[Gothic Metal] Evig Natt – Wildfire

Today the Norwegian metal band Evig Natt has released their official video “Wildfire” from their latest album “Evig Natt”. Dont get fooled by the simplistic photography, just listen to the music and enjoy the serendipity of Kirsten’s voice and make you realize that behind big names in the metal sphere, you have talented bands that have so much potential and talent that worth the share. Enjoy!

[Pharmacology/Junk Sciences] About the FDA recall on Dr. Hyland’s homeopathic tooth relief….

You may have heard about the recent FDA recall for Dr. Hyland’s homeopathic teeth relief and any products similar to it as listed in their report below (http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm523468.htm).

There are 10 children deaths and 400 adverse events reported with the association of this homeopathic product. Homeopathy has always lauded itself as “natural, effective and harmless”. Even when it was faced with the lack of efficacy, proponents of homeopathy always use the “what’s the harm?” as a defense. Seems that not only it will not treat your ailment. Worse it can kill you. Why? Simple pharmacology.

A tenet of pharmacology is known since Paracelsus with his famous citation “Every substance is poison. No substance is no poison. The dose and only the dose makes a substance a poison”. Even the natural products are poison. You see, Mother Nature in all its grandeur has developed a certain affinity for developing some of the most toxic substances designed to kill living species. Because of evolutionary constraints, plants have been very good as being “chemical plants” and use chemical warfare as a method of invasion and defense.

Now, you can use this poison effect to treat certain conditions. If you find the right dose, you may treat a condition. This is how pharmacology works. Under a certain dose, there is no effect. We only start to see some biological activity after a certain dose. This is what we call the Minimum Efficacy Concentration (MEC). On the other hand, if you reach concentrations high enough, then you start to hit on off-targets and develop the minimum toxic concentration (MTC). This is where we start to see side effects and if the doses are high enough you will see adverse and toxic effects.

Homeopathy is by definition an unproven therapy because its principles defy common laws of physics and chemistry. Because it is relying on extreme dilutions to explain its activity, the amount of active substance is so low that it can be compared to dilute one single molecule into a swimming pool.

In this case, we don’t exactly know what compounds and what amount of each alkaloids are extracted. We know the total amount is 0.0000000000003% or 0.3 pico-grams per 100mL of solution or 100g tablets.

belladonna

That amount is simply ridiculously low. First, we have to assume that its PO administration will result in a 100% bioavailability (that is probably false and surely below). Second, you should be able to detect the compound in plasma samples. At that level (pg), the odds of detection are very low if not non-different from background. Therefore the odds of having this single molecule finds its target inside a body is almost zero (and the probability is something like 0.0000000000000000000000000000001%).

Yet, homeopathic treatment are all starting from raw extract (usually an hydro-alcoholic solution as extracting solvent) called “tintura matter”. Thats a concentrate and it contains indeed active substances in a high concentration. The nature and quantity of active substance in it are not known and not even reported since homeopathic products are not falling under the FDA supervision (you can thanks the DHSEA provision for that). Basically, no one (even the manufacturer) will tell exactly what and how much of active compounds are inside this tintura matter.

This raises a problem because Mother Nature has been excelling in producing poisons, what only matter is the dose. In the case of the teething relief product, the main culprit appears Atropa belladonna, a common poisonous plant that get easily confused with edible berries.  One of the classical substances purified from Atropa is atropine, an acetylcholine muscarinic receptor blocker. Because Atropa belladonna is known for its poisonous activity, we had some disaster in waiting that was cooking here. Anyone working with drugs will tell you how dangerous it is to overdose on an active substance.

Acetylcholine is an important neurotransmitter in mammalian cells, with peripheral (heart, muscles, lungs….) and central actions. Acetylcholine is a key target of organophosphates and sarin gas, as these agents block its degradation by acetylcholine esterases (this is why you have atropine administered as a side treatment for poisoning).

However, atropine can and will have severe side effects if ingested in a poisoning event (see this case report of accidental ingestion of Belladona: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361210/)

So whats exactly happened in this situation? We dont know and only now the FDA can provide clues. The FDA is toothless and cannot execute any order unless there are fatality cases involved. On their page, they are aware of the anticholinergic side effects of it but minimized the risk (that logically make sense since the amount is ridiculously low)

belladonna2

At this point, I speculate that something wrong likely happened with these homeopathic products. My speculation is something went wrong with the preparations, resulting in inconsistant extraction and effective concentrations in tintura matter. Because homeopathy are not ruled by FDA, they do not have to follow the stringent quality control and good manufacturing practices (GMP) imposed on pharmaceutical companies. So we have here a production that was on a free ride without any oversight on the QC. Now you can easily imagine that we may have ended up on with overdosed preparations.

Considering the special population (pediatrics), this risk of overdosing was even more amplified. One thing we consider when we develop a drug and prescribe a drug is the benefits/risk ratio. If the risk or adverse effects are too high, the drug cannot be used because it overcomes the benefits.

In that case, not only the benefits were quasi-null, we provided access to a product that was deemed “safe because natural” but indeed has a risk of adverse effect. Now we have likely some precedent in directly demonstrating the danger of poisoning with homeopathic products. This is already the case with essential oils (there are cases of children poisonings with Eos) and now we have the same with homeopathic products.

[Sciences/Stem Cells] Happy #StemCellDay

Happy #StemCellDay! This year has a special flavor as we also celebrate the 10th anniversary of the seminal work by Yanamaka study describing the derivation of mouse induced pluripotent stem cells (iPSCs) from somatic cells. As a treat, you are more than welcome to AMA about stem cells! Anything you want to know about stem cells. I will do my best to give the most accurate and objective answers.

[Manga] Saint Seiya Sanctuary 30th Anniversary

Today marks the 30th anniversary of the airing of Saint Seiya – Sanctuary from TOEI animation on Japanese TV Network based on the original manga by Masami Kurumada. It was aired in France sometimes in 1987 as “Les Chevaliers du Zodiaque” (translated as Knights of the Zodiac) and from there will spawn a huge success across Spain, Portugal and by ricocheting through Latin America.
What makes this anime so awesome? Maybe a mix of different things that I will discuss more about in debt.
First the synopsis of the series. The series take place sometimes in the present era, on the eve of the Galactic tournament gathering the best martial arts fighters from the whole world. Interestingly, most of these fighters came from the same orphanage under the patronage of Mitsumasa Kido. According to the legend, every 200 years the evil force try to conquer Earth only to be stopped by Athena and an army of valiant knights, these knights being numbered as 108, the number of constellations in the sky. In the present era, Saori Kido (the granddaughter of Mitsumasa Kido) is believed being the incarnation of Athena. The birth of Athena is not known but it appears the Grand Pope in Greece plot to assassinate her, only saved by Sagittarius Aiolos, a Gold Saint. Aiolos dies on the feet of Mitsumasa by giving her Saori and his Sagittarius cloth. Back in Japan, Kido adopt Saori as his granddaughter and set her to reign on the Graude Foundation, that is in charge of the orphanage. Interestingly enough, Saori has a relationship with many of these knights as she used to wander in the orphanage and bully some of these orphans.
As these kids raise the age of 5, Mitsumasa decide to send each of these kids around the world to train to become Bronze Saints and earn the bronze cloth. The Galactic Tournament brings back all these kids now young men to fight this tournament in order to earn the Sagittarius golden cloth. However, things are not going the way it should and will trigger a frenetic chain reaction that kept the audience blast for over 50 episodes.
What makes this series so great is perhaps the absence of a single hero by its own. Yes, there is the main protagonist, Seiya (that gave the name to the Japanese title) that under the training of Eagle Marine learn to unleash his cosmo energy, such cosmo being both an energetic and psychic force capable to inflict remote damage to its opponent. We got introduced to Seiya by the first episode as he is fighting for the Pegasus bronze cloth a giant named Cassios. As Seiya is crushed in by Cassios hands, Seiya finally unleash his cosmo and earn the Pegasus bronze armor. At the beginning, Seiya compete against his former friends until the heist of the Sagittarius armor by the Black Bronze Saints (the antithesis of the Bronze Saints) headed by Phenix Ikki (brother of Andromeda Shaun) will force them to join their force and becoming a strong team. This idea of brotherhood and friendship is the key element of Saint Seiya as they all face the challenges together in all different parts of the manga.
Maybe the differences in temper between the different characters. From the cold and distant Cygnus Hyoga (still under the trauma of his mother death, trapped by the frigid waters of Finland) to the antipathic brother Ikki contrasting with the fragile and sensible mood of Shaun. Because of these different moods and strengths of each of them, at least each child could refer to one of them.
Maybe it is the endurance and perseverance of the protagonists, ready to sacrifice their life for justice, facing each week opponents each time stronger than ever. First they defeat the Black Bronze knights, to only defeat some of the best Bronze Knights (in particular, the epic fight of Dragon Shiryu and Algol Perseus in which Shiryu blind himself to avoid petrification by Medusa shield. This was also an episode that created some controversy as Perseus did not hesitate to use his shield to transform children trying to escape into stones. Not only the team defeated all the Bronze Saints that gave their allegiance to the Grand Pope and declared Saori as heretic, they also face Silver Saints that have a more powerful armor and speed to finally face on Gold Saints represented by the twelve signs of the Zodiac.
Maybe it is also the particular atmosphere and discussion raised by some characters sexual orientation. There is a discrete but consistent homoerotism in the series that may have surely intrigued young men growing into their puberty. For instance, Shaun is harboring Andromeda Bronze cloth, an armor color dominated by pink. Shaun also has this effeminate traits giving this androgyne look (this was also resurgent with Lizard Misty  Silver Saint and APieces Aphrodites Gold Saint). There is also this particular scene that surely has shaken many boys watching it. In one episode, Hyoga is trapped into a block of ice by Aquarius Camus Gold Saint (his mentor in the manga, the mentor Crystal Saint, mentor of Hyoga in the TV version) to avoid his confrontation and ultimate death. As Hyoga is untapped from his ice coffin, Shaun decide to bring Hyoga back from hypothermia by laying naked on top of him to exchange heat. That was some bold scene for a young male to watch.
Maybe it is the music of Seiji Yokohama that brilliantly mixed classical soundtrack instrumentations with metal tones giving this winning formula. The opening sequence is simply majestic, giving the tone of the whole series. Using the main themes of Yokohama and giving to Make-Up (a J-Pop band that was strongly influenced by the rock, punk and metal scene), it literally blow your inner cosmo. Just by listening to the opening, you realize how terrible anime opening and ending credits have become in 30 years. Just by watching it, you feel like to watch the whole series. This was not exclusive to Saint Seiya as a lot of anime of that period aimed to Shonen (young boys) were having this rock and rebel feel

The ending sequence is as well refined, as well by Make-Up and named “Forever Blue”

After the end of Sanctuary, TOEI decided to branch out and followed a non-canon direction with the second part by creating “Asgard” taking the Bronze Saints into the Scandinavian frozen lands and exploring the Nordic mythology, whereas the third chapter came back to the canon with “Poseidon”, this time a confrontation of Poseidon (impersonated by Julian Solo) and his Marine Generals.

I followed up to Saint Seiya Hades and Elysion in which the Bronze Knights fights off the army of Hades and reaches the Elysion to fight over deities. I kind of lost interest when the latest chapter “The Lost Canvas” explore the previous Holy War that took place 200 years before the original.

The anime has probably aged badly but definitively worth to be watched if you ever have chance. I am pretty sure you can grab some Mexican copies under the name of “Caballero Del Zodiaco” and I strongly recommended the original Japanese with english subtitles (Spanish worked very well for me, as I could translate some words into French and get the sense).

[Symphonic Metal] Epica – The Holographic Principle (90%)

It has been now almost a week since Epica released their latest album “The Holographic Principle”. I purchased the iTunes version of it (try to shop from some decent metal music in Best Buy, since there are no more any record store in town) and it has been fairly playing in loop for a week now both when commuting and at work typing a grant or prepping some quizzes to my students.
Well after what I can say, is wow. Simply wow. There are some stuff that I did not really liked it (I will talk about it later) but overall this has been a while that Epica bluffed me with their new release. “Requiem for Indifferent” was okay, “The Quantum Enigma” was fair but not what I was waiting from Epica. Epica is for me synomym of loud, heavy, orchestral and boombastic with fast-paced drumbeat and crazy bass shred.
The album (at least its iTunes version) contains 12 titles and 5 “easy listening” cover of same songs in the album, with a twist in their name.
It starts with some instrumental and orchestral opening sequence, clearly setting the tone: this is gonna be an heavy and loud album. It is rapidly followed by “Edge of the Blade” that has already been online for a couple of months:

That’s some Epica but yet fairly similar to what we have been used these few years. But this is also a great primer to promote the album to a more mainstream audience.  This is followed by “A Phantasmic Parade” that slowly and surely tunes up more aggressive riffs and faster drums. The stuff start to become serious once you reach the third song. The third title of the album is “Universal Death Squad” and here things starts to get seriously heavy and bold, reminding some of the best tracks of “Design Your Universe” but in the same time familiar to “The Quantum Enigma”. Its loud, fast-paced and nicely well crafted. Just listen to it:

The next title is “Divide and Conquer” that seems kind of a continuation of the story told in “Deter the Tyrant” and “Serenade of Self-Destruction” that have been following the Libyan Revolution. Mark Jansen is excelling in his growls, the tune is very good and motivating. The summun is certainly hearing Nicolas Sarkozy claiming “Vive Benghazi! Vive la Libye!”. We flow in the same direction with “Beyond The Matrix”.
Then comes the seven track “Once Upon A Nightmare”, certainly the most beauticul track of the album. Very well produced and orchestrated track, giving this sense of epic song into it that it litteraly gives you tears in your eyes.
The eight track “The Cosmic Algorithm” is sounding some good old Epica and “Ascension – Dream State Armageddon” that explore certain aspect of Melodic and Technical Death Metal. “Dancing In A Hurricane” brings back this Middle-Eastern sound that reminds us that before Epica was named Epica it was named Sahara Dust. “Tears Down Your Walls” closes the first part of the album with what best Epica can do, with a style blending Death Metal and Symphonic, giving a sound I found very similar to what I would expect from a Kataklysm album.
Finally we close the first part with the symphonic metal suite “The Holograhic Principle” starting crescendo and in my opinion is the second best track. It is very well designed and produced that is my second favorite track of the album
The second part of the album is certainly the annoying part I found. Not because it is bad but it is because it is non-metal versions of some of the songs from the first part. Some are good, some are more like “easy listening” in the chord of what you would expect to hear in a Starbucks or any hipster place. For me, it sounds annoying and sure I would not mind if it was as part of an extra edition or a Deluxe edition. I felt it was more than a chainball than anything else.
In conclusion, although some aspects of the album bothered me, it is still the best metal album of September, therefore gaining my “Album of the Month” sticker. Epica, once again, proves that their motto is crafting their album with time and love, as Rembrandt did with his painting. Go get it!

[Symphonic/Progressive Metal] Seyminhol – The Duellist

Looking for some interesting progressive/symphonic male-fronted metal band to discover lately? You should give a try to Seyminhol (France). Their recent release of an official videoclip named “The Duellist”, based on Shakespeare’s Hamlet. It sounds very promising, bringing on familial tones that I liked with the early days of Kamelot with Roy Khan in the command. It is fast, well-produced and have this epic tones that give this medieval atmosphere to it. Give a try and listen to their title.

[Metal/Melodic Death] Arch Enemy – Black Earth 20th anniversary

Today marks the 20th anniversary of the release of Arch Enemy “Black Earth”, seeding what I consider of one of the most favorite melodic death metal, in particular by the powerful melodic riffs of Michael Amott. His talented skills on melodic riffs are in my opinion awesome and makes Arch Enemy different from the mainstream death metal bands.
As a freshman album, you always this feeling of the drafty and finding out his niche if you compare side-by-side the Arch Enemy style of 1997 and Arch Enemy of 2016. Retrospectively, you will need to wait until their third album “Anthems of Rebellion” and the position of Angela Gussow to obtain the trademark of Arch Enemy. Yet, this album is already rich with Michael melodic riffs that contrast with the heavy and brutal of the death metal. The album is made of 12 songs and it is some very good death metal tunes and stand as a 20 year album head high to many modern production. The vocals of Johan Liiva (ex-Carnage, in which he and Michael came from) are great and clearly understandable, a staple in our days in which many death metal bands front singers are all sounding the same.
More recently, Michael has mounted several pet projects including the progressive rock “Spiritual Beggars” and even reformed the original lineup that formed this album and named it simply “Black Earth”.
If you like powerful melodic guitar riffs and the hard banging of death metal, you should give a try to their first album, a milestone in Arch Enemy album.