective, even life-changing, for treatment of a SPMS patient with therapy rationally based on the MSAdoCbl hypothesis. Epidemiology of MS In any study of the cause of a disease, it is important to assess common factors in identified clusters or ‘hotspots.’ Islands in the North Atlantic, including Iceland, Faroe, Orkney, and Shetland Islands constitute such epidemiological hotspots. Orkney Islands, had, in epidemiological studies conducted in 1974–1977, 309 cases of MS per 100,000 persons; in the Shetland Islands there were 184 cases of MS per 100,000 in 1974–1977; Orkney and Shetland islands represent the highest incidence rates for MS anywhere in the world and they also have the most cases of optic neuritis presenting as the initial symptom subsequently diagnosed as MS [7]. The agricultural products on these islands are pea, faba bean, lintil, grass pea, and chickpea all of which are legumes with rhizobia class bacteria in root nodules. [8] This is exceptional and may be the only location in the world having five or more major agricultural products that are legumes. These legumes form the staple diet of the islands and are predicted to contain a high percentage of odd-carbon-number fatty acids; this has not been specifically researched due to time constraints and could provide support for the MS-AdoCbl hypothesis once investigated. There is need for creation of a table of foods with percent odd-carbon-number fatty acids ranked from high to low content. The MS-AdoCbl hypothesis includes the concept that exogenous antigens responsible for eliciting the autoimmunogenic process producing MS are ATR-like enzymes contained in cobalamin- producing bacteria. In ‘‘Status of Cereal Cultivation in the North Atlantic Region” a map appears (page 12 of said article) showing these islands and describing cool weather legume cereal grains (likely containing odd-carbon-number fatty acids, etc.) as their principal agricultural products [9]. Another epidemiological hotspot, Olmstead County, Minnesota, with 160 cases per 100,000 is 2–3 times higher than the average in locations at that latitude [10]. Soybeans are the major agricultural product in Olmstead County with about 72,000 harvested acres of soybean [11]. Soybeans are legumes and Bradyrhizobium japonicum is the most common symbiotic bacteria [12]. The combination of local food rich in odd-carbon-number fatty acids that are legumes are predicted by the MS-AdoCbl hypothesis as factors producing epidemiological hotspots; the lowered AdoCbl concentration produces antigenic myelin from oddcarbon-number fatty acids. A bacterial PduO enzyme, homologous to human ATR, should produce a pronounced autoimmune response. Rhizobium and other bacteria found in legumes are predicted by (instrumental in the development of) the MS-AdoCbl hypothesis and contain conserved bacterial ATRs. Any cobalamin producing bacteria can be the exogenous antigen causing MS
although some bacteria are more efficient at causing MS. This multiplicity of exogenous antigens makes it difficult to identify a single bacterium as a highly significant exogenous antigen. Rhizobia bacteria have many ATP-binding cassette (ABC) transporters, e.g. Rhizobium leguminosarum has 183 ABC operons [13]. A study of bacterial genomes for bacteria found in legumes contains a phylogenetic tree of Rhizobial (and related bacteria) is presented (Fig. 1, pg. 616) in a study by Maclean et al. [14]. Nodule-producing bacteria are present in the soil even when crops other than legumes are grown in rotation. A person incurring a cut in such a field would be infected with bacteria common to legumes. There are many such bacteria possessing ATR-like enzymes, and each enzyme might be antigenic producing an immune response and antibodies that are cross-reactive to human ATR. Homology between a bacterial and a human ATR produces a stronger autoimmune response. Any bacterial IgG might or might not bind ATR strongly though a collection of IgGs have a cumulative effect and might bind ATR at different locations. Soil introduced into a cut will contain many different bacteria, not a single bacterium. The cumulative effect of infection with multiple cobalamin producing bacteria makes it difficult to identify a single exogenous antigen responsible for the development of MS. What is known, though, is that the ATR-like enzymes are from the class of bacteria producing AdoCbl. The higher risk in colder climates may be related to cobalamin metabolism and trafficking or differences in mitochondria since ATR is located within the inner membranes of mitochondria. Hypothetically a change in cobalamin metabolism (especially related to mitochondria) and trafficking occurs at puberty. These changes would be present in all persons as a function of average ambient temperatures and not MS patients alone. Possibly, the lower risk of MS in tropical regions is related to mitochondrial membrane thickness and mitochondrial membrane permeability investigations are needed. Another critical requirement in MS is BBB breach, which allows leukocytes with immune memory into the CNS blood system. No study of the BBB in relation to cobalamin trafficking proteins has yet appeared. Such a study, particularly one regarding populations residing at different latitudes, is obviously needed. Etiology of MS The MS-AdoCbl hypothesis describes a completely new understanding of the fundamental cause of MS. Rather than the current theories positing a generalized autoimmune assault on myelin brought on by some unknown immune-provoking event, the MSAdoCbl hypothesis cites autoimmune attack of ATR, reducing its concentration, and causing deficiency of AdoCbl as the main culprit initiating MS pathogenesis. The two bioactive forms of B12 are AdoCbl and methylcobalamin (MeCbl). MS pathogenesis follows AdoCbl deficiency which induces a cascade of metabolic changes wherein myelin becomes antigenic following metabolic turnover with antigenic structures incorporated into myelin. Metabolic turnover of polyphosphoinositides in myelin was studied by Eichberg and Dawson [15]. Davison and Gregson reported that turnover of a small fraction of myelin is rapid and the remaining fraction of myelin is metabolically stable with slow turnover [16]. Optic neuritis is a common presenting symptom and optic nerves likely have a rapid turnover rate; turnover could be studied with carbon-13 enriched foods followed by serial MRI. Development of antigenic myelin may take years to occur during which time the changes are subclinical. At some point the BBB happens to be breached allowing leukocytes to enter the blood supply in the brain and introducing leukocytes as markers in the CSF; the BBB breach may be the major immune provoking event. Normally, ATR with an adenosyl group from ATP converts B12 into AdoCbl. B12 deficiency can produce neurologic symptoms in SCD, similar to the symptoms of RRMS [17]. Left untreated, progressive spastic paraparesis and CNS impairments develop, with reversibility dependent upon the time elapsed before intervention with B12 [18]. Multiple sclerosis and B12 deficiency share many symptoms, including vision loss, muscle weakness, gait disturbances and cognitive impairment. Cobalamins are involved in myelin formation and repair while exerting immunomodulatory and neurotrophic effects. MRI studies of MS and SCD patients show striking similarities. B12 deficiency causes reduction of both bioactive forms, AdoCbl and MeCbl [19]. The MS-AdoCbl hypothesis predicts that the clinical signs of SCD and MS will be largely identical, having AdoCbl insufficiency as the basis for each. Aspects of MS are also indicative of a disturbance of MeCbl metabolism in the CNS, affecting anabolism, though slower to manifest clinical signs than AdoCbl deficiency and affecting protein synthesis and red blood cell maturation. This, according to MS-AdoCbl hypothesis, is because they both result from AdoCbl deficiency. If a SCD patient remains deficient in B12, the symptoms that manifest become similar to those of RRMS, again, for the simple reason that SCD and MS both result from an identical cause, deficiency of AdoCbl. If a SCD patient were not treated with B12 for years, the symptoms that would manifest are similar to symptoms of progressive MS; the reason SCD and progressive MS symptoms are similar is due to the cause for each being identical, deficiency of AdoCbl for an extended period of time. RRMS typically becomes SPMS and thus the two disease states are linked. Events precipitating AdoCbl deficiency in MS and SCD differ however, as shown in Fig. 1. In MS, autoimmune attack reduces the concentration of ATR and consequently AdoCbl. Because the clinical signs of SCD are easily recognized, laboratory tests are ordered without a long delay, revealing the underlying B12 deficiency, for which B12 is administered as a 1 mg intramuscular (im) injection [20]. This avenue of delivery has historically been preferred, possibly in order to take advantage of muscle tissue that provides a kind of timed release of the vitamin. From the perspective of MS-AdoCbl hypothesis and experimental MS therapy a sc injection between 4 mg and 8 mg AdoCbl might be preferred to rapidly supply AdoCbl to mitochondria and nerves. This also addresses the parallel requirement to replenish depleted cobalamin stores; no article discussing the importance of replenishing cobalamin stores in the liver or other tissues has been identified. The MS-AdoCbl hypothesis predicts depletion of stored AdoCbl, e.g., in the liver, a finding that awaits assessment in necroscopy liver samples from healthy individuals and MS patients, a key point. Paradoxically, administration of B12 is not helpful for a MS patient although SCD produces a similar MRI, since ATR deficiency prevents production of bioactive AdoCbl regardless of the concentration of B12 present. In therapy of SCD with B12, a common clinical mistake is to co-administer folic acid, which while lessening anemia, causes spinal cord lesions [21]. Administration
of folic acid further decreases the AdoCbl concentration by directing B12 along the pathway to MeCbl, rather than along the pathway to AdoCbl. Schubert and Hill published the crystal structure of ATP-bound human ATP:cob(I)alamin adenosyltransferase (ATR) along with bacterial PduO ATR enzymes showing its conserved AdoCbl binding sites and extensive homology, as shown in Fig. 2, and including an ATP binding site [22]. (This was isoform 239 K having lysine at position 239.) There are three types of adenosyltransferases (i.e. Cob-A-type, EuT-type, and PduO-type) based on structural similarity within a type; PduO is the most widely distributed and includes human, mammalian, and many bacterial ATRs. All have a common rotary mechanism of action [23]. Diverse ATRs are antigenic when crossing species by infection and therefore create an autoimmune response in the infected person (or animal). Autoimmune attack of ATR would be B-cell mediated, with exogenous antigens being ATR- like enzymes from the class of bacteria producing AdoCbl. Because the exogenous antigens are from any bacteria the class of AdoCbl producing bacteria, a 1:1 correspondence of MS with a single bacterium does not exist. Reduced AdoCbl concentration produces a cascade of events in the pathogenesis of MS including reduced production of cytokines, which require cobalamins for their [anabolic] production. AdoCbl is a cofactor for catabolism of odd-carbon-number fatty acids, branched chain fatty acids, and odd-carbon-number amino acids, via the methylmalonyl-CoA mutase (MCM) reaction that occurs in the mitochondrial matrix [24]. The term ‘‘vitamin B12” confounds identity of the four major cobalamin compounds in humans. The Cobalt +z (i.e., upper) ligand determines the biological activity for cobalamins, and the use of their specific names, cyanocobalamin (CNCbl), hydroxocobalamin (HOCbl), methylcobalamin (MeCbl), and adenosylcobalamin (AdoCbl) provide specificity to the individual cobalamin compounds. Today, radioimmunoassay (RIA) of cobalamins is the most common method in use [25]. RIA is stated to be specific, however it actually detects the corrin macrocycle and therefore measures combined corrin compounds, i.e., CNCbl, HOCbl, MeCbl, and AdoCbl rather than any one specifically, and cannot measure their individual concentrations, since each is masked by the other corrin
compounds. All studies attempting to correlate B12 concentrations and MS are flawed. Analysis with high performance liquid chroma tography-radioimmunoassay (HPLC-RIA) of the orphan stomach peptide, ghrelin, conducted after separation of proghrelins by HPLC, collection of fractions, and assessment of individual fractions by RIA has been reported [26]. To date, this tandem HPLC-RIA method has not been applied to individually quantify the four major cobalamins in humans. The MS-AdoCbl hypothesis predicts a low concentration of AdoCbl in the mitochondrial matrix (not analytically accessible), in serum and urine from MS patients compared to controls and this prediction can be tested after an analytical method with specificity and sufficient sensitivity is developed (potentially, cadaver mitochondria could be studied for AdoCbl content semiquantitatively). Serum analysis by RIA of B12 has a reference range for males of 200–1100 pg/ml (Quest Diagnostics, Irving, Texas), but as mentioned above, this represents the summation of all corrin compounds present. For example, RIA analysis of serum from a MS patient might show 1,000 pg/ml B12, while HPLC-RIA analysis of the same sample might show [CNCbl = 600 pg/ml + HOCbl = 100 pg/ml + MeCbl = 285 pg/ml + AdoCbl = 15 pg/ml] indicating a probable deficiency in AdoCbl; a normal AdoCbl serum concentration needs to be established. Current RIA protocols for cobalamin compound analyses are incapable of revealing AdoCbl deficiency. There is an acute need, therefore, for development of an accurate and precise HPLC-RIA protocol for the four major cobalamins in serum and urine in attogram/ml up to 1 mg/ml quantities to test for AdoCbl deficiency predicted by the MS-AdoCbl hypothesis. Also, the concentration of AdoCbl bound to transcobalamin2 (TC2) and other cobalamin binding proteins should be studied by HPLC-RIA after a test method is developed. Previous studies have demonstrated that RIA measurements of B12 concentrations do not correlate with MS [27,28]. The MS-AdoCbl hypothesis predicts that only abnormally low AdoCbl concentrations would correlate with MS. ATR concentrations and activity have been established for controls and are consistent with the typical 1 umol (or less) physiological concentrations of AdoCbl; the two known isoforms of ATR are 239 K, with a specific activity of 220 nmol min1 mg1 , and 239 M with a specific activity of 190 nmol min1 mg1 . These values are similar to bacterial ATRs, many of which have been characterized [29]. The typical ATR concentration for MS patients versus controls has not been reported; determination of ATR concentration would be a direct test of MS-AdoCbl hypothesis. Demonstration of antiATR antibodies would be a direct test of MS-AdoCbl hypothesis. Serum and mitochondrial ATR concentrations have not been compared for control individuals living at different latitudes or MS patients in various stages of MS and this should be accomplished semiquantitatively by a proposed extraction of mitochondria from cadavers, lyse mitochondria, polyacrylamide gel electrophoresis, stain, and use protein assay reagent. It is not possible to produce a massive dose of AdoCbl using a high concentration of cyanocobalamin or hydroxocobalamin since the ATR concentration is not sufficient even in control individuals. A study by Kira et al. [30] of therapy of 24 MS patients featuring massive doses (60 mg daily for 6 months) reported minor improvements in visual and auditory evoked potentials [30]. The finding was not corroborated; possibly the large concentration of MeCbl used served as a substrate for the low concentration of ATR and which produced, in turn, a small amount of AdoCbl. It was this AdoCbl that was responsible for whatever minor beneficial effects were observed. AdoCbl is water soluble and does not cause vitaminosis. The simplest heuristic is the trial-and-error method. Kira et al. used MeCbl as a therapeutic agent for treatment of MS and failed to produce significant results. The use of 60 mg daily MeCbl supports the idea that 10 mg daily AdoCbl would not pose a health risk. Pathogenesis of MS There six stages in the pathogenesis of MS. Stage I is the autoimmune attack by B cells of ATR after immune response to bacterial ATRs (found in bacteria that synthesize cobalamins) reducing its concentration and potentially eliminating it from many mitochondria throughout the body. Stage II is the resulting deficiency of AdoCbl causing failure of MCM catabolism of odd-carbon-number substrates throughout the body that may be referred to as subclinical AdoCbl deficiency. Sage III is the production of odd-carbonnumber fatty acids and other components that are incorporated into myelin rendering it antigenic and this stage might take years or even decades. Stage IV is a breach of BBB introducing immune system B and T cells into the brain that continue attack of ATR by B cells and initiate attack of antigenic myelin by T cells as well as any ATR enzymes or structures containing sequences similar to ATR. Stage V is attack of mitochondria, especially complex I, and any structural components having the epitope found in ATR. Stage VI is reduction of ATP production resulting from increased permeability of mitochondrial membranes thereby decoupling ATP production driven by the proton gradient across the inner mitochondrial membrane; many MS symptoms derive from ATP deficiency. The multiple stages are occurring somewhat simultaneously though manifesting different clinical signs. The clinical sign of demyelination results from R cell attack of myelin; the fatigue, muscle weakness, heat stress, and neuromuscular deficit result from attack of mitochondria reducing bioavailable ATP to cells. Symptoms such as fatigue, muscle weakness, or heat stress result from deficient ATP. Immune attack of PNS myelin is likely to be significant though really poorly understood. Damage to mitochondria and the PNS are extensive in MS. The immune response foundational to MS-AdoCbl hypothesis also damages mitochondria The amino acid sequence found in ATR also occurs in mitochondria and thus mitochondria are under immune attack limiting production of ATP. This is likely to be B cell mediated. Reduction of ATP availability attenuates the nerve pulse. Longer nerve tracts have more mitochondria in total than shorter nerve tracts and are affected first manifesting gait disturbance in the legs, then arms become weaker, and ultimately cranial nerves are affected resulting in Charcot’s triad (the near terminal stage: nystagmus, tremor, and scanning speech) described by Charcot in 1865. This attenuation effect is proportional to the length of the nerve tract and the total number of mitochondria involved. It is likely that greatly reduced ATP production causes plaque lesions characteristic of SCD or MS; no references were identified demonstrating reduced ATP concentration causing lesions and this should be investigated with spinal cord nerve cell cultures [31]. ATR requires ATP to produce AdoCbl, thus reduced ATP availability will also inhibit AdoCbl production. Optic neuritis as a presenting symptom of MS correlates with plaque lesions observable with MRI and this is often an early stage of RRMS. There are three pathogenic processes in MS, those being attack of ATR, demyelination, and mitochondrial damage reducing ATP production. The antigenic myelin (either conformational or having odd-carbon-number constituents) is produced from defective components created as a result subclinical cobalamin deficiency. RRMS has a stage change to SPMS when most antigenic myelin has been eliminated. Progressive forms have damage to mitochondria as the major pathogenic process. Patent790 claims the amino acid sequence RAVCRRAER forming the binding site for the corrin macrocycle prior to the production of AdoCbl (Patent790 claims other sequences as well). This sequence or a variant is likely
present in transport proteins or on mitochondrial membranes. There is need identify anti-ATR antibodies and to prepare fluorescent antibodies from them to label channels on mitochondria or other membrane structural features of mitochondrial membranes; it is beyond the scope of this article as it goes beyond proposing and testing the MS-AdoCbl hypothesis. In the specification of Patent790 an immunomodulator is described with ATR peptide sequences that are claimed, but financial limitations prevented its synthesis. It is vitally important to identify the presence of anti-ATR antibodies that are predicted by MS-AdoCbl theory. Studies show that when ATP production is significantly reduced from mitochondria within nerve cells axonal death results, though the details of how axonal death occurs in PPMS or SPMS are not known [32]. This would indicate that ATP is neuroprotective. Mao and Reddy [33] provide extensive discussion of MS as a neurodegenerative disease due to mitochondrial dysfunction and emphasize importance of mitochondrial DNA (mtDNA) [33]. In essence, this article advocates that progressive forms of MS are fundamentally a mitochondrial disease with the autoimmune target being mitochondrial complexes located inside the mitochondrial matrix. Mitochondrial damage results in decreased ATP production and many symptoms of MS result from deficiency of ATP in addition to demyelination. Much evidence is coming forth that mitochondrial dysfunction occurs in MS patients, mtDNA mutation, mitochondrial structural changes, and abnormal mitochondrial enzyme activities have been observed; impaired mitochondrial energy metabolism is important in the pathology of Alzheimer’s disease, Parkinson’s disease, and MS hence therapy targeting mitochondrial dysfunction has great potential [33]. Adenosine A2A receptors are increased in SPMS [34]. Studies confirm that mitochondria play a significant role in MS pathogenesis. Membranes with the respiratory chain composed of 5 enzyme complexes is located inside the inner membrane is controlled by both nuclear DNA and mtDNA; Rezaee et al. proposed that genetic factors in nuclear DNA and mtDNA contributed to Complex I anomalies in MS [35]. Kumleh et al. reported complex I activity was greatly decreased in MS patients although genetic mutations were not discovered [36]. It is proposed here that mitochondria and complex I are relentlessly under autoimmune attack (not primarily a genetic mutation) progressively at a slow pace since complex I is inside the inner mitochondrial membrane. Human complex I is responsible for electron transport and creating the proton gradient across the inner mitochondrial membrane creating the driving force for ATP production (other complexes are also involved). Human complex I consists of 14 subunits homologous to bacterial subunits [37]. Antibodies to complex 1 are proposed as potentially fundamental to progressive forms of MS possibly even initiating the attack of myelin in RRMS; there is need to investigate occurrence of these antibodies in MS patients. ATP binding cassette transporters (ABC transporters) are ubiquitous in living organisms, have highly conserved ATPase core structures in two highly conserved motifs: Walker A and Walker B; there are species specific regions as well as conserved regions and ABC transporters have been considered as targets for development of therapeutic agents [38]. There is need for investigation of antiABC transporter antibodies present in progressive MS patients, especially those originating in response to infection by Rhizobia bacteria. The reduction in AdoCbl is caused by autoimmune attack of ATR with the same peptide sequences likely present in the mitochondrion. Mayo reviews papers on the question if MS is a mitochondrial disease [33]. Mitochondria in nerve cells produce ATP utilized within the cell; the Enliten ATP Assay System (Promega) measures 1011 to 1016 moles of ATP and many solvent systems have been described with trichloroacetic acid being the best extractant for tissues. Studies are needed to compare ATP concentrations of MS patients (as a marker), nerve cell cultures, (or animal models) to controls and whether or not large dose AdoCbl therapy increases ATP production. In vitro studies of MS using cell culture where prepared nerve tracts could be utilized for MS studies with assay of ATP. Animal model studies in MS research While widely used and routinely cited as an animal model for MS, EAE is a poor approximation of the disease [39]. SCD resulting from cobalamin deficiency (actually AdoCbl deficiency) produces a realistic animal model; the totally gastrectomized (GTX) rat reproduces key morphological features of SCD and this is deemed as a good model of MS [40]. However, the GTX rat model is extreme by eliminating both AdoCbl and MeCbl completely and not separating those two variables. To extend this model to the proposed bacterial infection, a test animal would be inoculated with human ATR and bacterial PduO enzymes (or killed bacteria e.g. Rhizobia) triggering immune response to both the human and the test animal’s own ATR. The folate pathway for production of MeCbl would be active. Inclusion of folic acid in the diet will shunt cobalamins along the pathway to MeCbl. In this animal model the immune response to ATR would be B-cell mediated. Development of MS has an extended period of subclinical AdoCbl deficiency that produces antigenic myelin; Carmel indicates subclinical cobalamin deficiency is more common than generally recognized though the health impact is unclear [41]. Attack of antigenic myelin is likely T-cell mediated (based on EAE studies) [42]. An extended period of ATR and AdoCbl depletion prevents repair of myelin and introduces antigenicity in myelin. With an animal model it should be possible to accelerate induction of myelin antigenicity by providing a diet rich in odd-carbon-number fatty acids with minimal AdoCbl present (simulating subclinical cobalamin deficiency). The initial autoimmune target is ATR and the secondary immune system target is antigenic myelin. Potentially, AdoCbl is necessary for maintenance of BBB integrity. BBB breach allows white blood cells (WBCs) and other blood constituents (e.g. fibrinogen) to enter the brain crossing the BBB, activating the coagulation cascade, and recruiting T-cells and macrophages to cause CNS autoimmunity in the EAE animal model and potentially MS [43]. The proposed MS-AdoCbl animal model creates a more realistic MS model by depleting ATR and AdoCbl and then would introduce isolated WBCs into the brain’s blood system. Complete blood count (CBC) methods use filtration to separate individual types of leukocytes. Clonal expansion of human leukocytes is accomplished by cell culture with interleukins, with B Cell Receptor (BCR), with T Cell Receptor (TCR) and potentially other means that are not referenced here; the concept presented herein is to obtain leukocytes from buffy coats (WBCs) obtained by centrifugation followed by stimulation for clonal expansion of leukocytes; appropriate interleukins, BCR, or TCR may not be available for the test animal. Cross species experiments are advocated here i.e. attempting to utilize human interleukins for clonal expansion of leukocytes from test animals such as rat, mouse, or guinea pig. No references are provided since no such experiments were identified in the literature. If clonal expansion of leukocytes from a test animal were accomplished then filtration methods common to CBC could achieve separation of cell types. The final step in creating a realistic animal model of MS would be injecting individual cell types into the brains of test animals simulating BBB breach and observing the response. Progression of CNS demyelination in the test animal should be followed by MRI [44]. Traumatic brain injury has been studied in rats by MRI [45]. Creating a lab chow with only some MeCbl to prevent megaloblastic anemia and a large concentration of folic acid would ensure minimal AdoCbl is formed. Odd-carbonnumber fatty acids (FA) could be included in the lab chow diet.
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