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nanila posting in

It's challenge time!

Comment with Just One Thing you've accomplished in the last 24 hours or so. It doesn't have to be a hard thing, or even a thing that you think is particularly awesome. Just a thing that you did.

Feel free to share more than one thing if you're feeling particularly accomplished! Extra credit: find someone in the comments and give them props for what they achieved!

Nothing is too big, too small, too strange or too cryptic. And in case you'd rather do this in private, anonymous comments are screened. I will only unscreen if you ask me to.

Go!

siderea

2025 Dec 24: ScienceDaily [press release?]: "Scientists reverse Alzheimer’s in mice and restore memory":

By examining both human Alzheimer's brain tissue and multiple preclinical mouse models, the team identified a key biological failure at the center of the disease. They found that the brain's inability to maintain normal levels of a critical cellular energy molecule called NAD+ plays a major role in driving Alzheimer's. Importantly, maintaining proper NAD+ balance was shown to not only prevent the disease but also reverse it in experimental models.

WARNING WARNING WARNING: Yes, there are OTC supplements for tinkering with your NAD+, but they are apparently/allegedly CARCINOGENIC (cause CANCER) at typical doses. DO NOT run out and do something stupid. Tinkering with your whole-body cellular metabolism has some gnarly failure modes. From this article:

Why This Approach Differs From Supplements

Dr. Pieper cautioned against confusing this strategy with over the counter NAD+-precursors. He noted that such supplements have been shown in animal studies to raise NAD+ to dangerously high levels that promote cancer. The method used in this research relies instead on P7C3-A20, a pharmacologic agent that helps cells maintain healthy NAD+ balance during extreme stress, without pushing levels beyond their normal range.

Continuing from the article:

NAD+ levels naturally decline throughout the body, including the brain, as people age. When NAD+ drops too low, cells lose the ability to carry out essential processes needed for normal function and survival. The researchers discovered that this decline is far more severe in the brains of people with Alzheimer's. The same pattern was seen in mouse models of the disease.

[...]

Amyloid and tau abnormalities are among the earliest and most significant features of Alzheimer's. In both mouse models, these mutations led to widespread brain damage that closely mirrors the human disease. This included breakdown of the blood-brain barrier, damage to nerve fibers, chronic inflammation, reduced formation of new neurons in the hippocampus, weakened communication between brain cells, and extensive oxidative damage. The mice also developed severe memory and cognitive problems similar to those seen in people with Alzheimer's.

[...]

This approach built on the group's earlier work published in Proceeding of the National Academy of Sciences USA, which showed that restoring NAD+ balance led to both structural and functional recovery after severe, long-lasting traumatic brain injury. In the current study, the researchers used a well-characterized pharmacologic compound called P7C3-A20, developed in the Pieper laboratory, to restore NAD+ balance.

The results were striking. Preserving NAD+ balance protected mice from developing Alzheimer's, but even more surprising was what happened when treatment began after the disease was already advanced. In those cases, restoring NAD+ balance allowed the brain to repair the major pathological damage caused by the genetic mutations.

Both mouse models showed complete recovery of cognitive function. This recovery was also reflected in blood tests, which showed normalized levels of phosphorylated tau 217, a recently approved clinical biomarker used to diagnose Alzheimer's in people. These findings provided strong evidence of disease reversal and highlighted a potential biomarker for future human trials.

Note, potential conflict of interest: the head of the lab, Dr Pieper, above, has a serious commercial interest in this proving out:

The technology is currently being commercialized by Glengary Brain Health, a Cleveland-based company co-founded by Dr. Pieper.

The actual research article:

2025 Dec 22: Cell Reports Medicine [peer-reviewed scientific journal]: Pharmacologic reversal of advanced Alzheimer's disease in mice and identification of potential therapeutic nodes in human brain by Kalyani Chaubey et al. (+35 other authors!):

Abstract:

Alzheimer's disease (AD) is traditionally considered irreversible. Here, however, we provide proof of principle for therapeutic reversibility of advanced AD. In advanced disease amyloid-driven 5xFAD mice, treatment with P7C3-A20, which restores nicotinamide adenine dinucleotide (NAD+) homeostasis, reverses tau phosphorylation, blood-brain barrier deterioration, oxidative stress, DNA damage, and neuroinflammation and enhances hippocampal neurogenesis and synaptic plasticity, resulting in full cognitive recovery and reduction of plasma levels of the clinical AD biomarker p-tau217. P7C3-A20 also reverses advanced disease in tau-driven PS19 mice and protects human brain microvascular endothelial cells from oxidative stress. In humans and mice, pathology severity correlates with disruption of brain NAD+ homeostasis, and the brains of nondemented people with Alzheimer's neuropathology exhibit gene expression patterns suggestive of preserved NAD+ homeostasis. Forty-six proteins aberrantly expressed in advanced 5xFAD mouse brain and normalized by P7C3-A20 show similar alterations in human AD brain, revealing targets with potential for optimizing translation to patient care.

Full text here: https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(25)00608-1

kaberett

... which meant I thought it was very funny when later said afternoon I became aware that there's ongoing scrutiny of their operations from the Business and Trade Committee (first link I could find, it's bedtime). Also very funny that the time from name change to shed legacy of being Awful to Nah You're Still Awful was approximately -5, on a more national scale than I'd previously clocked...

cosmolinguist

I wrote and sent (luckily could retrieve in time!!) an email to them from my erik@ address, rather than the Gmail address I've had since 2004 and use for bank stuff and parent stuff and... that's about it now.

I have never even started to do such a thing before, I don't know what happened here! I'm feeling fine today, so for my brain to be so addled is very weird!

Luckily (??), emails sent from the erik@ account from my phone often bring up an error message that means I have to fiddle around a bit to get them sent, and when that happened this time my blood ran cold and I quickly deleted the email altogether. It never got from "outbox" to "sent" so that should be okay!

But sheesh what a near miss!

It was an email about my birthday present too so very obviously from me, I couldn't say it was just spam or something.

andrewducker

Christmas Eve dog walk
Original is here on Pixelfed.scot.

andrewducker

1. The seven reasons why reversing Brexit won't happen (at least neither quickly nor easily): (tags:UK Europe doom trade )

rmc28

Turns out one of my uni hockey friends has a long-standing history channel on YouTube, and of course he made a video about ice hockey history. I think I'd have liked it even if I didn't know the creator, enjoy:

Watch on YouTube

nanila posting in

awesomeers

kaberett

Slightly to my surprise, earlier today I got a text from my GP saying approximately "yes your serum ferritin is now 'normal', but also, uh, by this we mean '15, with a reference range of 13-150, after six weeks of supplements', so... keep taking the supplements and we'll retest in six weeks!!!"

It is possible that the reason this actually got flagged at all was in fact that I've got a slightly elevated white cell count, and had I just had normal serum ferritin I'd have had to submit the "uhhh sooooo..." eConsult. Which I'd been gearing up to do, because the serum ferritin result showed up in the NHS app sooner than anything else!

Unfortunately, I had been working myself up to mentioning some Possible Additional Signs Of Concern in said eConsult (the various unimportant bleeding, like "there is usually old blood when I blow my nose BUT/AND I am very much using a steroid nasal spray every day") and I now have a solid excuse to keep putting it off for another six weeks, but hey. No longer officially anaemic! Pity about what's going to happen when I run out of supplementary iron, huh!

wychwood

Christmas is here aaaaaaah I am somehow not mentally prepared for Christmas Eve to be tomorrow.

However, all my preparations are sorted except for the things I need to do on Christmas morning, and I have done the tragic washing up so my house is ready for me to mostly abandon it for a couple of days.

Choir went pretty well - our Christmas concerts have had real issues with falling audience numbers for the last few years; we used to sell out four or five concerts, but lately it's been more like "two or three half-full". So this year they obviously decided to try something new, and we did three different, although overlapping, concerts with different vibes - two were basically sold out, and the third was all but the top tier, which only had about 50 people in it, but was probably still better turnout than any of the concerts last year. So it looks like that has worked, and we can expect more of that in the future.

We did a lot more "popular" music - White Christmas, Mariah Carey, the JoBros, Shakin' Stevens... I'm kind of torn, because I'm not really good at that sort of thing, and I'm not really sure why you would want to come and see us do "Like It's Christmas" rather than a rock or pop choir, whereas we can do you a genuinely excellent rendition of O Magnum Mysterium or Stars or something like that which plays to our strengths. But the audiences really seemed to enjoy it, and most of the songs were quite fun to sing. And we did do Darius Battiwalla's arrangement of "O Holy Night", which is gloriously over-the-top (the bit where the fortissimo orchestra drops out from under the chorus!).

Our conductor kept encouraging us to "bop" while singing the more fun pieces, but I really wasn't sold - the community choir were doing something similar, and frankly I thought it looked messy and distracting no matter how often he claimed it was essential for the music. I think you do actually need to do properly synchronised movement if you want it to look good (NB: I absolutely do not want to do properly synchronised movement either! this is not why I am in a choir!).

Tomorrow I'm going for brunch with Miss H and then over to my parents', probably to help with last-minute prep before the rest of the family arrive! I won't see them, though, because I'll be off to church before they get there. That will be a Christmas Day treat.

brainwane

looking forward to the next episode of Pluribus

starting to read the scifi mystery Murder by Memory by Olivia Waite

making note of the upcoming Grolier Club exhibition on the mechanization of printing: "The Second Printing Revolution: Invention of Mass Media", starting January 14

thinking about whether I could make some use of the new Rx Inspector tool from Pro Publica

spreading word of the Otherwise Award's year-end fundraising campaign to celebrate scifi/fantasy/genre fiction that expands or explores our notions of gender (I'm on the board)

teaching activists how to use Signal features -- usernames, disappearing messages, nicknames, etc. -- to preserve privacy and improve convenience

listening to episodes of KEXP's Runcast (music) and an Australian guy's One Man, One Hammock (rambling monologues) as I do chores

playing an ad hoc guessing game with my spouse where I look up random records on the Guinness world records website and ask him to guess, e.g., how tall the tallest chocolate fountain is

dithering on whether to write a year-end retrospective for my blog

cosmolinguist

I started introducing it this way in 2023:

The questions here sometimes feel random and sometimes aren't very relevant to me (how many one-night stands, bless; that feels like such a fossil of the height-of-LJ days when I first encountered this meme), but I do like it as a way to think a bit differently than I normally do about my life, and some things that had a big impact on me (like what a dog-hospital year it was for Gary) barely show up here. I do find myself at random points through the year noting things I do that I haven't done before, or wondering what my musical discovery might be, or whatever.

So here we go for 2025

1. What did you do in 2025 that you'd never done before?:
Wrote an extensive as the writer and basically project lead on a report at work -- never did this before, did it three times in a row this year. Met a person from the internet and ended up having sex with them the same day. (Sorry if this is tmi, there will be no more details about it.)

2. Did you keep your new year's resolutions, and will you make more for next year?:
I didn't call it a resolution but when asked later about what I'd like to have this year that I lacked the previous one, I said

Another sexual and/or romantic partner? This feels impossible but so do the last four years' worth of things and they all happened!

Like three days after I wrote this I started talking to somoene on the social media site that's basically a kinky version of Facebook which, like regular Facebook, you can only access if you have an account and I was getting memes and events linked to by a friend until I got fed up and made an account. Six months later, I got a random message from someone who wrote a comment that I'd "liked" (as with Facebook, it tells you when people like your shit and then you can go look at their profile and all that) and in August I met him and it was fun to have a no-strings arrangement with a friend.

Will I make more for next year? I'm not sure, I think the coming year is more about keeping what I have stable: work, house, relationships, friendships, life....

( +47 )

50. What are your plans for 2026?
Laat year I wrote

Try to help everyone survive it with as much comfort and joy as we can manage, especially in the U.S. but everywhere really.

And I don't think I can improve on that answer either.

In a lot of ways it's been a rough year: the quick and steep decline of human rights in the U.S. has been hard to watch and harder to be affected by so personally. Work has been so difficult. I've had such a miserable experience trying to get referred for top surgery -- in the process bringing up so much medical fatphobia that I haven't even blogged about the whole saga, I can barely even think about it without panic or tears. Even my escapist hobby of MLB has been reminding me that billionaires feel

But in other ways it has also been a good year: it was really nice to be able to provide a safe landing place for angelofthenorth and Mr Smith, it was nice to get through a November without anything (new) and terrible happening. Connections with the local queers have been deepened and I'm delighted that D and I are now on the small committee of people who've taken over from the two founders who have reasonably been able to step back and enjoy the thing they made as the ordinary attendees the rest of us have gotten to be the last two years.

Current Music: "Christmas Dirtbag" is playing on the Doof

andrewducker

I called them back at 7:00. Got through to someone helpful who has given me the location of a pharmacy that we're going to visit first thing tomorrow morning, who have been instructed to help us.

No idea why that didn't happen the first time!

jazzyjj posting in

awesomeers

It's challenge time!

Comment with Just One Thing you've accomplished in the last 24 hours or so. It doesn't have to be a hard thing, or even a thing that you think is particularly awesome. Just a thing that you did.

Feel free to share more than one thing if you're feeling particularly accomplished!

Extra credit: find someone in the comments and give them props for what they achieved!

Nothing is too big, too small, too strange or too cryptic. And in case you'd rather do this in private, anonymous comments are screened. I will only unscreen if you ask me to.

Go!

andrewducker

I am an idiot who forgot my blood pressure medicine when I came down to Devon to see my parents.

So this morning I went in to the local pharmacy. Who can't help me because NHS England and NHS Scotland are two different organisations. But they told me to call NHS 111 and ask them for help.

NHS 111 said "We don't have anyone available who can prescribe, call us back after 6:30PM, or talk to a local GP as "Unregistered or Temporary Residents". So we went in to my dad's GP and they said "We don't help in that situation, go talk to NHS 111, they'll help you." - which would seem to leave me in an endless loop.

Just in case, I called my GP surgery in Scotland, who said that they can't prescribe in England.

At which point, as nobody is considering this very important, I think about the only options are to either call back after 6:30 tonight or to just do without for a week. Which, having checked online, doesn't look like a great idea.

Edit: I called them back at 7:00. Got through to someone helpful who has given me the location of a pharmacy that we're going to visit first thing tomorrow morning, who have been instructed to help us.

No idea why that didn't happen the first time!

$radiantfracture: Beadwork bunny head (Default)$

radiantfracture

Thank you,

james for the excellent dinosaur card!

I've been too exhausted to do any of the semi-bespoke painting I half-promised over the summer, but I had a last-minute compulsion to make hand-printed cards because anything that looks like work went into it makes me appear marginally better.

You see? the cards say. An Effort.

I don't mind how they turned out. Sort of "the Dove of Peace is pissed and wants you to get your shit together."

§rf§

cosmolinguist

Thanks for the nice comments on the previous entry. They, along with just writing it out in the first place and D holding me tight (normally I am the big spoon but he did a great job at it last night!) helped me have an okay night.

D had asked me, after we turned the lights off, if there was anything I wanted to do today -- the family had no real plans beyond making the homemade vegan wellington for my birthday dinner that D's sister had suggested and I'd gotten excited about before I remembered quite how much work it was last year, oops. But D and I helped and it felt a lot less of a production this year.

Anyway, before that we had no plans and I thought it might be nice to get out of the house and see something of Birmingham. We didn't actually make it as far as the city centre but the local high street allowed D to browse charity shops while I got a long-overdue haircut (I went from the longest hair I've had in quite a while to the highest skin fade I've maybe ever had, so it feels like a dramatic difference!), and we went for a very nice birthday lunch.

My birthday present from D might still be trapped in DRM hell but he told me what it is, and The Feminist Art of Walking by his old pal Morag goes very nicely with the birthday present I've already gotten from angelofthenorth, of short walks/hikes around Greater Manchester. I also got a bookshop.org voucher from D's mum, which can be added to the one that comprised the other part of my birthday present from Miriam, so I have to decide what to get there too, which is so fun.

Weirdly, my birthday also marks a year since Gary died. It feels so long ago but also I can still conjure him so clearly in my memory, and there probably hasn't been a day all year that I haven't thought of him. I still miss him so much.

I've had a much better day, and I'm looking forward to being home tomorrow.

jazzyjj posting in

awesomeers

It's challenge time!

Comment with Just One Thing you've accomplished in the last 24 hours or so. It doesn't have to be a hard thing, or even a thing that you think is particularly awesome. Just a thing that you did.

Feel free to share more than one thing if you're feeling particularly accomplished!

Extra credit: find someone in the comments and give them props for what they achieved!

Nothing is too big, too small, too strange or too cryptic. And in case you'd rather do this in private, anonymous comments are screened. I will only unscreen if you ask me to.

Go!

yhlee

Watch on YouTube

Orchestral mockup WIP featuring a "drunken" viola (Amati Viola). Because sometimes violas want to /burn longer/ have fun too. [1]

Trailure = "failure trailer." This is, fortunately, personal work at this point :) but my last composition summative assignment involved converging incrementally toward trailer format by getting all the errors out of the way one by one. I think the only thing I DIDN'T do was a cappella kazoo ensemble. :p

Meanwhile, back to Candle Arc 2D animation shenanigans: I have vocals recorded for one character, which means I can start nailing down timing on the animatic for lip sync. Still (joyfully) buried under composition/orchestration schoolwork! :3

[1] I was a student violist many a moon ago. :)

https://deuceofgears.bandcamp.com/

for the morbidly curious. :3

Ian

Just One Thing (25 December 2025)

Merry Christmas: Scientists reverse Alzheimer's in mice [sci/bio/med]

today EVRi actually managed to deliver a parcel, not only on time but early

Today in "hilarious ways to come out to my parents"...

Photo cross-post

Interesting Links for 24-12-2025

Ice hockey history

Just One Thing (24 December 2025)

[embodiment] huh

and bunting in the red town hall says "Merry Christmas to you all"

some things I'm currently doing

End of year meme

Update on my medical woes

Just one thing: 23 December 2025

A sudden withdrawal

Interesting Links for 23-12-2025

Cards! (Emergency printmaking)

44

Just one thing: 22 December 2025

orchestral mockup WIP: "Alto Clef Escapement"

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