Mojo came into rescue 5 years ago this month.  He was an owner surrender and he was partially paralyzed.   He received pain meds, a lot of care and therapy and regained the use of his back legs. 
He is a loving and sweet boy.  
It’s hard to believe that he is 13 years old. Happy birthday Mojo!  🎂🎉🎂
 

 

Tuk Tuk’s mom is a high school English teacher   The teachers in Virginia have begun.  Tuk Tuk doesn’t know how he feels about that.

Gigi thinks she should go.  She could help the students when they begin next week. 

Toasty is contemplating all this. 
“Tell me again why she has to leave us at home.”  There’s no good reason he can think of  

My daughter rides so she has fit in as many riding times as she can. Now she will have to ride after the school day. 
She came home yesterday to this scene.  So peaceful. A lot of deer live close by. 

Tuk Tuk was so happy she was home.  He’s definitely a mama’s boy. ❤️

Granger, my grand dog, came into rescue in 2016.   He was so good at first.  LOL But, then his personality came out. You could find him in a lot of places.   On a table...
In a cabinet. When he heard it was bath time, he tried to hide in the laundry.  He even said he wanted to learn to drive. He did get that bath.   Gigi did, too.  He likes to get on the bench in the yard.   That would have been a good place to watch his dad mow.But he really wanted to ride the mower.He had fun rolling in the newly cut grass.   Another bath.He liked to dig.   His original name was Digger-- we found out why.  And another bath.He's prepared for shade...
or sunshine One time, he wanted out of the room when his mom was gone.   So, he made his own exit.   Not his best day.  
He's older now, so he's not as active.  He likes vents to keep cool.  

And paper bags.   He's such a funny boy-- I've never had one who likes bags and boxes.At the end of the day, he finds a nice place to rest.   He's an adventurous, loving, funny, bad, good dog.   And we love him. 💓

The mRNA-based coronavirus vaccines were most prevalent in many countries, but there were many, many people worldwide who were dosed with some sort of adenovirus-vector vaccine as well. At the time I mentioned a concern about this sort of platform, i.e., the development of an immune response to the viral vector itself (rather than, or alongside the desired immune response to the antigens that it's delivering). That worry goes beyond adenoviruses (any viral vector could have this problem) and it goes beyond vaccines, too. Here's an article from earlier in the summer at Nature about gene therapy using adeno-associated viruses (AAV) platforms, and it's very much on the minds of people in that field.

That's because gene therapy, as it moves from the Maybe Some Day stage and into the real world, is showing its real-world wrinkles and complications. The hope was that these could be one-and-done therapies: you fix the defective gene in the patients' tissues with a blast of the correct one, and they go off to live a far better life. But the first treatment doesn't always do enough, and even when it does, the effects can and do wane as the body's cells turn over. That was always expected to some degree (with allowances for different tissue types), but the problem is that once you've hit someone with a whacking dose of some particular AAV, their immune system is probably going to shoot it down if it shows up again. And unfortunately you will probably need another treatment, sooner (to get the initial effect up to useful levels) or later (to make up for its diminuation over time).

Everyone was willing to kick that can down the road back at the time, because the big project was getting gene therapy to work in the first place, and to provide relief to patients who had no other options. An even nastier issue has been the discovery that some populations tend to already have such an immune response in place from prior exposure to wild-type viruses: there are regions where 70% of the population will inactivate an AAV vector before it has a chance to do any good at all. The expansion to viral-vector vaccines is not helping this much, either, honestly. Companies working in this area are well aware of the problem and have been taking care to use unusual viruses as platforms (rare subtypes, forms found only in chimpanzees, etc.), but the problem remains that some of these are going to have to be taken off the list in the future for anyone who's had them.

As that Nature piece shows, there are now early gene therapy recipients who could very much do with another treatment, but they simply cannot get one due to this vector immunity problem. This didn't get solved over the years, so now these folks are in a very tough situation. Here's a review of some of the approaches that people are taking to deal with this. There are modifications to the viral vectors themselves to change the immune response, different routes of administration and different formulations, administration of immune-modifying agents on a second dosing, and more. As with anything involving immunology, it's a complicated landscape: we may well end up with different approaches with different vectors, tissues, diseases, and patient populations. A general solution would be great, but will be very difficult to realize - we'd better be prepared to take what we can get.

 

Addendum: the entire phenomenon of "This looked so perfect at first" is neatly summed up by Robert Frost:

Nature's first green is gold
Her hardest hue to hold
Her early leaf's a flower
But only holds an hour.

Then leaf subsides to leaf
So Eden sank to grief
So dawn goes down to day
Nothing gold can stay.

I don't think anyone ever did the reverse-zoom effect from particular to general any better - see "Design" for another vivid example.

There have been many, many attempts over the years to link Alzheimer's disease (and other forms of dementia) with some sort of infectious agent. It's not an implausible idea, but given the slow development of the disease and its clinical variability, it's a very difficult one to prove. It seems clear that inflammation is a player in AD and other such conditions, and you can't rule out that being set off (or exacerbated) by some pathogen, perhaps even one that was first encountered many years in the past. From this point of view, the characteristic proteins seen in Alzheimer's diagnosis (beta-amyloid and tau) might be better viewed as the brain's response to infection rather than the cause of disease in themselves (although you also can't rule out such a response causing problems of its own if it goes too far).

It's been believed for some time that being vaccinated against herpes zoster virus confers some resistance to developing dementia later in life. There are a number of lines of evidence, such as this study in Wales that uses the 1933 birth date that was a cutoff for receiving the Zostavax vaccine to show that there really does seem to be a significant effect. And just recently, the same sort of thing has been shown with the newer recombinant vaccine for shingles (Shingrix). I've had that vaccination myself, so I was glad to hear it! Not that I want shingles, either - I got chicken pox when I was 23, in grad school, and I hope to never encounter the virus doing anything to me again after that experience.

These sorts of studies control for both other comorbidities and for other vaccinations. There is, for example, no apparent dementia protection conferred by tetanus or influenza vaccination, just against herpes zoster. And the fact that both the older live-virus vaccines and the newer recombinant one show the same effects is strong evidence in itself that this virus (at least in some people) has some connection with some types of dementia in later life. It would seem obvious that any such connection is worth examining in detail.

This recent article by Jennifer Couzin-Frankel here at Science reports on an upswing in the whole dementia-pathogen story. There are clues with the herpes virus, with yeast, with bacteria, and more, and I'm very happy to hear about it. My gradually developing antipathy to the classic amyloid etiology story of Alzheimer's is well-documented on this blog over the years, exacerbated most recently by the FDA's approvals of anti-amyloid antibodies for which I find the evidence of harm much more compelling than the evidence of any benefit. (For now, the EMA agrees with me on that one, recently refusing a marketing authorization for lecanemab). I am nowhere near ready to embrace the infectious disease hypothesis as The Answer, but I think (given the evidence) that it is very deserving of investigation, and that the dominance of the amyloid hypothesis over the years has made it difficult for alternatives to get the hearing that they might deserve. Let's see!

So many of you responded to my post about "drama dogs."   Yes, many of us have one.   Here's some that you posted.  Enjoy!   (I've included some of your comments.)

"Booger doesn’t want his cat brother Poco to get on the bed with him because he thinks he is going to get a treat, and doesn’t like to share."

Emmi can definitely create drama-- and she can be serious about it.  LOL  

"Reba. I'm adding her as the great instigator. Nothing like chasing the neurotic chihuahua, Chewy, into over reactions because she's barked at him. Yes, she torments her little brother because it's fun."
"Dolly saying Really Mom , I can’t believe you didn’t save me anything."
"Chewy, He's sweet, adorable, snuggles like a champ. But there's no reaction like over reaction. Why bark at leaf for falling when you can go running through the house in full panic mode, tearing up floor rugs, scratching up the floor, and the Chihuahua shakes that come with it."
"Gidget. She is so dramatic when you leave when she thinks she needs to go in the car when you come home when you go to the vet and lord when she gets a bath."  (I was Gidget's foster mom-- and she can SING!)
"Schmoo, don’t touch my schmooty booty!"
Bandit and Pepper--both thought they should be only dogs, but now they are besties.   I think they PLAN some of the drama.  
"Kam is sooo tired. You guys just wore me out."