1569 replies to this topic

[jabowery]

We developed a compound that is superior in the same fashion and action, but it is not one of the most promising agents in the scope of agents for such targets and conditions, and likewise.

Of the more promising agents, which have been shown to be orally bioavailable past the blood brain barrier in animal models of neurodegeneration?

[xks201]

Jabowery he doesn't even know what he is talking about. He's not even reading the data. lol All I can say is thank god we have him here to save us from properly interpreting data. 

Edited by xks201, 07 September 2014 - 06:58 PM.

[megatron]

As Veritas pointed out, there is something sketchy about this latest study. If you look at figure 7, how the f... do both the scopolamine groups start at at lower latency than the aCSF/dihexa group? That makes no sense. 

[VERITAS INCORRUPTUS]

As Veritas pointed out, there is something sketchy about this latest study. If you look at figure 7, how the f... do both the scopolamine groups start at at lower latency than the aCSF/dihexa group? That makes no sense. 

 

Actually there are a few things sketchy in a few of the studies.  I am very much not looking on pissing on the dihexa parade, but myself and my colleagues thoroughly reviewed all the studies and several related studies and really have come to a conclusion that dihexa is perhaps overhyped and even some bad/questionable science.  Not worthless by any means, but not a best in class agent by any means either.  As I have been saying all along to people, do not trust anything (science or anywhere) where there appears a hype of the nature of "10 Million Times XXXX (anything)".  Overhyped science can be just as corrupt as overhyped marketing of any type.  Still, there is general enough meat on the bones it requires to be certain to do a thorough evaluation and that is indeed what we did.  People who have asked us will note we have said it is of interest, however we are researching it and awaiting some conclusion to our evaluation.  This is it, lol.  (Again, for those quick to jump on that it is being outright 'dissed' and 'dismissed' in entirely, well note that is not what has been stated).

 

Potential agents we are looking at to hopefully release in some fashion sooner than later and that are primarily focused toward BDNF/synaptogenic effects (though may entail others) I can provide the information as follows with greater details that will come with their release:

 

1- A BBB penetrating (proven in our animal models) HGF agonist related to dihexa (we derived this after reviewing all the studies in depth and working on SAR modeling, which sometimes works well, sometimes does not)  Overall we feel it is well superior, enough to consider to patent.

2- Two (or maybe three) agents that modulate the NMDAr with no adverse effects (but do yield positive BDNF/synaptogenic effects)

3- One is a novel modulator of GLuR channels (even may work at sub-mg doses it seems, though variance between animal species exists as to efficacy)

4- One other which is nothing all that intrinsically novel and not at all our invention, but we feel bears offering (also sub-mg)

 

I will go on record that unfortunately none of these agents are 10 Million Times as Effective as BDNF

...though all appear to have significant action at far lower doses than dihexa

 

We also may bring forth the most superior dopamine system modulator that we are developing that seem to improve dysregluated (or even 'healthy') dopaminergic tone in the most significant manner.  Really like this one.

 

Anyway, lots more as well...so we'll hope and see...

Edited by VERITAS INCORRUPTUS, 07 September 2014 - 09:31 PM.

[Strangelove]

 

We also may bring forth the most superior dopamine system modulator that we are developing that seem to improve dysregluated (or even 'healthy') dopaminergic tone in the most significant manner.  Really like this one.

 

 

An approximate timetable for this one? 

[jabowery]

...though all appear to have significant action at far lower doses than dihexa

What route of administration?

[xks201]

 

As Veritas pointed out, there is something sketchy about this latest study. If you look at figure 7, how the f... do both the scopolamine groups start at at lower latency than the aCSF/dihexa group? That makes no sense. 

 

Actually there are a few things sketchy in a few of the studies.  I am very much not looking on pissing on the dihexa parade, but myself and my colleagues thoroughly reviewed all the studies and several related studies and really have come to a conclusion that dihexa is perhaps overhyped and even some bad/questionable science.  Not worthless by any means, but not a best in class agent by any means either.  As I have been saying all along to people, do not trust anything (science or anywhere) where there appears a hype of the nature of "10 Million Times XXXX (anything)".  Overhyped science can be just as corrupt as overhyped marketing of any type.  Still, there is general enough meat on the bones it requires to be certain to do a thorough evaluation and that is indeed what we did.  People who have asked us will note we have said it is of interest, however we are researching it and awaiting some conclusion to our evaluation.  This is it, lol.  (Again, for those quick to jump on that it is being outright 'dissed' and 'dismissed' in entirely, well note that is not what has been stated).

 

Potential agents we are looking at to hopefully release in some fashion sooner than later and that are primarily focused toward BDNF/synaptogenic effects (though may entail others) I can provide the information as follows with greater details that will come with their release:

 

1- A BBB penetrating (proven in our animal models) HGF agonist related to dihexa (we derived this after reviewing all the studies in depth and working on SAR modeling, which sometimes works well, sometimes does not)  Overall we feel it is well superior, enough to consider to patent.

2- Two (or maybe three) agents that modulate the NMDAr with no adverse effects (but do yield positive BDNF/synaptogenic effects)

3- One is a novel modulator of GLuR channels (even may work at sub-mg doses it seems, though variance between animal species exists as to efficacy)

4- One other which is nothing all that intrinsically novel and not at all our invention, but we feel bears offering (also sub-mg)

 

I will go on record that unfortunately none of these agents are 10 Million Times as Effective as BDNF

...though all appear to have significant action at far lower doses than dihexa

 

We also may bring forth the most superior dopamine system modulator that we are developing that seem to improve dysregluated (or even 'healthy') dopaminergic tone in the most significant manner.  Really like this one.

 

Anyway, lots more as well...so we'll hope and see...

 

Where is that text coming from?

[xks201]

 

As Veritas pointed out, there is something sketchy about this latest study. If you look at figure 7, how the f... do both the scopolamine groups start at at lower latency than the aCSF/dihexa group? That makes no sense. 

 

Actually there are a few things sketchy in a few of the studies.  I am very much not looking on pissing on the dihexa parade, but myself and my colleagues thoroughly reviewed all the studies and several related studies and really have come to a conclusion that dihexa is perhaps overhyped and even some bad/questionable science.  Not worthless by any means, but not a best in class agent by any means either.  As I have been saying all along to people, do not trust anything (science or anywhere) where there appears a hype of the nature of "10 Million Times XXXX (anything)".  Overhyped science can be just as corrupt as overhyped marketing of any type.  Still, there is general enough meat on the bones it requires to be certain to do a thorough evaluation and that is indeed what we did.  People who have asked us will note we have said it is of interest, however we are researching it and awaiting some conclusion to our evaluation.  This is it, lol.  (Again, for those quick to jump on that it is being outright 'dissed' and 'dismissed' in entirely, well note that is not what has been stated).

 

Potential agents we are looking at to hopefully release in some fashion sooner than later and that are primarily focused toward BDNF/synaptogenic effects (though may entail others) I can provide the information as follows with greater details that will come with their release:

 

1- A BBB penetrating (proven in our animal models) HGF agonist related to dihexa (we derived this after reviewing all the studies in depth and working on SAR modeling, which sometimes works well, sometimes does not)  Overall we feel it is well superior, enough to consider to patent.

2- Two (or maybe three) agents that modulate the NMDAr with no adverse effects (but do yield positive BDNF/synaptogenic effects)

3- One is a novel modulator of GLuR channels (even may work at sub-mg doses it seems, though variance between animal species exists as to efficacy)

4- One other which is nothing all that intrinsically novel and not at all our invention, but we feel bears offering (also sub-mg)

 

I will go on record that unfortunately none of these agents are 10 Million Times as Effective as BDNF

...though all appear to have significant action at far lower doses than dihexa

 

We also may bring forth the most superior dopamine system modulator that we are developing that seem to improve dysregluated (or even 'healthy') dopaminergic tone in the most significant manner.  Really like this one.

 

Anyway, lots more as well...so we'll hope and see...

 

Where is that text coming from?

[VERITAS INCORRUPTUS]

 

 

We also may bring forth the most superior dopamine system modulator that we are developing that seem to improve dysregluated (or even 'healthy') dopaminergic tone in the most significant manner.  Really like this one.

 

 

An approximate timetable for this one? 

 

 

Still working out the synthesis.  I hope sooner than later.  Sorry cannot say anything more definite.  

 

We wasted too much time/resources finding a strongest route to dihexa (half jk, and for now likely that which will not be pursued; but still not out of the question)

 

There are some moves that needed to be made firstly within this as well, but hopefully if things trend well more information will be made available in a couple of weeks.

[xks201]

Veritas..I am confused. Do you work for the inventor or what ? What are you a chemist.

[VERITAS INCORRUPTUS]

 

...though all appear to have significant action at far lower doses than dihexa

What route of administration?

 

 

Oral animal administration appears effective for most all, though for a couple it appears it may be best if administered within an intranasal manner, though as highly water soluble such is not an issue with even rat models.

 

We'll be discussing this more hopefully soon enough.  Two are based off of relatively obscure endogenous ligands.

[VERITAS INCORRUPTUS]

Veritas..I am confused. Do you work for the inventor or what ? What are you a chemist.

 

TeamTLR, a cooperative of scientists spanning chemists, neuroscientists, neuropharmacologists, animal modeling experts, phytochemists, psychologists, et al.

As well involved are those without degrees who have a knowledge and passion and assist in some manner as well.

 

Some within TeamTLR even have access to drug screen libraries that show 'potent' hits that were not pursued   (both for the target and off-target) 

 

You'd be shocked at how many gems are 'left on the table'.

 

Anyway, the goal is to bring some pretty strong candidates forth for progressive research in these areas, within a primary orientation to pursue agents that will have best benefit for antidepressant, anxiolytic, and other mental/cognitive health conditions.

Edited by VERITAS INCORRUPTUS, 08 September 2014 - 12:27 AM.

[VERITAS INCORRUPTUS]

Just please note, if things trend right with some needed issues, TeamTLR will hopefully bring forth a good deal more within all this.  Some may appreciate it, some may not, but this is a sincere effort to foster greatest progress within critical research areas.  As such, for those so interested please 'stay tuned' and hopefully some things of interests to come.

 

Again, hopefully movements will afford this ability and provide a movement toward betterment for all.

 

Thanks!

Edited by VERITAS INCORRUPTUS, 08 September 2014 - 12:28 AM.

[mindpatch]

Synaptogenesis is a hallmark of two of the most enjoyable recreational drugs, meth and cocaine. No one is saying taking Dihexa isn't fun. It does not seem to cause any cognitive or learning enhancement in healthy subjects. If you have a scopalamine habit it would be very helpful.

What is it with your Quixotic crusade?  

[xks201]

Veritas are you pulling these notes from that system ? Thank you mind patch. His crusade is truly disturbing.

[jabowery]

http://www.cambridgebrainsciences.com/ odd one out test score:

(16+15+14+15+15+13)/6
= 14.666667

Its been a few weeks since I last took the odd one out test or dihexa. This score is consistent with retained training improvements decaying slightly over time out of practice.

PS: I'm impressed by christallire's odd one out test scoring over 20. Perhaps my age related cognitive decline is greater than I had imagined at least in fluid reasoning (my first scores were around 12). Of course christallire may have learned some tricks or, the obvious explanation, have exceptional fluid reasoning capacity. I'm not sure what the relationship is between fluid reasoning and IQ scores but I know in my teens I tested well above the Mensa threshold. If I am, indeed, suffering from a good deal of age related cognitive decline I may resume dihexa at some point since that condition was ameliorated in animal models.

Thus far I have seen no indications of deleterious side effects from Dihexa.
 
I have slowed, if not suspended, further reports due to exingencies in Jan's condition that arose a few days ago.  They were serious enough that I decided to start her on Dihexa before I had intended, but the news, to me, that Dihexa is "1% or less" orally bioavailable has caused me to stop after 2 days pending a less profligate route of administration.  My surgery has been postponed and I'm also stopping my intake as well.  I may or may not start myself on it again depending on Dihexa's availability and my wife's needs.
 
I'll continue to occasionally take the "odd one out" test and Jan will continue to use "Singing Coach" with me recording her high scores and running averages.  I will continue to report the results of my tests as I get around to taking them.
 

No severe apneatic events at 11cm CPAP (2 events went to SpO2=92)
 
21mg dihex oral with morning coffee
 
11am
http://www.cambridgebrainsciences.com/ odd one out test score:
(17+15+16+16+15+14)/6
= 15.5
 
7:45pm
Immediately after dinner, I took the test.  
http://www.cambridgebrainsciences.com/ odd one out test score:
(16+16+16+16+16+14)/6
= 15.666667
 
This is the highest score so far and its consistent with earlier in the day. 
It appears a good night's sleep is really important -- not that that's too surprising.
 
 
 

A few severe apneatic events (SpO2<88%) -- probably obstructive rather than central so will raise CPAP pressure 10% tonight to see if it improves
Phone call woke me up after 6 hours of sleep.
 

I decided to continue the "food taster" role for Jan as she is still establishing a baseline learning rate with Singing Coach and it looks like the Nyles7 synthesis will eventually come through.
 

22mg dihexa oral with breakfast
 
2pm
Physician visit bp 100/74 -- borderline low
This not inconsistent with other physician visits
It is, however, very inconsistent with home bp meter
Sunbeam Model 7652 which consistently reports high normal to borderline hypertensive
Next physician's visit I'll calibrate
 
10:45pm
http://www.cambridgebrainsciences.com/ odd one out test score:
(16+15+12+13+15+12)/6
= 13.833333

Lower score (still higher than initial 2 groups of tests).
Sleep debt?
 

Made 4 or 5 mistakes that counted negatively.
 

Yesterday:
25mg Dihexa oral before breakfast
 
Cambridge sciences website was not responsive when I tried to take the 'Odd One Out' test at the usual time of day (evening).
 
Today:
 
I acquired a blood pulse oximeter to monitor apneatic events as I have had a recent change of CPAP pressure.  There were a few last night with a low SpO2 of 90% -- not too bad unless it is interfering with slow wave sleep, which is a good chance.  Unfortunately my Zeo headband is way old and there are no replacement electrodes on the market.
 
20mg Dihexa oral with coffee before breakfast
 
9pm 
http://www.cambridgebrainsciences.com/ odd one out test score:
(17+16+15+14+14+13)/6
= 14.833333
 
I'm not really interested in the slight decline in average score from last time (15) but I find the downward trend over today's 6 tests interesting.  Fatigue?
 
I'm a bit concerned about the news that Nyles7 synthesis didn't pass the purity test.  I may need to cut shorter than I would have liked my safety "food taster" role for Jan.
 
 

http://www.cambridgebrainsciences.com/ odd one out test score:
(16+13+16+15+15+15)/6
= 15
 
This is a rather large score increase.  
 
The earlier puzzles in a test are the easier ones and an interesting phenomenon is that this time through I took longer on a few of the easier (earlier) puzzles than I did on prior days, leaving less time to solve the harder puzzles that come later in the test.  I don't have quantitative measures on this phenomenon unfortunately.  This wasn't a strong effect but I did notice it.
 
It would be interesting to see how it compares with the performance increases experienced by others taking the "odd one out" test.  Do others get slower on the earlier ones as they get better overall or is this just a fluke occurance for me on this test today?  It would also be interesting to see how much random variance there is in the difficulty of a series of these tests.  Is anyone familiar enough with that system to tell me where to look?
 
I hesitate to interject my subjective experience of taking this test.  I will say I didn't sleep as well last night as I did the night before.  I had to take multiple naps today.
 
20mg dihexa oral after dinner
 
 

Cambridge Brain Sciences "Odd One Out" test scores:

(13+14+12+15+15+14)/6
= 13.833333
 
Higher score possibly attributable to better setting on CPAP machine as well as training.
I did make a few mistakes this time, but made up for them by getting more right on the same run.  
 

Noticed muscle spasms with slight cramps in right lower bicep/tricep in the middle of the night last night.
I've been using my right arm a lot due to my left arm needing upcoming surgery.
Also possibly related to genetic cramping condition.
 

20mg dihexa oral after dinner
 
I'm increasing my rate of intake of dihexa due to the upcoming surgery which will introduce noise into measurements taken afterwards.  If there are ill effects I'd prefer to see them before surgery.  I'm going to stop prior to surgery and then start Jan after surgery if I don't notice ill effects prior to surgery.
 
PS:  If I had it to do over again, I'd probably choose a test with more sensitivity than "Odd One Out" to improvements on the high end.  The distribution of scores on that test have a steeply descending slope on the high side of the mode (it's skewed to the right quite a bit).  In other words, a little score improvement represents a substantially greater increase in difficulty on the high side than on the low side.  Perhaps a better statistical moment to look for than left-skewness would be lower kurtosis.
 

 

Cambridge Brain Sciences "Odd One Out" test scores:

(12+15+13+15+12+15)/6
= 13.666667
 
(This increase is almost certainly entirely due to normal training and not due to the prior dihexa dose.  I learned that there was a penalty for guessing when stumped and little likelihood of additional correct choices after guessing.  I just stopped guessing when stumped.)
 
Then took 20mg dihexa orally* on empty stomach.
 
Again, mild short-lived increase in blood pressure.
 
*I shifted to oral since this is the most likely mode of administration for Jan.
 

Pre-dihexa Cambridge Brain Sciences "Odd One Out" test score skewed low with mode (mean and median) of 12 and high of 16.
 
10mg nasal insufflation.  Mild increase in blood pressure for several minutes then return to normal.  
 
Mild and immediate subjective effects will not be reported.

Edited by jabowery, 08 September 2014 - 01:37 AM.

[christallire]

 

140lb male

 

NOTE: also taking Uridine, CDPCholine, o-3(w/ high DHA,EPA), Vinpocetine, Multi vitamin (RDA), Vitamin B Complex, E Complex, D, K2, Calcium, Magnesium, AL-Carnitine, Alpha Lipoic Acid, Milk Thistle, Lion's Mane, Methyl Folate, Gingko, Gotu, CoQ10, P.Serine -- to provide building blocks/prevent deficit/regulate blood thickening, thinning

 

 

9/2, QD, 25mg, sub, no REM

noticed mild increase of bp, have to swallow some of it because of there was too many saliva while sublingual administration.

no notable positive / negative affect

 

Lumosity 1520 / no significant difference

O1O 22pt / not changed

D4B / not changed

 

also, i'm started to learning spanish using subliminal/by just hearing w/o textbook method (just like babies), able to recall/understand some of words after woke up, most of em is still jiberish to me

 

 

9/3, QD, 25mg, sub,

noticed moderate increase of bp about 10~20 second after administrating it, and i'm getting used to sublingual administration, noticed some of it or most of it is not absorbed at all

no notable positive / negative affect

 

Lumosity 1520 / no significant difference

O1O 22pt / not changed

D4B / not changed

 

I'm also thinking about DMSO(transdermal) administration but i'm avoiding it since it releases substance into bloodstream very slowly. (just like nicotine patch)

 

 

- Had slight headache(or stimulating) yesterday, disappeared after having dinner. glucose/glutamate deficit? (having low carb diet)

 

9/4, QD, 25mg, sub, no REM

noticed mild increase of bp about 30 second after administrating it

no notable positive / negative affect

 

Lumosity 1520 / no significant difference

O1O 22pt / not changed

D4B / not changed

Resistance training / no significant difference

 

One thing I noticed today while absorbing it, I was staring at wall. and felt that shades on wall is unusually solid.

Also I personally thinks no significant difference means that not saying nothing is happening in my brain.

It might everything would be a such a big placebo or not, but i'll report what i feel, what i think.

Will keep watch and provide more report at you guys.

 

 

9/5 (25mg). 9/6 (25mg), 9/7 (50mg), nasal, no REM

switched to nasal, felt like first time smoking after long time of ceasing it

noticed mild increase of bp

no notable positive / negative affect

at 9/7 i got upset stomach and followed by white muddy poop (i have no idea this is contributed by dihexa tho)

 

Lumosity 1570 / increased by 50, but i doubt it's due to dihexa

O1O 22pt / not changed

D4B / not changed, things more gotten easier tho, but lots of noise

Resistance training / did none, busy like hell these days

 

jabowery, I was always been good at pattern recognition (things like odd one out) since childhood, so no worries. i tested it to my friends they averaged 16pt

and I noticed O1O is poorly designed test, i considering to ditch it.

 

I'm really, really busy ATM. i did 2 days overnight working (48 hours straight), consuming lots of taurine, caffeine, nicotine. I'm worried about this negates test results..

 

I recommend everyone who wants to get good memory, I recommend doing painting. my colleagues, doing painting/artwork, everyone of them got almost perfect score (0.1%) at lumocity memory tests.. wow.

Edited by christallire, 08 September 2014 - 02:22 AM.

[jabowery]

50mg dihexa nasal insufflation

http://www.cambridgebrainsciences.com/ odd one out test score:
(14+13+16+13+14+14)/6
= 14

Obviously no immediate benefit measured for O1O (nor particularly expected). I was rather tired/brain-fogged from a coffee/caffeine crash before I took the dihexa so I'm not surprised at the lower score. Equally obviously it takes time to grow connections so follow up tests are in order.

At some point I may follow xks201's repeated admonishments exactly (30mg to 50mg oral on empty stomach) but I figured this was probably the best way to see for myself if there was some kind of threshold/loading dose effect at his last 100mg oral dose without using up a whole 100mg. With the next batch of dihexa arriving soon, I may increase Jan's dose so that's another reason to test xks201's theory on myself first.
 

http://www.cambridgebrainsciences.com/ odd one out test score:

(16+15+14+15+15+13)/6
= 14.666667

Its been a few weeks since I last took the odd one out test or dihexa. This score is consistent with retained training improvements decaying slightly over time out of practice.

PS: I'm impressed by christallire's odd one out test scoring over 20. Perhaps my age related cognitive decline is greater than I had imagined at least in fluid reasoning (my first scores were around 12). Of course christallire may have learned some tricks or, the obvious explanation, have exceptional fluid reasoning capacity. I'm not sure what the relationship is between fluid reasoning and IQ scores but I know in my teens I tested well above the Mensa threshold. If I am, indeed, suffering from a good deal of age related cognitive decline I may resume dihexa at some point since that condition was ameliorated in animal models.


 

Thus far I have seen no indications of deleterious side effects from Dihexa.
 
I have slowed, if not suspended, further reports due to exingencies in Jan's condition that arose a few days ago.  They were serious enough that I decided to start her on Dihexa before I had intended, but the news, to me, that Dihexa is "1% or less" orally bioavailable has caused me to stop after 2 days pending a less profligate route of administration.  My surgery has been postponed and I'm also stopping my intake as well.  I may or may not start myself on it again depending on Dihexa's availability and my wife's needs.
 
I'll continue to occasionally take the "odd one out" test and Jan will continue to use "Singing Coach" with me recording her high scores and running averages.  I will continue to report the results of my tests as I get around to taking them.
 

No severe apneatic events at 11cm CPAP (2 events went to SpO2=92)
 
21mg dihex oral with morning coffee
 
11am
http://www.cambridgebrainsciences.com/ odd one out test score:
(17+15+16+16+15+14)/6
= 15.5
 
7:45pm
Immediately after dinner, I took the test.  
http://www.cambridgebrainsciences.com/ odd one out test score:
(16+16+16+16+16+14)/6
= 15.666667
 
This is the highest score so far and its consistent with earlier in the day. 
It appears a good night's sleep is really important -- not that that's too surprising.
 
 
 

A few severe apneatic events (SpO2<88%) -- probably obstructive rather than central so will raise CPAP pressure 10% tonight to see if it improves
Phone call woke me up after 6 hours of sleep.
 

I decided to continue the "food taster" role for Jan as she is still establishing a baseline learning rate with Singing Coach and it looks like the Nyles7 synthesis will eventually come through.
 

22mg dihexa oral with breakfast
 
2pm
Physician visit bp 100/74 -- borderline low
This not inconsistent with other physician visits
It is, however, very inconsistent with home bp meter
Sunbeam Model 7652 which consistently reports high normal to borderline hypertensive
Next physician's visit I'll calibrate
 
10:45pm
http://www.cambridgebrainsciences.com/ odd one out test score:
(16+15+12+13+15+12)/6
= 13.833333

Lower score (still higher than initial 2 groups of tests).
Sleep debt?
 

Made 4 or 5 mistakes that counted negatively.
 

Yesterday:
25mg Dihexa oral before breakfast
 
Cambridge sciences website was not responsive when I tried to take the 'Odd One Out' test at the usual time of day (evening).
 
Today:
 
I acquired a blood pulse oximeter to monitor apneatic events as I have had a recent change of CPAP pressure.  There were a few last night with a low SpO2 of 90% -- not too bad unless it is interfering with slow wave sleep, which is a good chance.  Unfortunately my Zeo headband is way old and there are no replacement electrodes on the market.
 
20mg Dihexa oral with coffee before breakfast
 
9pm 
http://www.cambridgebrainsciences.com/ odd one out test score:
(17+16+15+14+14+13)/6
= 14.833333
 
I'm not really interested in the slight decline in average score from last time (15) but I find the downward trend over today's 6 tests interesting.  Fatigue?
 
I'm a bit concerned about the news that Nyles7 synthesis didn't pass the purity test.  I may need to cut shorter than I would have liked my safety "food taster" role for Jan.
 
 

http://www.cambridgebrainsciences.com/ odd one out test score:
(16+13+16+15+15+15)/6
= 15
 
This is a rather large score increase.  
 
The earlier puzzles in a test are the easier ones and an interesting phenomenon is that this time through I took longer on a few of the easier (earlier) puzzles than I did on prior days, leaving less time to solve the harder puzzles that come later in the test.  I don't have quantitative measures on this phenomenon unfortunately.  This wasn't a strong effect but I did notice it.
 
It would be interesting to see how it compares with the performance increases experienced by others taking the "odd one out" test.  Do others get slower on the earlier ones as they get better overall or is this just a fluke occurance for me on this test today?  It would also be interesting to see how much random variance there is in the difficulty of a series of these tests.  Is anyone familiar enough with that system to tell me where to look?
 
I hesitate to interject my subjective experience of taking this test.  I will say I didn't sleep as well last night as I did the night before.  I had to take multiple naps today.
 
20mg dihexa oral after dinner
 
 

Cambridge Brain Sciences "Odd One Out" test scores:

(13+14+12+15+15+14)/6
= 13.833333
 
Higher score possibly attributable to better setting on CPAP machine as well as training.
I did make a few mistakes this time, but made up for them by getting more right on the same run.  
 

Noticed muscle spasms with slight cramps in right lower bicep/tricep in the middle of the night last night.
I've been using my right arm a lot due to my left arm needing upcoming surgery.
Also possibly related to genetic cramping condition.
 

20mg dihexa oral after dinner
 
I'm increasing my rate of intake of dihexa due to the upcoming surgery which will introduce noise into measurements taken afterwards.  If there are ill effects I'd prefer to see them before surgery.  I'm going to stop prior to surgery and then start Jan after surgery if I don't notice ill effects prior to surgery.
 
PS:  If I had it to do over again, I'd probably choose a test with more sensitivity than "Odd One Out" to improvements on the high end.  The distribution of scores on that test have a steeply descending slope on the high side of the mode (it's skewed to the right quite a bit).  In other words, a little score improvement represents a substantially greater increase in difficulty on the high side than on the low side.  Perhaps a better statistical moment to look for than left-skewness would be lower kurtosis.
 

 

Cambridge Brain Sciences "Odd One Out" test scores:

(12+15+13+15+12+15)/6
= 13.666667
 
(This increase is almost certainly entirely due to normal training and not due to the prior dihexa dose.  I learned that there was a penalty for guessing when stumped and little likelihood of additional correct choices after guessing.  I just stopped guessing when stumped.)
 
Then took 20mg dihexa orally* on empty stomach.
 
Again, mild short-lived increase in blood pressure.
 
*I shifted to oral since this is the most likely mode of administration for Jan.
 

Pre-dihexa Cambridge Brain Sciences "Odd One Out" test score skewed low with mode (mean and median) of 12 and high of 16.
 
10mg nasal insufflation.  Mild increase in blood pressure for several minutes then return to normal.  
 
Mild and immediate subjective effects will not be reported.

Edited by jabowery, 09 September 2014 - 12:43 AM.

[FW900]

Man, these quoted quotes of quotes are really making things confusing. So this thread stays tidy, I suggest anyone quoting a post that is quote heavy, to hack out the irrelevant quotes.

[VERITAS INCORRUPTUS]

Man, these quoted quotes of quotes are really making things confusing. So this thread stays tidy, I suggest anyone quoting a post that is quote heavy, to hack out the irrelevant quotes.

 

It doesn't take genius level enhanced cognition to heed that suggestion (which should have been obvious, but apparently some need the enhancement j/k)

[StevesPetRat]

Man, these quoted quotes of quotes are really making things confusing. So this thread stays tidy, I suggest anyone quoting a post that is quote heavy, to hack out the irrelevant quotes.

Dude, if you were on dihexa, following these nested quotes would be no problem.

[jabowery]

Man, these quoted quotes of quotes are really making things confusing. So this thread stays tidy, I suggest anyone quoting a post that is quote heavy, to hack out the irrelevant quotes.

 
It doesn't take genius level enhanced cognition to heed that suggestion (which should have been obvious, but apparently some need the enhancement j/k)

What level IQ does it take to realize that the forum equivalent of a lab log is maintained by responding only to, and retaining the quotes from, the prior entry in the log?

Now, I'll agree it perhaps does take a genius level IQ to realize that there should be an option other than "Quote" which merely links back to the prior comment one is responding to rather than including the entire text. Although then one has to click through each link to get to the prior log entry.

One thing is for sure: It doesn't take a genius level IQ to bicker about whether a forum thread is the right place for a lab log. What are the alternatives in your opinion?

Edited by jabowery, 09 September 2014 - 07:06 AM.

[FW900]

What level IQ does it take to realize that the forum equivalent of a lab log is maintained by responding only to, and retaining the quotes from, the prior entry in the log?

Now, I'll agree it perhaps does take a genius level IQ to realize that there should be an option other than "Quote" which merely links back to the prior comment one is responding to rather than including the entire text. Although then one has to click through each link to get to the prior log entry.

One thing is for sure: It doesn't take a genius level IQ to bicker about whether a forum thread is the right place for a lab log. What are the alternatives in your opinion?

 

 

I wasn't criticizing you or your log. I've been reading it and I find it extremely interesting and I, for one, am glad that you are posting it. I'm not bickering, I said it in a lighthearted manner that wasn't even intended to offend.

 

Any users, especially mobile users, will have difficulty navigating through this many quotes though. It is not just your log; almost any long thread on Longecity tends to be a quote-heavy and there are posts outside of yours that are heavily quoted. And, people will reply to your log eventually, and may quote the entire thing. If anything, recommending that people remove irrelevant quotes in their post, will make it easier for you to see what they're talking about when they reply to your log.

 

Alternatives? For your log, I personally would put the earlier entries in a collapsible spoiler:

 

Spoiler

Example

 

To do so, just use the following BB code:

[spoiler] TEXT
[/spoiler]

[jabowery]

Now that's genius (or at least well informed, salient, helpful, etc.).

PS: It does seem that some interlocutors are here acting in bad faith.

Spoiler

 

What level IQ does it take to realize that the forum equivalent of a lab log is maintained by responding only to, and retaining the quotes from, the prior entry in the log?

Now, I'll agree it perhaps does take a genius level IQ to realize that there should be an option other than "Quote" which merely links back to the prior comment one is responding to rather than including the entire text. Although then one has to click through each link to get to the prior log entry.

One thing is for sure: It doesn't take a genius level IQ to bicker about whether a forum thread is the right place for a lab log. What are the alternatives in your opinion?

 
I wasn't criticizing you or your log. I've been reading it and I find it extremely interesting and I, for one, am glad that you are posting it. I'm not bickering, I said it in a lighthearted manner that wasn't even intended to offend.
 
Any users, especially mobile users, will have difficulty navigating through this many quotes though. It is not just your log; almost any long thread on Longecity tends to be a quote-heavy and there are posts outside of yours that are heavily quoted. And, people will reply to your log eventually, and may quote the entire thing. If anything, recommending that people remove irrelevant quotes in their post, will make it easier for you to see what they're talking about when they reply to your log.
 
Alternatives? For your log, I personally would put the earlier entries in a collapsible spoiler:
 

Spoiler

Example

 
To do so, just use the following BB code:

[spoiler] TEXT
[/spoiler]

[VERITAS INCORRUPTUS]

No real criticism here either, just indeed noting FW900 was giving sound advice. Was in same spirit as he.  It is fine contribution, though we can always look to refine our approaches.

[xks201]

Thank you Jabowery for meticulously logging your results.

[Infinityandbeyond]

Thank you Jabowery for meticulously logging your results.

 

agree very helpful and appreciated

[christallire]

Well, this is REALLY awkward.

 

I had strange situation today while working. (And I did overnight working, again, couldn't take dihexa for two days)

 

Usually I couldn't remember exact phrases/words written in the book

But I was able to recall all of phrases/words in few pages I read before sleeping yesterday.

 

It was.. like.. I was extremely busy concentrated to working and typing. Then suddenly two or three pages are poping up from my mind regardless of my will and it's not related to work either.

pages are.. not exactly photogenic but sort of.. 'letters on the big transparent plastic paper' is floating around.

 

Really strange.

 

I wants to be objective and don't wanna post placebo but this is really strange,

 

I will report more what happens.

 

P.S isn't dihexa supposed to be synaptogenesis? is this some kind of noise? i have recently changed my diet to healthy carb diet, could it be related? i had many caffeins from coffee and also had lots of green tea.  could this affect? And I tried to recall other pages but I coudn't. very confusing.

Edited by christallire, 11 September 2014 - 10:51 PM.

[jabowery]

Jan's singing has objectively improved.  She has not, in my subjective opinion, substantially improved in other areas except perhaps in attitude and motivation to participate in Singing Coach practice.  This, not being a double blind randomized clinical trial, etc. no strong conclusions may be drawn.  The reemergence of her insomnia, after it had degenerated into hypersomnolence (serious enough that she was recommended for sleep study), is consistent with a "reversal" of sorts.  Her improvement is consistent with training effect but if so it recommends Singing Coach as a treatment for Huntington's Disease if for no other reason than the improvements achievable from training boost morale.
 
From here I'm going to try to find a computer-based speech therapy system similar to Singing Coach.  Jan's speech is hard to understand and it has a serious impact on her quality of life.
 
Details in the "spoiler" below:

Spoiler

Images are screenshots of the Singing Coach score board. The dates of the screenshots are given by the image's gallery title.







 

8/16
21mg dihexa before breakfast



 

8/17
20mg before breakfast





 

8/24
10mg before breakfast
restarted daily coffee to overcome hypersomnolence
had stopped caffine to inhibit urinary incontinence
but big ben computer program on the hour reminding
her to empty her bladder seemed to inhibit incontinence 
 
8/25
10mg before breakfast



 

8/26
?mg before breakfast
10mg were measured but due to movement disorder much of the dose was spilled



 

8/27
9mg after breakfast
had some trouble getting to sleep even without coffee
 
8/28
10mg before breakfast
seems more energetic, had trouble getting to sleep again even without coffee
expressed boredom with movies for the first time
singing coach scores seem to be improving



 

8/29
11mg before breakfast
 
8/30
9mg before breakfast
 
9/1
11mg before breakfast
 
9/2
10mg after breakfast
Singing coach session scores for today lost due to computer crash.
 
9/3
11mg before breakfast
Fairly dramatic increase in singing coach score over last recorded score (8/28).



 

9/4
10mg before breakfast
 
9/5
11mg before breakfast



 

9/6
10mg before breakfast
In Singing Coach she switched from baritone to alto



 

9/7
9mg before breakfast



 

9/8
10mg before breakfast



 

9/9
9mg before breakfast
Jan left off "Easy" and started "Medium" difficulty songs in Singing Coach



 

9/10
10mg before breakfast



 

9/11
11mg before breakfast
 

Insofar as Jan's Huntington's, since:

• I haven't seen any deleterious effects in myself or reported from others (or, for that matter, from the animal models),
• I can't find unequivocal evidence of greater bioavailability via subcutaneous injection (see my prior post regarding the patent on hydrophobic drug administration)
• I'm still hopeful that the Nyles7 synthesis will come through

I've decided on a compromise solution to the problem of limited supply in the face of the purported low (1%) oral bioavailability:
 
10mg daily oral
 
Thus far she's received:
 
8/16 21mg, 8/17 20mg, hiatus as I reconsidered route of administration, 8/24 10mg, 8/25 10mg, 8/26 10mg, 8/27 9mg
 
This is all oral and I try, usually with success, to make it before she's eaten in the morning.  There was some wastage in these early doses as I dealt with oral administration issues like the hydrophobic nature of dihexa and the fact that Jan's movement disorder doesn't permit me to dump the milligram-scale measured dose directly from the weighing paper into her open mouth.  I've settled on taking a very small square of paper towel, pouring the dihexa onto it and rolling it up as a quasi-capsule.
 
The data from Singing Coach is limited to the current high score achieved in each of a number (about 10) of "easy" songs like "Twinkle Twinkle Little Star", "The Farmer in the Dell", etc.  They don't let you capture even that data without manually transcribing it from their interface, so I haven't yet recorded it in any form other than screen shots.  Nor do I have the time to monitor her sessions with SC even if I could schedule her sessions.  Any time she feels up to it is a good time for her to try to tolerate SC and I'm surprised she can tolerate it as well as she has during the establishment of her baseline given her debilitated state in stark contrast with her history as an opera singer.  If she doesn't improve I suspect she will become discouraged but I have tried to moderate her expectations.

 

Edited by jabowery, 11 September 2014 - 11:06 PM.

[StevesPetRat]

Jan's singing has objectively improved. She has not, in my subjective opinion, substantially improved in other areas...

Hi jabowery, I am very impressed with your diligence and determination in the face of such a tragic disease affecting your beloved. It may have been suggested before, and you probably even thought of it (in fact, now I am having a sense of déjà vu), but is there somebody who could see Jan every month or two to check on her progress? I imagine the most potent benefits of dihexa will also be the most gradual, and it might hearten you to learn of these when you might miss them in the daily ups and downs.

Yeah, 90% sure this approximate suggestion has been made before, but going to add to the thread count anyway...