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The Book of Guilt, by Catherine Chidgey

This is a difficult book to review as almost all of the plot is technically spoilery, but you can also figure out a lot of it from about page three. I'll synopsize the first two chapters here. We follow two storylines, both set in an alternate England where Hitler was assassinated in 1943 and England made peace with Germany.

In one storyline, a young girl named Nancy lives an isolated life with her parents. In the other, which gets much more page time, three identical young boys are raised by three "mothers," in a home in extremely weird circumstances. They rarely see the outside world, they're often sick and take medicine, their dreams are meticulously recorded by the "mothers," and all their schooling comes from a set of weird encyclopedias that supposedly contain all the knowledge in the world, which are also the only books they have access to. There used to be 40 boys, but when they recover from their mysterious illness, they get to go to Margate, a wonderful vacationland, forever.

I'm sure you can figure out the general outline of what's going on with the boys, at least, just from this. What's up with the girl doesn't become clear for a while.

( Spoilers through about the 40% mark )

( Spoilers for the entire book )

This book was critically acclaimed - it was a Kirkus best book of 2025 - but I thought it had major flaws, which unfortunately I can only describe by spoiling the entire book. It's not at all an original idea, and do think we're supposed to be ahead of the characters, but maybe not that much ahead. It also contained a trope which I hate very much and I thought its thesis contradicted itself, but how, again, is under the end cut. It's a very serious book about very serious real life stuff, but that part really didn't work for me because of spoilers.

Lots of people loved it though. It would probably make an interesting paired reading with a certain very acclaimed spoilery book (( Read more... )), which I have not read as I have been spoiled for the entire story and it doesn't really sound like something I'd enjoy no matter how great it is.

Content Notes (spoilery): ( Read more... )

Current Mood: grateful
Current Music: Emma Stevens - Written in the Stars

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2026 Snowflake Challenge #3 - A Love Letter to Fandm

Dear fandom,

I don't think I'd have the life I have without you.

That's not hyperbole.

You've been one of the most consistent threads in my life, even when everything else has shifted around you.

I found you young, in my teens, when being intensely passionate about fictional worlds and Australian pop stars was all I knew. At school, I had basically no friends - I was into the wrong things, the things that marked you out as odd rather than interesting. I listened to the wrong music, watched the wrong TV shows, and wore the wrong clothes, and I liked reading.

I know now that I'm autistic and non-binary, but I didn't know it then - I was just... weird. I wasn't like the girls, so they didn't want to know me, and the boys who liked sci-fi wouldn't talk to me because they thought I was a girl.

But online, I found you. And I found people who cared about the same things I did, in the same way. You were where I learned how to talk to people, how to connect, how to build relationships around shared enthusiasm instead of small talk. You gave me community when I didn't have one.

Honestly, I don't think I'd have any friends without fandom. I met everyone in my life either through bands or TV shows (mostly Good Charlotte, Supernatural and Leverage) - all of us blogging our fears, our hopes and dreams on LJ.

I even met my partner through fandom, via commenting on her kinky SG-1 fanfic on AO3 - which has somehow, five years later, turned into a whole life together. It still feels slightly unreal when I stop and think about it. We're having a civil partnership ceremony in April, which we affectionately call “not getting married”.

You've been there through so many versions of me. Younger me, who needed you desperately. Older me, who wanders off sometimes and then finds their way back. You've changed shape over the years - different platforms, different cultures, different rules - and not all of those changes have been easy. Sometimes you're messy. Sometimes you're exhausting. Sometimes you're sharp in ways that hurt.

And yet

You've given me joy that doesn't need to justify itself. You've given me people who get it, who speak the same strange shorthand, who understand why caring deeply about fictional characters or real-life athletes can matter so much. You've taught me that enthusiasm is not something to grow out of, and that loving something - openly, thoughtfully, obsessively - can be a form of resilience

These days, fandom looks like tennis feelings and fic, like small, niche corners of the internet where a handful of people care just enough about the same things I do. It looks like late-night rabbit holes, shared jokes, collective gasps, and moments of tenderness I didn't know I needed until they appeared on my screen.

I don't love you uncritically. I know your flaws well. But I love you honestly, and I'm still here. You've shaped my friendships, my writing, my sense of self - and even my romantic life.

Thank you for growing with me. Thank you for waiting when I wandered off. Thank you for still making room for me now. Thank you for the people. Thank you for the connections. Thank you for still being here, and for letting me still be here too.

Some Of The Best Products I Bought In 2025

Posted by Athena Scalzi

https://whatever.scalzi.com/2026/01/05/some-of-the-best-products-i-bought-in-2025/

https://whatever.scalzi.com/?p=58990

Things are tough out there. Money is tight, groceries are expensive, and day by day products are getting worse and worse. These days, you get far less bang for your buck.

You go on Amazon or Etsy to buy something, and everything is from a “brand” called QvorTply, and they sell the most suck-tastic dropship items. More and more often people tell me they’re buying things from Temu and Shein and that it’s all crap and a complete waste of money.

So, what is worth buying? Which brands can you trust, what products are worth buying, and which brands aren’t total bastards? Well, I don’t have all the answers, but I did buy a lot of stuff in 2025 with some mixed results. Today, I’m here to share some products and brands that I really like, and what I felt like was worth my money and a good purchase.

This will be a pretty interesting assortment of stuff, and while they’re in no particular order, I will be mostly trying to keep things of the same category together, like a big section of fabric/clothing items, then a section of food items, etc. Anyways, I hope you find something you like!

I’m going to start off with a brand I’ve actually talked about on the blog once before: Geometry. That’s right y’all, I liked it so much that I’m telling you all about it again just in case you missed it the first time!

Geometry is a home goods brand that specializes in towels, but has also recently branched out into blankets, linens, table cloths, things of that nature.

I never thought that I could love a dish towel so much, but Geometry’s Kitchen Tea Towels are the quite literally the greatest dish towels of all time. And to think, I was so hesitant to buy one of their towels because of the $18 price point, but now I can’t stop recommending them to all my friends.

So, what makes Geometry’s tea towels worth eighteen bucks a pop? Well, without even getting into the brand’s sustainability efforts and partnerships with artists, the towels themselves are huge in comparison to a regular dish towel. They are extra thin, making for quick drying time and way less musty-ness. They wash and dry so easy, and are even super wrinkle-resistant. I never knew how much I hated wrinkles in my dish towels until I saw Geometry’s come out of the dryer wrinkleless.

Whatever vibe you’ve got going for your kitchen, there’s a towel to fit it. You can filter the towels by styles such as retro, coastal, floral, abstract, or by color if you’re trying to stick to a specific color scheme. There’s so many different prints to choose from, and all of them are from real artists.

One of my favorite designers they have partnered with is Julianne Haness. They even have a little article over her and her art! I also quite like Ceyda Alasar, Rebecca Bobko, and Janna Sue Design. In a time of AI “art” and brands not wanting to pay artists for anything, it’s so nice to see a brand that respects the artists’ they partner with and provides tons of different designs from artists all over the world.

Aside from their tea towels, the only other product I’ve tried is their table runners. I bought three back in November or so, all of them in their large 16″ by 120″ size. I really like them! They’ve got a real nice heft and thickness to them that makes them feel like a quality product. I got two for the holidays, this Cedar print one, and this Doodles for the Holiday design. The third is for the summer, and is called Summer Air. I especially love this one because of the baguette.

So, I love the products of theirs that I’ve tried, and I love that Geometry partners with real artists. For my final trick, I’ll tell you about their sustainability efforts that really seal the deal on them being a cool brand. All of their products are made from recycled materials, and they say that a tea towel saves 3.5 water bottles from going into the landfill.

Geometry also has a recycling program called the Take Back Bag. Basically, you purchase this bag from them for $20 (stick with me here), you fill the bag with your old (clean) towels, linens, other textiles you no longer want, send it back to them, and you get $30 to use on Geometry products! A whole free ten bucks to spend on great tea towels just for recycling and making a positive impact on the environment.

So, yeah! Try a tea towel or two. Let me know what you think. In a perfect world, their membership program wouldn’t be full right now, and I’d be in it, but alas.

Continuing with fabric type goods, the next brand on my list is Fresh Clean Threads. How many times have you seen a shirt company advertising that their shirts are different? How many claim to be more comfortable, softer, and fit better on bigger bodies, so you take a chance on them, only to realize they’re not really as special as they claim to be? For me, the answer is a lot! There’s a lot of brands that had big claims, but only Fresh Clean Threads has delivered.

I absolutely love Fresh Clean Threads shirts, hoodies, crew sweatshirts, and joggers. To be clear moving forward, they have a women’s collection but I have only ever bought from the men’s collection. I’ve not tried any of their women’s stuff.

Anyways, a standard t-shirt is $23 and a long-sleeve is $25. The hoodies are just under $60 and the crew-neck sweatshirts are about $50. To me, this all seems pretty standard pricing, but they do have sales like, all the time. They even have a whole tab for just sale items if you’re feelin’ frisky. Like usually a pair of joggers is almost $50 but this two-pack is $30 right now?! Crazy deals to be had, I tell you what.

You can also build a bundle of five items and get a discount and it doesn’t even have to all be the same type of item. Pretty cool.

Their sizing is from S-3X for guys and XS-3X for women, and they have a “tall” option for men, too. I personally wear the 2X in men’s for all their tops and bottoms.

Fresh Clean Threads has, in my book, made the most comfortable shirts of all time. Like they actually nailed it. Even though I wear the men’s shirts and hoodies, everything fits so comfortably and no part is too tight on me. Especially the sleeves, I hate when sleeves are too tight or too short on my arms. They have perfected the sleeve game.

Plus, the hoodies are actually hefty and warm! Very soft inside. And best of all, none of their products come with scratchy tags. You don’t have to rip off any plastic tags or have anything itchy inside your shirt. I really value that in a shirt.

I swear every single shirt I own has shrunk in the dryer, but I’ve washed and dried my Fresh Clean Threads items a hundred times and they don’t shrink even a little bit and they haven’t worn out at all even through constant use. These are just really solid shirts, y’all!

You can wear them out and about as is, use them as a comfortable base for layering, and honestly the t-shirts are so comfortable I actually sleep in them on an almost nightly basis. They’re just really versatile, excellent staples, and I highly recommend them.

I’m also in their membership program, which is $19 a year and gets you 20% off every purchase, free shipping on every order, and early access to sales and new product launches. I can’t tell you how worth it it’s been for me to be a member, because I have ordered over twenty-five items from them (about half of which were gifts).

Finally, you know I have to mention their sustainability efforts. Fresh Clean Threads is partnered with the Coral Reef Alliance with a $50k minimum pledge each year, all of their factories are WRAP certified, and their packaging is 100% recyclable. Solid stuff!

For our next clothing brand we have the ever-popular Bombas. It took me far too many years to realize that the quality of your socks actually matters. I used to think that any ol’ sock was just as good as any other sock, it was of no importance to me the fabric of the sock or how thin it was. Well, now I know better! And Bombas are the best socks I’ve ever owned.

I actually didn’t buy Bombas for like, a solid year because I could not get past the price point. Between $15 and $20 for a pair of socks?! Who has that kind of money for socks? Well, after years of buying cheap packs and running holes through them and having to buy more cheap packs, turns out I do spend that kind of money on socks, so why not redirect it towards actually quality ones so I can stop buying the cheap packs?

I have been wearing the absolute heck out of my Bombas and they are literally just as intact and just as comfortable as day one of having them. I’ve not gotten any holes or threadbare spots or anything, and they feel nice and thick without being constricting or making my shoe too tight.

Personally, I really like their women’s half calf socks with this cute retro stripe design.

Bombas whole thing is that they donate an item for every item bought. Whether it’s underwear, shirts, or socks, they have given over 150 million items to 4,000 different community organizations in all fifty states. I honestly had a hard time believing they were really giving away a pair for every pair bought, but a couple months ago someone I know told me that her family member goes to a low-income dentist in Dayton, and they have a big basket of brand new Bombas free for the taking in their lobby. Turns out, Bombas was impacting my community and I didn’t even know it!

If the price point is really getting to you like it did to me, you can use code COMFORT20 for 20% off your first order, and there’s free shipping when you spend $75. Trust me, it’s a good investment long-term.

Moving on from textiles, I’d like to briefly mention AppyHour! The reason I say briefly is because I have already done three posts over AppyHour this past year (which you can see all three of here), but I just wanted to mention that I liked them enough to put them in this recommendation list.

AppyHour is a subscription based service and purveyor of fine meats, cheeses, and accoutrements that are shipped to your door so you have everything you need to make a yummy and impressive snack spread for you and your guests.

I think they’re a really nice small business with good customer service and are providing good quality products for a good price! I would say really the only thing to keep in mind is if you get the boxes long-term there do tend to be some repeats of items. Honestly this isn’t too much of an issue for me because the repeats I’ve gotten are some of my favorite items, like the Prairie Breeze Cheddar, and I’m plenty happy to put them on a board again.

And of course I’m still super grateful that when I posted about them in the past, y’all used my referral code for twenty bucks off your box, and all these months later I’m still working through the credits I got from that. I have enjoyed many a box paid for entirely by y’all signing up.

So if you’re in the market for some charcuterie goods to entertain visiting friends and family, definitely check out AppyHour! They’re pretty cool.

Branching out into jewelry, this next brand is the most new to me on this list, as I only found out about them during their Black Friday sale in November.

Nominal is a jewelry brand founded by a Palestinian Muslim Arabic-speaking woman and her husband, and each piece is inspired by the rich culture of the Middle East. Every order donates to Palestine relief aid, with over a million dollars donated so far. My favorite of all their jewelry is in their Palestine Collection.

I bought the Olive Leaf Earrings, the Palestine country map necklace, a super cute dainty watermelon bracelet, and watermelon studs.

All of their gold-plated jewelry is 18k gold with hypoallergenic stainless steel underneath. They say you can wear your pieces in the shower, sweat in them, wear them daily, and not worry about them tarnishing, fading, or causing skin irritation. I think Nominal has so many beautiful pieces for an affordable price, and has an amazing cause behind it. It’s something I feel good about purchasing and wearing on the regular.

Finally, I’d like to feature Le Creuset, as I am truly a ride or die customer for Le Creuset products.

Le Creuset is probably best known for their enameled cast iron Dutch ovens. While there are many brands that also make these types of products, Le Creuset is truly the cream of the crop. Yes, they are expensive, but if you have the money, you won’t find anything better.

Le Creusets are beautiful, come in a wide array of colors, and are going to be your new favorite pot to cook in, whether it’s on the stove-top or in the oven. Hefty, reliable, beautiful, their Dutch ovens are the best of the best.

But what about their other products? Well, aside from owning four of their Dutch ovens (one in Sea Salt, one in Marseille, a red heart shaped one, and one smaller one in White), I also have one braiser (with a glass lid (in Sea Salt)), a tea kettle (white with pink and red heart print), a set of mugs (in Shell Pink), two of these square baking dish sets (one in Sea Salt and one in Marseille), a heart shaped spoon rest (in Chiffon Pink), a baking sheet, this salt crock, two mini coquettes (one purple with a flower lid, one white and pink/red heart print one), and a pink pepper and salt mill set that I can’t find in their pepper and salt mill section so you’ll just have to use your imagination.

I love Le Creuset. So much. Their products are so wonderful and beautiful and you’ll be proud to showcase them on your stove or serving up soup to your guests at a dinner party. My wishlist of items from this brand are never ending. My self control is at a breaking point around these damn Dutch ovens. Plus, they have some crazy sales going on right now.

So, there you have it. Six brands I bought from in 2025 and think they’re worth recommending to others. Brands that supply you with actual quality products, and that are worth your money. Because there’s a lot of stuff that isn’t worth your money out there, and I am personally sick of wasting money on bad products.

I hope you found something you like amidst my recommendations! What’s a brand you’ve recently discovered that you’re a big fan of? Let me know in the comments, and have a great day!

-AMS

https://whatever.scalzi.com/2026/01/05/some-of-the-best-products-i-bought-in-2025/

https://whatever.scalzi.com/?p=58990

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Book Review: Beasts by Joyce Carol Oates

Title: Beasts
Author: Joyce Carol Oates
Published: Carroll & Graf Publishers, 2002 (2001)
Rating: 4 of 5
Page Count: 140
Total Page Count: 556,575
Text Number: 2088
Read Because: ??, borrowed from Open Library
Review: In the 1970s, at an all-girls college, a naive 20-year-old falls in love with her professor, but, "if you love a married man you exist in a special, secret, undeclared relationship with his wife." Fascinating to read this soon after Jackson's Hangsaman; which could be how it ended up on my TBR, I can't remember. Regardless, much the same premise, very different treatment. Oates, unsurprisingly, forgoes the subtlety of subtext for the horror of text. And I don't mind; I've had poor success with Oates in the past, finding her tryhard, style over grace; but the writing here really worked for me, punchy declarations and an effective use of repetition. Layered levels of unreality, the experience of early adulthood and being in love, of open secrets, of being taking advantage of in increasingly overt ways, builds an effective atmosphere within this brief, surprisingly dense novella. It makes me want to give Oates another try.

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Book Review: The Demon Lover by Dion Fortune

Title: The Demon Lover
Author: Dion Fortune
Published: S.I.L (Trading) Ltd, 1996 (1929)
Rating: 4 of 5
Page Count: 205
Total Page Count: 556,435
Text Number: 2087
Read Because: on this yearly best of post, borrowed from Open Library
Review: Chosen for her nascent powers as a medium, a young woman is held captive by a ruthless dark magician--a bond that persists after his apparent death. Fortune wrote fiction inspired by/representational of her own occult beliefs: "The 'Mystical Qabalah' gives the theory, but the novels give the practice." Unfortunately, this means that theory sometimes intrudes on the narrative, esoteric sidebars which are worldbuilding infodumps by any other name. But it also gives this a sincerity that productively complicates an already complicated would-be romance between two opposed, entwined, co-contaminating identities. This has a great atmosphere, especially in the second half, and handles its central relationship with an unsettling, compelling nuance.

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Pass It On 6

https://res.cloudinary.com/dc2cefbey/image/upload/v1767643128/hrtshjr_iovgsh.jpg

Next picture: Captain James T. Kirk (Star Trek 2009)

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Drive by hi!

( You're about to view content that the journal owner has advised should be viewed with discretion. )

Current Mood: busy

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Birdfeeding

Today is partly sunny and cool.

I fed the birds. I've seen a few sparrows and house finches.

I put out water for the birds.

.

Current Mood: groggy

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heated rivalry

data point re Heated Rivalry audience

( You're about to view content that the journal owner has marked as possibly inappropriate for anyone under the age of 18. )

Current Mood: thoughtful

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📝 What I’m Reading and Thinking About (Insurgent & Time Hop Coffee Shop)

This week's reading stack feels very deliberately split between intensity and comfort, which honestly says a lot about where my head is at right now.

On one side, I'm continuing with Insurgent. It's fast-paced and emotionally charged, full of difficult choices and escalating consequences. I'm always struck by how much this book is about identity under pressure - how people behave when the systems around them are breaking down, and neutrality stops being an option. It's the kind of read that pulls you along whether you're ready or not, and it definitely demands attention.

On the other side of the stack is Time Hop Coffee Shop, which couldn't feel more different if it tried. This one is all warmth and whimsy — alternate universes filtered through steaming mugs, quiet conversations, and the discovery of the things in life that really matter can be surprising. It's gentle without being dull, and it feels like the sort of book you read slowly, letting it settle.

Together, they make an oddly satisfying pairing. One is about upheaval and rebellion; the other is about pauses, connection, and care. Big stakes versus small kindnesses. Sprinting through plot versus lingering in atmosphere.

I think that balance is exactly what I want from my reading right now - something to engage me fully, and something to remind me to breathe.

If you've read either, I'd love to know how they landed for you. And if your reading week looks completely different, tell me what mood you're in - I'm always curious how other people balance their stacks.

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bundle of holding

Bundle of Holding: Champions 6E (from 2021) & Strike Force

More than two thousand pages of material for Champions, 6th Edition.

Bundle of Holding: Champions 6E (from 2021)

A bundle focusing on the late Aaron Allston's groundbreaking multiversal Strike Force superheroic campaign.

Bundle Of Holding: Aaron Allston’s Strike Force

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Pass It On 6

https://i.imgur.com/rzoEPaV.png

Next: The X-Files

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watching the screen

politics, porn, true crime

More screen time. I watched all of these on Netflix.

Hostage: The British Prime Minister's husband is kidnapped in French Guiana while working with Doctors Without Borders. I watched two episodes across several days, mostly for Julie Delpy as the President of France, but I just didn't care about these people's problems. And then Julie Delpy did a public end-run around the prime minister to get French troops stationed on English soil to stop migrants from entering France from the channel and my entire being just shriveled up and died with how much I didn't like that.

Minx: The evolution of an erotic feminist magazine in the early 1970s. A fun and raunchy show that wants people to succeed and be kind to each other—mostly. The main character, Joyce, is kind of a pill, but part of the fun is watching her become more flexible as she's exposed to new perspectives. The first season is about building a team and putting a magazine together, but the characters lose their way in the second season as they give in to fame and power (or are alienated by it) and the show similarly becomes muddled; appropriate, maybe, but it also felt very unfocused and even cruel at times, quite a departure from the first season. Contains: drug use, nudity, and lots of dicks.

The Staircase (2022): The thing about The Staircase (2004) is that it will make you detest Michael Peterson. Did he kill his wife? Well, an owl certainly didn't do it. Guilty or not, the man is an odious narcissist, and Colin Firth nails him right down to his way of speaking. So I hated him immediately of course. But not in a fun way. The series also stars Toni Collette! And wastes her! Outside of a death scene so raw I wanted to look away, she mainly spends her time drinking and being quietly sad, except for a scene with a leaf blower and two more death scenes that are similarly awful, but similar enough to the first that it kind of dulls the effect over time. The whole thing is pretty tedious, which might be excused in a documentary, but not in a drama. If you've seen one The Staircase, you don't need to see the other, and really, you probably don't need to watch either. It was really great to see Juliette Binoche again, though. Contains: a lot of blood; violence.

Current Mood: tired
Current Location: my desk

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Check-In Post - Jan 5th 2026

Hello to all members, passers-by, curious onlookers, and shy lurkers, and welcome to our regular daily check-in post. Just leave a comment below to let us know how your current projects are progressing, or even if they're not.

Checking in is NOT compulsory, check in as often or as seldom as you want, this community isn't about pressure it's about encouragement, motivation, and support. Crafting is meant to be fun, and what's more fun than sharing achievements and seeing the wonderful things everyone else is creating?

There may also occasionally be questions, but again you don't have to answer them, they're just a way of getting to know each other a bit better.

This Week's Question: What are your crafting goals for 2026?

If anyone has any questions of their own about the community, or suggestions for tags, questions to be asked on the check-in posts, or if anyone is interested in playing check-in host for a week here on the community, which would entail putting up the daily check-in posts and responding to comments, go to the Questions & Suggestions post and leave a comment.

I now declare this Check-In OPEN!

Reversing Alzheimer's?

https://www.science.org/content/blog-post/reversing-alzheimer-s

Many people have asked me about my opinion on this recent Alzheimer’s paper, and my opinion lands in the large zone of “interesting work that I hope is followed up on”. That may come as a disappointment, because some of the headlines about this paper have been breathless Cure-For-Alzheimer’s stuff, which is always a danger in this area, and for all I know there may be some folks out there who’d like to see me dismiss these results as yet another hopeless Alzheimer’s quest.

But that’s the hard part in working in this area (as I did once) or in writing about it as I do now: there are very few Alzheimer’s quests that are completely hopeless. Unfortunately, that phrase better describes our current ability to reverse the disease’s damage. I myself don’t think that the current antibody therapies even do a useful job of slowing it down, and no one is claiming that they can cause people to regain function that they have lost. But the title of this new paper starts off with “Pharmacologic reversal of advance Alzheimer’s disease in mice”, which is an attention-getter for sure.

The compound under study is called P7C3-A20, and here’s a 2014 paper on the neuroprotective effects of compounds in this class, along with a paper on their effects after traumatic brain injury. So this is not a sudden new development, and that’s not even the beginning of the story. The compound itself was described in a 2010 paper by the same group as the best hit out of a phenotypic screen for beneficial CNS compounds, and you’ll see references in those 2014 papers to effects on other neurological injuries or neurodegenerative disorders. These effects seemed consistent not with stimulating new neuronal growth per se, but with protecting the survival of new neurons as they are produced. The application of this compound to Alzheimer’s is not a surprise, and to be honest I’m surprised that it’s taken as long as it has given the earlier publications.

The 2014 work proposed a target for P7C3-A20, namely the nicotine adenine dinucleotide (NAD) salvage pathway. The compound appears to bind to (and enhance the activity of) the enzyme nicotinamide ribosyltransferase (NAMPT), which is the key enzyme in NAD re-synthesis. NAD itself is of course known as a very important small molecule in biochemistry, participating in a whole list of redox activities in the cell (many of which take place in mitochondria) and acting as a cofactor for a range of enzymes. Many of these reactions produce nicotinamide itself as a consequence of their mechanisms, and NAMPT is the enzyme for the rate-limiting step that produces fresh NAD from nicotinamide. (NAD can also be made de novo, but the “salvage pathway” is extremely important because not enough NAD can be produced otherwise).

Given its importance, the role of NAD levels and handling in diseases like Alzheimer’s has been investigated for a long time now. But just outright taking NAD supplements is not a slam-dunk idea, because many types of cancer cells have even higher NAD requirements than normal tissue. The worry has been that you will just be doing any incipient cancers a favor by raising your NAD levels across the board even though you might also be helping out beneficial cell lines like tumor-infiltrating T cells at the same time. Some studies have shown increased risks of some types of cancer with NAD supplementation, and overall, the recommendation has been to hold off on doing that until we understand the risk/benefit landscape better. (The paper under discussion has many links to the literature on this topic).

In this case, though, P7C3-A20 is claimed to restore NAD homeostasis without producing excess NAD per se, which would seem to be a better outcome. The new paper shows evidence for the robustness of NAD homeostasis and severity of Alzheimer’s, and this goes all the way up to humans. That’s through testing of brain sample of people who died showing signs of Alzheimer’s pathology in their tissue, while not exhibiting notable cognitive deficits.

That possible human connection is a big deal here, because the rest of the study is done in mouse models. These show some very interesting results where it does look like you can make the case that some deficits are being reversed, and that’s a rare thing to see in any neuronal-level CNS work. But I m not a good customer for rodent models of Alzheimer’s. My big problem is that rodent’s don’t actually get Alzheimer’s. Nor, to the best of my knowledge, do any other animals except humans. And that’s not just because we know human behaviors so much better or because we have all these higher brain functions to lose. No other animal shows the cellular-level brain pathology associated with Azlheimer’s disease. If you want to see something like that, you have to engineer it in.

How though, you might wonder, do we engineer Alzheimer’s mice when we’re still not certain of the fundamental causes of Alzheimer’s? Well should you ask. As the world knows, the main hypothesis for Alzheimer’s etiology over the decades has to do with the beta-amyloid protein,its overall levels and its handling in various regions of the brain. There are a lot of good reasons for that, as detailed in this post. And since I mention that, let me reiterate that no, the whole amyloid/Alzheimer’s field has not been based just on some work that has now been shown to be fraudulent (a statement that I still see being made by people not familiar with the history). That work did damage, but it was mostly by providing more confidence to many investigators to believe what they believed already.

You can see where this is going: the mouse models for Alzheimer’s are generally animals that have had mutations placed in pathways for amyloid production and handling. If you are more confident that amyloid handling really is a fundamental part of Alzheimer’s pathology, then this probably won’t bother you much. If (like me) you have come to doubt that connection more and more over the years, you may be less enthusiastic. But the glass-half-full position is that whether or not such animals are experiencing “real Alzheimer’s” or even something close to it, they most definitely are experiencing neuronal stress. And a compound that seems to alleviate it would be very much worth pursuing further.

So that’s where I land here. I think this compound (and/or this mechanism of action) seems worth pursuing in human trials after the usual preclinical checks, and my main question now is why it hasn’t been, after all these years and all these publications. I fear that part of the answer could well be the dominance that amyloid mechanisms (and to a lesser extent, tau protein mechanisms) have had over the field. This concentration looked for many years like a welcome level of targeted effort on the most promising hypothesis in the field, but as the decades have worn on, less so. Amyloidocentric ideas have advanced to the clinic over and over, and the absolute best of them have been - in my view - underwhelming and practically useless. If amyloid were really as central a player as we all used to think, this just should not have been the case.

The resulting starvation of alternate approaches might be well illustrated by the long-running story of P7C3-A20. I do wonder, though, if there are other factors at work. After all, other long-shot ideas in Alzheimer’s and neurodegeneration in general have made it into at least small trials based on what may well be less promising results than these. The potential for such drugs is so huge that you can often get people to put a little backing behind them, but I haven’t even seen that much here (from what I can see, P7C3-A20 has never made it into a human trial at all). Is there a Rest of the Story here? And where does the story we know about go at this point? I’ll be watching with interest.

https://www.science.org/content/blog-post/reversing-alzheimer-s

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Snowflake Challenge 3: Love Letter

Snowflake Challenge 3: Love Letter

Write a love letter to fandom. It might be to fandom in general, to a particular fandom, favourite character, anything at all.

An old-fashioned ornament of two young girls bundled up in coats and walking side by side is nestled amidst pine boughs.

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Cemetery in the snow

I went to the cemetery today to take photos of all the snow we've been getting, and it was gorgeous. Even better, the snow came out - only for about fifteen minutes but it was magical

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!challenge week

Challenge Week 01/2026

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1/4/2026 San Pablo Park // Berkeley Meadow

I'd gone by San Pablo Park a day or two ago and saw no one, but after last night's rain I checked again and found the Gull party in full swing. The entire field was covered in Gulls: Short-bill, Ring-billed, California. I cannot decide on numbers in a situation like this, maybe a thousand birds? Dunno. It's a phenomenon I love every time. There were also a few small flocks of Canada Geese here and there, and some Brewer's Blackbirds and European Starlings.

I continued down to park at Seabreeze Market Cove and crossed over to Berkeley Meadow. There was some water and a few ducks in the main pond, but still no one in the small peripheral ponds. The rain may only continue another day, so doesn't look like we'll get enough water for other ducks. ( The List: )

It was good to see a White-tailed Kite and a Belted Kingfisher. I did not to as far as North Basin nor did I try to skirt the flooding to take the East/West trail. If we get substantially more rain I'll go down again.