#Agonistes 2001 | Explore Tumblr posts and blogs

local-hellhound-steals-spaghetti · 2 months ago

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Oooooh here we go. We have the cetacean “experts” joining in to justify the bad handling of Moo Deng and discrediting me/shooting the messenger because I support responsible cetacean management. Because everyone just made up their mind that you can’t give dolphins the habitat they need because “it’s not the ocean.”

But it’s apparently totally okay to give other species substandard habitats. I guess Moo Deng doesn’t really NEED to live in a jungle. Concrete is fine for her :)

Now we do know that dolphins can thrive in human care and “suffering all the time” isn’t actually the case (at least, not from this generalisation basis there can absolutely be poor welfare in bad facilities) and basically any time anyone mentions the word SeaWorld everyone loses the ability to critically think.

You know what we never do with cetaceans? Grab at and harass their babies for clout. The only time we ever interact with the calf in those early days is to check their health parameters. And it is always with active participation and consent.

It’s important that we make sure the calf is doing well, especially in those critical early days where the calf is so vulnerable. So, with positive reinforcement, we teach the mother to bring over her calf voluntarily and do a very gentle restraint to collect samples.

This is the only time we’re touching the calf. And not every facility does this either, some will stay completely hands off besides feeding the mother.

But this is how you do safe, respectful and stress free animal husbandry, actually using desensitisation and conditioning positive emotional responses to being handled:

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When watching this video, keep in mind that restraining a dolphin physically with only a few people is almost impossible. This dolphin is staying with her carers because she trusts them and she has a relationship with them.

I know this dolphin and the people in this video. It’s an incredible thing to see cooperative care like this in action.

Commentary and tags like the one above goes to show how the “trust the keeper” argument is only for selective species that are being used for clout.

But trust the people who work with dolphins or orcas? Trust the people that work in dolphin welfare and who actively work to measure and improve it? No, because everyone and their dog are apparently cetacean welfare experts because they regurgitate Blackfish or the talking points of a handful of lobbyists parading as scientists.

And they’ll even use violent wording and thinly veiled death threats against keepers, justifying it with this idea that they want to “liberate” animals that they don’t have any idea about caring for.

Anyway here’s a bunch of research on dolphin welfare that supports positive welfare states in human care :)

• There are no scientific studies suggesting that dolphins in marine mammal facilities are more prone to disease than dolphins in the wild. In fact, peer-reviewed scientific studies have shown that the immune systems of wild dolphins are much more challenged than the immune systems of dolphins in human care (refs 1-2)

• Similarly, there are no scientific studies suggesting that dolphins in marine mammal facilities are any more stressed than dolphins in the wild. On the contrary, studies have shown that cortisol levels (i.e., the “stress hormone”) of dolphins in marine mammal facilities are either very similar to, or lower than, cortisol levels of wild dolphins, depending on the technique used to obtain the samples (See review in ref 3).

• Bottlenose dolphins in U.S facilities are living as long or longer than their wild counterparts (ref 4)

• Average life expectancy from 2001-2015 was 41.6 years in SeaWorld orcas, showing significant improvements in veterinary care and welfare (ref 5)

• Aggression and agonistic behaviour made up 1-2% of observed behaviours in orcas at Loro Parque, debunking claims of hyper aggression and chronic stress from supposed poor social structures. (ref 6)

(1) Ruiz, C. L., Nollens, H. H., Venn-Watson, S., Green, L. G., Wells, R. S., Walsh, M. T., ... & Jacobson, E. R. (2009). Baseline circulating immunoglobulin G levels in managed collection and free-ranging bottlenose dolphins (Tursiops truncatus). Developmental & Comparative Immunology, 33(4), 449-455.

(2) Fair, P. A., Schaefer, A. M., Houser, D. S., Bossart, G. D., Romano, T. A., Champagne, C. D., ... & Reif, J. S. (2017). The environment as a driver of immune and endocrine responses in dolphins (Tursiops truncatus). PLoS ONE, 12(5), e0176202.

(3) Proie, S. (2013). A systematic review of cortisol levels in wild and captive Atlantic bottlenose dolphin (Tursiops truncatus), killer whale, (Orcinus orca), and beluga whale (Delphinapterus leucas). MA Thesis, Evergreen State College.

(4) Jaakkola, K., & Willis, K. (2019). How long do dolphins live? Survival rates and life expectancies for bottlenose dolphins in zoological facilities vs. wild populations. Marine Mammal Science.

(5) Robeck, T. R., Willis, K., Scarpuzzi, M. R., & O’Brien, J. K. (2015). Comparisons of Life-History Parameters between Free-Ranging and Captive Killer Whale (Orcinus orca) Populations for Application Toward Species Management. Journal of Mammalogy, 96(5), 1055–1070. http://doi.org/ 10.1093/jmammal/gyv113

(6) Sánchez-Hernández, P., Krasheninnikova, A., Almunia, J., & Molina-Borja, M. (2019). Social interaction analysis in captive orcas ( Orcinus orca ) . Zoo Biology, (April), 1–11. http://doi.org/ 10.1002/zoo.21502

Positive behavioural states are demonstrated in cetaceans in human care: Peer-reviewed scientific studies show that:

• Dolphins show anticipatory behaviors before sessions of interacting with their trainers (with no food involvement). This shows they view the interactions themselves as positive. (ref 1)

• An increase in dolphin behavioral diversity and play behavior following interactive programs suggest that such programs are in fact enriching for the dolphins and add to their psychological well-being (refs 2-3).

• Dolphins observed swimming in sync with each other at zoological facilities displayed optimistic judgements in optimistic bias tests, indicating positive welfare. (ref 4)

• When given the choice, dolphins in one study showed a preference for being in a smaller pool, despite having access to larger pools, indicating that size of pool may not be influencing dolphin movement preferences. (ref 5)

(1) Clegg, I. L., Rödel, H. G., Boivin, X., & Delfour, F. (2018). Looking forward to interacting with their caretakers: dolphins’ anticipatory behaviour indicates motivation to participate in specific events. Applied Animal Behaviour Science, 202, 85-93.

(2) Miller, L. J., Mellen, J., Greer, T., & Kuczaj, S. A. (2011). The effects of education programmes on Atlantic bottlenose dolphin (Tursiops truncatus) behaviour. Animal Welfare, 20, 159-172.

(3) Trone, M., Kuczaj, S., & Solangi, M. (2005). Does participation in Dolphin–Human Interaction Programs affect bottlenose dolphin behaviour? Applied Animal Behaviour Science, 93, 363-374.

(4) Clegg, I. L., Rödel, H. G., & Delfour, F. (2017). Bottlenose dolphins engaging in more social affiliative behaviour judge ambiguous cues more optimistically. Behavioural brain research, 322, 115-122.

(5) Melissa R. Shyan , David Merritt, N. M., & Kohlmeier, K. B. & J. T. (2010). Effects of Pool Size on Free- Choice Selections by Atlantic Bottlenosed Dolphins at One Zoo Facility. Journal of Applied Animal Welfare Science, 5(3), 203–213. http://doi.org/10.1207/S15327604JAWS0503

Note how this is a body of evidence from multiple sources that are being developed and complied over time. That is what science is all about.

Anyone who tells you that the science is finalised on something eg. Lori Marino and Naomi Rose insisting that the science is settled on cetacean welfare being inherently bad in human care - be very very skeptical of them. They are trying to sell you ideology over science (and they’d love for you to donate your money to their sanctuary that hasn’t passed any approval to build for 5 years)

The science is rarely “settled” on anything.

As for SeaWorld themselves, they have not published enough welfare data for us to discuss. But their animals do show signs of positive welfare states including active participation in health care and training, engagement with enrichment, ability to learn and adapt (stressed animals can’t learn complex behaviours and won’t participate in sessions), stable social structures with occasional conflict ect.

#sighs for a million years #cetacean welfare

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bronzewool · 1 year ago

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Can we appreciate how Clive Barker made his own monster toyline back in 2001, Tortured Souls, and even wrote a novelette explaining their backstories:

Agonistes - A demon created by God on the seventh day after Adam and Eve. The manipulator of flesh, he uses his own body as a canvas to transform Supplicants into monstrous beings (including Judas. Yes, that Judas).

Lucidique - The daughter of a senator who was killed by a mob boss for criticizing the upper class and resurrected by Agonistes. She went on to murder said mob boss and his sons.

The Scythe-Meister - The son of a prostitute, this young assassin enjoys mutilating his victims before killing them. Tasked with killing a troublesome senator, only to be caught in the act by Lucidique, who brought him to Agonistes and remade him. With his new scythe form he would go on to kill the Emperor and fall in love with Lucidique.

Talisac - A mad scientist who experimented on himself and many others, Talisac made an artificial womb for himself to bring about the next "virgin birth"

Venal Anatomica - One of Talisac's failed experiments commissioned by the three generals to make a super soldier. Nine feet tall, made of rotting flesh and immune to pain, Venal was created to kill The Scythe Meister, only to then be blinded by Lucidique who sort revenge for her dead lover.

Mongroid - The "Son" of Talisac. A Frankenstein monster who ate his creator and fled to the sewers.

#Fandom: tortured souls #You have no idea how much i want to roleplay these not-cenobites #They are so cool and i want them #And thats just season 1 #The toyline was so successful he made six more monster figures

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warped-historian · 4 years ago

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Warped Tour, 2001

Dates:

June 22: Peoria, AZ

June 23: Las Vegas, NV

June 24: Fresno, CA

June 27: Chula Vista, CA

June 28: Ventura, CA

June 29: L.A., CA

June 30: San Francisco, CA

July 1: Lake Tahoe, NV

July 2: Boise, ID

July 3, George, Washington

July 5: Calgary, AB

July 6: Bozeman, MT

July 7: Salt Lake City, UT

July 8: Brighton, CO

July 10: Bonner Springs, KS

July 11: Maryland Heights, MO

July 12: Noblesville, IN

July 13: Milwaukee, WI

July 14: Somerset, WI

July 15: Tinley Park, IL

July 17: Sparta, KY

July 18: Antioch, TN

July 19: Little Rock, AR

July 20: Dallas, TX

July 21: Selma, TX

July 22: The Woodlands, TX

July 23: Corpus Christi, TX

July 24: New Orleans, LA

July 25: Atlanta, GA

July 26: Charlotte, NC

July 27: Orlando, FL

July 28: Pompano Beach, FL

July 29: Tampa, FL

July 31: Tampa, FL

August 1: Virginia Beach, VA

August 2: Pittsburgh, PA

August 3: Camden, NJ

August 4: New York, NY

August 5: Asbury Park, NJ

August 7: Cleveland, OH

August 8: Buffalo, NY

August 9: Boston, MA

August 10: Montreal, QC

August 11: Toronto, ON

August 12: Detroit, MI

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Lineup:

AFI

Blink-182 (Played 7/14)

The Bouncing Souls

The Distillers (Played 6/22-7/22)

Dropkick Murphys (Played 8/1-8/12)

Fear (Played 6/22-6/30)

Fenix TX

Inspection 12 (Played 7/27)

Less Than Jake

The Living End (Played 7/10-7/12 and 7/14-7/15)

Me First and the Gimme Gimmes

Obtik (Played 7/23)

Pennywise (Played 6/22-7/8 and 7/27-8/12)

Rancid

Rollins Band (Played 8/1-8/9)

311 (Played 6/22-7/29)

The Ataris

D12 (Played 7/31-8/3)

Dub Pistols (Played 7/10-7/24)

Flogging Molly (Played 7/31-8/12)

Guttermouth (Played 6/29 and 7/6-7/15)

H2O

Jimmy Eat World (Played 7/25-8/5)

Kool Keith

The Misfits (Played 7/10-7/17)

Morgan Heritage (Played 7/25-8/12)

New Found Glory (Played 6/22-7/2 and 7/14)

Sum 41 (Played 7/27)

The Vandals

3rd Strike (Played 7/15-7/26)

7th House (Played 8/2-8/5)

Alien Ant Farm (Played 6/22-7/25 and 7/31-8/9)

Amen (Played 8/3-8/9)

The Apex Theory (Played 6/22-7/8)

Bigwig (Played 7/31-8/12)

Black Halos (Played 7/5-7/8)

Bodyjar (Played 6/22-7/15)

The Business (Played 7/14-7/22)

The Casualties (Played 7/13-7/23)

Catch 22 (Played 8/7-8/12)

DeRoot (Played 7/27)

El Centro (Played 7/20-7/23)

Esham (Played 6/22-8/3)

The Explosion (Played 7/17-7/29)

Good Charlotte (Played 6/22-8/5)

Grand Theft Audio (Played 8/9-8/12)

Hank 3 & Assjack (Played 6/22-7/15)

Hesher (Played 7/10-7/23)

Home Town Hero (Played 6/22-6/29)

Jaya the Cat (Played 8/2-8/5 and 8/9)

Jersey (Played 7/31-8/5)

The Juliana Theory (Played 6/22-7/3)

Liars Inc. (Played 6/28-7/12)

Little T and One Track Mike (Played 8/9-8/12)

Lost City Angels (Played 7/11-7/12 and 7/14-7/15)

Midtown (Played 7/17-7/29)

No Motiv (Played 7/31-8/12)

Pressure 4-5 (Played 7/7-7/8)

Rehab (Played 7/31-8/5)

River City High (Played 7/25-7/29)

River City Rebels (Played 7/12-7/14)

Rogue's March (Played 8/3-8/4 and 8/8-8/9)

Showoff (Played 7/25-7/31)

Slightly Stoopid (Played 6/30-7/8)

The Spitvalves (Played 7/27)

Sugarcult (Played 6/22-7/5)

Sum 41 (Played 7/10-7/26 and 7/28-8/12)

Thrice (Played 6/22-6/27)

The Youth Ahead (Played 8/5)

Zooloft (Played 8/4)

2 Cents Worth (Played 6/23)

Agent 51 (Played 6/27-6/29)

Anchor Man (Played 7/27)

Bargain Music (Played 6/22-6/27)

Belvedere (Played 7/5 and 7/31-8/5)

The Benjamins (Played 7/11-7/15)

Bumrukus (Played 7/26-7/29)

Defiance of Authority (Played 8/5-8/8)

DeRoot (Played 7/10-7/15, 7/20-7/23)

Destruction Made Simple (Played 7/29-8/1)

Deviates (Played 6/27-7/10)

Dover (Played 8/4)

Downway (Played 7/5-7/7)

The Eyeliners (Played 7/20-7/23)

Fatman's Belly (Played 7/5)

Grade (Played 8/8-8/12)

Hollywood Beach Brian (Played 7/27)

Idol Hands (Played 6/28)

The Impossibles (Played 7/31-8/5)

Jackpot (Played 6/30-7/3)

Japetto (Played 7/31-8/5)

The Know How (Played 7/28-7/29)

The Lawrence Arms (Played 7/5-7/10)

Lefty (Played 7/27 and 8/7-8/12)

The Line

Lovetone (Played 8/2-8/4)

Luckie Strike (Played 6/29-7/1)

Madcap

Mest (Played 7/15-7/19)

Obtik (Played 7/20-7/22)

Pepper

Pinhead Circus (Played 7/11-7/13)

Project Wyze (Played 8/9-8/12)

The Planet Smashers (Played 8/7-8/12)

Potluck (Played 6/30-7/1)

The Rocking Horse Winner (Played 7/26-7/29)

Shutdown (Played 8/8-8/10)

Sloppy Meateaters (Played 7/3 and 7/20-7/25)

Stunt Monkey (Played 6/30-7/1)

Switch (Played 7/8-7/19)

Sw1tched (Played 7/27)

Thursday (Played 8/1-8/4)

Tree (Played 8/7-8/9)

Tsunami Bomb (Played 6/22-6/28)

Userfriendly (Played 6/22-7/3)

Wanted Dead (Played 6/22-6/24)

Welton (Played 7/19)

151 (Played 6/29)

2540 (Played 7/26)

28 Gates (Played 7/29)

3NT (Played 7/20)

3rd Man In (Played 6/23)

40 Watt Hype (Played 6/24)

5 Spot (Played 7/5)

$50 Flander (Played 7/27)

The 7 Method (Played 7/25)

7minds (Played 8/5)

7th Rail Crew (Played 8/9)

AAK (Played 8/7)

Absolve (Played 8/9)

Addictive (Played 7/19)

Afrodesia (Played 7/19)

Aging Process (Played 6/23)

Agonistic Resemblance (Played 6/30)

All Access (Played 7/18)

Asbestos (Played 7/17-7/20)

Atomic Number 9 (Played 7/13)

B9 (Played 6/29)

Backhand (Played 7/24)

Benevolent Souls (Played 7/8)

Bi-Level (Played 7/11)

Big Dictator (Played 6/28)

Bill the Welder (Played 7/8)

Bird3

Blacklist Sunshine (Played 7/10)

Blend Engine (Played 8/4)

Blindshot (Played 8/12)

Blister 66 (Played 7/8)

Breakaway (Played 8/4)

Bruise Bros. (Played 8/9)

Buck32 (Played 7/25)

The Brodys (Played 6/30)

The Cartel (Played 8/10)

The Cartwrights (Played 7/11)

Chump (Played 7/7)

Civilized Animal (Played 7/3)

Closer Than Kin (Played 8/8)

ColdSnap-9 (Played 7/6)

Copper (Played 7/18)

Crowned King (Played 7/5)

Day Old Donuts (Played 7/23)

Deceiving Ralph (Played 7/17)

Dinkus9 (Played 8/8)

Dirtnap (Played 6/24)

Distorted Conduct (Played 7/21)

Distorted Penguins (Played 8/2)

D.O.S. (Played 6/28)

East Coast Pimps (Played 8/3)

Eastcide (Played 8/8)

Edinburgh (Played 7/12)

Enamel (Played 7/15)

The End of Julia (Played 7/20)

Epagee (Played 7/6)

Evil Engine 9 (Played 7/12)

Explosion 9 (Played 7/10)

Farmacy (Played 6/28)

Faster Than Eddie (Played 8/11)

FATE (Played 7/18)

Fixit (Played 7/2)

Flipside (Played 8/4)

Flipsyde (Played 7/14)

The Fonzarellis (Played 7/10)

Fullerton (Played 7/27)

Fusebox (Played 6/27)

GAGE (Played 8/9)

Gamma Rays (Played 7/31)

Glasseater (Played 7/28)

Going Nowhere (Played 7/28)

Gravity Crush (Played 7/14)

The Groovaholics (Played 7/11)

Guilt Trip (Played 7/5)

Happy Hour (Played 7/29)

Haverbrook (Played 7/25)

Hellshock (Played 7/15)

Higher Down (Played 8/10)

Hit By A Semi (Played 7/1)

IH5 (Played 7/23)

Ill Collaboration Unit (Played 8/1)

Implant (Played 6/30)

In Between Stars (Played 8/5)

INTAK (Played 7/17)

Ivet (Played 8/7)

Jackmove (Played 8/1)

Janis Figure (Played 7/14)

Jinxed (Played 8/11)

Just A Joke (Played 6/27)

Killshot (Played 8/12)

Kronik (Played 7/19)

Krystal Lake (Played 6/29)

Last Chance Hero (Played 7/22)

Last Place Champs (Played 7/13)

Law Of Motion (Played 7/6)

Lazerwolfs (Played 7/3)

Lesson 11 (Played 7/19)

Letterbox (Played 8/5)

Liquid Youth (Played 7/22)

Live For Today (Played 8/3)

Logiene (Played 7/20)

LoKey (Played 7/21)

Loopus (Played 8/8)

The Lost Cause (Played 7/6)

Lost For Words (Played 6/23)

Low Profile (Played 7/7)

Lucky Strikes Out! (Played 7/14)

Lure609 (Played 7/17)

Maladjusted (Played 7/7)

Marlinspike (Played 7/5)

May Flood (Played 7/24)

Miseuphoria (Played 7/31)

Mold (Played 8/10)

The Monjees (Played 7/28)

Motor Betty (Played 8/4)

MT Minds (Played 7/26)

Munkyfinger (Played 7/29)

The MunX (Played 7/24)

Mynis (Played 6/24)

Next To Nothing (PLayed 7/22)

Nine Lives (Played 8/4)

No Faced (Played 7/2)

Non Zero Sum (Played 7/3)

Nosedive (Played 6/24)

NoseDive (Played 8/7)

Omega Red (Played 6/28)

One Short (Played 8/11)

Outplay (Played 7/24)

The Pathetics (Played 6/30)

Peepin' Tom (Played 7/21)

Phrenik (Played 7/1)

Plight (Played 8/10)

Poptart Monkeys (Played 8/2)

The Proms (Played 8/7)

Racecar (Played 7/13)

REV-7 (Played 7/29)

Rudiger (Played 6/29)

Ruskabank (Played 7/10)

Scream Sophie (Played 7/26)

Secret Agent 8 (Played 7/22)

Shift (Played 6/27)

Shootin' Blanks (Played 6/23)

Sick (Played 7/8)

Skalami (Played 7/2)

Slack Season (Played 7/27)

Slingshot9 (Played 7/12)

Something Left to Learn (Played 6/22)

Space Nelson (Played 8/12)

The Spicoli's (Played 8/11)

Spindle (Played 6/22)

SpiralJinx (Played 8/3)

Squeezetoy (Played 8/1)

Stiff One Eye (Played 7/23)

StoneKracker (Played 7/21)

Stop Tyler (Played 6/22)

SubVert (Played 7/2)

Sundog (Played 8/2)

SuperGiant (Played 7/31)

Swerve (Played 6/27)

Swinging Lovehammers (Played 7/15)

Ten Ninety (Played 7/18)

Tenfold (Played 7/1)

Third Try (Played 7/15)

Tod. (Played 7/12)

Toque (Played 8/1)

Tornacade (Played 7/17)

Tragically Undecided (Played 7/25)

Twice The Sun (Played 7/28)

Twin Cam (Played 8/12)

The Twirpentines (Played 8/2)

Unfisted (Played 7/27)

Unfold (Played 7/7)

UnWell (Played 7/13)

UXB (Played 7/31)

Vally Lemmons (Played 7/23)

Wakz (Played 7/11)

Where's Arnie (Played 7/20)

Who's Your Daddy? (Played 7/3)

Willknots (Played 7/1)

Wyred (Played 8/3)

Years Apart (Played 7/26)

Zero State (Played 6/22)

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voice-of-anarchy · 3 years ago

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ARCH ENEMY Celebrates 25th Anniversary: 'It's Been An Awesome Experience,' Says MICHAEL AMOTT

Swedish/Canadian/American metallers ARCH ENEMY are celebrating their 25th anniversary in 2021.

When ARCH ENEMY released its debut album, "Black Earth", in 1996, death metal was stagnating and in desperate need of a kick up the ass. Guitarist Michael Amott's blueprint for the purest of metal strains proved an instant underground hit, both in Europe and Japan, and almost single-handedly resurrected death metal as a viable art form with mainstream potential. Signed to Century Media Records for 1998's sophomore effort "Stigmata", ARCH ENEMY marched purposefully towards a new millennium with a rapidly growing reputation. 1999's "Burning Bridges" added to the band's momentum, their razor-sharp blend of brutality and epic melody becoming more refined with each creative step. But it was in 2001, when original vocalist Johan Liiva stood aside and mercurial frontwoman Angela Gossow stepped in, that ARCH ENEMY truly took off.

Released in 2001 in Japan and nearly a year later in Europe, "Wages Of Sin" showcased a revitalized line-up and newfound gift for immortal anthems, Gossow's feral roar adding many layers of charisma and power to ARCH ENEMY's already-monstrous sound. Swiftly dedicating themselves to a relentless touring schedule, the band's upward trajectory continued throughout the first decade of the 21st century, with each successive album enhancing the band's reputation and bringing legions of new fans to this resolute heavy metal campaign. Albums like 2003's vicious "Anthems Of Rebellion" and 2011's pitch-black and savage "Khaos Legions" ensured that Amott and his loyal henchmen — Gossow, drummer Daniel Erlandsson, bassist Sharlee D'Angelo and Michael's guitarist sibling Christopher — remained firmly at the top of the extreme metal tree: respected veterans at the height of their powers.

Always focused but impervious to other's rules and expectations, ARCH ENEMY evolved once more in 2015 following the departure of Gossow (now the band's manager). Replacing one of the most iconic vocalists of the modern age was never going to be easy, but in the shape of former THE AGONIST frontwoman Alissa White-Gluz, ARCH ENEMY found the perfect candidate. Unveiled on the ferocious, anthem-laden triumph of 2014's "War Eternal", Alissa's powerful identity and extraordinary vocal talents proved a natural and instantly welcomed fit. Further extensive touring cemented the new line-up's thrilling efficacy, before one final line-up change — the arrival of legendary guitarist Jeff Loomis, formerly of NEVERMORE — completed the musical puzzle that Amott had been tinkering with for the best part of 20 years.

Amott comments: "I must admit that it feels somewhat surreal that the year 2021 marks the 25th anniversary of ARCH ENEMY. I never imagined that we would reach a point in our career where we'd be looking back on two and a half decades of creating music, releasing albums and playing live shows all over the planet! It's been an awesome experience, to say the least.

"As a group, we have been fortunate enough to achieve some incredible highs and accomplishments, but we have also lived through difficult times and lows. This is life, peaks and valleys… I have to say, whatever adversities we faced — we've always come through it all stronger than before. Overall, it's been a great journey and one that I am extremely proud of. I wouldn't change a thing.

"Obviously, the COVID-19 pandemic has prevented us from doing any elaborate grand celebrations of the 25th anniversary, but we are doing some special merchandise and some other cool things - so keep your eyes peeled for that.

"A lot of my memories about the earliest days of ARCH ENEMY are connected to Japan. The first trilogy of albums, 'Black Earth' (1996), 'Stigmata' (1998) and 'Burning Bridges' (1999) were all released first in Japan and we toured there on all those three albums. Before much of the rest of the world really cared about us, we had gained a fantastic Japanese fan base that has supported us throughout the years — to this day. Domo Arigato Gozaimasu!

"With the release of our fourth album 'Wages Of Sin' in the early 2000s, we famously changed singer, a dramatic change from the classic Swedish death metal voice of original singer Johan Liiva to Angela Gossow — an unknown female German vocalist. A new concept at the time, and a bit of a gamble... I remember not being sure how the fans would react to the big change in the band. The new music we had written and recorded was also in a more straightforward style and the overall sound was a somewhat new direction for us. I needn't have worried, the 'Wages Of Sin' album was received very warmly by the fans in Japan, quickly becoming our biggest-selling album there. But maybe more importantly, it finally broke the band into the international metal arena in a big way. We found ourselves embarking on a rigorous touring schedule in Europe, USA and beyond. We had arrived!

"One thing ARCH ENEMY always did was tour a lot. We strongly believed in building the band by proving ourselves on the live stage, city by city, country by country…one show at a time. We really loved performing the concerts and the touring lifestyle — we still do.

"ARCH ENEMY is always pushing to play new uncharted territory — we have on many occasions been the first metal band to perform in a city or even country, which is always a huge thrill. Alongside building our own fan base on our countless headline tours and festival appearances, we also received fantastic opportunities with some of our early influences such as IRON MAIDEN, MEGADETH and SLAYER. They all brought us out as special guest on their tours, introducing us to their audience — for that we will always be thankful to them.

"In 2014 we released the 'War Eternal' album and introduced our new singer Alissa White-Gluz to the world, kicking off a new exciting chapter in the evolution of the band. We hit the road harder than ever before, eager to show the world what the band could do with the new lineup. In the seven years that have passed since then, the band has grown far beyond my wildest dreams. ARCH ENEMY's music continues to connect with new fans every day — it's hugely inspiring and keeps us pushing forward.

"On a personal note, ARCH ENEMY has been my band, my passion as well as my work for half of my life now and I can't really imagine what I would do if this band had not come to be all those years ago. I am eternally grateful to all the people that have helped us along the way in some way, shape or form... My dear band members/friends, all the people in the music business and underground metal scene that believed in us, producers and engineers for making us sound great, our tireless road crew and all the ex-members of course. Most importantly, the incredibly loyal fans that we have, whom I'll never be able to thank all in person. I can only promise that ARCH ENEMY will keep on making music (YES, there is a new album on the way!) ... and, of course, we will be out there playing live shows as we embark on what will be our biggest tour ever! I am very positive about the future.

"Here's to hopefully another 25 years! See you in the pit! Metal is forever!"

#arch enemy #AE25 #Michael Amott #2021 news

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emerald-studies · 4 years ago

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The wise Cornel West

Early Years & Education

Cornel Ronald West was born on June 2, 1953, in Tulsa, Oklahoma. Cornel West and his three siblings grew up in Sacramento, California, where they were raised by a mother who taught elementary school and a father who worked as a civilian administrator for the U.S. Air Force.

Harvard & Princeton

In 1970, West started attending Harvard University. Just three years later, he graduated magna cum laude with a major in near Eastern languages and civilization. West then enrolled at Princeton University. By 1980, he had earned both a master's degree and a doctorate in philosophy from Princeton.

West began his working career as a lecturer. The schools he first taught at include Harvard, New York City's Union Theological Seminary, the University of Paris and Yale University's Divinity School. West accepted a religion professorship at Princeton University in 1988. Following a six-year stint at Princeton, he chose to become a professor of African-American studies at Harvard. A 2001 blow-up with Harvard's then-president, Lawrence H. Summers, ended with West decamping to Princeton. In 2011, West opted to return to Union Theological Seminary.

Cornel West Books

In 1982, West's Prophesy Deliverance: An Afro-American Revolutionary Christianity was published. During the rest of the 1980s and early '90s, West brought out more books that touched on philosophy and religion, such as Prophetic Fragments: Illuminations of the Crisis in American Religion and Culture (1988) and The Ethical Dimensions of Marxist Thought (1991).

West's writing also addressed racial and sociopolitical phenomena. The essays in the best-selling Race Matters (1993) focused on the plight of struggling African Americans. West's major written works have since included The Future of the Race (1997), written with Henry Louis Gates Jr., Democracy Matters (2004) and a memoir entitled Brother West: Living and Loving Out Loud (2009).

Politics and Activism

West's political activism dates back to his childhood, when he participated in civil rights demonstrations with his family in Sacramento. While West was teaching at Yale University, he took part in protests against South Africa's apartheid regime, and was subsequently arrested.

Controversial Views on Obama

In terms of political affiliation, West's loyalty lies with the Democratic Socialists; he has been a member of that party since 1982. West campaigned for Barack Obama during his first presidential run, but then deemed Obama "a black mascot of Wall Street oligarchs and a black puppet of corporate plutocrats" (true honestly) in 2011. However, during the 2012 presidential election, West stated that he preferred Obama to Mitt Romney. Still, West continued his scathing critique on President Obama, calling him "a Wall Street presidency, a drone presidency, a national security presidency," in a 2014 interview.

Support for Bernie Sanders

In 2016 West supported the Democratic presidential candidacy of Bernie Sanders. When Sanders exited the race, West went on to support Green Party presidential candidate Jill Stein.

The Matrix Franchise, More Books

In 2003, West made his big screen debut in The Matrix Reloaded. He also appeared in the final film of the Matrix trilogy, The Matrix Revolutions (2003). West's other creative outlets include the recording of spoken word albums. Some of his work was featured on Terence Blanchard's Choices, winner of France's Grand Prix award for best jazz album of 2009.

In 2010, West began co-hosting the radio show Smiley & West with Tavis Smiley. The two also co-wrote The Rich and the Rest of Us: A Poverty Manifesto (2012). Other more recent works include Pro+Agonist: The Art of Opposition (2012) and Black Prophetic Fire (2014). (source)

#academia #blm #blacklivesmatter #black lives matter #blackactivists #cornel west

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wknc881 · 4 years ago

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Band of the Week: Arch Enemy

I first heard of Arch Enemy when my dad showed me the music videos for My Apocalypse and Nemesis. We were both in awe of the talent that this band had (and still has). They have melodic death metal down and create beautiful songs that have amazing harmonies by the guitars and vocals. The first time I saw Arch Enemy was at the Masquerade in Atlanta, Georgia. My dad and I traveled down there just to see Arch Enemy! We got VIP tickets and were able to meet the band! They are so nice and down to earth and are very thankful for their fans supporting them through the years.

Arch Enemy is a Swedish melodic death metal band that formed in 1995. The band was originally a supergroup with members from Carcass, Armageddon, Carnage, Mercyful Fate, Spiritual Beggars, The Agonist, Nevermore, and Eucharist. The mastermind behind Arch Enemy is Michael Ammot, (Carcass, Carnage, and Spiritual Beggers) who created Arch Enemy once he left Carcass. This band is known for having some of the best female vocalists and has really influenced women in the metal scene to get more involved. I know as a young girl watching Arch Enemy, seeing a badass female perform high screams and deep low gutterals was great to see and influenced me to do more within my metal community. The band was originally fronted by Johan Liiva, but was replaced by Angela Gossow (a German vocalist) in 2000. Gossow left the band in 2014 to become the band’s manager and was replaced by Alissa White-Gluz (a Canadian vocalist).

Arch Enemy’s musical style has been classified as melodic death metal, but their sound has a unique blend of progressive and death metal influences. Their influences are cited as Iron Maiden, Judas Priest, Black Sabbath, Manowar, Metallica, Megadeth, Slayer, Testament, Pantera, Death, Obituary, Carcass, Mercyful Fate, and King Diamond. You can hear these influences in their songs when listening to the melodies and harmonies of the guitars. They have mastered their own sound and I love the progression that Arch Enemy has taken.

Current Members:

Michael Amott (guitarist)

Daniel Erlandsson (drums)

Sharlee D’angelo (bassist)

Jeff Loomis (guitarist)

Alissa White-Gluz (vocalist)

Discography:

Black Earth (1996)

Stigmata (1998)

Burning Bridges (1999)

Wages of Sin (2001)

Anthems of Rebellion (2003)

Doomsday Machine (2005)

Rise of the Tyrant (2007)

Khoas Legion (2011)

War Eternal (2014)

Will to Power (2017)

Favorite Songs:

My Apocalypse, Nemesis, Bloodstained Cross, The World Is Yours, First Day in Hell, The Eagle Flies Alone, As the Pages Burn, War Eternal, and You Will Know My Name.

Have you seen Arch Enemy live? What are some of your favorite songs?

Stay Metal,

THE SAW

#WKNC #WKNC 88.1 #The Saw #The Saw's Butcher Shop #Band of the Week #Arch Enemy

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bigbouquetfart-blog1 · 4 years ago

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OEFENINGEN OM DE SPIERMASSA TE VERHOGEN (III)

De beste oefeningen om de spiermassa te vergroten (Deel 3: Bench Press)

We gaan verder met het derde deel van deze serie artikelen dat ik wilde wijden aan de beste oefeningen om de spiermassa te vergroten. Bij deze gelegenheid hebben we die voor het onderlichaam achtergelaten, om plaats te maken voor het beste voor het bovenlichaam.

Als u de eerste twee artikelen niet hebt gelezen, raad ik u aan dit wel te doen, omdat u zeker enkele gegevens zult ontdekken die u niet wist over de belangrijkste basis- of meervoudige gewrichtsoefeningen gericht op training van het onderlichaam:

? De beste oefeningen om de spiermassa te vergroten (1e deel: squats of squats) .

? De beste oefeningen om de spiermassa te vergroten (2e deel: deadlifts).

In dit artikel zal ik me concentreren op de bankdrukken (mogelijk de meest geliefde oefening door sportschoolgebruikers) en enkele van zijn verschillende varianten.

ANATOMISCHE EN FYSIOLOGISCHE BETROKKENHEID.

Dit is de 'koning'-oefening voor de extensor-spieren van het bovenlichaam, aangezien het spieren zoals de borstspier (de hoofd- of agonist), de claviculaire deltaspier, de triceps brachii en zelfs de anterieure serratus omvat.

We weten dat de pectoralis major bestaat uit drie porties of bundels, die hun naam krijgen, afhankelijk van het bot, botgedeelte of lichaamsgebied waarop ze zich bevinden, ingebracht of ontstaan ??(namelijk: superieur gedeelte of sleutelbeenbundel, midden of borstbeen) gedeelte, en onderste of rib of buikgedeelte). In de volgende afbeelding zien we de indeling van deze delen:

Bij de bankdrukken zijn de belangrijkste gewrichten van het bovenlichaam betrokken, dat wil zeggen: de humerus-radius-ulnar (elleboog) en de scapulo-humerus (schouder).

Gericht op het specifieke werk van de pectoralis major, moet worden opgemerkt dat de hoofdlocatie tijdens deze oefening zich bevindt op de sternale en abdominale delen, wat veel auteurs sterno-costale bundel noemen, ongeveer 66% tegen de resterende 34% die zou terugvallen op de claviculaire straal, 100% van de borstbetrokkenheid. Deze cijfers zijn echter berekend op basis van door Hern gepubliceerde elektromyografische onderzoekenández, Gª Onder meer Manso en Tous zouden in 2001 aanzienlijk toenemen met een strakkere grip dan normaal.

Mogelijk bent u geinteresseerd: Online Personal Training Course.

TECHNIEK.

Voor deze oefening gebruiken we een bar en schijven (bij voorkeur Olympische), met hun respectievelijke stops, klemmen of "kragen", en een speciale bank voor deze oefening ( fig. 02 ). Degenen onder jullie die beginnen, kunnen het op een Smith-machine doen (onthoud dat dit de beroemde multipower is , fig. 03 ), het plaatsen van een hulpbank (Afb.04 ) in het midden of op een andere soortgelijke machine.

Om een ??correcte bankdrukken uit te voeren, raad ik u aan deze richtlijnen te volgen:

Startpositie:

? Liggend (met de voorkant naar boven) op de bank liggen.

? De voeten op de bank of op een daarvoor ontworpen oppervlak (knieen gebogen, logisch). Ze kunnen op de grond worden ondersteund, omdat dit meer stabiliteit biedt en daarom de mogelijkheid om meer gewicht op te heffen, maar met het nadeel dat we bij het neerlaten van de voeten, als de bank erg hoog is, hyperlordose (overmatige concaafheid) zullen veroorzaken lumbale en grotere druk op dit gebied bij het tillen van dat gewicht. Daarom is de eerste optie de veiligste voor de lumbale wervelkolom.

? Het hoofd moet goed worden ondersteund op de bank en de ogen moeten in een rechte lijn onder de stang liggen.

? De schouderbladen moeten teruggetrokken zijn, dat wil zeggen proberen ze tegen de wervelkolom bij elkaar te brengen, waardoor de borst naar boven steekt. Dit geeft ons meer bewegingsvrijheid, het vermogen om meer gewicht te verplaatsen en vermindert het risico op letsel, vooral in het scapulo-humerusgewricht. In de volgende afbeelding kunnen we zien wat ik bedoel:

? We grijpen de stang met een scheiding van de handen van ongeveer een spanwijdte (min of meer, afhankelijk van de breedte van elk) van het buitenste punt van het laterale deel van de deltaspier, naar buiten. Zoals altijd een "grijper" grip wordt aanbevolen.

Beweging:

? Excentrieke fase: we zullen de stang van de steunen verwijderen en verticaal neerlaten zodat de handen altijd boven de schouders zijn en de ellebogen naar de grond wijzen. De afdaling zal plaatsvinden totdat de balk slechts enkele centimeters verwijderd is van de middellijn van de borstspier (iets boven de lijn van de tepels) of ze lichtjes aanraakt, zonder ze te stuiteren. Tijdens deze fase zullen we inspireren.

? Concentrische fase: van onderen zullen we de lat hoger leggen tot bijna de maximale extensie van de armen (ellebogen licht gebogen) en we zullen de neerwaartse beweging herstarten. Gedurende deze fase zullen we uitademen.

Halter variant.

Als we om wat voor reden dan ook geen Olympische bar hebben (of in ieder geval een niet-Olympische straight), of als we het type weerstand willen varieren, hebben we de mogelijkheid om de bankdrukken met dumbbells te doen ( fig. 07 ). Deze variant stelt ons in staat om een ??convergente of "driehoek" beweging (van buiten naar binnen), met respect voor de biomechanica van de beweging.

Natuurlijk, omdat het een van de oefeningen is waarbij we de stabiliteit van de balk verliezen, zullen we de set van de bovenste ledematen in grotere mate moeten activeren om een ??maximale stabilisatie te bereiken. Dit betekent dat we niet dezelfde belasting kunnen verplaatsen als bij de originele barbell bench press.

De techniek varieert ook, zoals ik eerder heb aangegeven, waarbij een convergerende beweging plaatsvindt waarbij de halters beginnen vanaf de hoogte van de schouders en, terwijl ze stijgen in de concentrische fase, naderen in een driehoek, totdat ze elkaar bijna raken (je hebt om schokken te voorkomen, hoe klein ze ook zijn).

Mogelijk bent u geinteresseerd: Online Personal Training Course.

Varianten voor beginners.

Er is een grote verscheidenheid aan geleide machines die u, degenen die beginnen in de wereld van fitness of bodybuilding, kunnen helpen om op een zeer vergelijkbare manier te werken als de bankdrukken, maar met meer veiligheid, gemak en de mogelijkheid om lagere belastingen (zelfs minder dan het minimum om te bewegen in een Smith-machine, bijvoorbeeld die van de geleide balk zelf). Het kunnen varianten zijn in zitten (zitten) of in een liggende houding (liggend naar boven), convergent of vast pad, met schijven, platen, enz. In de volgende afbeeldingen zien we enkele varianten:

DE PERSEN VAN BANCA HELLING EN AFWIJKING.

Uitgaande van de originele bankdrukken (plat of horizontaal), zijn er andere varianten, afhankelijk van of we een grotere impact willen hebben op een of ander deel van de pectoralis major of dat is tenminste wat we geloven ...

De hellingpers (Afb.12) wordt precies hetzelfde uitgevoerd als de originele platte pers, hoewel op een bank met een helling die meestal rond de 30 isº-40º (er zijn meningen voor alle smaken) en het verlagen van de lat op het pectorale claviculaire gedeelte.

Aan de andere kant wordt de bank waarop de geweigerde pers wordt uitgevoerd, uitgevoerd (Afb.13) , heeft een helling rond -10º (of een declinatie van 10º, zoals u liever uitdrukt) en de balk daalt tot het praktisch het buikgedeelte van de borstspier raakt.

Sinds mensenheugenis is de helling (of "bovenste") bankdrukken is geassocieerd met een grotere betrokkenheid van de sleutelbeenbundel en daalde met de speciale rekrutering van buik- of ribvezels.

Het duurde echter tot 1995 voordat Barnett, Kippers en Turner, in een studie gepubliceerd in het Journal of Strength and Conditioning Research, zeiden dat bankdrukken oefeningen meer voordelen opleveren voor het buikgedeelte van de borstspier dan de pers zelf afnam. Bovendien concludeerden ze dat de hellingspers slechts een beetje meer activering veroorzaakt dan de platte pers, of zelfs de afgewezen pers.

Als we in gedachten houden dat wanneer we de bank hellen bij het uitvoeren van een pers, de synergetische spieren van de borstspier belangrijk worden bij de extensiebeweging (met name claviculaire deltaspier en brachiale triceps), kunnen we bevestigen dat de pectorale betrokkenheid afneemt. Als we hieraan de bevestiging van de vorige paragraaf toevoegen, zullen we begrijpen dat het de vlakke bankdrukken is die de overhand zou moeten hebben bij onze borsttrainingen.

Terug naar de studies van Hernández, Gª Manso, Tous, enz., In 2001 is het de moeite waard om iets merkwaardigs op te merken: het is de dalende pers (specifiek tot 9º) die, hoewel in geringe mate, betere resultaten oplevert voor de pectoralis major, zowel in zijn geheel als gescheiden door delen (claviculair en sternokostaal specifiek) dan de platte bankpers zelf, vooral als deze wordt uitgevoerd met een gesloten grip ( schouder breedte).

Maar hier is een 'maar': we weten dat hoe strakker de grip, hoe meer de triceps brachii erbij betrokken zijn, daarom is het mogelijk dat deze synergetische spier van de borstspier major sneller uitgeput zal raken en de training zal beperken.

Aan de andere kant gebeurt er in de geweigerde pers iets waar niet veel mensen rekening mee houden: omdat de positie van het hoofd in een vlak lager dan de romp ligt, neemt de druk van de schedelvaten toe (Willmore en Costill, 2007; Isidro, Heredia, Pinsach en Costa, 2014), wordt een van de oefeningen met enig gevaar, vooral voor mensen met hoge bloeddruk. Op zichzelf verhoogt de inspanning zelf de intracraniale druk, vooral als de fout wordt gemaakt bij het maken van een Valsalva-manoeuvre (min of meer is het om je adem in te houden); Als we daaraan toevoegen de afgenomen positie van het lichaam, wordt de afgenomen bankdrukken naar mijn mening een van de gevaarlijke oefeningen die ik gewoonlijk niet aanbeveel.

Uiteraard kunnen beide oefeningen met alternatief materiaal worden uitgevoerd, zoals we bij de originele bankdrukken hebben gezien. In de volgende afbeeldingen zien we de haltervarianten:

Voor alle in dit artikel beschreven, concludeer ik dat, zonder twijfel voor mij (en voor nog veel meer trainers), de flat bench press de meest geschikte optie is om onze borst te werken.

Juan Francisco Marco Satorre

Professor in hoge prestaties

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prediabetessymptoms2-blog · 5 years ago

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Prediabetes: Preventable Diabetes

Prediabetes symptoms Diabetes has expanded to pandemic proportions. Roughly 8. 3% of often the YOU population, or 20. 6 million people, have got diabetic. About 95% associated with these get type 3 diabetes. Diabetes is the actual main root cause of kidney malfunction, limb blessure, and new-onset blindness with American older people. People with diabetic are generally more likely than men and women not having diabetes to produce and cease to live from ailments of the heart and soul as well as blood vessels, called being obese. Adults with diabetes include heart disease death fees in relation to two to some instances higher than grownups without diabetic. The threat for stroke is definitely a couple of to four moments bigger among people with diabetic.

Prediabetes symptoms

Prediabetes refers to the particular intermediate metabolic states concerning normal and also diabetic sugar and carbohydrates homeostasis. That term ended up being first introduced within 79 to replace 'borderline' diabetic. Pre-diabetes is becoming considerably more common plus much more recognized inside the United States. Often the United. S. Department regarding Health insurance and Human Services reports that will 79 million Tourists acquired prediabetes in 07. Around 314 million persons across the world have prediabetes, along with the variety is believed to grow to help 418 million in 2025.

The reason worry about prediabetes? Is probably the best estimated that between 35% and 65% of people with prediabetes will acquire non-insulin-dependent diabetes within six decades of typically the prediabetes identification. Even before growing directly into full blown diabetic, all these people have an enhanced charge of microvascular (retinopathy, health proteins in the pee, polyneuropathy) in addition to macrovascular (heart attack as well as stroke) risks.

How do you spot Prediabetes? Prediabetes is commonly informed they have any one or maybe more of the adhering to blood test readings: A new fasting blood glucose amount of: a hundred and ten to one hundred twenty five mg/dL (6. 1 milimeter to 6. being unfaithful millimeters, according to the Universe Wellbeing Organization criteria as well as 75 to 125 mg/dL (5. 6 mM in order to 6. in search of mM), relating to the American Diabetic Association criteria. A sugar level of 140 to be able to 199 mg/dL (7. main for you to 11. 0 mM) in late two hours immediately after taking a standardized 70 initial public offering glucose solution seeing that part of some sort of a pair of hour glucose fortitude test out. A glycated hemoglobin (HbA1c) between 5. 8 and also 6. 4 per-cent.

Usually are you at risk? At this time there are certain symptoms in which you have or could be in increased chance of developing prediabetes. These kind of include increasing age, idleness, sleeping less than a few a long time per day along with being overweight or even chronically overweight. Certain races have a a increased risk, namely Wok cookware Americans, Hispanics/Latinos and non-hispanic blacks. Other risk variables include abnormal lipids, specially high triglycerides and minimal HDL (the good cholesterol) and diagnosed cardiovascular disorder. If you bought gestational diabetes (high blood sugar level during pregnancy), or perhaps gifted birth to a new child analyzing more in comparison with 9 lbs, that you are in addition at risk. Two different rather uncommon conditions, such as polycystic ovarian syndrome in addition to acanthosis nigrans also point out increased insulin resistance as well as predisposition to prediabetes and also diabetes. And finally, people having psychiatric disorders, mainly schizophrenia, on multiple psychotropic prescription drugs, also have the high incidence involving prediabetes.

Symptoms: Prediabetes can often be asymptomatic and suspicion typically breaks solely on possibility components mentioned above. If provide, the symptoms of prediabetes, are similar as those connected with diabetes: continual hunger, greater thirst along with urination, mysterious weight loss, increase in pounds, general malaise, blurred imaginative and prescient vision, slow-moving healing from trivial acute wounds like cuts in addition to craters, tingling or losing experiencing in the hands or maybe feet, frequent or repeated gum, skin, vaginal as well as bladder infections.

How complete you cure? The get in touch with for early remedying of prediabetes is gaining traction. Various recent studies have looked at the role of life-style changes and medications for any treatment of this condition:

one Exercise: Regular real activity avoids progression straight into diabetes. Inside Da Qing IGT as well as Diabetes Examine of 129, 660 adult males and women in China( Diabetes Care 1997; 30: 537-44. ), progression to help diabetes decreased from 67. 7% to 41. 1%, when comparing an unchecked set to a operated exercise team over any period of 6 several years.

2. Diet: In some sort of Finnish study (N Engl M Med 2001; 344: 1343-50), there was the incidence associated with 23% regarding progression in diabetes throughout a control party in contrast to only 11% within the intervention group over a new time period of 4 years. Compétition ended up aimed at minimizing weight 5% if not more, lessening dietary fat to a lot less than 30% of the full calorie intake and increasing nutritionary fiber to 15g every 1000 fat laden calories ingested.

three or more. In geologi large examine involving tenty-seventh clinical locations around the US(N Eng J Med, January 6, 2002), 3234 prediabetic fat participants were separated into a couple groups. One class got intensive training in eating habits, physical activity, and actions adjustment. The aim seemed to be to reduce body volume by means of 7% and maintain losing, and exercise 150 a few minutes a week. The secondly group gotten metformin eight hundred fifty mg twofold a morning. At the end involving the study, the remedy group reduced diabetic evolution by 58% when compared to 31% in the metformin set.

4. A prediabetes undertaking force (American Association connected with Clinical Endocrinologists 18th 12-monthly Meeting, Houston, Tx. 2009) suggested a more violent very worthwhile approach to these kind of patients, advising treating high-risk individuals with diabetic remedies such as metformin, acarbose, glucagon-like peptide 1 agonists and thiazolidinediones. These solutions are not yet MAJOR REGULATORY BODIES approved to get prediabetes, although are backed by robust scientific data indicating this battling insulin resistance first protects the pancreas and also prevents progression into diabetic.

The health and economical charges of prediabetes usually are not well-known. But diabetic is an high priced sickness, costing about $174 f billion annually the united states solely. Direct medical prices profile for about $116 tera- and indirect costs including disability payments, time misplaced from work, and earlier death account for often the remaining $58 billion.

Enormous amounts of lives along with tremendous of dollars can possibly be preserved by aggressive life-style in addition to therapeutic intervention with affected individuals suffering from prediabetes.

Remember: Prediabetes means former diabetes. Almost all means avoidable diabetes.

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toyboxobscura · 6 years ago

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What do you get when you combine the highly detailed figures of McFarlane Toys and the twisted mind of horror writer Clive Barker?

Back in 2001 you got Tortured Souls, a set of original Cenobite-esque characters complete with their own story. From that set, this is Agonistes. Ain’t he pretty?

#toys #figures #figure #photography #toybox obscura #toylife #mcfarlane toys #clive barker #horror #tortured souls #Agonistes

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savage-kult-of-gorthaur · 11 months ago

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"...HE ENJOYED SEVERELY MUTILATING HIS VICTIMS BEFORE KILLING THEM."

PIC(S) INFO: Spotlight on promotional shots of the newly-dubbed "Scythe-Meister," once an assassin of Primodium, now an inhuman abomination with an even greater bloodlust, six inch action figure from Clive Barker's "Tortured Souls" toyline, released by McFarlane Toys in July 2001.

BRAND: Clive Barker's Tortured Souls

GENRE: Horror & Fantasy

PRODUCT TYPE: Action Figure

SERIES: Clive Barker's Tortured Souls

MINI-BIO: "A young assassin from the poorest part of Primodium. He enjoyed severely mutilating his victims before killing them. After meeting Lucidique and murdering her father, he decided to ask Agonistes to turn him into a monster. After 8 nights and days, he was resurrected as the Scythe Meister. The Scythe Meister then proceeded to kill the current emperor of Primodium. Scythe Meister fell in love with the monster Lucidique and they became lovers. He was later killed by Venal Anatomica."

-- CLIVE BARKER FANDOM

Sources: https://mcfarlane.com/toys/the-scythe-meister & https://clivebarker.fandom.com/wiki/Tortured_Souls.

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fumblebeefae · 7 years ago

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Why are some insects so shiny and iridescent?

First here’s a post I answered on HOW insects form shiny or iridescent exoskeletons. It’s always good to know the answer to how because it can give context to the why. So why are some insects iridescent or shiny?

This can be split into two main categories; communicative functions and non-communicative.

COMMUNICATION

1. Mate Selection

While insects tend to use chemical communication more as a means of attracting potential mates colouration can however play a significant role in mate selection in a number of ways.

Honest signalling - in which the colouration reveals the quality of the individual as these colourations are costly to produce. Therefore only individuals that are high-quality are able to afford the cost of producing these signals (in this case the iridescence or shiny colouration)

Example:

A study (Fitzstephens & Getty, 2000) found that male Calopteryx maculata (Black-winged damselfly) with higher fat stores had a much bluer iridescent colouration compared to males on low fat diets.

Amplifier traits - iridescent / shiny colours may be used to amplify the differences in the signals of quality (however no studies have directly focused if this is a function of iridescence)

Sensory drives - iridescent colouration was favoured due to being more effective in signalling in certain ecological environments

Receiver Bias - females (or in rare cases the males or hermaphrodites) as the receivers may have favoured certain iridescent colouration due to being better received by their sensory system therefore resulting in the evolution of this colouration

2. Species Recognition

Man species use iridescent / shiny colouration in order to identify members of their own species! As simple as that!

Example:

Colias eurytheme (orange sulfur butterfly) use UV iridescence to communication with conspecifics

3.Agonistic interactions

Iridescense / shiny colouration may be used in intrasexual encounters; mostly male-male agonistic encounters and can be used as a territorial signal.

4.flocking behaviour

Can help insects that school together facilitate their orientation or direction within their schools / flocks. This is seen in many aquatic species of fish and even squid.

5. Predation avoidance

Iridescense / shiny colouration can be used to order to actually avoid predation! Although at first glance you’d assume this would make them more visible, this isn’t always the case.

Mimicry / camouflage - insects can avoid predation by mimicking objects, leaves, raindrops, other harmful species or even by blending into the background

Examples:

A number of iridescent jumping spider species (Salticidae); such as Brettus adonis in this study (Jackson & Hallas 1986) were found to mimic raindrops to avoid predation

The iridescent green leaf beetles such as the (Dogbane Leaf Beetle, Chrysochus auratus) similarity use their iridescence colouration to mimic dew on leaves.

Species like tiger beetles ( Cicindelinae) even use their iridescence to create an unsaturated appearance that allow them to blend into their envrionment (Schultz 1986, 2001)

Warning colouration - insects may use their colouration to communicate their toxicity or unpalatability serving as aposematic warning.

Example:

Panamanian tortoise beetle (Charidotella egregia) that change from gold to red when disturbed by predators(Vigneron et al. 2007).

Startle displays - some species will use their iridescence colouration to create a flash that may startle potential predators long enough for them to escape due to the way in which the iridescence reflects light.

Example:

The tiger beeltes again! Some of them have bright colouration like below that they use as startle defenses against predators (Sargent 1990).

NON-COMMUNICATION

1. Thermoregulation

There’s much debate over whether Iridescense / shiny colouration has any function in either heat absorption or dispersion.

Some found evidence that the structures used to created iridescense / shiny colouration acted as heat collectors, like in the wings of butterflies ( Miaoulis & Heilman 1998). However other’s have found no evidence of thermoregulation in tiger beetles Schultz & Hadley (1987).

2.Friction reduction

iridescense structures may reduce the friction in burrowing insects

Example: Carabid Beetles (Brachininae) (Seago et al. 2009).

These are just some of the proposed and studied functions of iridescense and shiny colouration in insects, there are more that aren’t as well studied or understood just yet!

Also Read: How to Loose 150 Pounds

Billy Gardell Weight

Billy Gardell’s Weight is 158Kg Before he Starts to Loss Weight and The Current Weight of Billy Gardell is 94Kg.

How Billy Gardell Weight Loss?

Now I talk about, Billy Gardell's Weight loss big story, coming out and how different reports, show.

You might know him, this is a picture of him, Billy Gardella, from mike and molly, and bob has abhisheka, some popular tv show.

I want to give you, how he’s doing it and things that you, might want to try on your way to, taking ownership of your own path to, better health.

Billy Gardell has these quotes out, said I grew up fat and then there are, some days I feel like rolling around in a pizza.

I’m trying to keep the good days, outnumbering the bad ones so like, and leave a comment if that’s you if you, feel like rolling around a pizza.

In pizza or um sometimes I feel like an actual pizza myself, those are very relatable things how he, lost the weight.

Let me give you a little, back story he was diagnosed with type 2, diabetes, and his doctor prescribed him, Ozempic.

Also Read: How to drink kombucha for weight loss (Ultimate Guide)

Which is semi-gluten medication, dosage for, diabetes management especially type 2, diabetes I’ve been covering a lot of um, information on some of the glutathione.

As it, develops of semifluid I’ll leave a link, to that, is a gap-1 receptor agonist approved for, weight loss recently, and prescription is a higher dose than, the dose for diabetes management.

But, it’s the same drug um same compound and, so what happens to the makers of the Olympics, they started a commercial series called, my type 2 transformation.

This reality, advertising mini-series by Novo Nordisk, tracks Gardell from his first Olympic, shot, through a six-month program with a trainer chef and a life coach.

Uh three different people to help him, manage the disease okay so a lot of, people think that these celebrities just, lose weight magically.

Or something just happens it’s not always like that a lot, of times they have a coach or coaches or, other professionals that give them, accountability.

Accountability is a core, of the guilt-free framework and game, plan so the three tips of the three, people he worked with to help him.

The first tip you have here is staying, active he increased his physical, activity a lot, uh he actually worked, with duvet quince.

So they definitely, stepped up his physical activity and, that’s something that supported his, weight loss a tip.

You can try off, of that is get active for 22 minutes on, two days this week so that’s the first tip.

Second tip, healthy eating so he didn’t just start, taking these weight loss injections and, like walk, more healthy eating was a key, factor and he had some more celebrity, health, help, by franklin becker, from top chef masters here’s a picture, of him getting it in.

And they broke down a lot of nutrition, and the thing that they emphasize is, that it doesn’t have to be, a bunch of bland food it shouldn’t be.

Bland food because you’re not going to, eat it or like the same thing every day, you can have a variety of things to eat, that, is suitable to your palate and help you.

Stay on a track that you enjoy eating, obviously, you want to enjoy what you’re, doing in order to lead a healthy, lifestyle that’s sustainable for you.

So, um what they talked about a lot I put a link to the Novo Nordisk website, type my type 2 transformation so you can, look at it yourself.

The big thing he, said is to try meal planning with healthy, delicious recipes, Three uh stress management so, Billy Gardell when he was on his weight, loss journey also worked with a life, coach Marlene Boaz.

She’s a board-certified life coach with a Ph.D. in, psychology she used to do clinical, psychology here’s a picture of her from, her website. Billy Gardell Weight Loss

So you can tell that billy Cardell had a lot of support and, accountability to help him reach these, goals.

Let me pull that back up, and some of the top tips she had for, stress management were to get seven hours, of sleep drink half your body weight.

In, ounces of water um that one’s for me, but it’s another way that’s going to, manage your stress and get active 22, minutes per day.

All these have stress, managing qualities, and properties so you can make better decisions uh when you’re, stressed out.

So, a lot of times when people are trying to, make changes they get frustrated, then they or something happens, challenging their day and they like, drink a bunch of beer.

And maybe some, wine and then eat some junk food or they don’t have the meals prepped, and they just go to mindless snacking or, eating comfort foods a lot of times.

Those are fried foods um pizza is, another big one right all these things, add up so people, make less healthy choices when they are, stressed out.

So getting more sleep will help with your stress management your, response to stress staying hydrated has, surprising benefits to helping you

Perceive less stress and make better, choices, and then getting active um can, reduce anxiety and depression symptoms.

So there are tons of benefits to all three, of those a life coach can help hold you, accountable or a, you know food coach a chef or a personal, trainer, getting support for lifestyle.

And health, habits make a huge impact on weight, loss and diabetes prevention, and the management you see it’s been super, effective for Billy Gardell

As he, lost weight visibly, so much that people are searching for Billy Gardell weight loss they want to know.

How he did it and so I wanted to tell you, how he did it um with accountability if, you want more accountability or support, or more health tips.

I do have free, group scale smashers on Facebook links, in the below would love to, see you in there we’re doing daily tips. Group Link

here are recipes there are weekly, challenges there’s a little community, growing in there and we’re having a great time.

Friends If you also want to lose weight I give you some Ultimate guide to losing your weight without any fitness trainer and without any surgery.

Below I mention Billy Gardell’s Net Worth and Billy Gardell Shows List and Below them, I Mention How you are Able to Loss Weight.

So If You are not interested in Billy Gardell’s Net Worth and Billy Gardell Show List then You Skip this Content and Read Below Blow where I can tell you in detail how Loss your weight in Detail.

So If You are Serious About Your Weight then Read the Full Blog.

How to drink kombucha for weight loss

Billy Gardell Net Worth

Friends Billy Gardel is a Famous Personality in the USA. Billy Gardell is Actor, Producer, and Stand-Up Comedian now the point coming to your mind is what is Billy Gardell’s Net Worth?

So Friends Billy Gardell’s Net Worth is Around 8 Million dollars.

#billy gardell #billy gardell weight loss #weight loss tips for beginners #how to lose weight #weight loss hacks #weight loss guide #celebrities weight loss

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local-hellhound-steals-spaghetti · 2 years ago

Note

Just a general handful scientific resources about dolphin welfare that might help:

Similarly, there are no scientific studies suggesting that dolphins in marine mammal facilities are any more stressed than dolphins in the wild. On the contrary, studies have shown that cortisol levels (i.e., the “stress hormone”) of dolphins in marine mammal facilities are either very similar to, or lower than, cortisol levels of wild dolphins, depending on the technique used to obtain the samples (See review in ref 3).

Bottlenose dolphins in U.S facilities are living as long or longer than their wild counterparts (ref 4)

Average life expectancy from 2001-2015 was 41.6 years in SeaWorld orcas, showing significant improvements in veterinary care and welfare (ref 5)

Aggression and agonistic behaviour made up 1-2% of observed behaviours in orcas at Loro Parque, debunking claims of hyper aggression and chronic stress from supposed poor social structures. (ref 6)

(1) Ruiz, C. L., Nollens, H. H., Venn-Watson, S., Green, L. G., Wells, R. S., Walsh, M. T., … & Jacobson, E. R. (2009). Baseline circulating immunoglobulin G levels in managed collection and free-ranging bottlenose dolphins (Tursiops truncatus). Developmental & Comparative Immunology, 33(4), 449-455.

(2) Fair, P. A., Schaefer, A. M., Houser, D. S., Bossart, G. D., Romano, T. A., Champagne, C. D., … & Reif, J. S. (2017). The environment as a driver of immune and endocrine responses in dolphins (Tursiops truncatus). PLoS ONE, 12(5), e0176202.

(4) Jaakkola, K., & Willis, K. (2019). How long do dolphins live? Survival rates and life expectancies for bottlenose dolphins in zoological facilities vs. wild populations. Marine Mammal Science.

Positive behavioural states are demonstrated in cetaceans in human care:

Peer-reviewed scientific studies show that:

• Dolphins show anticipatory behaviors before sessions of interacting with their trainers (with no food involvement). This shows they view the interactions themselves as positive. (ref 1)

An increase in dolphin behavioral diversity and play behavior following interactive programs suggest that such programs are in fact enriching for the dolphins and add to their psychological well-being (refs 2-3).

Dolphins observed swimming in sync with each other at zoological facilities displayed optimistic judgements in optimistic bias tests, indicating positive welfare. (ref 4)

When given the choice, dolphins in one study showed a preference for being in a smaller pool, despite having access to larger pools, indicating that size of pool may not be influencing dolphin movement preferences. (ref 5)

(2) Miller, L. J., Mellen, J., Greer, T., & Kuczaj, S. A. (2011). The effects of education programmes on Atlantic bottlenose dolphin (Tursiops truncatus) behaviour. Animal Welfare, 20, 159-172.

(3) Trone, M., Kuczaj, S., & Solangi, M. (2005). Does participation in Dolphin–Human Interaction Programs affect bottlenose dolphin behaviour? Applied Animal Behaviour Science, 93, 363-374.

Impact of zoos and aquariums:

Peer-reviewed scientific studies show that:

• Experiencing live animals creates emotional connections [e.g., refs 1-3];

• Such emotional connections increase conservation mindedness [e.g., refs 4-5]; and

• Experiences with live animals at zoos and aquariums positively impact visitors’ conservation-related attitudes, knowledge, and behavior [e.g. refs 4, 6, 7].

(1) Myers, O. E,. Saunders, C. D., & Birjulin, A. A. (2004). Emotional dimensions of watching zoo animals: An experience sampling study building on insights from psychology. Curator, 47, 299–321.

(2) Bruni, C., Fraser, J., & Schultz, P. (2008). The value of zoo experiences for connecting people with nature. Visitor Studies, 11, 139–150.

(3) Clayton, S., Fraser, J., & Saunders, C. D. (2009). Zoo experiences: Conversations, connections, and concern for animals. Zoo Biology, 28, 377–397.

(4) Skibins, J. C., & Powell, R. B. (2013). Conservation caring: Measuring the influence of zoo visitors’ connection to wildlife on pro-conservation behaviors. Zoo Biology, 32, 528–540.

(5) Powell, D. M., & Bullock, E. V. (2014). Evaluation of factors affecting emotional responses in zoo visitors and the impact of emotion on conservation mindedness. Anthrozoös, 27, 389–405.

(6) Miller, L. J., Zeigler-Hill, V., Mellen, J., Koeppel, J., Greer, T., & Kuczaj, S. (2013). Dolphin shows and interaction programs: Benefits for conservation education? Zoo Biology, 32, 45–53.

(7) Moss, A., Jensen, E., & Gusset, M. (2014). Evaluating the contribution of zoos and aquariums to Aichi Biodiversity Target 1. Conservation Biology, 29, 537–544.

ive gone through your seaworld tag and didnt really find this so excuse me if youve answered similar before, but: as someone who grew up under the impression that seaworld is unethical, could you debunk some of the most common misconceptions about seaworld? i've been convinced that theyre unethical but im always willing to challenge my perceptions of things if factual sources say otherwise. if seaworld is ethical, thatd make me much happier to know. reason why im not searching myself is its hard to find things that arent just ARA talking points disguised as facts, as someone who knows very little about whales. if you dont want to answer, i understand, as im assuming this is a bit of a loaded and broad thing to request.

It’s no bother! I do have some similar asks to yours currently in my inbox that I plan on answering in the coming weeks (I’m going to be very busy as vet school starts back in a few days), so keep an eye out for those. Do you have any specific questions you’d like answered?

#I always have this ready to copy paste if needed!#dolphin welfare

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your-dietician · 3 years ago

Text

Allopregnanolone agonist therapy for treating depression

New Post has been published on https://depression-md.com/allopregnanolone-agonist-therapy-for-treating-depression/

Allopregnanolone agonist therapy for treating depression

Introduction

Mental illnesses are highly prevalent in the United States (USA), with approximately 51.5 million (20%) of US adults indicating a mental illness in a 2019 survey.1 Major depressive disorder (MDD) affected nearly 17.3 million adults in the USA as of 2017, and between 2001 and 2003 there were 2.8% of US adults diagnosed with bipolar disorder (BPD).2,3 Effective treatment of depressive disorders is imperative as the cost is high. Approximately 15% of people with MDD will attempt and/or think about dying by suicide.4 Currently available therapies for the treatment of depression and adjunctive treatment of BPD primarily target modulation of the neurotransmitters serotonin and norepinephrine. These therapies are limited by delayed onset (4–6 weeks), lack of acute improvement in suicidality, and risk of mania when used to treat bipolar depression.5,6 Increasing evidence supports the idea that neuroactive steroids, specifically allopregnanolone, represent a novel target for the treatment of depression.7 In the presence of acute stress, allopregnanolone concentrations increase significantly.7 The increase in allopregnanolone is hypothesized to be neuroprotective. However, under chronic stress and in MDD, decreases in allopregnanolone concentrations in the central nervous system have been demonstrated, resulting in altered gamma-aminobutyric acid (GABA) and glutamate transmission.8 Allopregnanolone is thought to improve depressive symptoms through modulation of the GABAA pathway and regulation of the hypothalamic–pituitary–adrenocortical (HPA) axis, which facilitates recovery of physiological homeostasis.9 Allopregnanolone agonists are being developed as a potential treatment option for mental health disorders, exploiting the GABAA pathway activated by neuroactive steroids.

For decades, GABAA receptors have been considered to have a role in the pathophysiology of depression; however, the precise mechanisms are still not completely understood. The GABAA receptor complex is an ion channel comprised of five subunits with a multitude of binding sites. With 19 known subunits (six α; three each β, γ, and ρ; and one each δ, ε, π, and θ), there are over a million different potential receptor conformations; however, fewer than 50 are thought to naturally occur and even fewer have pharmacological targets. In animals, decreases in α2-, γ2-, and δ-subunits have been associated with symptoms of depression and anxiety.10 In addition, decreased δ-subunits have been associated with maternal neglect, and agonists of GABA receptors with the δ-subunit (eg, allopreganolone) have been linked to improved maternal care. The benzodiazepines, for example, bind preferentially to receptors with α- and γ-subunits with a binding site between the two subunits.11 Throughout the 1980s, numerous clinical trials evaluated the effect of benzodiazepines on depressive symptoms.12,13 Despite initial promising results, benzodiazepines were abandoned as primary treatment for depression owing to a lack of consistent benefit on core symptoms as well as a better understanding of the risks of abuse/dependence and possible association with worsening depression.14 Although benzodiazepines are still commonly used in practice for depression, current treatment guidelines relegate benzodiazepines to short-term adjunctive treatment of anxiety or catatonia associated with depressive episodes.5,15,16

The neurosteroid and metabolite of progesterone, allopregnanolone, also acts as a GABAA receptor modulator with preferential activity at receptors with a δ-subunit. While benzodiazepines are thought to bind only to intrasynaptic sites, allopregnanolone also binds to extrasynaptic sites, which may have clinical implications (eg, differences in tolerance over time).17 The full implications of the extrasynaptic binding are not known at this time. The interplay among progesterone, allopregnanolone, and GABA receptors is complex and can vary throughout the menstrual cycle and pregnancy.18 In addition, evidence suggests that the conformation of GABA receptors themselves and the subunit make-up can change in different hormonal and mood states.18,19

Brexanolone, the first synthetic version of allopregnanolone, was approved in 2019 for the treatment of major depression after pregnancy, also known as postpartum depression (PPD).20 Allopregnanolone levels increase steadily throughout pregnancy and decrease drastically to normal concentrations in the postpartum period, indicating that allopregnanolone may provide a specific pathophysiology for PPD.21 Brexanolone is an intravenous infusion administered stepwise over 60 hours, making the coordination of administration challenging. In addition, brexanolone has a risk evaluation and mitigation strategy (REMS) program due to excessive sedation and loss of consciousness.20,21 A heterocyclic analogue of allopregnanolone, zuranolone, has been investigated as an oral alternative for treatment of PPD and other psychological and neurological disorders.17 This paper aims to review the current efficacy and safety literature available for all forms of allopregnanolone agonists and to discuss the role of these medications in the treatment of mental health disorders.

Literature Search

A PubMed search of English-language articles was conducted, and clinical trials returned with the keywords of brexanolone (SAGE-547) and zuranolone (SAGE-217) were extracted. Since the aim of this review was to review clinical safety and efficacy, included articles were limited to phase II and phase III trials. To find zuranolone clinical trials in progress, the National Institutes of Health US National Library of Medicine Clinical Trials Database (clinicaltrials.gov) was utilized. After visiting the website of the drug manufacturer (Sage Therapeutics) to search for any preliminary results on zuranolone, a press release was found which referenced an abstract from the Psych Congress Annual Meeting. This led to a review of all 2019 and 2020 Psych Congress Annual Meeting abstracts and posters for trials involving zuranolone. Studies included in the review are summarized in Table 1.

Table 1 Summary of results of brexanolone and zuranolone clinical trials

Results

Brexanolone: Clinical Efficacy and Safety

Brexanolone has been studied for efficacy and safety for the treatment of PPD in one phase II (PPD-202A) and two phase III clinical trials (PPD-202B and PPD-202C). All three studies included patients who were aged 18–45 years, ≤6 months postpartum, and had stopped lactating or were not actively breastfeeding. Patients with active psychosis, a medical history of seizures or BPD, or attempted suicide with the index case of PPD were excluded. Patients were diagnosed with a major depressive episode that began no earlier than the third trimester and no later than 4 weeks following delivery, and were required to have a 17-item Hamilton Rating Scale for Depression (HAM-D) total score of ≥26 (for PPD-202A and 202B) or 20–25 (for PPD-202C), indicating moderate to severe depression. Patients were allowed to continue their current stable antidepressant regimen, but could not initiate any other pharmacotherapy regimen until the 60-hour infusion and 12-hour post-infusion assessment had been completed.21,22 The primary outcome for all three studies was the change in baseline HAM-D total scores at the end of treatment.

Study 202A

Twenty-one patients were included in this phase II, double-blind, randomized, placebo-controlled trial. Patients were randomized 1:1 to a single 60-hour infusion of either brexanolone 90 µg/h (n=10) or placebo (n=11).22 Patients had a median age of 28.1 years (range 20–40) and a median body mass index (BMI) of 31 kg/m2. Nearly two-thirds of patients were Black. Previous psychiatric disorder diagnoses, except for anxiety, and antidepressant use were similar between groups, with three patients in each group taking antidepressants at baseline. Baseline HAM-D scores were 28.1 and 28.8 in the brexanolone and placebo groups, respectively.

At the end of the 60-hour infusion, the mean reduction in HAM-D total score was 21.0 points in the brexanolone group and 8.8 points in the placebo group (least squares [LS] mean difference −12.2 points, 95% CI −20.77 to −3.67, p=0.0075; effect size =1.2). This effect was maintained during the follow-up period after the infusion up to 30 days (LS mean difference −11.9 points, p=0.0095). In addition, Montgomery–Asberg Depression Rating Scale (MADRS) scores were significantly different at 60 hours and 30 days (mean difference −12.1, p=0.0104; and −11.19, p=0.0100, respectively). Remission rates, defined as HAM-D total score ≤7, were higher in the brexanolone group compared to the placebo group, with 70% of patients achieving remission at both 60 hours and 30 days compared to 9% and 18%, respectively, in the placebo group.

Brexanolone was well tolerated, with no deaths, serious adverse events, or discontinuations occurring in either group. Adverse events were less common in the brexanolone group (n=4) compared to the placebo group (n=8). The most common adverse effects of brexanolone included dizziness (20%) and somnolence (20%). One patient in the placebo group had a severe treatment-emergent adverse event of insomnia.

Study 202B

In total, 138 patients were included in this phase III, double-blind, randomized, placebo-controlled trial. Patients were randomized to a single 60-hour infusion of either brexanolone 60 µg/h (BRX60, n=47), or brexanolone 90 µg/h (BRX90, n=45), or placebo (n=46).21 Additional exclusion criteria for studies 202B and 202C were women with a history of renal or hepatic failure, anemia, or known allergy to the study drug, or who were receiving electroconvulsive therapy. Baseline characteristics were similar between the three groups. Patients had a mean age of 27.8 years and a mean BMI of 30.7 kg/m2. Nearly two-thirds of the patients were White. Treatment was discontinued in nine of 122 patients who received the study drug; one in the placebo group (lost to follow-up), three in the BRX60 group (two withdrew consent and one was lost to follow-up), and five in the BRX90 group (three withdrew consent and two were lost to follow-up). Baseline HAM-D scores were 29.1, 28.4, and 28.6 in the BRX60, BRX90, and placebo groups, respectively.

At the end of the 60-hour infusion, the mean reduction in HAM-D total score was 19.5 points in the BRX60 group, 17.7 points in the BRX90 group, and 14 points in the placebo group (LS mean difference −5.5 points, 95% CI −8.8 to −2.2, p=0.0013; and LS mean difference −3.7 points, 95% CI −6.9 to −0.5, p=0.0252, respectively). This effect was maintained during the follow-up period after the infusion up to 30 days for both the BRX60 and BRX90 groups (LS mean difference −5.6 points, 95% CI −9.5 to −1.8, p=0.0044; and LS mean difference −3.8 points, 95% CI −7.6 to 0.0, p=0.0481, respectively). Remission rates, defined as HAM-D total score ≤7, were higher in the BRX60 group compared to placebo, with 51% of patients achieving remission at 60 hours, but not 30 days, compared to 16% in the placebo group. Patients in the BRX90 group did not have significantly higher remission rates compared to the placebo group at either 60 hours or 30 days.

Brexanolone was well tolerated, with no deaths, serious adverse events, or discontinuations occurring in either group. The total number of adverse events was similar across the three groups (BRX60=90, BRX90=22, and placebo=22) The most common adverse effects of BRX60 included headache (18%), somnolence (18%), and dizziness (16%). The most common adverse effects of BRX90 included headache (15%), somnolence (5%), and dizziness (15%). One patient in the BRX60 group had two serious adverse events of suicidal ideation and an intentional overdose attempt, which were not considered to be related to the study drug. Another patient experienced somnolence and loss of consciousness during treatment, but completed treatment following interruption of the infusion with rapid resolution of adverse events.

Study 202C

A total of 108 patients were included in this phase III, double-blind, randomized, placebo-controlled trial. Patients were randomized to a single 60-hour infusion of either BRX90 (n=54) or placebo (n=54). Patients had a mean age of 27.9 years and a mean BMI of 32.3 kg/m2.21 Sixty percent of the patients were White. Treatment was discontinued in four of 108 patients who received the study drug; one in the placebo group (lost to follow-up) and three in the brexanolone group (one withdrew consent, one adverse event, and one lost to follow-up). Baseline HAM-D scores were 22.6 and 22.7 in the BRX90 and placebo groups, respectively.

At the end of the 60-hour infusion, the mean reduction in HAM-D total score was 14.6 points in the BRX90 group and 12.1 points in the placebo group (LS mean difference −2.5 points, 95% CI −4.5 to −0.5, p=0.0160). This effect was not maintained during the follow-up period after the infusion up to 30 days (LS mean difference 0.5 points, 95% CI −2.0 to 3.1, p=0.6710). Remission rates, defined as HAM-D total score ≤7, were higher in the BRX90 group compared to placebo, with 61% of patients achieving remission at 60 hours, but not 30 days, compared to 38% in the placebo group.

Brexanolone was well tolerated, with no deaths, serious adverse events, or discontinuations occurring in either group. The total number of adverse events was similar (BRX60=90, BRX90=9, and placebo=6). The most common adverse effects of BRX90 included headache (18%), infusion site pain (10%), nausea (10%), and dizziness (10%). One patient in the BRX90 group had two serious adverse effects of altered state of consciousness and syncope, which were moderate in intensity and were related to treatment. Two patients in the BRX90 group had severe adverse events of fatigue (n=1) and presyncope (n=1). Across both studies 202B and 202C, five patients had excessive sedation which was determined to be due to brexanolone. In all cases, infusion was stopped and the events resolved within 90 minutes. All patients who lost consciousness regained consciousness within 15 minutes of infusion cessation. There were no differences in laboratory parameters, vital signs, or electrocardiograms between brexanolone and placebo groups across both studies.

These studies demonstrated the efficacy and safety of brexanolone for PPD, with statistically and clinically meaningful reductions in HAM-D scores compared to placebo. The antidepressant effect was rapid and the majority of patients achieved remission (51–70%) at the end of the 60-hour infusion. Although brexanolone was not consistently superior to placebo at 30 days in all three studies, the antidepressant effect was sustained in patients with both moderate and severe PPD, and no patients relapsed after treatment. These studies are limited by the short follow-up period of 30 days and significant placebo response rate, although that is common for antidepressant studies.

Zuranolone: Clinical Efficacy and Safety

Zuranolone efficacy and safety data have been published in one phase II study. In this double-blind trial, 89 patients were randomized 1:1 to receive either zuranolone 30 mg (n=45) or placebo (n=44) daily for 14 days.23 Patients aged 18–65 years who had a diagnosis of MDD with a HAM-D score of 22 or higher were included in this trial. Patients could continue stable doses of antidepressants if they had been prescribed for at least 30 days. Initiation of new antidepressants was not allowed during the 14-day treatment period, but antidepressants could be adjusted or added during the 4 weeks after the treatment period, at which time secondary outcomes were assessed. Patients were excluded if they had a history of a suicide attempt or treatment-resistant depression, a recent history or current clinically significant manifestations of other acute or chronic medical conditions, a positive pregnancy test, a history of seizures, or a history of BPD, schizophrenia, or schizoaffective disorder. The primary outcome was change in 17-item HAM-D total scores from baseline at 15 days.

Patients had a mean age of 43.7 years and a mean BMI of 29.95 kg/m2, and 72% were Black. The use of antidepressants at baseline was similar between the groups, with 12 patients in the zuranolone group and 10 patients in the placebo group using antidepressants. Baseline HAM-D scores were 25.2 and 25.7 in the zuranolone and placebo groups, respectively. On day 15, the mean reduction in HAM-D score was 17.4 in the zuranolone group and 10.3 in the placebo group (LS mean difference −7.0, 95% CI −10.2 to −3.9, p<0.001). This effect was maintained during the follow-up period up to 28 days (LS mean difference −4.1, 95% CI −7.6 to −0.5), but not for days 35 and 42 (LS mean difference −2.3, 95% CI −6.0 to 1.4 for both). In addition, MADRS scores were significantly different at 15 days (LS mean difference −7.6, 95% CI −12.3 to −2.8), but not at 28, 35, or 42 days. The response rate at 15 days, defined as a reduction of at least 50% from baseline HAM-D scores, was 79% in the zuranolone group and 41% in the placebo group (OR 9.6, 95% CI 2.9 to 31.6). Remission rates, defined as HAM-D score ≤7, were higher in the zuranolone group (64%) compared to the placebo group (26%) (OR 5.3, 95% CI 2.1 to 13.3).

Zuranolone was relatively well tolerated, with no deaths, serious adverse events, or discontinuations occurring in either group. Adverse events, none of which was serious or severe, were more common in the zuranolone group (n=24) than in the placebo group (n=20). The most common adverse effects of zuranolone were headache (18%), dizziness (11%), and nausea (11%). Six patients in the zuranolone group had dose reductions from 30 mg to 20 mg, five for adverse events: dizziness (n=2), somnolence (n=1), sedation (n=1), nausea/vomiting (n=1), and sleepiness (n=1).

In the first phase III clinical trial, 581 patients with MDD were randomized to zuranolone 20 mg, 30 mg, or placebo daily for 14 days.24 There was minimal separation from placebo at day 15 (LS mean difference −1.4, p=0.115) in the 30 mg group and no separation in the 20 mg group. At day 42, the reduction in depressive symptoms was maintained; however, the difference between zuranolone and placebo was not significant (LS mean difference −0.5, p=0.807). A post-hoc analysis was performed to evaluate the effects of performance factors on the primary outcome at day 15. Patients with measurable serum concentrations of zuranolone, those with HAM-D >24, and those with both measurable drug serum concentrations and HAM-D >24 had significant differences from placebo. Adverse effects in this trial are similar to those reported in other zuranolone trials discussed in this review. The investigators of this study concluded that the 9% of patients with undetectable drug serum concentrations may have significantly contributed to the negative findings.

Interim Reports: MDD

An interim report of a phase III, open-label, one-year longitudinal study (NCT03864614) presented at Psych Congress 2020 assessed a 14-day course of 30 mg daily of zuranolone in patients aged 18–75 years with a diagnosis of MDD (HAM-D ≥20).25 Patients were included if they had a diagnosis of MDD with symptoms that had been present for at least 4 weeks and a MADRS total score of ≥28 and HAM-D total score of ≥20. Patients were excluded if they had a suicide attempt associated with the index MDD episode, had a history of BPD, schizophrenia, or schizoaffective disorder, or had undergone treatment with vagal nerve stimulation or electroconvulsive therapy, or used any form of ketamine during the index MDD episode.25

The primary outcome was change in HAM-D scores from baseline at 15 days. In total, 725 patients, with a mean baseline HAM-D score of 25.3, were treated with 30 mg of zuranolone. At day 15 of the initial course of therapy, the mean reduction in HAM-D scores was −14.9, the response rate (≥50% reduction in HAM-D scores) was 71.6%, and the remission rate (HAMD ≤7) was 39.8%. The most commonly reported adverse events were somnolence (9.5%), headache (8.7%), and dizziness (5.4%), of mild or moderate severity.

Patients who responded to therapy in the first phase (n=494) could be retreated with a course of zuranolone (30 mg until May 2020, and then 50 mg). The majority of patients (44.5%) required only the initial zuranolone course, while 26.7% used two total courses, 13.4% used three total courses, 10.3% used four total courses, and 5.5% used a total of five courses. In the interim sample of patients who were initially treated with 30 mg who then received repeat treatment with 50 mg, patients had higher rates and intensity of adverse events. Patients were reassessed for the need for repeat treatment every 14 days and were given another course if HAM-D scores were ≥20 or Patient Health Questionnaire-9 scores ≥10. There was a minimum of 56 days between zuranolone courses.

A new cohort initially treated with 50 mg of zuranolone (n=52) had a mean HAM-D score of 25.1 at baseline. There was a change in HAM-D scores from baseline of 15.9; 75% of patients responded to treatment and 48.1% achieved remission. Of the 76 patients with safety data available from the 50 mg cohort, adverse events were similar to the 30 mg cohort. The most frequently reported adverse events were somnolence, dizziness, sedation, headache, and tremor of mild or moderate severity. .

A phase III, multicenter, double-blind, placebo-controlled study of zuranolone in MDD is completed, but not results are not yet available (NCT04442490). In addition, a phase III, randomized, double-blind study comparing zuranolone plus an antidepressant to placebo is recruiting, (NCT04476030).

Interim Analysis: PPD

An interim report of a phase III, double-blind, parallel-group, placebo-controlled trial (NCT02978326) presented at the American Society of Clinical Psychopharmacology 2019 Meeting assessed a 14-day course of zuranolone 30 mg daily (n=76) or placebo (n=74) once daily.26 Inclusion criteria for this trial were the same as those for the brexanolone studies 202A and 202B. Patients had a mean age of 28.4 years, 56% were White, and the baseline HAM-D score was 28.4 in the zuranolone group and 28.8 in the placebo group.

The primary outcome was change in HAM-D scores from baseline at 15 days. At day 15, the mean reduction in HAM-D scores was 17.8 in the zuranolone group and 13.6 in the placebo group (p=0.0028). The response rate, defined as ≥50% reduction in HAM-D scores, was greater in the zuranolone group compared to the placebo group (94.7% vs 64.9%, p=0.0049), as was the remission rate, defined as HAM-D total score ≤7 (59.2% vs 31.1, p=0.0110). The most common adverse effects were somnolence (15%), headache (9%), dizziness (8%), upper respiratory tract infection (8%), and diarrhea (6%), most of which were mild or moderate. Six patients experienced severe adverse events, three from the zuranolone group (one sedation, one confusion, one migraine) and three from the placebo group (one back pain and muscle spasms, one headache and oropharyngeal pain, and one menorrhagia). Two patients, one from each group, experienced serious adverse effects. This study has completed recruitment. Another phase III, double-blind, placebo-controlled study (NCT04442503) evaluating the efficacy and safety of zuranolone for PPD is underway, with an estimated completion date of December 2021.

Interim Analysis: BPD

An interim analysis of an open-label, phase II trial (NCT03692910) presented at Psych Congress 2020 assessed a 14-day course of 30 mg of zuranolone in patients aged 18–65 years with a documented history of mania/hypomania and a diagnosis of BPD I or BPD II, in a current major depressive episode (HAM-D ≥22).27 Patients with a history of rapid cycling BPD or a depressive disorder with mixed features, or history of a suicide attempt or current suicidal ideation with plan, were excluded. Primary outcome measures were the safety and tolerability of zuranolone as assessed by the frequency and severity of adverse events, Columbia Suicide Severity Rating Scale, and Young Mania Rating Scale. Secondary outcome measures were the change in HAM-D and MADRS total scores from baseline at 15 days.

Thirty-five patients with a mean age of 47.6 years were included in part one of this clinical study. The majority of patients had BPD I (88.6%), and were Black (51.4%), and female (65.7%), with a mean BMI of 32.3 kg/m2 and a mean baseline HAM-D total score of 25.7. Zuranolone was generally well tolerated in this population, with no severe or serious adverse events, no mania, no required dose reductions due to adverse events, and no increased suicidal ideation or behavior. Two patients experienced mild hypomania, which occurred in the treatment follow-up period. The most common adverse effects reported were somnolence (11.4%) and headache (8.6%). With regard to efficacy outcomes, there was a reduction in MADRS total score (−15.5) and a reduction in HAM-D total score (−11.4), both sustained through day 42. Response, defined as ≥50% reduction of HAM-D total score, was achieved in 45% at day 15, with 50% achieving a response at day 42. This study is phase A of a two-part study, with plans for a double-blind, randomized, placebo-controlled, parallel group trial of zuranolone compared to placebo in BPD from Sage Therapeutics.

These studies have demonstrated the efficacy and safety of zuranolone for a variety of depressive illnesses for patients with severe depression, including PPD, MDD, and BPD. Antidepressant effects appear to be rapid and have a sustained effect, with high response rates (45–94.7%) and remission rates (39.8–64%) at the end of the 14-day treatment course, in some cases up to 42 days. These studies are limited by the lack of complete data, short follow-up periods, and significant placebo response rates.

Discussion

Place in Therapy (PPD)

PPD is a common complication of pregnancy, as one in eight women reports symptoms of depression after giving birth.28 Perinatal depression includes major and minor depressive episodes that begin during pregnancy or in the first 12 months after delivery.29 As allopregnanolone agonists have not been studied during pregnancy, these medications should be limited for use in moderate to severe PPD after delivery has occurred.

Exogenous allopregnanolone (brexanolone) and the analogue zuranolone represent first-in-class medications with regard to mechanism and indication for PPD. Allopregnanolone levels peak during the third trimester and decline rapidly following childbirth. While their unique mechanism of action is not fully understood, the hypothesis is that administering allopregnanolone agonists could restore allopregnanolone concentrations and reset neural networks, resulting in improved PPD symptoms.20

In clinical trials, brexanolone is unique in the treatment of depression in that response and remission occur rapidly, within 60 hours, with a sustained effect to at least 30 days. In addition, the response and remission rates in trials exceed those seen with traditional antidepressants (~50% and ~30%, respectively). Mechanistically, if PPD is due to a rapid decline in allopregnanolone levels, exogenous administration over days to allow a smoother decline in levels makes clinical sense. This relatively rapid time to improvement in depressive symptoms (60 hours for brexanolone, 15 days for zuranolone) provides a potential advantage over other antidepressants such as selective serotonin reuptake inhibitors (SSRIs), which can take 4–6 weeks to provide remission. It should be noted, however, that brexanolone and zuranolone have only been studied in comparison to placebo at this time. In addition, these medications are only given once for their allotted treatment time (60 hours for brexanolone, 14 days for zuranolone) and not continued for months or years, therefore reducing the potential pill burden.

It should be noted that in clinical trials of brexanolone, the rate of historical non-PPD depression ranged from 24% to 60% and the rate of previous PPD ranged from 27% to 70%. Based on the available published data, it is not clear whether a past history of MDD impacts the likelihood of response or remission. Future studies should focus on differentiating new-onset or recurrent PPD from recurrence of MDD in the postpartum period. Defining the optimal time for administration (eg, the point at which allopregnanolone levels stabilize postpartum) and whether there is a role for prophylactic dosing in women with a history of PPD are additional questions to be answered.

The 60-hour continuous infusion administration of brexanolone has several barriers that should be considered by both clinicians and patients. The REMS program requires the infusion to be administered in a medically supervised setting where patients can be continuously monitored for excessive sedation and loss of consciousness. Patients receiving brexanolone must not be the primary caregiver of their children during the infusion.30 Furthermore, the cost of the medication (>$30,000 per 60-hour infusion) and the cost of admission to a medically supervised setting could limit access for some patients. Healthcare settings should utilize a multidisciplinary approach to develop optimal procedures for REMS program compliance, patient safety, and cost reimbursement.

Place in Therapy (MDD and BPD)

The trial of zuranolone for MDD did not demonstrate the same maintenance of response after the end of treatment, with improvement dissipating by day 28 (14 days after the end of treatment). Furthermore, in the open-label study, over 50% of patients required additional courses of treatment. The BPD study, however, did find a sustained improvement as far as day 42, with a slight improvement over the initial response rate. This may be related to the plasticity of GABAA receptors and differential effects of allopregnanolone in MDD, BPD, and PPD. The rapid improvement in MDD symptoms over 14 days without sustained benefit harks back to the clinical trials of benzodiazepines for depression. Future studies should include concurrent initiation of traditional antidepressants as maintenance. With two patients experiencing hypomania in the follow-up period, the risk of mood switch in BPD and the impact of concurrent mood stabilizers also warrant assessment.

Despite rapid improvement in symptoms, patients with treatment-resistant depression or suicidality were excluded from all of the clinical trials discussed. While this is standard in clinical trials of antidepressants, it would be beneficial to include these patients in future clinical trials as they are often the most in need of rapid response. In addition, given the widespread use of benzodiazepines in patients with depression, the clinical impact of concurrent use of two different GABAA receptor modulators requires more understanding.

Conclusion

The novel mechanism of allopregnanolone agonists on GABAA receptors provides a promising innovation in the treatment of depressive disorders. The quick onset of remission with these agents is a benefit over standard therapies and they may have a niche as an induction agent or a bridge to maintenance therapy with SSRIs. Considering the role of endogenous allopregnanolone in PPD, the benefit of these agents may outweigh the costs and severe risks of untreated PPD. In contrast, in MDD, the mechanism of allopregnanolone agonists mirrors that of benzodiazepines, which are no longer recommended, potentially indicating a lack of benefit in this indication. The data, overall, are encouraging, but the results of further studies with direct comparisons and combination drugs are eagerly anticipated.

Disclosure

Dr. Leader reports consulting for Wolters-Kluwer on medication use in pregnancy and lactation and Pfizer, Inc. on their menopause portfolio. Dr. Cooke reports participation in a Sage Therapeutics, Inc. Site Activation Advisory Board Meeting in November 2019. The authors report no other conflicts of interest in this work.

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