[Metal] The Agonist – Five (80%)

img_0399November is ending and I just realized I missed to review one album that came out during this month. This album that I almost missed is “Five” from the Agonist. The second album with Vicky Psarakis fronting, replacing Alissa White-Gluz (now front singer of Arch Enemy).
With her second album with the band, how does Vicky vocal performance stands? Good, very good indeed. Louder, stronger, better. Let’s go through the album, a 14-track album totaling 58 minutes.
It all starts with “The Moment”, simple but loud and heavy, nicely alternating Vicky’s cleans and growls. We are still in the range of the Agonist but I felt the sound and melodic tone have matured in a good manner. This feeling is present all along the album.

Then comes the second track “The Chain”, bringing on the fast-pace that were acclimated with the Agonist, again a nice track if you like the Agonist when they speed up their tunes. We keep in the same tunes with “The Anchor and The Sail”,  “The Game”, “The Ocean”, “The Hunt”.

Some safe placement but also nothing that I found exceptional, except the latter that I really like from all four. Then comes “The Raven Eyes” like an interlude in the middle, mostly acoustic almost with this pleasing jazz-feeling, in which Vicky’s voice nicely matches. Following “The Raven Eyes” comes “The Wake”, a mostly instrumental track playing on the symphonic tunes.
This relaxing feeling is indeed a trick from the band, as “The Resurrection” brings back the death metal on the table, like a sudden wakeup. Nice but nothing out of the ordinary. In contrast, “The Villain” shakes up much more with Vicky unleashing her growls in it, all in her rage and furor. My second favorite one. The album continues with “The Pursuit of Emptiness”, another track falling in the classic Agonist sounds. What comes from the ordinary is the 12th track, “The Man Who Fell to Earth”. Slow, dark and sensual track going out of the ordinary. Another in my favorite list. The album concludes with “The Trial”, following the same step than the previous one, with Vicky’s performance mostly clean but a higher level of heaviness.
The final track of the album is indeed a cover of Hozier “Take Me To Church” that received the 2014 Grammy rock song of the year, giving a much more punchy and heavy tone to the song making it more enjoyable.
In conclusion, this album proves the potential of Vicky. She has matured and progressed. Same can be told for the band. It is a nice album but still a dramatic release that would shake my library. Still it is a nice album to get your hands on,  give a try on iTunes and see if you like it.


[Junk Sciences/BBB] Does bone broth leads to a leaky brain? (aka the stupid, it burns!) 

Everyone should have recovered from the post-Thanksgiving food comatose (no, it was not due to the turkey’s tryptophan), the post-election discussion and the Blck Friday melee fight for that 55″ UHDTV that is justin time to play on your XB1S with a 4K resolution.
Seem the woo is never running short of idea, piling up fallacy over another fallacy as iHop piled up pancake in a post-Thanksgiving breakfast ride.
The latest fallacious claim cames from a “nutrition blog” claiming that bone broth, leads to elevated glutamate levels following bone digestion (!), such glutamate results into a leaky gut. Leaky gut means utomtically leaky brain, letting glutamate flows into the brain as boiling pasta water flows through the hole of the pasta strainer and ultimatelly leads to neurological disorders, with a special mention of neurodevelopmental disorders such as ADHD and ASD, because these are two conditions that scares parents as hell nd therefore makes a juicy alibi to milk on parents withtheir precious $$$ and torture kids with dubious or completely scam treatment (including bleach enema, putting kids on casein-free/gluten-free diet, hyperbaric oxygen chamber or chelation treatment).
Because I am the one claiming the claim of this blog post is bogus, it is my duty (and my pleasure as a BBB Scientist) to debunk it.

1. About the bone broth….

In the post, the author first claim that bone broth prepation (slow cooking) results in a dissolution of the tendrils and connective tisues to dissolve, as cited as the following
So what’s the dark side of Bone Broth? It lies in the “long” part of the “slow and low and long” cook time. Bone Broth simmers at a low temperature for many hours, long enough to allow the connective tissues to dissolve and the minerals to be drawn into the broth.Thats partially true. Bone broth is composed by two major type of tissue: connective (bones, tendrils, muscles) and non-connective tissue (basically the bone marrow). The preparation of bone broth will primarily dissolve the bone marrow (rich in bone marrow stem cells) that gives that yummy flavor in dishes, my fond being the French “Pot-Au-Feu” (the yummiest soup during the holiday season). The cooking process will tenderize the meat but very unlikely to dissolve bones and tendrils.
To dissolve bones and tendrils, you need something……very acidic. Only an extreme acidic and hot environment will dissolve bones and tendrils.
Therefore her first claim is not fully backed by science. Now let’s assume you have some connective tissue that solubilize, you will have mostly collagen dissolved. Collagen is the main protein involved in most connective tissues. The author claims that such processing releases tons of glutamic acid (that is also glutamate) as described here “The result of such long cook times is a tremendous amount of glutamic acid. And that’s the dark side of Bone Broth
.Collagen is a polymer made of a same repeat motif Glycine-X-Y, with X and Y being often proline and hydroxyproline (the hydroxylation of proline into hydroxyproline is made by prolylhydroxylase, using vitamin C as a co-enzyme. This is why scurvy (lack of vitamin C) is characterized by defect in connective tissues).
It comes with different flavors depending on the function (collagen type I  being the predominant form in connective tissue; collagen II found in tendrils; Collagen III in cartilages and bones; Collagen IV in basement membranes……). This second fact discredits her claim that collagen will increase the amount of glutamate.

2. What is the blood-brain barrier (BBB) and how glutamate is processed?
After giving her culinary explanation, the author jumps into explaining glutamate into her own terms: “As you may or may not know, glutamic acid and glutamate are highly regulated by the human brain“. You can already note the red herring about the author as she treats glutamic acid and glutamate as two distinct chemical entities.  This is an obvious lack of understading of biochemistry  as glutamate is the the ionized (salt) form of glutamic acid. This is a typical misconception that I see with folks peddling on woo (folate/folic acid anyone?). It also raises concern about the credentials of someone making dubious health claims. Garbage in, garbage out.
Not only the author makes blatant mistakes but also makes fallacious associations as mentioned here If you have a leaky brain, as those with a leaky gut often do, high amounts of glutamic acid can trigger seizures if you’re prone to them. Yes, seizures. It can also trigger other neurological symptoms you may already be sensitive to, including brain fog, migraine headaches, dramatic mood swings, stimming, and nervous tics, to name a few.
I have been discussing over and over about the BBB in my blog, so I will not repeat over and over again. I will keep it simple. The BBB is what we call a component of the neurovascular unit (a combination of the cardiovascular and nervous system) that is designed to protect the brain from any interferences from the periphery. Therefore the environment in which the brain bathes in is strictly controlled, with a defined composition. The BBB provides two kind of barrier: a physical and a chemical barrier supported by the brain microvascular endothelial cells (BMECs) lining the inner side of blood vessels. They provide a tight blood-brain interface that strictly regulates what comes in and out the brain. The physical barrier is harbored by the presence of tight junction complexes, whereas the chemical barrier acts as a selective filter that pick and choose which molecules goes into the brain through an array of transporters, represented by the super-family of solute carriers (SLCs). Each solute carriers are adapted to let the entrance of specific molecules (for instance SLC2A1 lets glucose enters the brain, SLC16A1 lets T3 thyroid hormone enters the brain….).
In many aspects, BMECs share a lot of features than intestinal cells. But a leaky gut and a leaky BBB cannot explain her claims.  In order to understand how her claim is bogus, I will argument using a recent review by Hawkins RA and Vina JR (the first author has a publication records in regards of glutamate transport accross the BBB). If glutamate
However, glutamate is firstly poorly transported inside the brain because it remains trapped inside the BBB . Thats already hit her claim.
If we follow her logic, we are facing a massive increase in glutamate level in the food uptake (due to the broth). Because you have a leaky gut (a concept I have been already explained in my previous blog as still debated and mostly inaccurate in terms of diseases), you have your body flooded with glutamate and ultimatelly flooding your brain with glutamate. This makes sense only if you have a deficit. Chemicals flows into two compartment following the Ficks law, it diffuse from the most concentrated to the least concentrated compartment. Because it is considered as a non-essential amino acid (your body knows how to build it up from other molecules), the brain is not in need for glutamate and can produce its own. Glutamate plasma concentrations range from 50-100microM, brain concentrations ranges from 10’000-12’000 microM. We are talking about 200 times more in the brain than in the plasma. Therefore, you need to achieve a concentration higher in the brain to expect to see any changes. Thats simply impossible and destroy the rest of her argument!

3. But, but…….I have a leaky brain! (No you have not).
The idea of a leaky brain is simply the most ridiculous claim. If your brain was indeed leaky, you would not be here reading this post. You will be six feet under, dead from a massive brain edema.
Leaky brain happens when you have a disruption of the BBB, in particulat from the tight junctions lining BMECs. This results into an onset of “vasogenic cerebral edema” and in an unrestricted entrance of water and ions inside the brain.
This happens if you are experiencing high-altitude mountain sickness (in particular high-altitude cerebral edema), stroke or brain trauma (traumatic brain injury). Because the brain is contained inside a rigid structure (skull), it cannot expand and swell as you would experience if you experience and injury in the periphery. This results in an increase of an intracranial pressure (ICP) and brain injury by mechanical stress (imaging squishing a sponge in your hand) that leads to neuronal cell death. Untreated, brain edema is fatal. However, there are cases of cerebral microbleeds that do not induce cerebral edema formation. This could be something that can be considered as “leaky brain” but their intensity and extend is a far cry of the former word meaning. 
Thus, the concept of leaky brain is completely fallacious as it is taken out of context and grossly exagerrated. 


[Neurosciences] ….and another Alzheimer clinical trial bites the dust :(

….And another Alzheimer’s disease clinical trial bites the dust. This one is a Phase III trial (that means hundreds of volounteers). Eli Lilly new candidate, an antibody targeting amyloid beta plaques formation failed to show any improvement compared to placebo in their latest clinical trial.
That means Lilly will stop injecting money (we are talking about already $100 million spent in R&D considered lost, as the company will not be able to make return on investment) and bring us back to the blackboard: is amyloid beta the real culprit or are we missing it? Thats tilt in the favor of the tau team (that consider tau hyperphosphorylation the main culprit).
Thats some disappointing news for everyone and gives an idea why new treatments are so expensive once they enter the market upon FDA approval.

Source for this post: ACS Chemical & Engineering News (image: Lilly)
Lilly Alzheimer’s drug fails | November 23, 2016 Issue – Vol. 94 Issue 47 | Chemical & Engineering News

[Metal] Metallica – Hardwired…To Self-Destruct (80%)

Metallica just released their tenth album “Hardwired…To Self-Destruct”. Depending on how you got into Metallica, it was a eight year hiatus since “Death Magnetic”….or 25 years since “Metallica” (aka the black album). If you grew up listening to Metallica, you surely have in mind  “Master of Puppets”, “Ride The Lightning” or “Kill’Em All”. You also have some rancor when the band decided to explore novel artistic directions after their black album, enough to classify Metallica as “before” or “after” such album.
I will be sincere: “Load”, “Reload”, “St.Anger” (certainly one of the most hated album) or “Death Magnetic” are simply not in my Metallica discography. The question you may ask if you have growing with the Metallica of the 90s is “why so much hate?”
For me, it is simple. Metallica sound had its own trademark that set the sound of the US metal back in the early 80s. Back in the days, UK metal bands were acting like a tsunami on every single continent with what we call the “New Wave of British Heavy Metal” (NWOBHM) with bands such as Iron Maiden, Judas Priest or Ronnie James Dio. These bands were great by bringing  melodics (using two lead guitars and a bass) and the tell-tale lyrics from charismatic front singers (like Bruce Dickinson, Dio or Rob Halford. It was a clear distinctive sound, much more complex and captivating than the punk from the Sex Pistols or The Clash.
In the other side of the Atlantic Ocean, some bands were fueled by the rebellious attitude of punk but also considered the melodics are an important part. However, neither the punk nor the NWOBHM could fit their style. This is how bands like Motorhead, Metallica, Slayer and Anthrax blended into two genres: speed and thrash metal.
The distinctive feature of these bands is their fast drums pace, the aggressive guitar riffs and the incendiary lyrics. This was the staple of such bands with albums such as “Whiplash” or “Reign in Blood”. Listening to them would provide you with superpowers, fully pumped on adrenaline rush.
But Metallica was also something else, capable of remarkable guitar ballads thanks to the work of Kirk Hammett and late Cliff Burton. Listen to “One”, “Sanitarium”, “Orion” but also to complex songs such as “One”, “Master of Puppets” or “For Whom the Bell Tolls”.
By the time the band released “Metallica/the Black Album”, you could already hear the transition the band was but really was obvious with “Load”, as Lars drum sets were pitched to higher frequency and to different tempo pattern. Metallica soften up their style and by the same time infuriated their hardcore fans. This was also the time I kind of dropped from Metallica asI grew up from my teenage years. It was 1995. Grunge was dead with the suicide of Kurt Cobain and had an heavy toll on the classic heavy metal.
Now you either secluded into something more brutal (with bands such as Pantera setting up the death metal genre with “Vulgar Display of Power”) or more melancholic and slow-paced with the appearance of gothic and doom metal (with the pioneering work of Anathema, Paradise Lost and My Dying Bride). As I grew up from my teenage rebellious mind and entered college, I also transitioned from Metallica to gothic and doom.
So, after 20 years of waiting and several disappoint albums, the arrival of their last album was setting high expectations on Metallica: Will they purse on their post-black direction or will they re-discover their pre-black composition?
Luckily for me, Metallica being Metallica (they still sell 5000 copies of the black album each month!), I could grab their album as a physical copy (the 2CD version) straight from the nearest Best Buy. A bliss considering the anemic metal section in my local Best Buy.
What I can tell? It’s good, honestly. Sure it is not a natural child of a “Master of Puppets” but you are still faring way better that anything post-black. There are some very good songs and some okay songs.
Lets go through the 12-track album, note the average song is lasting 6-7 minutes. Sometimes it was a pleasure to keep listening, sometimes it was “okay now it is sounding repetitive”. A special for this review, Metallica has a video for EVERY SINGLE songs of the album on Youtube. An interesting twist considering the outrage of Lars Ulrich that costed Napster its final blow and created the P2P file sharing system.

First track: “Hardwired”. It sets the tone. We are in the thrash metal, baby! A very good primer for the rest of the album reminiscent of “Kill’Em All” and “Ride The Lightning”

The second track is “Atlas, Rise!”, that is less aggressive than “Hardwired” but reminiscent of something from “Metallica”. Nice track but I have heard better.

The third track is “Now That We’re Dead” that sounds okay but a bit hollow. Again, as “Atlas, Rise!”, sounds a soften Metallica.

As you feel a bit asleep with track 3 and 4, here comes “Moth Into Flames” that comes and raise up the bar, a damn good song with fast-paced drums and good guitars that is certainly a song you would not mind hearing in a  rock FM radio.

Then comes track number 5 “Dream No More”, thats is also okay, feeling something a bit something you would hear in any post-black album.

Track 6, last track of Disc 1: “Halo On Fire”. The metal song! My favorite of this disc, with nice guitar solos and slow-paced. Not thrash but sounds damn good.

There comes the Disc 2, that in my opinion contains the meat of the whole album and really excited much.
Here comes track 7, that starts with an air of “Mars, The Bringer of War” brining some good old metal sound (almost feel like in the tunes of Ghost) and discussing about post-traumatic stress disorder. The videoclip is awesome.

In track 8, Metallica is taking up a “black metal” paint on their clip but kind of in dissonance in the song. I would have appreciated something much heavier.

The track 9, named “Here Comes Revenge” is my most favorite track of the album by its song and by its videoclip. The video is simply insane.

Track 10, “Am I Savage” is nice, starting with Kirk Hamett solo guitar and getting crescendo.

Track 11, “Murder One”, is a special track. A whole hommage to Lemmy, in particular the video was absolutely fantastic.

Finally the album concludes on “Spit Out The Bone”, the “plat de resistance” and one favorite of the album. A fast-paced song straight from a “Kill’Em All” coupled with a damn gore video. This is the Metallica that I know: brutal!

My take? Dang it is good to listen to Metallica that not something that I have been picking from a pre-black album. 35 years later and Metallica show they can still kick some ass. Sure, we are not having another “Master of Puppets”, but for me it completely reset anything for the past 25 years.

[Sciences] First clinical trial using the CRISPR/Cas9 in China.

You may have heard about the news on the first clinical trial in China that was consisted of inoculating cells modified by the CRISPR/Cas9 technique. In this post, I relaying the original article published in Nature online about the trial (source: http://www.nature.com/news/crispr-gene-editing-tested-in-a-person-for-the-first-time-1.20988?WT.mc_id=SFB_NNEWS_1508_RHBox)

For many of you, CRISPR may not be much explanative except the word that sounds like something being “crispy”. Indeed the technique is.
But let’s understand the technique to better understand why it is a breakthrough. There is a nice video made by iBiology and featuring Dr. Jennifer Doudna (the co-discoverer of CRISPR/Cas9) explaining very nicely exhaustively in lay terms the CRISPR/Cas9 technique that I will quickly resume to keep that post short


CRISPR/Cas9 acts as a little genetic scissors, that permit us to cut and paste genetic data into cells. Stricto sensu it is not new and we have doing it in bacteria, yeasts, plants, fruitflies, zebrafish and mice for a while now. But one thing we have been facing is editing genomes in bigger animals like rats, primates and humans. It is extremely difficult and very poorly efficient.

With CRISPR/Cas9, we suddenly have a magic wand that now makes the impossible-possible by making the gene edition in higher mammals much more easier. Also CRISPR/Cas9 allows us a more targeted editing, precisely.
However the technique has known some possible off-target gene editing, such caveat is enough to raise concerns for patients safety. However, as science goes, there is a rapid interest in the technique and improvements are coming in the fast pace.

In this trial, the investigators have taken immune cells from a patient suffering from a lung cancer and removed a gene called PD-1. PD-1 is a receptor for a molecule called PD-1 ligand, a protein secreted by cancer cells. Upon interactions with PD-1L, PD-1 results in a immune suppression and shutdown of the immune system. By removing PD-1, the immune system is no more silenced and now can target and strike cancer cells. This is a new concept in fighting cancer cells called immunotherapy.

This trial will tell us two things. First if the technique is safe and second if it is efficacious. The treatment appears safe (because the cells have been engineering outside the body and reprogrammed in a dish before being reinserted) but we cannot exclude any severe if not fatal side effects.
The second is the efficacy. There are evidence of PD-1 targeting being a novel treatment that showed promising results in Phase II and III clinical trials. But that will work with lung cancer? We will have to wait and see….

If it works, that would be fantastic and open the possibility to revive the gene therapy that has been mostly stuck in limbo by our lack to insert and correct defective genes in patients.

[Junk Sciences] The Fair Trade Commission clamps on OTC homeopathic products

Winter is coming, thanksgiving is one week away and of course comes the classical cold/fever/pain reliever triad. If you use to shop on OTC products, you often cross on homeopathic products. Not only these products are basically useless, but these products use packaging tactics making you believe that they are as efficient as conventional OTC.
Of course, you realize that you picked the wrong bottle as your condition does not improve even after swallowing the whole bottle. Because they are not designed as drugs, homeopathy gets a free-ride by escaping the FDA regulations unless serious and fatal effects are reported following their use (see the teething gel story that I posted few weeks ago).
Because homeopathic products efficacy have not been backed by science, they avoided to put themselves in hot water by providing a statement like this one: “the case for efficacy is based solely on traditional homeopathic theories and there are no valid studies using current scientific methods showing the product’s efficacy“.
In other words, it works only if you believe in it enough. It has the same validity to say that unicorns exist only if you believe in them. There are no scientific proof that unicorns exist but if you believe enough in it, you can see unicorns.
The Fair Trade Commission decided such statement as deceptive and ordered any OTC homeopathic produces to harbor the following statement:
1) there is no scientific evidence that the product works; and 2) the product’s claims are based only on theories of homeopathy from the 1700s that are not accepted by most modern medical experts.”.
Although such statement will not stop the sell of homeopathic products, it sets the fact straight. There is no scientific evidence that it will work, such treatment is simply outdated and not recognized as medicine.

Source: FTC Issues Enforcement Policy Statement Regarding Marketing Claims for Over-the-Counter Homeopathic Drugs | Federal Trade Commission

[Metal] Mercy Isle – Undying Fire (80%)

In all its Hell of the course teaching/grants & manuscript writing/scientific meetings that blew on me from September until now, I have been caught away to review some metal albums that were released during this time.
One of them is Mercy Isle “Undying Fire”, the first full-album from the band. The band is by itself original as it is a combination of Dutch and US members, fronted by Kassandra Novell. You can almost feel it in the notes the Batavian influence. You know that there should be something good about the band, as they made the cut and performed at the latest Metal Female Voice Fest (last October). So I gave the album a commuting test and here is my review on the album.
The album is composed by 10-track and has for those that has previously purchased their first EP “Storm” a feeling of deja-vu because some of the tracks are also inside this album. Just you get warned about, so you dont get disappointed.
First, I like that the album is not trying to surf on the “Symphonic Metal” wave that I found right now over-saturated by too many bands. It swings between gothic and progressive metal, giving it a degree of artistic freedom.
It starts with “Wake Up”, an easy and simple introduction to the album that sounds an easy shot for a promotion into a mainstream audience. Its fine for me but not enough to impress. In the opposite, “Storm” was more convincing and more enjoyable to listen, giving a better composition and space to Kassandra voice. We keep on the same quality by transitioning with “Stop, Kiss Me” that is also pretty good to listen. “If I could” could be the power ballad song of the album. Here we can appreciate Kassandra talent and potential talent. It gives a nice and relaxing interlude. “Uncaged” is another track from the EP, so it may seem as deja vu but also brings a heavier tone than the first track. I feel things are getting serious here. “No One Will Save You” is also coming from the EP, so I will not discuss more about it. “I Am” has this feeling of Lacuna Coilesque from their previous work on Karmacode. “Saying Goodbye” is certainly the best track of the album, reminding me of Nightwish by its musical arrangement. “Come to Me” comes and shake up all and bring the heavy-o-meter into 2 scales up making it also enjoyable. Finally, “The Ghost” closes this chapter with the same heaviness.
If you like something similar to Lacuna Coil, but have been on saturation mode with “same old, same old” of certain bands, you should give a try to Mercy Isle. They have here a decent first album that is really accessible to share. Just a reminder, dont purchase the EP as you will have a redundancy in your playlist.