Long-forgotten virus could help solve antibiotics crisis

This article is a repost promoting content originally published elsewhere. See more things Dan's reposted.

Fantastic lightweight introduction to bacteriophages and how they can potentially be our next best weapon against infection as we approach the post-antibiotic age. Plus an interesting look at the history and the discovery of bacteriophages!

The Scrotum Is Nuts

This article is a repost promoting content originally published elsewhere. See more things Dan's reposted.

Why are testicles kept in a vulnerable dangling sac? It’s not why you think.

Some of you may be thinking that there is a simple answer: temperature. This arrangement evolved to keep them cool. I thought so, too, and assumed that a quick glimpse at the scientific literature would reveal the biological reasons and I’d move on. But what I found was that the small band of scientists who have dedicated their professional time to pondering the scrotum’s existence are starkly divided over this so-called cooling hypothesis.

When I first saw this article and its clickbait subtitle, I almost didn’t read it. After all, I thought I knew the answer: that testicles hang outside the body (and in a sac with a large surface area) because this helps them to keep cool, which aids the production of sperm. It turns out that this is far from an established fact, and a significant number of biologists dispute it and/or subscribe to one of a number of alternate hypotheses. Read for yourself…

The Bad Hair, Incorrect Feathering, and Missing Skin Flaps of Dinosaur Art

This article is a repost promoting content originally published elsewhere. See more things Dan's reposted.

llustrating long-extinct creatures is difficult, but important work. With no living specimens to observe, it’s up to “paleoartists” who draw, paint, or otherwise illustrate the creatures of prehistory as we think they might’ve been. Their work is the reason that when we talk about velociraptors, stegosaurs, or even woolly mammoths, we have some idea of what they looked like.

But since all we have to go on are fossils, deciding how a dinosaur would have looked is as much art as it is science. And there’s at least one paleoartist who thinks we might be getting things wrong…

Into the Lair of the Bladder Monster

Warning: this blog post contains pictures of urine, invasive equipment, and the inside of a bladder. It’s probably safe for all audiences, but you might like to put your glass of apple juice down for a minute or two. The short of it all is that I’m probably healthy.

Since my hospitalisation the other month with a renal system infection, I’ve undergone a series of investigations to try to determine if there’s an underlying reason that I fell ill. As my doctor explained to me, it’s quite possible that what I’d experienced was a random opportunistic infection (perhaps aided by a course of unrelated antibiotics I’d been on earlier this year or by certain lifestyle habits), but if that wasn’t the case – if there were some deeper explanation for my health problems – it was important to find out sooner, rather than later.

A sterile pot full of Dan Q's urine.
I’ve peed in so many little pots over the last few months! If you laid them end-to-end across your kitchen counter, then people would think that you were some kind of weirdo.

Early on I had several ultrasound scans of my bladder (at a number of different times and at a variety of levels of fullness) and one of my kidneys, the latter of which revealed some “minor scarring” of one of them which apparently isn’t something I should be worried about… although I wish they’d started the two-page letter I got with that rather than opening with, effectively, “Contrary to what we told you at the hospital, we did later see something wrong with you…” But still, good to be reassured that this is probably not an issue.

Ultrasound scan of one of Dan Q's kidneys.
An ultrasound scan of one of my kidneys. Can you tell the sex yet?

More recently, I went to the hospital to have a “flow rate test” and a cystoscopy. The flow rate test involved the most-ghetto looking piece of NHS equipment I’ve ever seen: functionally, it seemed to be little more than a funnel on top of a large measuring beaker, in turn on top of a pressure-sensitive digital scale. The scale was connected up to the only fancy-looking bit of equipment in the room, a graphing printer that output the calculated volume (based on their weight) of the same and, more-importantly, the rate of change: the “flow rate” of the stream of urine.

A stream of urine pours down into a funnel.
I’m right, aren’t I? That’s basically a kitchen funnel, isn’t it?

I suppose one advantage of using equipment like this is that it basically operates itself. Which meant that the nurse was able to give me five seconds worth of instruction and then leave the room, which saved us from our own Britishness forcing us to make small-talk while I urinated in front of her or something. Ultimately, I turned out to be within the range of normalcy here, too, although I was a little disappointed to find that the ward didn’t maintain a daily “score board” of flow rates, as sort-of a science-backed literal pissing contest.

A graphing printer describes Dan Q's urine flow. The 'flow rate' graph shows an initial peak, then a trough, then continues to a higher sustained peak.
Apparently not all men experience that ‘spurt-and-then-full-pressure’ thing you’ll see on the upper graph, when they start to pee, but some of us do, and I’m told it’s perfectly normal. I’m learning so much!

Finally came the cystoscopy, and this was the bit that I’d been most-nervous about. This procedure involves the insertion of a long flexible tube into the urethra at the tip of the penis, under local anasthetic, and pushing it all the way down, through the sphincter, down through the prostate and then back up into the bladder. It’s then used as a channel to pump water into the bladder, filling it to capacity and stretching out the sides, after which the fibreoptic cord (and light) that runs along its length is used to look around inside the bladder to inspect for any of a plethora of different problems.

Cystoscopy equipment, ready for insertion.
You’re going to put that WHERE?

The doctor invited me to watch with him on the monitor, which I initially assumed was because I was clearly interested in everything and kept asking questions, but in hindsight I wonder if it’s just that he – quite rightly – assumed that I might have panicked if I’d have been looking in the direction of the piece of equipment he brought in and jabbed at my penis with. I only looked at it while it was on its way out, and my god its a scary-looking thing: sort of like a cross between a tyre pressure gauge and a blowtorch. The first few inches were painless – the local anasthetic had made me completely numb right up to and including the external sphincter, which is at the base of the penis. However, what I can only assume was the second sphincter complained of the discomfort, and it stung pretty sharply any time the doctor would twist the cystoscope to change the angle of the picture.

View up a urethra, from a cystoscope.
The view as you ‘travel’ up the urethra looks pretty much like I expected. With a motion simulator, it would make a pretty cool ride!

Seeing the inside of your own body is an amazing experience. I mean: it’s not amazing enough to even be worth the experience of a cystoscopy, never mind the illness that in my case preceeded it… but it’s still pretty cool. The ultrasounds were interesting, but there’s nothing quite so immersive as seeing a picture of the inside of your own bladder, gritting your teeth while the doctor points to an indentation and explains that it’s the opening to the ureter that connects to your own left kidney!

Unfortunately I neglected to take my phone into the operating room, having put it into a locker when I changed into a gown, and so I wasn’t able to (as I’d hoped) take photos of the inside of my own bladder. So you’ll have to make do with this video I found, which approximates the experience pretty well. The good news is that there’s probably nothing wrong with me, now that the infection from earlier this year has passed: nothing to suggest that there’s any deeper underlying issue that caused me to get sick, anyway!

The bad news is that while the procedure itself was shorter and more-bearable than I’d expected, the recovery’s been a real drag. A week later, it still hurts a lot to urinate (although I’ve stopped yelping out loud when I do so) and my crotch is still too sore for me to be able to cycle. I’ve also discovered that an errection can be painful enough to wake me up, which is definitely not the most-pleasant way I’ve been roused by a penis. But it’s getting better, day by day, and at least I know for sure that I’m more-or-less “right” in the renal system, now.

The Bladder Monster

As I mentioned last week, I’ve been ill. For those who wanted the grisly details, well: here you go.

Warning: this blog post contains frank subjective descriptions of the symptoms of slightly-icky medical conditions including photographs. It’s probably safe for all audiences, but you might not want to be drinking anything while you read it.

The trouble began, I suppose, about a month and a half ago, when a contracted what seemed to be a minor urinary tract infection. If you’re a woman then, statistically-speaking, I probably don’t need to tell you what that is, but for the benefit of the men: it’s what happens when bacteria (or, sometimes, a fungus or virus) infects the renal system: the kidneys, bladder, ureters, and especially the urethra. It’s not pleasant: it gives you the feeling of needing to pee the whole time, makes it harder to pee, and – when you do – it feels a little bit like you’re piss is made of lava.

Microscope view of infected urine.
This urine contains white blood cells (the big circles) and bacteria (the tiny ‘wormlike’ things). Healthy urine contains little to none of these. Anybody else feel like they’re playing Spore?

Despite it not being common for men (more on that later), I’ve had mild UTIs on a couple of ocassions in my life, and I’d always found that ensuring that I got plenty of water and a full RDA of vitamin C was more than enough to make it clear up all by itself within a couple of days. So that’s what I started doing. But then things took a turn for the worse: I started getting a stabbing pain in my left kidney. Recognising this as being pyelonephritis, I went to the doctor who prescribed me a course of the antibiotic ciprofloxacin. Within a couple of days I was feeling right as rain (of course I continued to finish the course of drugs, although I was interested to see that that advice is starting to become controversial).

Dan and Annabel have a picnic in the park.
Happy, healthy, and out for a picnic. I guess everything turned out okay, right?

Naturally I was a little disappointed when, the week before last, I started getting UTI-like pain again, followed very swiftly this time by pain in my bladder that constantly felt a little like I was recovering from being punched. Back to the doctor I went, where (after the usual tests to work out what the most-likely best-antibiotic to use was) I was prescribed a course of nitrofurantoin. I’d never had this particular drug before, and it wasn’t initially clear which of the escalating ill-effects I was experiencing were symptoms of the infection and which were side-effects of the medication: it started with joint pain, then nausea, then diarrhoea, then a full-on fever. It was at the point that I was fully-clothed in bed, running a temperature and soaked in sweat but still feeling cold and shivering that Ruth called 111, who told her to take me to A&E.

(Which, like her care for me in general, she did fabulously well, except for a little bit where she sort-of ran me over in the car park of the hospital: thankfully some friendly paramedics were standing around and were able to drag me into the building. Anyway, I don’t have much memory of that bit and I certainly don’t have any amusing photos, so I’ll skip over it.)

Dan, shortly before inpatient admission but already recovering from the worst parts of his hospital visit, last week.
Feverish to the point of delirium, I don’t have much recollection of the first few hours(?) in the hospital. But I was alert enough to request that a photo was taken for the inevitable blog post. Ruth, however, insisted upon waiting until I apparently looked a lot less like I was about to die: so here it is!

A few tests later, the medical staff seemed confident that what I was experiencing was not an allergic reaction to the antibiotic (however, I see that they still made a note of it as a risk on my notes!) but was a progression of the infection, which seemed to have crossed over from the tissues of my renal system and into my bloodstream and was now generally causing havoc by attacking the rest of my body. They hooked me up to a drip of an intravenous antibiotic and kept me stocked with painkillers, then sent me up to the urology ward and set me up with a “bed” (urology mostly deals with outpatients, and so my ‘bed’ was actually a trolley, but they wanted to keep me close to the urologists in case of any complications).

The view from my hospital ward window: Oxford city is visible in the distance.
It was only the following morning, with the delirium passed, that I realised that I was on the sixth floor. Looking out of my window, I could just make out the spires of the Bodleian Library in the distance, so I dropped my coworkers an email to apologise for not being on my way there.

A consultant switched me to a week’s course of yet-another different antibiotic – co-amoxiclav – and recommended keeping me in for another night. Now, I think that co-amoxiclav is a really interesting drug, so I’m going to be a bit of a nerd and tell you about that for a bit (I promise we’ll get back to my health in a moment: if you don’t want the science bit, just scroll past the diagrams to the next photo).

Amoxicillin, with lactam ring highlighted.
This is amoxicillin. I’ve highlighted in blue the lactam ring, which is the important bit.

Co-amoxiclav is a mixture of two drugs. The first is the antibiotic amoxicillin. Amoxicillin belongs to a class of antibiotics (which includes penicllin) called β-lactams, which is the most-commonly used family of antibiotics. These antibiotics contain a four-point lactam ‘ring’ (highlighted in blue above), and the way that they work is that this part of the molecule bonds with a particular protein common to all gram-positive bacteria. Normally this protein is responsible for producing peptidoglycan, which is an essential ingredient in the cell walls of these kinds of bacteria, but when it gets locked to a β-lactam ring it stops working. As a result, when the bacterium reproduces the new child doesn’t have a proper cell wall, and can’t survive long in even the least-hostile environments.

Of course, we’re in a medical arms race right now because some of the bacteria which we’re targetting with antibiotics are becoming resistant. And here’s one what that they’re doing so: some of these bacteria have evolved to produce beta-lactamase, also bonds with beta-lactam rings, adding an OH to them and making them useless. Bummer, eh?

Clavulanic acid, with beta-lactam ring highlighted in blue.
And this is clavulanic acid. Recognise that shape on the left-hand side of the molecule (highlighted in blue)? Yup: it’s another lactam ring.

The second drug in co-amoxiclav, then, is clavulanic acid, which was discovered in the 1970s and started being added to drugs in the 1980s. Despite having a β-lactam ring (as you’ll see in blue above), clavulanic acid by itself it isn’t an effective antibiotic (for reasons I can’t quite get my head around – anyone want to help me?). But what it’s great at is bonding that lactam ring to beta-lactamase, thereby deactivating the bacterial counter-offensive and allowing the amoxicillin to carry on working, combating resistance.

So what you’ve got in co-amoxiclav is a an antibiotic and a chemical that counteracts the effects of a chemical that deactivates that antibiotic. Wow! It’s things like this that really make me wish I had a brain for biology!

A cannula in the back of Dan's hand.
These things aren’t terribly comfortable when you’re trying to sleep.

I was eventually discharged from hospital and released to go home for lots of bed rest and water, along with a further week’s course of co-amoxiclav. Unfortunately it turns out that I’m one of the unlucky folks for whom amoxicillin makes me dizzy, so I spent most of that week lying down in-between wobbly vertigo-filled trips to and from the bathroom. But it worked! Within a few days I was feeling much better and by the end of last week I was able to work from home (and actually feel like I was useful again!).

Free of symptoms and off the drugs, I returned to work properly on Monday morning and everything seemed fine. Until, late in the morning, I went to the bathroom and started pissing blood.

A kitten lying on its side.
I took a picture, but it’s too grim even for this blog post. Here, have a kitten instead. Do an image search for ‘gross hematuria’ if you want a clue: the kitten will still be waiting here when you need it.

Now apparently blood in your urine, while horrifying when it happens to you unexpectedly, isn’t actually a sign of a medical emergency. I was starting to get bladder pain again, quite intensely, so I excused myself from work and called the urology ward, who decided that I wasn’t in bad enough a condition to go and see them but sent me straight to my GP, who gave me another fortnight’s worth of co-amoxiclav. They’re monitoring my progress with urine and blood samples and if by Friday it’s not having an impact, they’re going to want to send me back to hospital (hopefully only as an outpatient) and pump me full of the intraveneous stuff again. So… fingers crossed for a good result out of these drugs.

Co-amoxiclav tablet in packaging.
My co-amoxiclav tablets each come individually wrapped in a nitrogen-filled foil bag. I’ve no idea what it is that they’re concerned that they’ll react with, but I’m eating three of them a day anyway.

I was hoping that by this point I’d be writing this blog post and telling you all about how I’d fought the bladder monster and won. But it looks like I won’t be able to claim that victory for another week or two, yet. All I know is that I searched for “bladder monster” and found this. Yeah: that feels about right.

Content Freeze

Isn’t memory strange?

Last week, we updated to the latest version of the CMS that powers the Bodleian‘s web site. During the process of installing and testing the new version, we initiated a “content freeze”, disallowing the 100+ regular content editors access to the administration sections: any changes they’d have made wouldn’t have been replicated in the new version, and we didn’t want a discrepancy in content while we were testing that the change had taken! We still had back-end access, of course, and a few minor “emergency” changes were made (on both the old and the new version), but in general, the site was in a read-only mode for several days.

A similar thing happened to my head during this weekend’s house move.

While running  a van-load of stuff from Old Earth to New Earth, Ruth, JTA and I stopped off at Argos to buy a few bits and pieces for our new home. We parked in one of the few remaining parking spaces capable of accommodating our extended wheel-base van. Unfortunately this brushed us up very close to an unfortunately-placed tree, whose branches reached in through the door as I clambered out. I spent a while trying to reposition them so as not to slam them in the door while Ruth and JTA walked ahead, towards Argos, and so when I was done they were quite a way ahead. I turned and ran to catch up with them…

BAM! Something struck me on the top of my head. We’re still not all in agreement as to whether it was a branch or the wing mirror of the van, but it hurt like hell. My knees buckled up and I collapsed into a heap.

Before long I was on my feet, but as I began to feel dizzy and nauseous, we started to worry that I might be concussed, and Ruth took me to the hospital. By then, I was unable to keep my eyes open without feeling like the world was spinning and I was going to throw up, and I kept feeling like I was moments away from falling asleep.

By the time I’d seen a doctor, about three hours later, I was starting to feel a little better. We took a leaflet of “things to watch out for after a concussion”, which advised that I shouldn’t lift any heavy things (“But I’m moving house today!”) nor use a computer or drink alcohol (“This is my life you’re talking about!”), all of which I ignored to some degree or another.

I napped on and off for a lot of Sunday and some of Monday, but it was on Monday that the amount of damage I’d done became most apparent. I got out of bed and staggered downstairs to find that Ruth and JTA had at some point bought a shoe rack. They weren’t around, but neither was the van, and I reasoned that they must have been out collecting more boxes, but I thought I might as well make myself useful by assembling this shoe rack they’d gotten. It was of the variety that hangs on the back of a door, so I spent some time deciphering the instructions and putting it together… only to find that it wouldn’t actually fit onto any of the (quite thick) doors in our new house.

That’s when Ruth & JTA arrived. “I saw you’d bought a shoe rack,” I said.

“Yes,” they replied, “We bought it yesterday. We told you about it.”

“Oh. I don’t remember that. Anyway, I built it, but it turns out that it won’t fit any of our doors.”

“Yes, we know: we told you that too. We were about to take it back to the shop.”

I have no recollection whatsoever of that conversation. Or several other conversations, it seems. In the hospital, I remember that Ruth talked to me for an hour or more (I wasn’t capable of conversation myself, some of the time, but it was nice to hear a familiar voice), and I still can’t remember any of it except for snippets (something about her father’s new house?).

For much of Sunday, my brain went into “content freeze”, too. A read-only mode where my memories worked fine, except that I couldn’t construct any new ones: everything just went in one ear and out the other. Maybe this is to be expected: a quick look at some maps of brains and an examination of the bump on my head indicates that the blow came to a point squarely in the centre of the middle frontal gyrus (the dorsolateral prefrontal cortex)  of the right hemisphere of my brain: an area associated with emotional self-control, social judgement, lateral thinking, and the transfer of working memory.

Still: it was certainly a strange experience to be told about events from only a day earlier that I simply can’t remember. It also made Tuesday interesting: long weekends are confusing at the best of times, but parts of my memory made it feel like I’d had only a two-day weekend (as parts of Sunday are simply missing from my memory), and so it was even harder than usual to shake the feeling that it was Monday when I arrived at work on Tuesday. That’ll be a pleasant surprise on Friday, anyway, when the weekend “comes early”: maybe I should bang my head every time there’s a long weekend.