# La naiba Vittu Kurat Kurwa!

![r/coolguides - A COOL GUIDE TO SWEAR IN EVERY COUNTRY](https://preview.redd.it/a-cool-guide-to-swear-in-every-country-v0-blz2vpiugnzd1.jpeg?width=640&crop=smart&auto=webp&s=67a52200a5e188fa11539e1914392d1fef391a14 align="left")

## Visualizations

### [Reddit: after all this years?](https://sherwood.news/tech/the-rise-of-reddit-social-media/)

![](https://cdn.hashnode.com/res/hashnode/image/upload/v1732614961572/d63c6f5b-cb76-4ed2-81d7-f9cb06c75f52.png align="center")

### [Ramen in the US is climbing...too...](https://sherwood.news/business/how-instant-ramen-noodles-are-conquering-america/)

![Morgan Stanley chart](https://sherwoodnews.imgix.net/mwphzyq69oso/en-US/assets/files/Screenshot%202024-10-24%20at%208.49.05%E2%80%AFAM.png?auto=compress%2Cformat&cs=srgb&fit=max&w=3840 align="left")

### [Give birth or don't](https://sherwood.news/world/fertility-falling-worldwide-birth-rates)

With South Korea [falling below 0.7](https://www.salzburgglobal.org/news/latest-news/article/south-koreas-fertility-rate-should-be-a-warning-to-the-world) not [for the first time](https://koreajoongangdaily.joins.com/news/2023-08-30/business/economy/Koreas-fertility-rate-continues-to-tumble-as-divorce-acceptance-rises/1858646), despite stimulation measures, the world is not lagging behind too much:

![Falling fertility rates around the world](https://sherwoodnews.imgix.net/global-fertility-rates.png?auto=compress%2Cformat&cs=srgb&fit=max&w=3840 align="left")

![Fertility rates in Europe have stagnated](https://sherwoodnews.imgix.net/europe%20fertility.png?auto=compress%2Cformat&cs=srgb&fit=max&w=3840 align="left")

![Eastern hemisphere fertility rates](https://sherwoodnews.imgix.net/asia-africa-fertility.png?auto=compress%2Cformat&cs=srgb&fit=max&w=3840 align="left")

And the reason is:

![Why people don’t want children survey](https://sherwoodnews.imgix.net/reasons-no-kids.png?auto=compress%2Cformat&cs=srgb&fit=max&w=3840 align="left")

### [Jobs vs unemployed in US](https://sherwood.news/markets/the-job-openings-to-job-seekers-ratio-is-getting-smaller)

[Ain’t that some bullshit?](https://www.youtube.com/watch?v=9v3phndhIvE)

![Job openings vs unemployment chart](https://sherwoodnews.imgix.net/job-openings-chartr.png?auto=compress%2Cformat&cs=srgb&fit=max&w=3840 align="left")

## CRISPS and sides

### [Zoomers discovering off-target effects](https://www.swissinfo.ch/eng/science/repair-with-gene-scissors-can-lead-to-new-genetic-defects/88023429)

* ![News: Explainer: What Is Prime Editing and What Is It Used For? - CRISPR  Medicine](https://d2qa4785ekzzy0.cloudfront.net/typo3temp/assets/images/csm_Prime_Editing_Article_--_Figure_2_-_Prime_Editing_Process_in_detail_99e1a9de03_d9282ba083.png align="left")
    
    CRISPR is introducing off-target effects, with [some modifications reducing them](https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2023.1339189/full) ([nice overview by our friends P and C](https://www.perplexity.ai/search/gene-editing-without-off-targe-ZGDB1STFQE2mBxuxjroJNw))
    
* Prime editing aims to [reduce off-target effects to zero](https://www.dovepress.com/recent-advancements-in-reducing-the-off-target-effect-of-crispr-cas9-g-peer-reviewed-fulltext-article-BTT), in super-dumb terms:
    
    * nCas9 cuts the DNA strand in two
        
    * A short sequence to start/prime reverse transcriptase (RNA → DNA) attaches, RT template including the edited part follows
        
    * RT synthesizes the DNA
        
    * Cell incorporates the new DNA into the sequence
        

## Postpartum…

### [Psychosis](https://psychopharmacologyinstitute.com/section/postpartum-psychosis-pharmacologic-strategies-2826-5786)!

![](https://psychscenehub.com/wp-content/uploads/2022/08/Hormonal-changes-in-postpartum-psychosis.png align="left")

* Closely related to [bipolar + hormones](https://psychscenehub.com/psychinsights/postpartum-psychosis-review/):
    
    * Reduction of estradion and progesterone →
        
    * Imbalance in dopaminergic and glutamatergic signalling →
        
    * Et voila, psychotic depression!
        
    * (Allopregnagolone is crawling nearby)
        
* Lithium is the gold management standard, yet **should be considered carefully because of sleep disruptions**
    
* Lamotrigine **readily passes to the milk**, about 14% of relative lithium dose passes
    
* Valproic acid **can be used** during breastfeeding despite not being used in pregnancy
    
* **Dehydration** → more chance of lithium toxicity for the kid
    
* So it’s lithium all the way + managing hydration + benzodiazepines symptomatically (not an advocate of antipsychotics, [but they’re mentioned - quetiapine looks the most bening here](https://pubmed.ncbi.nlm.nih.gov/23724438/) as well as helping with sleep disturbances)
    

### [Depression and breastfeeding!](https://psychopharmacologyinstitute.com/section/postpartum-depression-pharmacologic-considerations-for-breastfeeding-mothers-2826-5783)

![Occurrence of Depression During 17 Weeks of Postpartum Sertraline or... |  Download Scientific Diagram](https://www.researchgate.net/publication/8479579/figure/fig1/AS:348670907174912@1460141030838/Occurrence-of-Depression-During-17-Weeks-of-Postpartum-Sertraline-or-Placebo-Treatment.png align="left")

* All the medications pass into breast milk, most are compatible
    
* The choice of medication/breastfeed-not **should be made depending on mother’s condition**
    
* *Sertraline showed >placebo* (possibly because of its additional effect of [allopregnagolone synthesis stimulation](https://psychopharmacologyinstitute.com/section/the-role-of-brexanolone-and-zuranolone-in-postpartum-depression-2826-5785)?); but then *sertraline=nortryptiline* and *nortryptiline=placebo*. So, by logic laws, *sertraline>=placebo*?..
    
* Venlafaxine and Fluoxetine don’t meet safety criteria of <10% relative dosage in breast milk
    
    ![Which antidepressants will work best for your post partum depression? -  Pillcheck](https://www.pillcheck.ca/wp-content/uploads/2019/02/blog_table.jpg align="center")
    
* Usual advice if already on treatment: maintain but limit exposure (like, lower the dosage?)
    
* **Breast is not a drug reservoir!** The substances of <200 Da weight get into the milk when feeding, with up to 1000 Da possible.
    
* Lipid solubility is also a thing: a **drug has to be somewhat lipid-soluble** to pass into breast milk
    

### [Depression and allopregnagolone!](https://psychopharmacologyinstitute.com/section/the-role-of-brexanolone-and-zuranolone-in-postpartum-depression-2826-5785?utm_medium=email)

![](https://cdn.psychopharmacologyinstitute.com/transcripts/%5B8410%5D%20The%20Role%20of%20Brexanolone%20and%20Zuranolone%20in%20Postpartum%20Depression/image14.jpeg align="left")

* Brexanolone is FDA-approved, but:
    
    * Has to be **IVed over 60 hours** (!!!), limiting its applicability
        
    * Patients have to be monitored for hypoxia and sleepiness → wut…
        
* Zuranolone is taken orally, and doesn’t have as much side effects
    
* Y U NO [etifoxine](https://www.sciencedirect.com/science/article/abs/pii/S0006899307022329), which raises allopregnagolone? Not approved for breastfeeding as there’s not enough data, but still preferable to SSRIs I presume
    

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