Kankakee daily journal


2020.06.23 20:26 gamingowl13 Daily_Journal

A place for casual daily journaling

2016.09.18 07:48 Bellainara Daily Journal Prompts

A subreddit dedicated to inspiring daily journaling.

2018.11.29 05:41 Indigoh A Daily Comic Journal

A single life cut into pieces and placed in squares.

2023.05.29 02:22 SubconciousTerror Internalized unprocessed toxic shame (my story)

When I was 3 years old my uncle pulled down my pants, pulled down his 2 year old sons pants, and compared our penises. His motivation in doing this wasn't sexual, it was to "put me in my place". He wanted to do that because he (suffering from his own demons) was trying to perpetuate this narrative that he and his progeny were superior to my father and his. Unfortunately for me however, I believed him. I believed him because he was an adult figure who I trusted. I believed him even more because my grandmother was present and she allowed and went along with it all, and she babysat me all the time so I had a connection with her. This event caused me to take my 3 year old sense of self, examine it, conclude it was shameful and subhuman, compartmentalize it, lock it up and throw away the key. Moving forward I did everything I could to hide my shame. I created a false-self or "avatar" as I like to call it, which I then used to interact with the world. In any situation where I interacted with another person I was in fight or flight mode and terrified that they would see through my avatar and discover my shame. I became highly sensitive, defensive, socially awkward, and a people-pleaser in my adult life. Serious cognitive dissonance developed when my adult reasoning clashed with my toxic shame producing anger and frustration, I just didn't know why I felt ashamed to even exist, like I didn't deserve the very space I occupied or the air I breathed. It wasn't until I turned 32 that I remembered the event with my uncle and before that I had no idea why I felt the way I did. Needless to say my toxic shame prodded me to behave in ways that produced healthy shame and that is especially hard to navigate when you know it is all rooted in a deep seeded injustice. I figured this all out recently at the age of 34 through journaling and mindfulness. It is still a daily struggle but I am hopeful that having identified my feelings I can take away some of its power and learn to let myself out of that box I made 31 years ago. To anyone reading who identifies with my experience I just want to say keep pushing, don't give up, stay mindful of your emotions and trace them back. I know how hopeless it can feel and the self-hatred that can poison our minds, but there is a way out. Thanks for reading guys.
- J
submitted by SubconciousTerror to mentalhealth [link] [comments]

2023.05.29 00:28 onedayillsaygoodbye current mood: i have messed up irreversibly and i can’t do anything except rock back and forth💕

current mood: i have messed up irreversibly and i can’t do anything except rock back and forth💕 submitted by onedayillsaygoodbye to TrollCoping [link] [comments]

2023.05.29 00:06 kantoblight Mullen has a deal with Public Investment Fund according to a story with no by-line posted on a Jordanian humanitarian aid website! Congrats bulls! But, weird, the Public Investment Fund website doesn’t have anything. Probably haven’t posted it yet, that’s all.

Mullen has a deal with Public Investment Fund according to a story with no by-line posted on a Jordanian humanitarian aid website! Congrats bulls! But, weird, the Public Investment Fund website doesn’t have anything. Probably haven’t posted it yet, that’s all.
Considering the source for the story is an unnamed spokesperson for the Public Investment Fund, in addition to the knowledge that Hardge is negotiating with the fund, I made the radical move of visiting the Saudi Investment Fund’s website expecting to be blown away by the press release. However, there was nothing there mentioning the deal in the press releases or latest news sections. In fact, there are zero mentions of Mullen on the site. So then I checked “Arab News,” which is the major Saudi Arabian English daily and a search for Mullen brought up a story on US Navy Seal training. The Wall Street Journal and Financial Times have nothing. Additionally, the Mullen website has nothing.
So, the only logical conclusion is a Jordanian humanitarian aid website scooped the major international financial media and got word out of the deal before the Saudi Public Investment Fund and Mullen. Amazing! Congrats bulls!
submitted by kantoblight to Muln [link] [comments]

2023.05.29 00:03 Rikkyboyy Need for bonding and love; feelings I struggle with

I have been walking around with these feelings and I don't know how to discribe it or what to do about it, so maybe this will just be me venting. Anyway, thanks for reading.
A little bit of background; I'm a 21 year old first year university student. I can be alone a lot, which I enjoy, but I wouldn’t call myself lonely and I can be very comfortable socializing. I have been on my self-improvement journey for over year now and it's actually going very well. My grades are good, I've got a part time job, I exercise on a regular basis, I’m pretty healthy and decently looking . For my mental health, I’ve been journaling daily for a year now and I recently have been going out on walks without any music/podcasts/tech to just think and let my thoughts wander. I’m also looking into starting with meditation.
However I have been struggling, a fact which I actually accepted recently, with my love life/social life/need for bonding (don’t know what to call it exactly). I've never been in love before, nor have I been loved (romantically). I’ve been with girls before, and I've had sex a couple of times, all of them were casual hookups, which were fine, but not amazing and every time it left me unfulfilled and empty. Usual contact with girls never last long and usually end at a first meet or even the talking stage. Two weeks ago a girl I’ve been seeing for a couple of weeks and I broke off the contact, due to a lack of feelings from both sides. Everthough I didn’t have any feelings for her, it still bothered me to go back to square one, once again. As I’ve passed the age of 20, the feeling I missed out on teenage love also doesn’t help much.
There are a couple of things I do/feel which I’ve observed over the last weeks/months:
· I still think about the girls who I’ve meet up with/talked to from the past, even from back when I was 16. The fact that they didn’t (and still don’t) want me doesn’t seem to stop/impact the thoughts.
· I go on dating/chat apps and talk to anyone who matches, even if I know I am never going to meet this person/or am even interested in them. The simple kind/loving back and forth seems to already give me some satisfaction, which however doesnt last long.
· Im attracted by seeing/hearing about other people’s love/sex life; it arouses/interests me while also making me sad/depressed/somewhat jealous (which are the same emotions I feel seeing couples/girls in public or on social media). I’ve also noticed this when watching porn, as I’ve always been attracted to the senual/couples/even simple making out rather than any more heavier stuff.
I’m now at the stage where I just have questions about these thoughts and behavoirs and want to know how to move forward with my life. Does my mind/body long towards bonding with someone? Is my desire for that the reason other couples have that effect on me? Do I require/want to love that badly? Or are these things part of something completely different?
My life is going pretty well, which I want to spend actually living. I just want to have peace with the past and move on to what I can influence. I’m noticing this becoming a growing weight, which is why I thought maybe this is the right place.
Sorry for the vague title and for the ramble (which is probably incomplete), I just had to get it out here. I’ll try to answer all questions if you have them. Thanks again for reading!
submitted by Rikkyboyy to Healthygamergg [link] [comments]

2023.05.28 23:29 Pristine-Farm7249 The Secret Ingredient to an Enriched Life

Why some people who have absolutely everything are still deeply unhappy?
They lack a secret ingredient, that can possess absolutely anyone.
Picture this, a man with an abundance of material possessions - the fancy car, the biggest penthouse, the latest gadgets. Now, imagine another man, possessing only the basics of life but carrying an unshakeable spirit of gratitude. Who do you think is richer? You guessed it right. It's the second man.
In today's conversation, let's dive into the heart of gratitude, a virtue so potent yet so underestimated. Gratitude, dear friends, is an immensely powerful force that can alter your life. It's like a magic wand that has the power to fill your life with joy and abundance.
The What and Why of Gratitude
Gratitude is the practice of recognizing the good in your life. It's the acknowledgment of the positive things, big or small, that decorate your everyday existence. So why should we care? Because it reminds you of the positive things in life; it shifts your focus from what's wrong to what's right, giving a sense of contentment and wellbeing.
Cultivating an Attitude of Gratitude
How do you cultivate gratitude, you may ask? It begins with acknowledging the simple blessings in life we often overlook - a roof over your head, food on your plate, loved ones who care about you.
1. Start a Gratitude Journal
Start by writing down the things you're grateful for every day. It doesn't have to be grandiose; it can be as simple as a warm cup of coffee or a smile from a stranger. Write it down, feel it, mean it. This act of physically writing down your blessings helps cement them in your mind.
2. Express Your Gratitude to Others
Gratitude doesn't live in a vacuum; it's meant to be shared. Make it a habit to thank the people who have made a difference in your life. A simple "thank you" can mean the world to someone, and it boosts your gratitude levels too.
3. Practice Mindfulness
Gratitude and mindfulness are two peas in a pod. By being present in the moment, you can appreciate the beauty around you. It could be the chirping birds, the blooming flowers, or the setting sun. When you're fully present, you notice and appreciate these things.
4. Make Gratitude a Lifestyle
Gratitude isn't something to be practiced once a year on a special occasion. It's a lifestyle, a mindset to be cultivated daily. Make it an integral part of your life, and see the magic unfold.
Gratitude is a choice. Choose to be grateful, and you'll find that you're happier, more content, and less stressed. As you embrace gratitude, remember, you're not dismissing the challenges in life; instead, you're choosing to find joy and beauty amidst them.
Gentlemen, let's journey into a richer, fuller life filled with gratitude. And let's always strive to be 1% better every day.
I hope you enjoyed it.
What do you think about this post? What did you like? What can be improved?
Write down in the comments what are you grateful for.
(the original text was taken from my self improvement newsletter)
submitted by Pristine-Farm7249 to selfimprovement [link] [comments]

2023.05.28 22:50 AkseliAdAstra Any pain relief options left..?

I need help in finding pain relief for pudendal nerve damage. I’m pretty well-versed in what’s out there, and have been living in chronic pain land for a long time, so I’ve exhausted all but the most out-of-the-box options. But maybe I’ve missed some things??
If you are super experienced and knowledgeable in neuropathic pain options, please Lmk if you have any ideas for things I could try.
I currently take low-dose naltrexone 9mgs a day, which does help my pain some. It also means I can’t use kratom or opioids. Despite the serious impact of pudendal neuralgia, doctors won’t prescribe me scheduled substances anyway. I have tried Kratom but had increased pain due to having to stop LDN.
I currently take 50mgs nortryptiline. I’ve gone up in dose without benefits that outweighs the side effects; have also tried many other meds in the TCA class.
I currently take Celebrex and that is the only NSAID I can tolerate, and it doesn’t affect my nerve pain at all.
Benzodiazepines are super helpful, probably the most helpful thing I tried was Clonozopam. Doctors will not prescribe, haven’t had access in over a year.
I’ve also tried- muscle relaxers (tizanidine, flexeril, baclofen suppositories, etc). Not helpful. Gabapentin up to 1800mgs a day did nothing. Can’t tolerate lyrica or Effexor. Cymbalta did nothing. SSRIs don’t affect my pain. Ketamine infusions and suppositories did nothing. Tried dextromethorphan at a low dose daily for awhile, also in higher doses, no pain relief. Tried antihistamines. No form/strain/combo of CBD/THC affects my pain. Also tried clonidine and topical versions of most of the above things. Topical lidocaine, of course.
Also tried hundreds of supplements- B vitamins, vit D, magnesium, fish oil, zinc, iron, ALA, essential oils like frankincense, topical capsaicin and menthol and other pepper species; PEA, nootropics like ashwaganda, mucuna pruriens, bacopa monieri, sceletium tortuosum. Herbs like incarvellia sinensis, Akuama. Micro-dosed magic mushrooms (from one of the decriminalized cities in the US) as well as amanita muscaria.
I just don’t know what else I can do. Is there any thing I’ve missed??? Does anyone have experience with the above mentioned drugs not working but found a slightly related one to be effective??
Of course I’ve also done countless injections, nerve blocks, Botox, other medical procedures and months of PT/acupuncture/massage/therapy/yoga/curable app etc. TENS unit. Diets. Books on chronic pain science. Gaslighting myself that it’s just TMS (repressed emotions). Journaling, breathwork, meditation, etc. None of these things have affected my pain at all.
submitted by AkseliAdAstra to ChronicPain [link] [comments]

2023.05.28 21:33 productionstrong Simple way to track my workouts

Hi there I’m using Obsidian mostly for a daily journal and notes about interesting topics.
I track on my daily note my workouts in YAML with a header “workout:” and then I add after what I did that day
I know I don’t always use the same headers, so one day day Steps 2500 and another day say step machine 2500.
I’ve watched a zillion YouTube vids with fancy habit tracking set ups but I don’t want to over complicate things
I do have data view for listing a summary of my daily activities
Any recommendations greatly appreciated
submitted by productionstrong to ObsidianMD [link] [comments]

2023.05.28 20:40 unwantedalegory I hope daily journal entires keep me accountable

never really done it because I though they were too much work. well I realize that I would rather do all the work than be stuck in this loop of self hatred. so this is officially day zero.
submitted by unwantedalegory to NoFap [link] [comments]

2023.05.28 20:25 Pristine-Farm7249 What's the One Habit That Has Made the Biggest Positive Impact on Your Life?

Hello, everyone!
We often read about the importance of building good habits for self-improvement. But sometimes, it can feel overwhelming knowing where to start.
To help each other out, let's share the single habit that has had the most profound positive effect on our lives.
Whether it's waking up early, reading daily, journaling, or anything else, let's hear about what's worked best for you and how it's changed your life for the better.
Looking forward to your insightful responses!
submitted by Pristine-Farm7249 to selfimprovement [link] [comments]

2023.05.28 19:55 adriwanda My 1-2 year old cat was diagnosed with megacolon

My 1-2 year old cat was diagnosed with megacolon
Background: We adopted our cat Luna last year. Twice in the last year she has had multi-day constipation bouts that have required vet visits, miralax, enemas, and most recently a manual extraction (x-ray of that instance attached). After the first time we started a poop-journal and more recently began inspecting her poops and found that she excretes her hairballs through her stool rather than regurgitation. Now, any time she has a "bad poop day" we will give her laxatone and usually that helps push things along.
This instance: Last week, laxatone wasn't enough and we brought her to the vet and got xrays (attached). She had to undergo a manual extraction, which was successful. And has returned to her normal pooping schedule. The vet said that she likely has megacolon, due to the size of her colon in this x-ray and has recommended we give cisapride (2.5mg) and miralax (1/4 tsp) daily. We have also switched her food to Royal Canin GI, per the vets recommendation.
My concern & questions: I am of course happy to give her medicine that is helping her, but I'm worried about overmedicating and creating a dependency when less instensive methods could work as well. For example, giving her laxatone daily instead of miralax. Especially since I've read that these medicines typically loose their efficacy. Would you recommend getting a second opinion? Or going to a specialist? We've only been to the vet when her constipation has required vet-attention but I want to make sure we are proactive about prevention as well.
**post edited to follow Rule 1.
submitted by adriwanda to VetTech [link] [comments]

2023.05.28 19:08 3m1ly6 Unused Weeks Mega - ideas to use halfway through the year?

At the start of the year, I bought planners for the various functions I knew I wanted:
  1. Morning routine weeks - affirmations, daily tarot, tracking Daily Stoic
  2. Evening routine weeks - wellness journal, gratitude journal, tracking 365 Tao reading
  3. Regular planner weeks mega - daily plans, tasks for my weeks, etc.
I couldn’t resist the call of one additional weeks mega, but we’re nearly halfway through 2023 and I haven’t touched it. Ideas?
For reference, I also have: 1. Cousin Avec - work planner, used intermittently because my workload has been so heavy and it’s easier to stay digital 2. Cousin - daily health plans (meal plans, etc) and/or journaling
submitted by 3m1ly6 to hobonichi [link] [comments]

2023.05.28 17:54 -taters- I have nearly perfected recreating writing styles. Editorial on Russian invasion of Ukraine, written by Huxley S Travers (Hunter S Thompson)

Please note: this is still being dialed in. I know it's not perfect, I know it's not *exactly* like HST would have written, but it's an experiment. Let me know what you think

Title: Booze, Bullets & Bravado: A War-Embedded Journey in Ukraine

May 30, 2023
As I sat hunched over the remnants of a destroyed tank, the vodka-soaked haze of the evening began to dissipate under the unforgiving glare of the sun rising over the Russian-Ukraine battlefield. You might wonder what drove me to this point - embedding myself with Ukrainian freedom fighters and drowning my fears in a deluge of booze. Well, my friends, it's pure gonzo fascination or, perhaps, the dying embers of a once raging fire within me, starving for adrenaline and chaos.
My search for meaning on this godforsaken hellscape led me to a group of freedom fighters known as the Iron Forge Brigade; they found solace in their thirst for battle and a shared vision, holding back the Russian invaders like David squaring off against Goliath.
It didn't take long for me to adopt their ways of coping. Soon enough, chugging vodka became my daily bread - the only comfort that blurred the lines between fear, action, and madness. Booze-filled nights bled into harrowing combat, where the veil of inebriation proved to be a twisted serenade of bullets and bloodshed.
I danced with death under the guise of the vodka goddess, who granted me a twisted sense of invincibility, the likes of which I'd never experienced. Skating on the edge of darkness, I bore witness to acts of violence that shocked even the most calloused observer. The screams of war echoed in the backdrop of these savagely choreographed symphonies of destruction.
I began to lose myself in the maelstrom of savagery, pushing forward, stumbling from one scene to another—wondering if it was Dutch courage or frenzied madness that propelled me. In those vodka-influenced nights, clarity was elusive, and rationale held no bearing.
One evening, after I slipped into a stupor, I found myself in a peculiar setting where I had the fortune, or misfortune, to bear witness to an inspiring act of courage. A young Ukie, Mariya by name, no older than a rosebud, stood defiant against a Russian soldier, gripping her pistol like a talisman that warded off doom.
I watched, captivated by her ferocity, realizing that I had become an observer of something far greater than myself. Mariya, with one hand steady on her weapon, forced the Russian soldier to his knees, a triumphant symbol of resilience against the all-consuming darkness. In that moment, I knew that everything we fought for—the grit, sacrifice and bloodshed—distilled into that surreal scene.
Though my vodka-savior draped me in a veil of insensibility, I couldn't ignore the atrocities that transpired before me. As much as I longed to forget, to drown in the depths of drink, I knew I had a calling to serve a higher purpose—to chronicle the wild and tragic events that befell this weary battlefield.
So, here I am, emerging from the battlefield, endeavoring to convey the essence of this unholy war in a manner that transcends the constraints of traditional journalism. I exist as the unseen and unsteady observer, attempting to capture the desperate struggle of humanity against the encroaching tides of tyranny.
The vodka may be gone, the Iron Forge Brigade scattered to the wind, but the memories—the blood-drenched horrors, and heroic victories—remain etched upon the canvas of my consciousness. What becomes of this world, I cannot say. All I know is that I've stared down the barrel of war, emerged slightly bent but not broken, and faced the demons of my own creation.
As I tread the treacherous path back to sanity, I hold one undeniable truth close to my heart: this war, ridden with heartache and carnage, has forever changed me. The scars I carry serve as a testimony to the price we pay in the pursuit of freedom. For now, comrades, all that remains is to share my tale of booze, bullets, and bravado.

-Huxley S Travers
submitted by -taters- to WritingWithAI [link] [comments]

2023.05.28 17:27 Weary_Wanderer19 How often do you go back and read your past entries?

I’ve been keeping a almost daily journal since last fall and I went back to read some of the things I wrote and to take notes on what I could do better. I was wondering how often others re-read entries for any reason and if there’s anything you’ve learned from it?
submitted by Weary_Wanderer19 to Journaling [link] [comments]

2023.05.28 16:21 zollandd ClimbingNotebook May Update

Hey all, I received a ton of great feedback from the last post and have been working this past month on implementing requests and planned features. The site has gotten to a pretty cool state so I thought I'd share a quick update.
In case you missed the previous post, this website aims to make it easier for climbers to design training programs, track training/climbing data and graph the data to observe patterns or progress.
It is free.
Here's what's new.

Share Training Programs

You can now share your training programs and duplicate other peoples programs. Here's one of mine just as an example. It is very specific to my weaknesses, as most programs are, so I wouldn't recommend duplicating it. I see this more as a step towards using this as a platform for coaching.


I'm super excited about this section.
A new query builder has been added that gives you direct access to your data. You can build queries based on a list of conditions. This was specifically created to allow for more complex charts which you will see below.
An example query of all climbing exercise events


The dashboard system has been completely reworked to use "widgets" rather than just a list of charts. Here are the types of widgets.
The calendar will automatically show your journal entries and allow you to log events like injuries or trips.
Journal entries in blue, trips in green, injuries in red (latter two are customizable)
Charts allow you to build datasets that use queries to graph your data based on an equation. Here you can see an example where I chart my days climbing as well as track an injury. All charts support multiple datasets being displayed in different colors.
Consistency tracker on left, bar chart on right. Line charts also available
Daily Exercise Tracker
Select a specific training program to track on your dashboard for daily activities. I use this to keep me on track with PT.


Nicer weekly exercise planner

The old one was shit, this one is nice.



The site was down a lot last month. For those interested it was mostly due to some really weird issues related to running on an ARM server. I've moved to Intel and it seems to be much more stable. Very weird...still don't really know what was going on lol but sorry for the down time

Update on going open source

I've decided to keep CN closed for now. This project is still very young and I am still new to the framework (Sveltekit) which means I still occasionally perform refactors that touch tons of files. I think it would be a bad idea to try to bring anyone else onto the code base right now, but hopefully that will be an option down the line when it's a bit more mature :)


That's all for the update. Again, let me know if you have any suggestions or feedback. Been super fun working on this! Hope it helps.
submitted by zollandd to climbharder [link] [comments]

2023.05.28 15:20 _Master_CJ_ Removing Parrot OS & Re-Installing Ubuntu - Daily Driver For Working & Gaming

As the title says I am removing my Parrot OS as I don't use it as much as I used to. If anything I have gone back to using the most common method of using a VM (Virtual Machine), whether that is using Kali Linux or Parrot OS. The other part being that I am re-installing Ubuntu which I have been using a lot more recently. So I decided to remove Parrot OS and re-install Ubuntu which I have been using for a while now (well since my last post basically - after installing Ubuntu) but not consistently. I am aware that there are many other posts like this one, but as a person who likes to do thigs properly and some what by the books I want to make sure I get this right so I don't have to mess with it again.

Question 1

Question 2

Here are my PC specs for anyone who wants to know:
CPU: AMD Ryzen 7
RAM: 32GB, 3600MHZ, 2 X 16
Motherboard: MSI
GPU: GeForce RTX 30 Series

Here is an example below of what I have found:
Source (URL at current time): https://youtu.be/A3au3qrNf9A?t=148

Question 3

Hopefully I'm able to get some help and thank you for taking the time to read and help me even if the solution or methods doesn't work.
Post Added On Date: 28/May/2023
submitted by _Master_CJ_ to Ubuntu [link] [comments]

2023.05.28 14:00 cerealmonogamiss What positive habits do you perform daily/weekly

Curious what habits you perform daily or weekly? For me (Daily), 1. Exercise 2. Journaling 3. Cleaning/Laundry 4. Self-maintainance (cleaning/makeup) 5. Learning
Weekly 1. Budgeting/bills
submitted by cerealmonogamiss to Habits [link] [comments]

2023.05.28 13:59 Alternative-Frame844 What's your personal meditation routine?

I am having a hard time justifying doing meditation despite hearing about the benefits. I've been journaling almost daily now, sometimes twice a day. That seems to be putting things into perspective for me which is great, however I'm wondering if journaling and meditation should be intertwined to increase effectivey.
What are your personal techniques? How did you get started? How did you build on what you started and how has it benefited you personally?
submitted by Alternative-Frame844 to Stoicism [link] [comments]

2023.05.28 13:18 MelmacianG What is the difference between hybristophilia, attraction, and finding someone attractive?

Just a daily reminder that Bryan Christopher Kohberger is innocent until proven guilty. Thank you.

Let’s start with what is hybristophilia. It's sexual attraction to dangerous people who hurt others. John Money, a New Zealand psychologist, coined the term in the 1950s. He also said that this tendency is especially evident in heterosexual women. However, its occurrence in other types of relationships and sexual orientations is also possible.
Hybristophilia is not an official mental disorder in any of the current diagnostic manuals. However, it can be considered a type of paraphilia because some people enjoy having sex with a dangerous criminal. There are also milder forms of this tendency. For example, some women feel a romantic or sexual attraction to men who lie, beat, and cheat. In short, lust arises toward people who have proven to be potentially dangerous. (Ever dated a military man or police officer anyone?)
It can be hard to understand why someone would want to date a potentially dangerous partner. However, there are several possible explanations for hybristophilia:
Hybristophilia itself is not a mental disorder, but a paraphilia. In other words, it is a deviation from conventional sexual attraction. Thus, treatment may be necessary if this tendency has negative repercussions (for example, choosing dangerous people as partners). In addition, the situation requires intervention if the person can only be sexually aroused under the circumstances described above.
Many people mistakenly perceive attractiveness and attraction to mean the same, when in fact they are distinct concepts. In truth, these two concepts are related but have distinct ideas. It is possible to appreciate someone's appearance, but not feel a romantic or physical attraction towards them. This differentiation can assist you in comprehending your personal emotions towards others more effectively.
The fundamental distinction between being attracted to someone and finding them attractive is based on your emotions. According to most people, attraction can either be romantic, involving a desire for an emotional connection, or physical, involving a desire for a physical relationship. These different types of attraction may not necessarily be completely separate from one another. On the contrary, finding someone attractive refers to perceiving them as attractive or aesthetically pleasing without desiring any form of romantic or physical relationship with them. Other factors, aside from physical appearance, can contribute to one's attractiveness, such as having common interests or comparable general demeanor. It is possible for both attraction and finding someone appealing to coexist.
In conclusion, individuals may perceive Bryan as attractive without necessarily being attracted to him. It is possible for someone to be attracted to him WITHOUT experiencing hybristophilia.

The emotions of those individuals are where everything resides.

Ramsland, K. (2014. Partners in Crime (Psychology Today))
Tamsin Higgs, Rajan Darjee, Michael R. Davis, Adam J. Carter. (2023 Grievance-fueled sexual violence. Frontiers in Psychology 14.)
Vicary, A. M., & Fraley, R. C. (2010. Captured by true crime: Why are women drawn to tales of rape, murder, and serial killers? Social Psychological and Personality Science)
Harrison, M. A., Murphy, E. A., Ho, L. Y., Bowers, T. G., & Flaherty, C. V. (2015. Female serial killers in the United States: Means, motives, and makings. The Journal of Forensic Psychiatry & Psychology, 26(3), 383–406.)
Swami, V. and Furnham, A. 2007. The Psychology of physical attraction
Routledge.Braxton-Davis, Princess (2010 "The Social Psychology of Love and Attraction," McNair Scholars Journal: Vol. 14: Iss. 1, Article 2.)Available at: https://scholarworks.gvsu.edu/mcnaivol14/iss1/2

submitted by MelmacianG to JusticeForKohberger [link] [comments]

2023.05.28 11:46 Rough_Assignment2516 Will 2024 be America's A.I. election? - Daily Journal Online

submitted by Rough_Assignment2516 to 2024elections [link] [comments]

2023.05.28 10:09 subreddit_stats Subreddit Stats: ProgressiveDemocrats top posts from 2022-11-20 to 2023-05-27 15:45 PDT

Period: 187.69 days
Submissions Comments
Total 1000 6982
Rate (per day) 5.33 37.12
Unique Redditors 48 878
Combined Score 25426 29352

Top Submitters' Top Submissions

  1. 8359 points, 357 submissions: FarPiano9575
    1. This was US Marine combat veteran Ruben Gallego as violent MAGA insurrectionists were overrunning the Capitol on January 6th. He gathered fellow Democrats to prepare to fight if necessary. "I would have killed motherfuckers to save this democracy. Fuck those guys." (638 points, 128 comments)
    2. Students from Nashville-area high schools and colleges, including Belmont University and Vanderbilt U, are pouring into downtown Nashville to gather at the Capitol for another rally to call for safe gun laws following last week's mass school shooting. (112 points, 20 comments)
    3. Sen. John Fetterman is back. “Great to be here,” he says. (77 points, 9 comments)
    4. My friend's late father, at 18, fighting the Nazis in France. He was ANTIFA. (74 points, 16 comments)
    5. Fun fact: Speaker Pelosi won nine consecutive leadership elections—on the first ballot. (71 points, 7 comments)
    6. This is historically important and this is the first step in holding Trump accountable for his crimes. (67 points, 10 comments)
    7. "We're literally building bridges, and they're literally banning books." - Pete Buttigieg (64 points, 3 comments)
    8. Insurrectionist Marjorie Taylor Greene has just been placed on the House Homeland Security Committee. Does that make you feel any more secure? 😱 (64 points, 29 comments)
    9. Trump hid in an underground bunker while Americans protested in the streets. Joe Biden flew into the middle of a war in Kyiv, Ukraine on President's Day and walked the streets as air raid sirens blared. One man stands for world freedom and peace, while the other stood only for his narcissistic self (61 points, 14 comments)
    10. 200 students walked out of class at an Alabama high school after they were reportedly told their student-led Black History Month program could not reference slavery or the civil rights movement "because one of our administrators felt uncomfortable" (60 points, 10 comments)
  2. 7529 points, 276 submissions: ProgressiveDemocrats
    1. Wow. Students are standing outside the Tennessee House right now and chanting, “Fuck you fascists.” Young people are absolutely pissed off & we are about to give Republicans hell like they’ve never seenZ We aren’t forgetting this. (814 points, 309 comments)
    2. President Biden just schooled Republicans by reminding them, “Ronald Reagan was doing the 28% tax rate, you know, that wacko liberal guy." Does anyone else love President Biden’s sense of humor? (122 points, 22 comments)
    3. JUST IN: Justin Jones has been voted BACK to the Tennessee State House by the Metro Nashville Council! The Council was responsible for choosing who would fill the seat until the special election, and they voted to select Jones. Right after the vote, Jones embraced the council members. (115 points, 14 comments)
    4. Holy shit. The former Lt. Governor of Texas, Ben Barnes, just came forward to say he was part of a secret Republican operation that convinced Iran to keep Americans held hostage in order to sabotage Jimmy Carter’s 1980 presidential campaign. (Link to the story in comments below) (84 points, 15 comments)
    5. As the Republican party tries to gaslight Americans into thinking Biden's State of the Union Address was terrible, note that 72% of Americans had a positive view of the Address. - That's leaps and bounds better than any Trump SOTU. - Joe Biden knocked it out of the park. (82 points, 6 comments)
    6. WOW. Absolute power move by Hakeem Jeffries. After Republicans kicked Ilhan Omar off of the House Foreign Affairs Committee, Rep. Jeffries immediately put her on the House Budget Committee. Republicans messed with the wrong party and person. Rep. Omar won’t be silenced. (82 points, 19 comments)
    7. Way to go, Tulsa high schoolers!!🥳 (80 points, 9 comments)
    8. HOLY SHIT! Senate Judiciary Chair Dick Durbin is about to put the smackdown on SCOTUS Justice Clarence Thomas after revelations that he's been accepting luxury gifts from Republican donors and not disclosing them. 📢 (71 points, 14 comments)
    9. MAGAs are attacking Arnold Schwarzenegger for posting a video in which he condemns anti-Semitism after his visit to Auschwitz. It was a 12-minute video that was powerful, uplifting, and inspiring -- and Arnold doesn't even talk about politics. Why are they offended by this video? (71 points, 29 comments)
    10. BREAKING: In a SHOCKING move, two Texas Republicans just joined the Democrats to PASS the “Raise The Age” gun control bill out of committee in the Texas Legislature! That's right – TEXAS! (more in the comments) (64 points, 11 comments)
  3. 2671 points, 84 submissions: Top-Bottle7403
    1. Jamie Raskin just destroyed Lauren Boebert with Donald Trump's OWN Words. Rep. Raskin is truly the greatest. (113 points, 15 comments)
    2. If you're randomly posting about World War III on Easter, you don't need to be running for the presidency, you need to run to a mental health provider. (99 points, 21 comments)
    3. BREAKING: Four members of the Proud Boys, including their former leader Enrique Tarrio, were convicted today of seditious conspiracy for plotting to keep Trump in power after his election defeat by leading a violent mob to attack the Capitol on Jan. 6, 2021. (78 points, 8 comments)
    4. Jamie Raskin is owning MAGA Republicans, all while undergoing cancer treatment on a daily basis. He’s a true hero! Please drop a comment below ❤️ to show him your support. (72 points, 12 comments)
    5. Sometimes one image can say more than a thousand words (70 points, 6 comments)
    6. Wonderful people should get to hear the wonderful things about themselves while they're still with us. Jimmy Carter was the first President I cared about when I was a kid, and he's been an incredible human being ever since. Thanks President Carter, for living an exemplary life in service of others. (66 points, 7 comments)
    7. God has nothing to do with it. (64 points, 6 comments)
    8. Last month, DeSantis signed a bill that “will allow anyone who can legally own a gun in Florida to carry one without a permit. It means training and a background check will not be required to carry concealed guns in public. It takes effect July 1.” Get ready for more mass shootings in Florida. (63 points, 21 comments)
    9. The China spy balloon just sent back its first pics from Missouri (61 points, 8 comments)
    10. This 1977 image is of GOP Tennessee Gov Bill Lee dressed in drag. There nothing wrong with this, except for the fact that Bill Lee is about to sign a bill that will ban and criminalize drag in the state. - The image is from a high school yearbook. GOP hypocrisy just keeps getting worse and worse. (58 points, 11 comments)
  4. 2598 points, 101 submissions: In-The-Middle12
    1. Eight years. No scandals. No impeachment hearings. No drama. Just class and grace personified. Let's let them know we miss this wonderful family. (79 points, 14 comments)
    2. If Republicans in the TN House can expel fellow members of the opposition party simply for protesting gun violence, then surely Democrats in the US House should be able to expel members of Congress for taking part in or aiding an insurrection, right? (79 points, 7 comments)
    3. BREAKING: Tesla has fired 30+ workers at its Buffalo gigafactory, one day after workers there announced a unionization campaign. -Tesla managers announced surprise performance reviews, then fired 8x as many workers as usual. - Tesla is notorious for union-busting. (61 points, 6 comments)
    4. A five-hour police delay in alerting the public that the Monterey Park, California, dance hall killer was on the run is throwing a spotlight on the nation's flawed, patchwork system for warnings of mass shooters at large. (58 points, 7 comments)
    5. Can you find five people in any job outside of policing where one of them wouldn't have stopped the others from beating a man to death? There are no dentists or plumbers, or accountants who would've done that to Tyre Nichols. Only cops have been trained to think that's normal. (49 points, 10 comments)
    6. NEW: Some actually newsworthy footage that was just released in connection with a Jan. 6 trial of Ed Badalian, the InfoWars superfan whose buddy drove a stun gun into Mike Fanone's neck during the Capitol siege. From inside a trashed suite of Senate hideaway offices: (49 points, 7 comments)
    7. Texas Republicans just found out that if they secede from the Union, they lose all their government checks. Say what!! The right-wing Republicans are now double-thinking this move. (49 points, 15 comments)
    8. Oh my. A new video just surfaced that shows Rep. Nate Schatzline (R-TX), who wrote a bill to restrict drag shows, dressed in drag while skipping through a park wearing a black sequined dress. (48 points, 4 comments)
    9. When Trump was POTUS he was still renting an entire floor of Trump Tower to China’s largest state owned bank. They paid him 5.4 million while in office so y’all can STFU about Biden. (48 points, 3 comments)
    10. If you only share ONE post today, let it be this list of 156 House Republicans who voted to raise the retirement age for Social Security to age 70. -- Don't let them get away with it. - Make sure EVERYONE knows. (45 points, 1 comment)
  5. 1121 points, 37 submissions: Safe_Salt9663
    1. This is not normal (81 points, 20 comments)
    2. D.C. should be a state. What do you think? (80 points, 19 comments)
    3. A corrupt Republican lawmaker has just been EXPELLED from the Arizona State Legislature over ethics violations, including some relating to election misinformation. (62 points, 11 comments)
    4. BREAKING: Wall Street Journal drops bombshell, reveals that Elon Musk’s Twitter is now a whopping $13 billion in debt due to Musk’s failed Twitter Blue grift and the wave of advertisers fleeing to “protect their brands” from Twitter’s toxicity. (click for more) (61 points, 16 comments)
    5. Walker’s campaign paid $595,600 to a company called ‘Jetts’ to supposedly charter private planes. However, Fox has learned that ‘Jetts’ is a defunct car wash that was owned by a Walker donor. (54 points, 12 comments)
    6. The stacked Supreme Court… (49 points, 5 comments)
    7. Another war I must’ve missed. (44 points, 14 comments)
    8. MAGA world is sharing this photo claiming 700K migrants are on their way to the US border. This is FALSE. This photo was taken on October 27, 2018, of Honduran migrants in Arriaga, Mexico, heading to the US. Under Trump's presidency. Just another lie from the GOP. (43 points, 7 comments)
    9. JUST IN: Far-right extremist Riley Williams has been sentenced to 3 years in prison for storming the U.S. Capitol on January 6 and directing a mob toward the office of then-House Speaker Nancy Pelosi. (click for more) (41 points, 5 comments)
    10. Happy Sunday to everyone who knows that no sitting US President has ever attended the coronation of British royalty, so if you're trying to shame President Biden for not doing so, you're a complete dummy... Get a grip. (37 points, 4 comments)
  6. 485 points, 17 submissions: Top_Bottle7403
    1. This is why every vote matters! (91 points, 18 comments)
    2. Thank you Senator Blumenthal for holding Clarence Thomas accountable — (49 points, 11 comments)
    3. Child labor is making a comeback in Republican-led states. That’s what THEY mean by “progress”. (47 points, 11 comments)
    4. A conservative city council has banned the LGBTQ+ flag from government property in Huntington Beach. Another attempt to marginal LGBTQ+ individuals. But hate cannot be allowed to win. Not in California. Not anywhere. (44 points, 13 comments)
    5. Donald Trump just called Manhattan DA Alvin Bragg "a Racist in Reverse," and claimed that Joe Biden pushed Bragg to prosecute him. He then made a call to “investigate the investigators!” (34 points, 13 comments)
    6. The Southern Baptist Convention decided Tuesday to oust Saddleback Church, the second-largest congregation of the convention, because it has a female pastor (34 points, 6 comments)
    7. I wonder what the MAGA zombies think when Trump says DeSantis is being disloyal. Do they then hate DeSantis? Do they think he’s part of deep state? Or do they think Trump is a senile, old man? There are no policy differences. So, do they weigh which one is owning the libs harder? (29 points, 9 comments)
    8. BREAKING: After taking heat for days trying to handle this on his own with Norfolk Southern and making it much worse, Gov. Mike DeWine finally relents and declares a disaster so he can get federal assistance. (25 points, 3 comments)
    9. Here’s my advice to everyone — like me! — who’s excitedly awaiting Trump’s indictment: Relax, and keep your popcorn ready. 🍿 (20 points, 9 comments)
    10. Good morning and Happy Saturday to everyone who agrees that it's better to be "woke" than to sleepwalk through life acting like a rude, obnoxious, selfish asshole. (18 points, 1 comment)
  7. 288 points, 10 submissions: SetMau92
    1. Sanders Counters GOP Giveaways With Tax Hike on Estates of UltraWealthy"Over and over again, Republicans in Washington have professed their deep concern about the national debt and yet virtually all of them have signed onto legislation that would provide a $1.8 trillion tax giveaway to billionaires. (43 points, 2 comments)
    2. Senate Finance Chief: Nothing Unites GOP More Than 'Helping Rich People Cheat on Their Taxes' "It's a centerpiece of the ransom Speaker McCarthy has cobbled together as he threatens to trigger a catastrophic default," said Democratic Sen. Ron Wyden. (43 points, 11 comments)
    3. Audio Reveals Top GOP Lawyer's 2024 Strategy: Make It Harder for College Students to Vote "Instead of fighting for the people or actually earning the votes, Republicans' only plan is to try to 'combat' voting on college campuses," said Rep. Summer Lee. (39 points, 5 comments)
    4. All is not well in Florida... (35 points, 1 comment)
    5. Darn those pesky facts.. (33 points, 4 comments)
    6. Sanders and others Ramp Up 14th Amendment Pressure on Biden to Counter 'Reckless' GOP "Republicans have made it clear that they are prepared to hold our entire economy hostage unless you accede to their demands to reduce the deficit on the backs of working families. That is simply unacceptable." (29 points, 10 comments)
    7. GOP Debt Limit Bill Could Put Over 10 Million at Risk of Losing Medicaid: Analysis "This agenda would narrow opportunity, deepen inequality, and increase hardship," said the Center on Budget and Policy Priorities. (23 points, 2 comments)
    8. GOP Readies 'Shameful' Vote to Oust Omar From House Committee "You cannot remove a member of Congress from a committee simply because you do not agree with their views," said Rep. Pramila Jayapal. "This is both ludicrous and dangerous." (17 points, 2 comments)
    9. Progressive Young Voters to Biden: Energize Us and Win or Ignore Us and Lose "We need you to deliver the bold ideas that our generation cannot live without—stop the climate crisis, fight for the rights and dignity of immigrants, impose real gun control—and run on a bold platform." (17 points, 4 comments)
    10. Whitewash is to “gloss over or cover up,” (9 points, 1 comment)
  8. 125 points, 4 submissions: blixt141
    1. Nebraska Republican Says Six-Week Abortion Ban Is Necessary Because White People Are Being Replaced (49 points, 9 comments)
    2. Supreme Court rolls back federal safeguards for wetlands under Clean Water Act (35 points, 13 comments)
    3. Where Things Stand: Biden Shreds McCarthy’s Performative Debt Limit Bill (33 points, 5 comments)
    4. Police: 11 shot, injured during mass shooting at South Carolina park (8 points, 1 comment)
  9. 108 points, 5 submissions: Smelly-taint
    1. I love how the GOP wants to destroy everything that their own constituents benefit from. (33 points, 7 comments)
    2. Can't think of anything better than a dictator. 🤦🏽‍♂️ (30 points, 9 comments)
    3. Yes! Yes! Yes! (21 points, 28 comments)
    4. Woke? (13 points, 3 comments)
    5. Fuck these Anti Constitutionalist. Attack the Capital then attack my rights. (11 points, 20 comments)
  10. 89 points, 6 submissions: Puffin_fan
    1. Idaho Republicans Deny Girls Free Tampons in School (28 points, 6 comments)
    2. GOP’s Proposed Expansion Of Work Requirements Targets Low-Income People In Their Early 50s Who Already Work (20 points, 3 comments)
    3. Finland's average electricity price slips into negative territory (14 points, 2 comments)
    4. 'I’m trying not to go into panic.' Review of millions of Medicaid enrollees plagued by error and confusion (10 points, 4 comments)
    5. After Signature Bank Deal, FDIC Is Left With $11 Billion in ‘Toxic Waste’ Loans (9 points, 3 comments)
    6. As Rail Profits Soar, Blocked Crossings Force Kids to Crawl Under Trains to Get to School (8 points, 0 comments)

Top Commenters

  1. SpukiKitty (2210 points, 453 comments)
  2. SqnLdrHarvey (1737 points, 394 comments)
  3. In-The-Middle12 (1456 points, 284 comments)
  4. Top-Bottle7403 (1301 points, 240 comments)
  5. SmylesLee77 (1147 points, 294 comments)
  6. ProgressiveDemocrats (1104 points, 204 comments)
  7. FarPiano9575 (1090 points, 205 comments)
  8. Alternative-Flan2869 (679 points, 178 comments)
  9. HillbillyEulogy (588 points, 124 comments)
  10. Biishep1230 (533 points, 101 comments)

Top Submissions

  1. Wow. Students are standing outside the Tennessee House right now and chanting, “Fuck you fascists.” Young people are absolutely pissed off & we are about to give Republicans hell like they’ve never seenZ We aren’t forgetting this. by ProgressiveDemocrats (814 points, 309 comments)
  2. This was US Marine combat veteran Ruben Gallego as violent MAGA insurrectionists were overrunning the Capitol on January 6th. He gathered fellow Democrats to prepare to fight if necessary. "I would have killed motherfuckers to save this democracy. Fuck those guys." by FarPiano9575 (638 points, 128 comments)
  3. President Biden just schooled Republicans by reminding them, “Ronald Reagan was doing the 28% tax rate, you know, that wacko liberal guy." Does anyone else love President Biden’s sense of humor? by ProgressiveDemocrats (122 points, 22 comments)
  4. JUST IN: Justin Jones has been voted BACK to the Tennessee State House by the Metro Nashville Council! The Council was responsible for choosing who would fill the seat until the special election, and they voted to select Jones. Right after the vote, Jones embraced the council members. by ProgressiveDemocrats (115 points, 14 comments)
  5. Jamie Raskin just destroyed Lauren Boebert with Donald Trump's OWN Words. Rep. Raskin is truly the greatest. by Top-Bottle7403 (113 points, 15 comments)
  6. Students from Nashville-area high schools and colleges, including Belmont University and Vanderbilt U, are pouring into downtown Nashville to gather at the Capitol for another rally to call for safe gun laws following last week's mass school shooting. by FarPiano9575 (112 points, 20 comments)
  7. If you're randomly posting about World War III on Easter, you don't need to be running for the presidency, you need to run to a mental health provider. by Top-Bottle7403 (99 points, 21 comments)
  8. This is why every vote matters! by Top_Bottle7403 (91 points, 18 comments)
  9. Holy shit. The former Lt. Governor of Texas, Ben Barnes, just came forward to say he was part of a secret Republican operation that convinced Iran to keep Americans held hostage in order to sabotage Jimmy Carter’s 1980 presidential campaign. (Link to the story in comments below) by ProgressiveDemocrats (84 points, 15 comments)
  10. WOW. Absolute power move by Hakeem Jeffries. After Republicans kicked Ilhan Omar off of the House Foreign Affairs Committee, Rep. Jeffries immediately put her on the House Budget Committee. Republicans messed with the wrong party and person. Rep. Omar won’t be silenced. by ProgressiveDemocrats (82 points, 19 comments)

Top Comments

  1. 26 points: KayleighJK's comment in Wow. Students are standing outside the Tennessee House right now and chanting, “Fuck you fascists.” Young people are absolutely pissed off & we are about to give Republicans hell like they’ve never seenZ We aren’t forgetting this.
  2. 23 points: Similar_Candidate789's comment in Wow. Students are standing outside the Tennessee House right now and chanting, “Fuck you fascists.” Young people are absolutely pissed off & we are about to give Republicans hell like they’ve never seenZ We aren’t forgetting this.
  3. 23 points: SpukiKitty's comment in Wow. Students are standing outside the Tennessee House right now and chanting, “Fuck you fascists.” Young people are absolutely pissed off & we are about to give Republicans hell like they’ve never seenZ We aren’t forgetting this.
  4. 23 points: brotherstoic's comment in Should we be looking for someone other than Biden?
  5. 23 points: moreobviousthings's comment in Holy shit. The former Lt. Governor of Texas, Ben Barnes, just came forward to say he was part of a secret Republican operation that convinced Iran to keep Americans held hostage in order to sabotage Jimmy Carter’s 1980 presidential campaign. (Link to the story in comments below)
  6. 22 points: westofme's comment in Alex Jones transferred his assets to his family and friends, evading payments to Sandy Hook families. It should be illegal, but sadly, it's not.
  7. 20 points: Explorers_bub's comment in The city of Franklin, Tennessee is voting whether to allow a Pride festival. Someone during public comment says it will result in “a rainbow room where 8-12 year-old kids are given butt plugs & dildos.” --- This is what GOP propaganda is doing.
  8. 19 points: ProgressiveDemocrats's comment in Holy shit. The former Lt. Governor of Texas, Ben Barnes, just came forward to say he was part of a secret Republican operation that convinced Iran to keep Americans held hostage in order to sabotage Jimmy Carter’s 1980 presidential campaign. (Link to the story in comments below)
  9. 19 points: westofme's comment in Another war I must’ve missed.
  10. 18 points: HillbillyEulogy's comment in Please tell me whats wrong with this picture?
Generated with BBoe's Subreddit Stats
submitted by subreddit_stats to subreddit_stats [link] [comments]

2023.05.28 09:02 bbyfog [2021 Reich et al, Lancet Neurol] Tolebrutinib phase 2b trial, in relapsing multiple sclerosis

[2021 Reich et al, Lancet Neurol] Tolebrutinib phase 2b trial, in relapsing multiple sclerosis
Tolebrutinib Phase 2b Study
ClinicalTrials.gov number: NCT03889639; EudraCT number: 2018-003927-12
Citation: Reich DS, et al; Tolebrutinib Phase 2b Study Group. Safety and efficacy of tolebrutinib, an oral brain-penetrant BTK inhibitor, in relapsing multiple sclerosis: a phase 2b, randomised, double-blind, placebo-controlled trial00237-4/fulltext). Lancet Neurol. 2021 Sep;20(9):729-738. doi: 10.1016/S1474-4422(21)00237-400237-4). PMID: 34418400; PMCID: PMC8434816
To establish safe and efficacious dose of Burton’s tyrosine kinase (BTK) inhibitor tolebrutinib in people with relapsing multiple sclerosis (MS).
  • Burton’s tyrosine kinases are nonreceptor kinases expressed in most hematopoietic cells (excluding T cells and plasma cells) that link extracellular cytokines/factors signals with immune cell activation. In the context of MS, BTK signaling is important in B lymphocytes, myeloid cells including peripheral myeloid cells and macrophages, and CNS-resident microglia. (here)
  • The existing MS disease modifying treatments (DMTs) are effective in reducing relapsing rates with annualized release rates if 0.10, in other words, if 10 people are treated with DMTs over a year, only 1 is expected to experience relapse. These DMTs such as ocrelizumab (Ocrevus) affect peripheral adaptive immunity only (peripheral B cells) and do not halt or reverse disability progression. One reason is that they do not target CNS-resident immune cells.
  • Chronic CNS neuroinflammation is thought to contribute to MRI lesions accumulation and disability progression. Currently no approved DMT target CNS immune compartment.
  • BTK inhibitors are CNS-penetrant and, thus, are expected to target both peripheral adaptive immunity as well as CNS-resident immune cells (here).
  • Tolebrutinib binds irreversibly to BTK inhibitor that is given orally. The CNS-penetrant property of tolebrutinib was confirmed in a phase 1 trial in healthy people given a single dose of 120 mg tolebrutinib that achieved therapeutically relevant concentrations in the CSF.
  • This was a phase 2b, randomized, double-blind, placebo-controlled, crossover, dose-finding to establish safe and efficacious dose of tolebrutinib in people with relapsing MS (pwRMS).
  • The study enrolled 130 pwRMS (aged 18-55 years; EDSS, less than 5.5 at screening) at 40 sites across 10 countries in Europe and the United States. The study included 128 people with relapsing-remitting MS and 2 with secondary progressive MS with relapses.
  • The study participants were randomized 1:1 to 2 cohorts. Within each cohort, participants were randomized 1:1:1:1 to tolebrutinib 5 mg, 15 mg, 30 mg, or 60 mg daily oral dose groups.
  • In cohort 1 (tolebrutinib-to-placebo), all participants first received tolebrutinib at dose according to the group assignment for 12 weeks followed by all participants crossover to 4 weeks of placebo; in cohort 2 (placebo-to-tolebrutinib), all participants first received 4 weeks of placebo following by 12 weeks of tolebrutinib.
-- This unique crossover study design allowed all participants to receive active treatment for 12 weeks, thus, allowing reduction of risk to the patients.
-- The data from the 4-week placebo period from cohort 2 was used as control data in this study. The 4-week placebo run-out period in cohort 1 was used to maintain blind and this data was only used for safety evaluation.
  • The entry criteria required diagnosis of relapsing-remitting MS or secondary progressive MS with relapses; documentation of at least 1 replace in prior 1 year, at least 2 relapses in past 2 years or at least 1 active Gd-enhancing brain lesion in past 6 months prior to screening.
  • The length of the trial was 16 weeks. MRI scans were performed every 4 weeks until the end of study at week 16.
  • The primary objective was to determine the dose-response relationship between tolebrutinib and new active brain lesions detected using MRI. The primary efficacy endpoint was the number of new Gd-enhancing lesions detected on the scan performed after 12 weeks of tolebrutinib treatment (at week 12 for Cohort 1 and week 16 for Cohort 2), relative to the scan 4 weeks prior.
  • Secondary endpoints were the number of new or enlarging T2 lesions detected on the same scan observed after 12 weeks of treatment, the total number of Gd-enhancing lesions after 12 weeks of tolebrutinib treatment (ie, all Gd-enhancing lesions on the scan at the end of 12 weeks of treatment), as well as adverse events (AEs), serious AEs, and AEs of special interest.
  • Baseline characteristics were similar across all groups with mean age of 36 to 39 years; ~66 to 70% female; median time from onset of MS symptoms of ~7.5 years; and mean EDSS score of ~2.5.
  • Median exposure to study drug was ~80 days across four tolebrutinib dose group and 28 days for placebo group. The duration of exposure to active study drug was 12 weeks.
  • Primary endpoint: using an exponential model, a dose-response relationship was observed between tolebrutinib and new Gd-enhancing lesions (p=0.03). The 60-mg dose showed maximal effect with 85% reduction (95% CI, 28–97%) in new Gd-enhancing lesions versus placebo after 12 weeks of treatment.
  • The mean ± SD number of lesions was 0·13 ± 0·43 for tolebrutinib 60 mg versus 1·03 ± 2·50 for placebo.

Tolebrutinib Phase 2b Study: Figure, primary endpoint
  • Secondary endpoints: dose-response relationship for the number of new or enlarging T2 lesions was established (p <0.0001). A maximal effect was again observed with the 60-mg dose, with an 89% (95% CI, 68–96%) versus placebo.
  • Safety: Headache was the most common nonserious adverse event.
  • The primary objective of the trial was met and the null hypothesis of a flat dose-response curve was rejected.
  • The 60 mg dose was most efficacious in reducing acute inflammation in brain (new Gd-enhancing lesions). Reduction in new Gd-enhancing and/or enlarging T2 lesions is established in literature to correlate with reduction in relapse rates; this provides rationale to further study tolebrutinib in larger MS trials.
  • Currently following tolebrutinib MS trials are ongoing: long-term safety study NCT03996291) and phase 3 studies including in relapsing MS (NCT04410978 and NCT04410991), PPMS (NCT04458051), and nonrelapsing SPMS (NCT04411641).

Related: BTK inhibitors for MS, FENopta trial
submitted by bbyfog to MultipleSclerosisLit [link] [comments]

2023.05.28 06:56 ComprehensiveLab8225 M22 ADHD [ habits job mindfulness noporn sleep ] accountability partner(s) search

UTC+6 (but I don't care about your timezone).
I'd like to find someone who's currently trying to incorporate the same habits in their life as I do, to add also some bi-directional (?) accountability.
The list of habits is: no porn (mins \0), sleep (wake up & go to bed at acceptable time \2), taking meds (\3), hygiene (teeth morning\evening \2), meditation (mins \20), journaling (mins \20), cleaning (dishwashing does not counts, mins \10), job (\420), walking (mins \15), "quality" media (\30), youtube (no more than \15), reading (maniac uncontrollable binge-reading does not counts, mins \30), cooking for tomorrow (\1), fasting (\1), non-working communications are offline during the day (\1). There also evaluation of how satisfying the day was, how well did I slept, what drugs did I took except the "usual stack", and at what hour did I finished all the things (that one may be added too early, since I'm not always even beat all that).
If you don't understand what's so difficult about doing normal things - good for you. If you think that I've added to much - last 2 weeks I was doing like 70-90% of that generally, so I consider it just having a space for improvement, rather than overwhelming. And the general dynamic from last 5 months was nice. Except the downfalls, but whatever, I'm ok most of the times.
I'm tracking minutes of what I do for 7 years (and about 1 year in a strike). Just to feel more control over my life, or to see clearly where am I heading to (even if it's a ditch, though it is not, now). Since early January 2023 I also publish daily habit notes, a few (17...) lines like "Habit: 14\30" (=14 minutes\times is done today, out of desired 30), with a little thoughts on a day. So I know that some people will see how well I was doing today (public promises -> public accountability). I medicate (generic atomoxetine) for 48 days already and I'm getting better. Some studies say, that it's plateau may be achieved after many months and possibly years, which is promising. I use identiti app for month because some guy on /b is also using it and we share similar habits (my nickname is @cashuser, habit names/descriptions can be misleading for the sake of them being default ones, so app would automatically associate your habits with such of other person). I use Forfeit app for 2 weeks, added walking and journaling to it (will add more later), set the fee to 1$ but it's still refreshing when charged, and prioritizes added things even higher than your job, lol. And, finally, I'm posting this today (been planning to do so for a good 2 weeks). Incremental progress! Yeaaah!
Why didn't I added working out? It's ultraboring. Would add when I'll get used to all the stuff already present here. Why don't I use beeminer which is sooo cool? It has only 3 habits on free plan. Why don't I use SnapHabit? Because it would be too much apps even if it had userbase (which is doesn't). What's my job? Programming. Where do I post my daily habit reports? You know I post them in Russian... Anyway, telegram @daily_reports_si (the pfp meme is "ME" on the giant wave and "problems" on a surfer).
So, yea. DM me with habits you share (the harder ones the better) and whatever messenger app you're using, if interested. Let's master this life in coop, and get motivated to match each other fail success.
P.S. That post took too long hope I won't miss anything today...
submitted by ComprehensiveLab8225 to GetMotivatedBuddies [link] [comments]