What does the last bit of a novel drug / immune modulator stand for?

I am asking about the 4 character combination after the hyphen.

Example:

1. tildrakizumab-asmn

2. Adalimumab-adbm

I have Google News feeding me any and all stories related to Candida auris with a goal that these outbreak stories hit my radar faster than an Elon tweet surfaces on the radar of Tesla investors. If you are currently invested in or considering an investment in Scynexis, I suggest that you do the same with whatever news platform you use.

These outbreaks will continue to happen over the near-term as COVID keeps hospitalization numbers near all-time highs and as certain COVID treatments keep immune systems suppressed in small subsets of hospitalized patients. The white swan of this story is any outbreak of Candida auris, such as the one that just happened in late December (and is covered in the news story linked at the very bottom of this post) or the two outbreaks that happened this past summer in Texas and Washington, D.C. that killed several people.

The black swan event is an outbreak of multi-drug resistant (MDR) Candida auris that resists the echinocandin and azole antifungal drug classes. The headline for that event will read "Outbreak of Multi-drug Resistant "Superbug" Fungus Emerges in US hospital". This will be especially true if it finds a way to circumvent current hospital containment procedures.

What is Candida auris?

Candida auris is a species of fungus from the genus Candida. Candida cause a number of different fungal infections in the body, the most common of which is Vulvovaginal Candidiasis, also known as a vaginal yeast infection. Yeast infections are largely caused by the species Candida albicans, against which Fluconazole is highly effective at treating.

C. auris does not cause vaginal yeast infections (though many other species of Candida do and are worthy of attention for anyone trying to predict near-term annual sales numbers for Scynexis). Instead, C. auris has gained widespread attention for being a recent cause of invasive candidiasis which is an infection of the bloodstream and is highly fatal for those that get it (30-60% mortality rate).

Invasive candidiasis is caused by other Candida species, too. But, C. auris is particularly bad because some of its strains resist the first-line and step-down therapies for fungal infections of the blood. These patients typically have no other treatment option. Resistance to one of the leading antifungals for Candida species (Fluconazole) is almost an innate trait of C. auris at 90% resistance (I've seen as high as 96% in some research papers; either way

Disclaimer: I’ve had some great experiences on it when I first used it. Then I would get to the point where I was chasing those initial experiences and holes, but would never get there and take too much trying to get there. Then I would black out for an hour or two and then come-to extremely dysphoric and confused. Forgetting was day it is, where I am, what the purpose of life or anything else is. Just extremely dysphoric overdoses of it. Easily some of my worst drug experiences.

I took a few years off from it and all other dissos. Recently tried it again. Stupidly went back to my old habits chasing an experience that will never come back. Didn’t black out, but just extreme confusion, forgetting what reality and daily life is. Feeling extremely hopeless. Just a classic OD on 3-ho-pcp that happens way too often and, is extremely easy to do accidentally.

After a break from that and deciding I will never do higher doses again I tried low doses in a nasal pray for a mild experience. Never felt all that much in terms of good or bad effects. Did this a few days in a row using probably 10mg so ready out through the day. I proceeded to have the worst mental state I’ve had for a long time even after stopping for a few days. Unrelenting depression, near constant thought of suicide. Utter despair.

I don’t know if it is the current batch I have that is going around right now, but I am having a hard time getting an enjoyable or worthwhile experience out of it.

I’m curious if anyone else has felt this way. I’ve done around a dozen dissos and this just feels the most mentally and physically toxic one ive done, but I always see it recommended here.

I can confidently say it is the easiest to accidentally overdose on and those experiences are easily the most unpleasant ive ever had.

Anyway, gettin rid of it again. 3-Meo-pcp is superior in every way.

Edit: To copy and paste a comment below.

“I definitely understand my use I described is in no way safe or healthy. I’m very self aware about my drug abuse. Been managing it for a very long time. Pcp analogs have always been my main weakness. Shouldn’t have caved after so long and gotten this again.

Anyway, I’ve had abuse patterns similar to this will nearly all the rc dissos over the years and have never had suicidal thoughts or depression like this before. Even after stopping a 6 month period binge of mainly 3-meo-pcp, then close to everyday stimulant use, occasional benzos, daily kratom and weed, alcohol, etc.

Artist: Porter Robinson

Album: Nurture

Genre(s): Electropop, synthpop, folktronica, electronic dance music, ambient

Release date: April 23, 2021

Listen here: Spotify / Apple Music / YouTube

#GOODBYE TO A WORLD

The electronic scene of the early 2010s was one that everyone experienced, whether they liked it or not. From the initial 'club boom', to the monumental popularity of dubstep/brostep in the mainstream, to the inclusion of full on electronic dance tracks making their way up the charts, it was truly inescapable. Porter Robinson was one of the artists that participated in this phenomenon, being very young at the time yet also being incredibly talented. But eventually, this style would grow tired and end up fading - and Porter would be someone responsible for that.

2014's Worlds has been cited as one of the most influential electronic albums of the 2010s. With its focus on expressing something more emotional, focusing less on the dance-heavy production style that electronic music saw during that time and instead taking sensibilities from pop and indietronica music to create something that was truly special, it wasn't just a dance banger EDM album, but rather something that would shift the scene for good. In the years following the release of Worlds, we saw the ever-dominant electro-house stylings become less and less prominent. Instead, influences from genres such as future bass and chillwave would replace it, bringing with them lighter and more vibey production styles that took notes from Worlds in attempts to create music that could be truly perceived as a piece of art.

It's no surprise that this placed a heavy burden on Porter, still a very young artist at the time. We saw less output from him during this time, with no full body of work being released under his name. Instead, Porter released the Grammy-nominated trance project Virtual Self under the alias of the same name, and of course the weeb classic "Shelter" with fellow EDM trailblazer Madeon. The song featured vocals provided by Madeon, which Porter cites as something that influenced the direction *N

I don't want to step on anybody's toes here, but the amount of non-dad jokes here in this subreddit really annoys me. First of all, dad jokes CAN be NSFW, it clearly says so in the sub rules. Secondly, it doesn't automatically make it a dad joke if it's from a conversation between you and your child. Most importantly, the jokes that your CHILDREN tell YOU are not dad jokes. The point of a dad joke is that it's so cheesy only a dad who's trying to be funny would make such a joke. That's it. They are stupid plays on words, lame puns and so on. There has to be a clever pun or wordplay for it to be considered a dad joke.

Again, to all the fellow dads, I apologise if I'm sounding too harsh. But I just needed to get it off my chest.

Dennis Prager made news recently with his interview appearance on Newsmax host Chris Salcedo’s show, where he made a number of questionable claims. This will focus on one claim made during this interview, which aligns well with Prager’s own political biases and the goal of his PragerU channel but are on shakier ground as claims of fact. For reference, this is covering the two minutes of the interview available here.

Prager began this portion of the interview by attacking the efforts of the Biden administration to combat global warming, claiming that the US and other countries with similar efforts are “governed by fear of global warming… an idiotic, irrational, sick fear of extinction of the biosphere,” and opined that historians will one day come to ask how the US was governed by “irrational fears,” seguing into complaints about stigma around the “unvaccinated” with his more notable and absurd claim that the “unvaccinated” are a “pariah group unlike any I’ve seen in my lifetime,” and questioning “During the AIDS crisis, can you imagine if gay men and intravenous drug users, who were the vast majority of people with AIDS, had they been pariahs the way the unvaccinated are? It would have been inconceivable.”

Now, to anyone with even a passing familiarity with the AIDS crisis, this claim is on its face absurd. To suggest that gay men and intravenous drug users were not pariahs during the AIDS crisis, or even were not as stigmatized then as unvaccinated are today, requires a very large and deliberate refusal to engage with the historical record.

The US AIDS crisis began in 1981 with reports of a mysterious disease hitting mostly those in the gay community, particularly those in New York and California. The first report in June of 1981 focused on five gay men in Los Angeles who were previously of great health but had seen a near total collapse of their immune system. By July of 1981, the New York Times had began reporting on the “gay cancer,” as the earliest reports of the disease focused on the appearance of the rare Kaposi’s Sarcoma cancer among some homosexuals. At this time, there was no official name for the disease that would afflict over 300 Americans by the end of 1981, with reports merely referring to “opportunistic infections” among the victims. In May of 1982, still before an official name for the disease was given, the New York Times published a piece giving the nascent epidemic a n

https://pub.epsilon.slu.se/2160/1/Molin_E_091112.pdf

Started reading this, then realized I'm not conquering this in one day! :)

The contents alone seem exciting (I can't even believe I'm saying this!), so I thought I'd share. It seems to cover a wide territory in a simplistic manner (sort of).

It's "just" a thesis but this person has done a ton of research!

1 Introduction 11 2 Background 13 2.1 Sarcoptes scabiei 14 2.1.1 Classification and Morphology 14 2.1.2 Life Cycle 15 2.1.3 Transmission, Survival and Infectivity 15 2.1.4 Clinical Features and Diagnosis 16 2.1.5 Epidemiology 18 2.1.6 Host Interaction and Immunology 19 2.1.7 Host Specificity 20 2.2 Treatment of S. scabiei Infections 21 2.2.1 Acaricide Resistance and S. scabiei 22 2.3 Resistance Mechanisms to Acaricides 23 2.3.1 Macrocyclic Lactones 23 2.3.2 Organochlorines 24 2.3.3 Pyrethroids 24 2.3.4 Organophosphorous Compounds and Formamidines 25 2.3.5 Drug metabolism 25 2.4 Glutathione Transferase 26 2.4.1 Glutathione 26 2.4.2 Classification, Nomenclature and Evolution of GST 27 2.4.3 S. scabiei GSTs 29 2.4.4 GST Gene Organization, Regulation and Expression 29 2.4.5 Structure of Soluble GSTs 30 2.4.6 Active Site of GST 31 2.4.7 Acaricide Resistance and GST 32 2.4.8 Acaricide Resistance and S. scabiei GSTs 33 3 Aims of the Thesis 35 4 Comments on Materials and Methods 37 4.1 The S. scabiei DNA (I-III) 37 6 4.2 Phylogeny (I) 37 4.3 Genomic Organization (II) 38 4.4 Recombinant Protein Preparation (I-III) 38 4.4.1 Subcloning 38 4.4.2 Protein Expression and Purification 39 4.5 Western Blot Analyses and Immunolocalization (I) 40 4.6 Structure Determination of SsGSTD1-1 (III) 41 4.7 Homology Modeling and Docking Studies (III) 42 4.8 Kinetic Analysis (I-III) 42 4.8.1 Steady State Analysis (I-III) 42 4.8.2 Inhibition Analysis with Acaricides and DEM (II-III) 43 5 Results and Discussion 47 5.1 The GST Family in S. scabiei (I-III) 47 5.2 Expression, Purification and Steady State Analysis (I-III) 51 5.2.1 Protein Expression and Purification 51 5.2.2 Steady State Analysis 52 5.3 Localization of S. scabiei GSTs in the Mite 54 5.4 S. scabiei GSTs as Diagnostic Antigens 55 5.5 3D-structures of S. scabiei Delta GSTs (III) 55 5.5.1 Overall structure and the active site of SsGSTD1-1 55 5.5.2 Homology modeling of SsGSTD2-2 and SsGSTD3-3 58 5.5.3 Active site and electrostatic surface potential comparisons 58 5.6 Enzyme-Acaricide and Enzyme-DEM Interaction

Do your worst!

Happy Sunday everyone.

I hope you're all well, and excited for the second instalment in the case discussion series!

As with the last one ( Case Series #1 - Confusion, Chemotherapy and Diarrhoea : JuniorDoctorsUK (reddit.com) ), this is a real case, but with a few details changed for the sake of anonymity. This one has more of a liver flavour to it, and one I was involved with in my specialty capacity rather than as the general medical registrar; whilst some of the finer points will not be relevant to your personal practice unless you also look after a lot of livers, there are some broad strokes which are definitely applicable to general medicine, and aspects of practice and discussion which are worth highlighting.

I have taken feedback onboard from the last time around, and I will try and keep to a timeline (which I will update as we go along).

As before, please don't make a new top-level comment, but instead reply to one of mine so that we can keep discussion organised.

Without further ado, onto the case!

-------

A 49 year old woman is brought to A&E by her concerned daughter. It is 0300am. The daughter has brought her to hospital because she's very worried; over the past two days, she has developed obvious jaundice, diarrhoea and become confused.

There's not much else to be gleaned in a collateral history. The daughter tells you that the patient has lost some weight recently, but that she has been well up until 2 or 3 days ago, with no apparent signs of being unwell.

This woman has a PMHx of HTN and diet-controlled T2DM, and four years ago was told she had a “fatty liver”, but there’s no history of anything more significant than that. As far as the daughter is aware, she is a social drinker, and will drink maybe once or twice a month, and would have “maybe three or four” glasses of wine at each of those occasions. She is an ex-smoker, having quit 5 years ago after being a 40/day smoker most of her life.

Her vital signs are as follows:

O/E:

Overtly jaundiced

Normal central cap refill, prolonged peripheral cap refill of 4s

Normal cardiac examination

Normal respiratory examination, barring obvious tachypnoea

Mildly distended abdomen, no clearly appreciable ascites. Diffusely mildly tender.

Metabolic flap present

Dependent oedema in ankles and elbows

Furt

I'm surprised it hasn't decade.

So "-ine" is used for alkaline substances, the first systematic use of which is apparently "morphine", a French renaming of the German "Morphium" by Joseph Louis Gay-Lussac. Various sources state that Gay-Lussac began this nomenclature, such as https://www.google.com.au/books/edition/Drug_Discovery/jglFsz5EJR8C?hl=en&gbpv=1, and that it was stated in his editorial note to his translation of Sertürner's paper. However, I have found no such mention in the editorial note (https://gallica.bnf.fr/ark:/12148/bpt6k6568603v/f47.item.zoom).

So is this the actual origin of the systematic use of "-ine" for basic substances? If so, where did Gay-Lussac state it?

For context I'm a Refuse Driver (Garbage man) & today I was on food waste. After I'd tipped I was checking the wagon for any defects when I spotted a lone pea balanced on the lifts.

I said "hey look, an escaPEA"

No one near me but it didn't half make me laugh for a good hour or so!

Edit: I can't believe how much this has blown up. Thank you everyone I've had a blast reading through the replies 😂

It really does, I swear!

Because she wanted to see the task manager.

They were cooked in Greece.

Heard they've been doing some shady business.

but then I remembered it was ground this morning.

Edit: Thank you guys for the awards, they're much nicer than the cardboard sleeve I've been using and reassures me that my jokes aren't stale

Edit 2: I have already been made aware that Men In Black 3 has told a version of this joke before. If the joke is not new to you, please enjoy any of the single origin puns in the comments

BamBOO!

They’re on standbi

A play on words.

Pilot on me!!

Christopher Walken

Nothing, he was gladiator.

Or would that be too forward thinking?

Dad jokes are supposed to be jokes you can tell a kid and they will understand it and find it funny.

This sub is mostly just NSFW puns now.

If it needs a NSFW tag it's not a dad joke. There should just be a NSFW puns subreddit for that.

Edit* I'm not replying any longer and turning off notifications but to all those that say "no one cares", there sure are a lot of you arguing about it. Maybe I'm wrong but you people don't need to be rude about it. If you really don't care, don't comment.

What did 0 say to 8 ?

" Nice Belt "

So What did 3 say to 8 ?

" Hey, you two stop making out "

When I got home, they were still there.

I won't be doing that today!

Where ever you left it 🤷‍♀️🤭

This morning, my 4 year old daughter.

Daughter: I'm hungry

Me: nerves building, smile widening

Me: Hi hungry, I'm dad.

She had no idea what was going on but I finally did it.

Thank you all for listening.

[Removed]

There hasn't been a post all year!

You take away their little brooms

It was about a weak back.