Ugh #2

Antimicrobial Agents - Inhibition of DNA and Protein Synthesis

Bacterial chromosome replication

DNA replication

Bacterial Topoisomerases 

maintain DNA in appropriate state of supercoiling 

cut and reseal DNA

DNA gyrase (topoisomerase II) introduces negative supercoils 

Topoisomerase IV decatenates circular chromosomes 

these are the targets of the quinolone antibacterial agents 

Quinolones

bind to bacterial DNA gyrase and topoisomerase IV after DNA strand breakage 

prevent resealing of DNA 

disrupt DNA replication and repair 

bactericidal (kill bacteria)

Fluoroquinolone is particularly useful against

Gram +ves: Staphylococcus aureus, streptococci 

Gram -ves: Enterobacteriacea; Pseudomonas aeruginosa 

Anaerobes: e.g. Bacteroides fragilis 

many applications e.g. UTIs, prostatitis, gastroenteritis, STIs 

Adverse effects

Relatively well tolerated

GI upset in ~ 5% of patients 

allergic reactions (rash, photosensitivity) in 1 - 2% of patients 

Inhibition of Bacterial Protein Synthesis 

Macrolides 

in 1952: Erythromycin was isolated as the first macrolide (Streptomyces erythreus) 

Newer macrolides: clarithromycin, azithromycin 

Structurally they consist of a lactone ring (14- to 16-membered) + two attached deoxy sugars 

Mode of action 

bind reversibly to bacterial 50S ribosomal subunit 

causes growing peptide chain to dissociate from ribosome → inhibiting protein synthesis 

bacteriostatic (stops reproduction)

Macrolides’ spectrum of activity

good antistaphylococcal and antistreptococcal activity 

treatment of respiratory & soft tissue infections and sensitive intracellular pathogens • e.g. Chlamydia, Legionella 

Adverse effects

Generally well tolerated

nausea 

vomiting 

diarrhoea 

rash 

Aminoglycosides

large family of antibiotics produced by various species of Streptomyces (“mycin”) and Micromonospora (“micin”) 

include: streptomycin, neomycin, kanamycin, gentamicins, tobramycin 

Structure = linked ring system composed of aminosugars and an aminosubstituted cyclic polyalcohol 

Mode of action of aminoglycosides

Bind irreversibly to 30S ribosomal subunit 

disrupt elongation of nascent peptide chain 

translational inaccuracy → defective proteins 

bactericidal 

Spectrum of activity 

broad spectrum; mainly aerobic G-ve bacilli (e.g. P. aeruginosa) 

used to treat serious nosocomial infections (hospital acquired infections)

First TB antibiotic

Used for cystic fibrosis 

Adverse effects

all aminoglycosides have low Therapeutic Index (only a small amount needed to become toxic)

renal damage, ototoxicity, loss of balance, nausea 

okay, here’s a really cool concept:

You’re ridiculously confident. Confident enough to not give a single eff about what they’re thinking when you go do the crazy things that you do.

You’re brave. Brave enough to stay true to your deepest values and desires where most follow the crowd blindly.

You’re insane, or at least that’s what they call you. Insane to want big dreams and then chase them with all of your might when others are still stuck in cages of self-doubt and hesitance.

You’re kind. Kind enough to portray your compassion and true humanity in a world where most are living fake, plastic lives and refuse to show just a little more kindness.

You’re beautiful. Always were and always will be. Your eyes sparkle with hope and positivity and your smile is angelic. When you laugh, it’s pure joy, and seeing you happy makes others happy as well.

You’re strong. Strong enough to get through all the difficulties and resistance you’re experiencing now and find faith and love on the other side.

You’re capable, wildly capable. Capable of your dreams and the desires that keep you awake at night, keep you alive. You truly deserve to make them a reality.

But most importantly, you’re free. Free now. Alive now. You have the freedom, the time and the responsibility to choose what kind of a person you want to be today when you go out into the world. So choose now. And choose to be the real you, not someone else that people have made you believe you are. Choose.

Pregnancy - physiology

Hormones

hCG - human chorionic gonadotropin - present in blood and urine, produced by blastocyst and placenta

Low levels of hCG could mean miscarriage, ectopic pregnancy, miscalculation of dates

High levels = molar pregnancy (cells that normally form a baby dysfunction and form cysts instead), multiple pregnancy (twins etc), miscalculation of dates

Progesterone increases fat deposition in early weeks and stimulates appetite

Increased oestrogen from corpus luteum promotes mammary gland development (breasts enlarge)

And inhibits ovulation via negative feedback [OES decreases GnRH release by hypothalamus –> linhibition of FHS and LH –> no ovulation]

Relaxin (secreted by corpus luteum) softens connective tissue in preparation for labour - not specific, all joints can be affected

Peaks in early and late pregnancy

Physical changes

Blood pressure

As early as 4 weeks into pregnancy 

plasma volume increase

caused by the affects of oestrogen and progesterone on the kidneys

OES and Prg cause vasodilation 

less resistance = less pressure

Heart rate increases by 25% to compensate

stroke volume increases 

increased overall cardiac output by 50% in third trimester

Direct action of enlarged uterus:

compresses the descending aorta and inferior vena cava 

decreased venous return - less blood in means less blood out, less blood in ventricle –> reduced pressure on walls –> reduced force to exit –> reduced placental perfusion

increased aortic pressure

increased heart rate

[shouldn’t sleep on back for this reason]

Outcomes:

Fall in blood pressure (can cause collapse if serious)

Can cause foetal hypoxia even without mother symptoms

Haematological changes

red cell mass increase by 20% (renal - increased erythropoietin production in response to detection of blood oxygenation and sodium/water balance)

Plasma volume increases more than RBC count does, causing the impression of decreased haemoglobin (anaemia)

Increased tendency to clot (hypercoagulable)

due to increase in clotting factors and plasma fibrinogen

platelet production increase (however count drops due to increase in activity and consumption) - function remains normal]

WBC count may increase due to an increase in granulocytes

Respiratory changes

Increased chest diameter, diaphragmatic expression and elevation

dyspnoea common (difficulty breathing)

breathing becomes more costal (mouth) than abdominal 

mainly mediated by progesterone levels (cause bronchial and smooth muscle relaxation and hypersensitivity to CO2)

Changes to the urinary system

cardiac output increase –> increase in renal plasma flow and glomerular filtration

increase in urea, creatinine, urate and biocarbonate clearance 

with progesterone, renin and aldosterone up water retention increases

can lead to urinary stasis and increased risk of UTI

Any drugs given that are excreted renally must be given in much higher quantities consequently

Gastrointestinal changes

Appetite increase + cravings 

Gastric reflux sphincter relaxation (increased indigestion, also due to increased intra-gastric pressure (expanding uterus)) 

gallbladder dilated 

GI motility decreased and transit time slower 

albumin and protein decrease 

cholesterol twice normal value

Muskuloskeletal 

Calcium reuptake into bloodstream results in mild decalcification of bones 

relaxin softens joints (pubic symphysis + alters gait (waddling))

abdominal muscles stretch to elastic limit 

stretch marks (stria gravidarum) caused by rupture of elastic fibres and small blood vessels 

Reproductive changes

Massive increase in mass

Placenta growth (nutrition, excretion, immunity, endocrine) 

Parental blood supply 

Lmao what did Ariana do that means she needs to get booed at Manchester?

google is free and this article does a good job of explaining but because i dont want anyone to continue to give this girl money for being shit person, here we go.

besides being a cishet white woman HEADING a PRIDE EVENT (Which is something i shouldnt need to explain why its bad.. pride is by and for lgbt people and should not be HEADLINING a cishet.) 

Racism

this is her like 5 years ago vs her now. she is a white girl wearing blackface.  and before you go “thats not blackface! thats just a tan!!!” 

this is her on stage next to nicki minaj, a black woman. she is darker than nicki minaj. this is what a tan looks like

a tan is supposed to give you a more golden sun touched look, NOT MAKE YOU LOOK LIKE A DIFFERENT RACE! (also tan is a golden/yellow brown, not a deep brown… this is not an accident)

her hair, by the way, is in fact exensions. again, making her hair thicker and darker in order to pass as a poc… she steals from black musicians too… like its not news that white people steal culture from poc then market it as a new trend but… she really takes it to a whole new level and acts as if her new look is some fucking brand she made. 

remember shen she got a tattoo for 7 rings but didnt finish it and said “oh thats just fine :)” ? 

transmisogyny

in her video “thank you next” she has a man in a dress stereotype for a trans girl, then painted said person as desperate for a date.  this is a transmisogynist caracature. she is a cishet girl. this is transphobic. end of discussion.

homophobia

shouldnt have to explain why a het girl using sexualized lesbians that look like they came out of a porno for men in a music video for views isnt ok.

etc

she ignores when everyone first tried to tell her NICELY that what she was doing is wrong but as soon as people got less than kind about it, got all guilt trippy like a 3 yr old and went “why cant we just all get along its so sd to see people hating like this :(((((( be nice :(( “ 

she is friends with Pierce Morgan (known facist) and is QUITE PUBLIC ABOUT THIS, she constantly preaches the “we should just sit down and talk to people who are flaming bigots. their bigotry is just a difference of opinions ❤️❤️❤️” which is propaganda created by, surprise, the very bigots it refers to. if we dont fight or get upset then they can continue to be horrible people without consequence. 

she is now INSISTING on headlining pride, and i have seen more homophobic people than i can count say theyre going to buy tickets to pride just to see her. let me repeat that. homophobes are going to pride to see a homophobic artist. this is disgusting. this puts every gay and trans person there in danger. actually, it puts everyone there in danger because it is a pride event and any homophobes will see you there and assume youre gay anyhow so! 

tldr: ariana grande is a racist, transphobic, homophobic white girl parading around in blackface and appropriates black, latino, and asian cultures for $$$ and uses lgbt people for views.

becoming an adult cheat sheet!!!

learn how to coupon

how to get free therapy

clean bathroom tips

what to do when you can’t pay your bills

learn time management skillz

recipes that take 30 minutes or less

see if you’re paying too much for your cell phone bill

create a resume

how to make a doctor’s appointment

organize your closet

find the right career

a list of stress relievers

how to pick a major

how to take care of yourself when you’re sick

things to bring to a doctor’s appointment

what the hell is a mortgage?

buying a used car

how to pick a health insurance plan

read the news

leave your childhood traumas behind

how to quit smoking

a list of hotlines in a crisis

what to expect from your first gynecologist appointment

what to do if you get pulled over by a cop

things to keep in your car in case of an emergency

The International Space Station: Apex of International Collaboration

It’s National Space Day! To mark the occasion, we’re reflecting on the International Space Station, which has been continuously occupied since Nov. 2, 2000. As our orbiting laboratory that enables us to conduct important science off our home planet, the ISS allows researchers from all over the world to put their talents to work on innovative experiments in the microgravity environment. An international partnership of space agencies provides and operates the elements of the ISS. The principals are the space agencies of the United States, Russia, Europe, Japan and Canada. Although each space station partner has distinct agency goals for station research, each partner shares a unified goal to extend the resulting knowledge for the betterment of humanity! Here are 5 fun facts about our about our out-of-this world floating laboratory:

1. The ISS is a unique scientific platform that has enabled more than 3,600 researchers in 106 countries and areas to conduct more than 2,500 experiments in microgravity through February 2018—and the research continues. 

2. Astronauts and cosmonauts have conducted more than 205 spacewalks (and counting!) for space station construction, maintenance and repair since December 1998.

3. The station’s orbital path takes it over 90 percent of the Earth’s population, with astronauts taking millions of images of the planet below. 

4. Six spaceships can be connected to the space station at once.

5. An international crew of at most six people live and work while traveling at a speed of five miles per second, orbiting Earth about every 90 minutes.

Currently, six humans are living and working on the International Space Station, which orbits 250 miles above our planet at 17,500mph. 

Make sure to follow us on Tumblr for your regular dose of space: http://nasa.tumblr.com.

If you're tired, read this. Please.

Hey, amigo.

It’s hard, isn’t it?

I know. Sometimes, it’s painful too.

Sometimes you really wanna give up, throw the books, hide in a corner and never take any action again.

I understand. I really do.

But I’m not here to collaborate on the pity party. I’m not going to join in on the groaning challenge, or complain about how hard it is.

First, get this though. It is hard. I won’t lie. It is worth groaning upon. Maybe one or two pity parties are affordable too.

Yet, there’s a pact we’ve make together, and I’d like to remind you of it, before we talk further. New here? We call it the Shush Pact.

Don’t do it. Don’t complain. Don’t whine. Don’t give in so easily. Don’t.

Go ahead. Make the pact. Now.

Go on! Do it.

Tell yourself, today’s hard. Tiring. But, I won’t give in to this. Nor will I complain and moan about it, and waste my energy. Not today, Amelia! Today’s not that day.

Done?

Sure?

Okay. Let’s go.

If you’re tired.

If you’re tired, exhausted of the hustle, and almost at your breaking point, I want you to remember how MUCH this means to you.

I don’t know what’s driving you nuts. Maybe it’s a math problem you just can’t crack. The presentation due next week that isn’t up to the mark. Maybe it’s 3 gigantic books you have to read up on before your next theology class. Perhaps your business has come at a standstill, and you can’t get it to grow. Or maybe you hate your job, and have finally, bravely, taken the step to work the 6 hours after you come home on building the art portfolio of your dreams, because in your heart, you’ve always been an artist. Maybe you’re juggling three jobs and working late nights to save enough money to catch the dream bus.

I don’t know. But I do know that it means a lot to you.

I know how passionate you’re about this, and how much it means to you.

And yet, you’re tired.

You’re tired of it!

You’re tired of studying so much. You’re tired of DMing every business in town, to have none reply back. You’re tired of working so much, handling so much, and you feel like you haven’t had a break since you were a kid. You’re tired of the pressure, you’re tired of the hustle and you just… wanna quit.

Don’t.

Please.

It’s hard to be positive in this dark, numb time and you’re starting to work mechanically, questioning your existence with every hour, but I have to make you understand! You’re worth this! You’re so worthy of this, my love.

Please don’t quit.

Don’t give up. It’s hard, but seal those lips, and trust your gut. I know you can make it. You’ve worked so hard for this! You’ve struggled so much, invested in so many weeks of work, and right now, at your breaking point, I want you to realise that you’re worthy. Of getting that grade, that degree, finding a job you love, your crazy ambitions of opening a flower shop… everything! All of it!

You deserve the world.

Listen to me. Open your ear and listen: you’re tired, yes. But here’s the truth. You’re not done yet.

You’ve got so much to prove to yourself. So many identities to identify yourself with. Exams to slay, jobs to get, money to make, dreams to build, people to meet and love to spread.

Listen. There’s more to this. There’s more to YOU.

Don’t give up now.

Not today.

You’re not done yet.

Tiredness will pass, and I want you to just try pushing through this. Just try. You’ll see you’re so capable of winning and it’ll blow your mind when you look back and realise the strength you truly possessed because you were able to push through.

Winning is your blood. It’s your oxygen.

Tiredness is a toxic. A poison. You’re not tired, you just think you are. When the human brain says it’s done, it’s actually got 70% more to give.

Don’t forget. Your legacy awaits. If this truly means everything to you, if you’ve already put in hundreds of hours of work into this, PUSH THROUGH! You’ve got to, because your future self deserves a better life! Don’t let them tell you that you need a break. A Hawaii vacation. They’ll say you’re getting nowhere and urge you to take a break.

You and me, we both know you don’t need one. You just needed a reminder of your capabilities.

And I’ve given you that now.

Just remember, you’re not done yet.

So fuck tiredness.

Go win.

Ugh #1

Fucking up when you knew you would is so funny.

Your depression is there to tell you you are a worthless piece of shit who has to fuck other people up.

But you are ready.

Anxiety already prepared you for fucking up. 😝 you knew that would happen

tag yourself: note takers edition

Takes digital notes: tries to keep up with notetaking but eventually falls behind after 5 lectures, drinks coffee only to stay awake, tries the aesthetic of drinking hot tea while taking notes but fails, wakes up early once in a century and thinks they’ve reached their peak, wants a better organisation system but is too tired, worries about studyspo for 2 mins before saying fuck it

Takes handwritten notes: have really nice handwriting but they don’t realise it themselves, headers!! are!! everything!!, have a love-hate relationship with taking notes, studying only when they feel like it, only writes key points as notes because everything else is too much, drifts off a lot while notetaking to daydream

Doesn’t take notes: wears hoodies like 90% of the time, tries really hard to take care of themselves but it’s hard™, hair in a bun because hairstyles?? too much work, yells “fuck the system” as they study more than anyone else, studies straight from books and Knows what to study, can’t study for more than 45 mins at a time, is productive nonetheless, kinda exhausted but still carrying on

Takes notes only in class: take! notes! in! class! save! your! time! fuckers!, in a constant state of chaos but they’ll never admit, have a great relationship with the professors, raises eyebrows at everything it’s a Brand, likes lunch dates a lot, hates people who talk during lectures, wants a vacation already

Is still rotating between handwriting and typed notes: “did we have any homework” at the beginning of every lecture, is really friendly but tired of everything, likes laughing at stupid jokes, hates studying but is still doing it anyway, Major Chaos™, everyone loves them but they don’t have a lot of close friends, will fight for their friends to death, the mood: they’re just being their ball of anxiety, let them live thnx