[Neurosciences/Cancer] About Sen. McCain brain tumor……and glioblastoma multiforme

You may have heard the tragic news that broke hell under the feet of Senator McCain (R-AZ) and his family on Wednesday. According to several sources, Senator McCain biopsy taken from his recent medical examination revealed to be classified as “glioblastoma multiform” (or GBM) for short.
I am not a brain cancer specialist but I have been doing some collaboration with a research group focused on GBM and I know all too well what does it mean and what is the prognosis. This is a type of tumor I would not wish my fiercest archenemy to get. I thought it would maybe help me to make a lay summary on GBM and explain why the BBB in that case is one of our fiercest challenge for drug delivery.

1. What is glioblastoma multiforme?
Glioblastoma multiforme (aka GBM) is a primary brain tumor characterized by its heterogeneity. However, we assume that GBM is originating from tumor astrocytes. Astrocytes are an important cell type of the macroglia, outnumbering neurons from 3:1 to 5:1. For a long time, astrocytes were considered as “glue cells”, playing only a function of scaffold and nourishing cells to neurons.
However, in the last 50 years, astrocytes have been shown to play much more important roles including the induction of the blood-brain barrier phenotype, regulation of the cerebral blood flow, modulation of neuronal cell activity, ability to form a parallel signaling network and also to play an important function in terms of protection of the brain during diseases.
The World Health Organization (WHO) classify GBM as a grade IV brain tumor (https://link.springer.com/article/10.1007/s00401-016-1545-1), meaning this type of cancer is classify as highly aggressive. Because the brain is a very soft tissue, tumor cells can easily proliferate, migrate and invade the surrounding healthy tissues.
The cause of GBM remains unclear, however we know that some GBMs are evolved from other types of brain tumors that have a lesser malignancy like lower-grade astrocytomas (grade II) or anaplastic astrocytomas (grade III). GBM is considered the most common type of primary tumor (not caused by metastatic cells) but also remains pretty rare with a case of 2-3 new patients diagnosed with the condition for every 100’000 inhabitants. There is a possible sexual dimorphism, as men are more likely to be affected than women (3:2 ratio), with an increased risk with age (https://www.ncbi.nlm.nih.gov/pubmed/17373878).
There is no particular risk factor associated with GBM. So far, we assume it has a strong genetic background, as several genes have been associated with GBM including some abnormalities (including loss of DNA in a chromosome domain) on the chromosome 10, mutations in various genes including TP53 (tumor suppressor gene, its function is to repair cell DNA or to induce cell death by apoptosis if it fails to repair), MDM2 (pro-survival gene, its function is to promote cell survival), EFGR and PDGFRα (these are two receptors that induce cell growth, cell proliferation and cell survival upon stimulation by growth factors).
Also noteworthy, there has been speculation and a perpetuated myth that wireless cell phones activity are associated with an increased risk of developing brain tumors. There is no reliable studies (both on epidemiological standpoint and on animal models) that can show an association between the use of cell phones with increased risk of brain tumors.

2. What are the treatments and prognosis for patients with GBMs?

This is where I cannot have much optimism. GBM is a very aggressive type of cancer. The average survival rate is about 18 months, with less than 5% of patients making through the 5-year milestone.
Like any type of cancer, there are different options proposed: radiation therapy, surgery and chemotherapy.
Surgery is commonly practiced but have several challenges: Firstly, it is very hard to identify GBM tissue from the healthy tissue by naked eye during surgery. The neurosurgeon has to rely on the MRI cliches to resect the tumor tissue. Secondly, the neurosurgeon wants to maximize the removal of tumor tissue but also he/she wants to limit the damage to the surrounding healthy tissue to not induce further brain damage. Thirdly, GBM is prone to form glioblastoma stem cell-like cells (GSCs) that share several features with stem cells. These cells can tolerate very aggressive environment and can rapidly proliferate. This is one of the common complication occurring in GBM patients. After you remove the tumor and see no trace of it under the MRI, you conclude it got eliminated. Only to find out three months later that the tumor grew back in size and started to invade more brain tissues.
Chemotherapy arsenal for GBM is very limited. So far, temozolomide is the way to go for GBM. However, 50% of the patients will not respond to temozolomide due to a mutation in the MGMT gene capable to inactivate it (http://www.sciencedirect.com/science/article/pii/S2352304216300162). Other anti cancerous agents including EGFR inhibitors (e.g. lapatinib) fail to show any activity to the presence of a pathological form of the blood-brain barrier (BBB) called “brain-tumor barrier” (BTB). This abnormal form of the BBB involve interactions with brain tumor cells. For a long time, the scientific community thought that BBB surrounding brain tumors was leaky and therefore accessible to chemotherapeutics. However, we know that indeed there is a BTB that can act as a barrier for the penetration and delivery of drugs into the tumor region.

There are some new avenues and approaches to target GBM but they are still very experimental. Amongst them, the possibility to use oncolytic viruses like a modified form of the polio virus capable to set brain tumor cells into “auto-destruction” mode. The second avenue explored is possible use of immunotherapy. The rationale behind is to help the immune system “to learn” about the tumor cells as foreign agents and strike them. There are some success using antibodies targeting tumors and also by reprogramming patients own cells (CAR-T cell therapy).

The diagnosis of GBM is probably one of the most difficult one a neurologist or neurosurgeon has to set, as it has a very poor prognosis. Let’s be honest, it is not looking good and for someone like Senator McCain that has been facing death several times during his military duties this is probably the toughest one to overcome.

3. Concluding remarks

This is why we need to foster research in brain tumors, this is why we need funding to help research findings, this is why we need clinical trials to pick the most promising drug candidate to fight this type of cancer, this is why we need to have a public health policy that ensure healthcare coverage for everyone can have access to treatment to beat the odds and not have to decline treatment because of the huge costs associated that health insurance may simply refuse to share the burden.

I am so embarrassed to say that right now the only thing we can provide Senator McCain and anyone with GBM and their relatives are our sympathies and our wishful thinking. This is why I have colleagues, peers working days and nights, weekends to bring on a “silver bullet” capable to annihilate such condition.

If you are looking to help, the best I can advise is to support research by donating to association like ABTA (http://www.abta.org) that focuses on funding research on brain tumors. Also considerate to let your voice heard and support healthcare policies that ensure an universal coverage of the population regardless of their age, gender, socio-economic status. Because refusing treatment by fear of letting your most loved ones with a humongous amount of debt should be the last of your worry.

 

 

 

 

 

 

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[Movies/Horror] George A. Romero (1940-2017)

Today, one of the masters of horror left us alone. Indeed, horde of zombies and living dead are orphan tonight. George A. Romero left us today at the age of 77.

What can I tell about Romero? He is the father of the zombies as we know it. All the zombies (not the infected ones like 28 days later) have in my opinion to follow the Romero’s canon: originated from an infectious agent, resulting in their transformation into creature solely driven by their reptilian brain and nourishing from flesh-eating.

But beyond the living dead image, Romero was indeed a very talented filmmaker, because the zombies, the living dead, were indeed us, a mirror image reflecting on our society.
Romero’s genius resided in his ability to shock and awe the viewer, but only to ask them to think about the symbolism and the meaning. Through the tetrad of the “Living Dead” (Night/Dawn/Day and Land), Romero was behind his movies stinging us in the heart of the society.

“Night” was indirectly bringing on the table the case of Vietnam war veterans and the racism that was still alive and kicking 100 years after the Civil War and just a couple of years after the Civil Rights Movement. Romero shook the American audience by having Duane Jones, an African-American, as one main character. This was a very bold and progressive move from Romero, but also a very provocative one. Jones was the hero, he was the one that set a barricade, where the “white savior complex” got slashed through the entire movie. The white man is coward, hide from the danger and will kill any non-white on sight. Duane Jones performance was fantastic and at the end of the movie *SPOILER ALERT* survived the whole living dead siege only to be shot from distance by a sheriff *SPOILER ALERT*.

“Dawn” was set about 10 years later than “Night” and at another period, another criticism of our society. That time, a virulent prosecution of the consumer society. It starts with the siege within a TV station in which the channel director fulminates on how the usual programming grid is interrupted in a middle of a major chaos. When we end with “Night”, we have this false sense that the situation is under control, that it was just some isolated incident. “Dawn” shows the gravity of the situation. Big cities are in total chaos, SWAT teams with National Guards and some enthusiastic drunken gun-totting civilians try to keep the situation in order. We see the society crumbling before our eyes, with law and order of the civil society sinking into abyss. The only refuge of all this chaos is…..a shopping mall. A f***ing shopping mall with living dead wandering around, as a reflection of their past lives. Again, another African-American takes the lead impersonated by Ken Foree. Where all people of the survival group lost themselves into their delusion, Ken stood still and focused and again one of the only one to survive, with an open-ending that keeps us with a question unanswered: with an helicopter running out of fuel and the two last survivors flying over in the horizon, did they make it safe or did they just die?
The contribution of Dario Argento resulted in two major directors cut, with my favorite is of course the Argento cut.

“Day” is again set 10 years later and again Romero’s use to fingerpointing at his best. The US is now invaded by living dead, only small pockets of resistance are maintaining their survival. This group ironically found refuge in a former ICBM silo. This one goes heavily on the US military, with the absurdity of the military in pursuing insane research, just look at Bubba experiment, such absurdity culminates at the end of the movie and only those that kept their ethics straight.

“Land” was certainly one that was the most misunderstood. It got half-bombed in the box office but was indeed one of the most visionary version 20 years early. A divided US, between those surviving in junk towns and the only happy few (a clear illustration of what we call “The 1%”) living literary in their ivory tower in a delusional world, dreaming of their “Make America Great Again” promised by the ruling class on the pleb, with pleb dreaming that one day they will also belong to that 1%.

George A Romero also had other movies that encountered much a mitigated success but George also acquired the highly distinguished title of “Master of Horror” with his collaboration on “Creepshow” with Stephen King.

Tonight, one Master of Horror gave us his latest salute. May your soul rest in peace and let your filmography haunt us with your spirit 😦

[Neurosciences/BBB] 8th GLUT1 Deficiency Conference – Summary

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Today wrapped the second and last day of the 8th GLUT1 Deficiency conference that was held in Nashville, TN this year. It was my second time I am attending this conference and honored to be a guest speaker this year.

 

The whole conference took place at the Inn at Opryland, part of the Gaylord Resort at Opryland. It is a fairly impressive complex with shuttle to the Opry Mills outlet shopping center and, the Gaylord Resort & Convention Center (in which the AACP is also holding a meeting starting today but I am just attending one day meeting there).

According to the organizers, we had about 220 attendees, with 68 families present. What I liked this year was the blending between parents, healthcare providers and scientists. In the previous conference, the first day was family and healthcare providers and the second day was the professional day. This allowed a unique interactions, questions & answers and discussion.

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It was also a very good time for updating my knowledge on the disease. Not much on the basic science, but more on the current treatment and dietary intervention with various experts of the field including Pr. Jorg Klepper (University of Essen, Germany); Pr. Juan Pascual (UT Southwestern, Dallas, TX); Pr. Eric Kossoff (John Hopkins University, Baltimore, MD) and other scientific experts.
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My learning from the conference is that the disease in an evolutive disorder. We learn more about the disease as we learn from the patients growing in. As the patient grows, he or she displays different symptoms: “funny eyes movements” during infancy, presence of absence seizures during toddler times and learning attention and deficit during early school age, presence of movement disorders in both during childhood and adulthood and migraines, hemiplegia and “writers hand fatigue” syndrome. This seems to be linked by an impaired glucose uptake in the cerebral cortex and the thalamus.  It also seems that there is at some point in the disease the presence of a sexual dimorphism, as female patients seems to experience in their teenage years a “paroxysmal dystonia” that seems triggered by moderate and vigorous exercise. So, the GLUT1DS is not a static disorder. It is a disorder evolving over time with its clinical manifestations evolving as well.
The second thing I learned is the variety of “ketogenic diets”. There is not one single “keto diet” but several variants with different dosages and variety, including a Modified Atkins Diet.

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It seems there is not a “one size fits all” but rather different types of diets that also seems to vary with age.

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The younger age appears to need the following of a strict keto diet and as the patients age, some softening and flexibility can be introduced. It seems the critical time for the keto diet is infancy and childhood. The earlier the child is introduced, the better. There are also several companies providing cookbooks, supplements like keto powders or kets-friendly products aimed for patients.

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In terms of diagnosis, some interesting news came from a French biotech startup that can measure GLUT1 levels in RBC within 24 hours using a proprietary cell assay (that looks like an antibody assay) using a flow cytometry-based approach.
Another interesting result is the outcome of the ketogenic diet for GLUT1DS patients. For the vast majority of GLUT1DS patients (95% of patients), the keno diet significantly decrease the number of seizures by at least 50%. In contrast, other types of epilepsies combined only show a 50% of patients showing a responsive outcome to keto diet. Still, 5% of GLUT1DS do not respond to keto diet and there is a fraction of patients that show a normal glucose CSF levels and/or GLUT1 expression. We certainly have a lot of patients that undergo undiagnosed or misdiagnosed for years as “drug-refractory epilepsies”. But it seems that some patients maybe falsely diagnosed as GLUT1DS. Hopefully, with the decrease in price for DNA testing (it seems 23andMe can detect some GLUT1 SNPs) may help to broaden the diagnosis and identification of patients.
Some interesting topics presented at the conference was some possible drug adverse effects reported in G1D heterozygous mice in particular to diazepam and phenobarbital but also other drugs. Some parents noted the anecdotical adverse reactions following certain treatment. However, the absence of studies directly investigating such drug adverse effects in G1D patients most of the time go under the radar, with the health practitioner attributing it to the disease condition rather than some particular drug adverse effects. Having from screening tools can greatly help.
Another interesting presentation is the study of G1D heterozygous mice. These mice seems to display a lower brain vascular density compared to wild-type. This is not surprising considering the recent work of Pr. Peter Carmeliet (Universidaed Leuwen, Belgium) on endothelial cell metabolism. According to Pr. Carmeliet, brain endothelial cells highly depend on glycolysis to function despite being in presence of plenty amount of oxygen levels.
There have been also discussion of trying to setup a comprehensive guide for parents for a consensus on GLUT1DS diagnosis and management that can help them as a source for documentation during their visit with their doctors. There is also a discussion of improving the community outreach to professionals and politicians to improve the funding and the recognition of GLUT1DS as a condition, discussing about supporting open-access options for certain papers allowing parents a free-access to these new studies and also finding ways to support GLUT1DS awareness and management among minority populations and in other geographic areas (especially South America).
The person missing at this meeting by his presence was certainly Pr. Daryl DeVivo (Columbia University, New York, NY). Little patients left him some very kind words and their name on a paper board. I found it was a very cute gesture and remembered us that his absence was felt.
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The interesting silver lining comes from Europe, as they have set now a sister association that held their first European GLUT1 meeting last fall and plan to hold it in London in 2018 and in Paris in 2020.
For me, I am looking forward to attend the 2019 meeting in Washington DC and hopefully bring on some more breaking news from my lab there.

 

 

 

[Metal] Joyeuses fete du 14 Juillet, ma liste des groupes de metal Français

Since today is the French National Holiday, I wrote down the rest of this post in my native language…..that is French! Nom de Dieu!
A l’occasion de la fete de la prise de la Bastille, qui eu lieu en ce jour, j’en profite pour mettre en avant les groupes de metal français qui peuplent ma discotheque. Si vous ne trouvez point chaussure a votre taille, il y a certainement deux raisons: soit sous êtes passe en dehors de mon collimateur, soit ne j’ai point eu un effet boeuf.
Sans trainer plus, ma liste de groupes de metal français:
Adrana (Tours, France): du metal opera avec Anne derriere la voix mezzo-soprano. Du très bon calibre.
Alkemy (Genève, Suisse): un petit groupe metal sympathique venant de nos cousins Helvetes qui font pas mal de covers, avec Katia et Jess. A découvrir.
Alwaid (Lille, France): Les chti’mis connaissent leur metal et savent l’art du raffinement. Deux albums: deux styles de metal different (le premier était dans le genre atmosphérique, le deuxième bien plus power metal) mais la meme solution détonante.
Arcadia (Mulhouse, France): Une petite pousse de l’Alsace Bossue qui avait un EP assez sympa sorti l’automne dernier.
Asylum Pyre (Paris, France): Un tres bon groupe de prog/power metal de la region IDF. Surtout de plus que Oxy Heart a récemment joint le groupe.
Au Champ des Morts (Clermont-Ferrand, France): Une découverte Bandcamp de cette année avec leur premier album intitule “Dans La Joie”. Je suis pas un fan de black metal, mais il dire que ce groupe nous fourni un sacré “sweet crude” produit raffine, surtout que c’est un des quelques bandes qui chantent en Français (ca vaut le petit coup de pouce supplémentaire). A découvrir.
Azylya (Bruxelles, Belgique): Un sacre bon groupe de gothic metal venant de nos voisins belges, avec Jamie-Lee Smit au vocal.
Blazing War Machine (Marseilles, France): Si tu cherches un groupe de metal surfant dans le black melodic a la Dimmu Borgir/power metal avec une voix feminine en premiere line, voila un groupe a découvrir. Effet cathartique assure.
Bloody Melody (Tours, France): Un petit groupe de gothic metal, alternative qui avait un son bien sympa avec leur EP. Je me demande ce que mijote dans leur marmite? Ca va faire une peu plus de deux ans et pas trop entendu de nouvelles de leur part.
Dreamslave (Lyon, France): Du power metal a la Francaise, avec memes des pépites de pirate metal. A essayer.
Ethernity (Bruxelles, Belgique): Du prog metal en provenance de Belgique, un premier album vraiment sympa.
Erzebeth/ex-Darkonelly (Dijon, France): Marion a cloture son project Darkonelly et a decide de larguer les amarres vers d’autres horizons avec son nouveau projet “Erzebeth”. Si vous êtes dans l’ambience médiévales, elle tourne actuellement avec Tony tels des troubadours quelques festivaux pour animer de sa voix suave les longues nuit d’été. En parallèle, Marion a lance son projet solo sous le nom de Marion Lamita avec deux videos en ligne: https://www.youtube.com/watch?v=OAk0Zb9lkG4 et https://www.youtube.com/watch?v=gViPbhKuajI
FT-17 (Nantes, France):  Les suédois ont Sabaton, nous on a FT-17. De plus, feru de la “Der des Ders” que je suis, aux anges de la mort fut-ce. Decouvert lors de la récente campagne Bandcamp. Du très bon calibre, avec des interludes de lettres d’un poilu décrivant les quatre années de la premiere guerre mondiale.
Heonia (Lille, France): Un autre groupe des corons. Aggressif, bimodal. A essayer!
Inhepsie (Paris, France): Un autre groupe de gothic metal chantant dans la langue de Molière.
Lethian Dreams (Paris, France): La littérature française a contribue de manière importante a la vague “romantique” du XIXe siècle, qui naturellement servi de source pour le mouvement goth et bien entendu pour le doom metal. Lethian Dreams connait son doom metal et nous en démontre sa maitrise avec trois excellent albums.
Midnight Sorrow (Strasbourg, France): Yay, un groupe de metal Strasbourgeois, symphonique de plus. De quoi être un peu chauvin, surtout que leur premier album “Pick A Tale” sorti ce printemps était un très bon robuste premier album. A essayer de toute urgence!
Pray Manticore (Toulouse, France): Un groupe de death metal de la ville rose.
Pyrah (Strasbourg, France): Un autre groupe de Strasbourg, cette fois de prog metal.
Seyminhol (Metz, France): Un groupe de power metal, si vous aimez Kamelot et chercher un equivalent Français.
Veil of Mist (Reims, France): Un groupe de metal bien sympa, a découvrir.
Whyzdom (Paris, France): La creme de la creme du symphonic metal Francais. Avec Vynce Leff derriere l’instrumentation et Marie McLeod au vocal, on a un melange detonant de baroque, d’orchestration et de rugeur de metal.

 

 

 

 

 

[Metal/Arch Enemy] Leader (of the f***ing a**holes) sneak peek

Arch Enemy is teasing us today with a cover of The Shitlickers (a Swedish hardcore punk) “The Leader (Of the f***ing a**holes)” through the hands of Michael Amott and the growls of the Alissa White-Gluz. Michael already show us his broad range by playing melodic death with Carcass and with Arch Enemy and by playing some psychedelic rock/stoner with his side project The Spiritual Beggars. Now we can add into the list some hardcore punk. I personally found the cover version much more elaborated, cleaner and more aggressive than the original. Just judge by yourself. The rage and the fury!

The cover:

The original:

[Music/Metal] Iron Maiden Book @ Isleta Amphitheater (Albuquerque, NM – 06/27/2017)

I know, you may wonder why write down about a live concert two weeks after attending it? Well, sorry not sorry. A lots of writing have been thrown on my face: one paper in revision sent back to a journal, another paper submitted to another journal, a grant writing and some experiments. So, finally I was able to catch some breath and bring some of my feedback on the biggest concert I have even attended.Long time Iron Maiden fan (since I was a teenager in the early 90s), don’t ask me why and how it took me so long to attend one of their concert.
When I saw Iron Maiden came in Albuquerque, NM that was a big game changer. First, it was a drivable distance from where I live. I either have Albuquerque or Oklahoma City (4 hours each either West or East) or drive all the way to Dallas (5.5 hours). Second, I don’t know about other concert places, but tickets to attend the Iron Maiden concert was also more affordable than attending Metallica (that was negotiating about $100+ for a decent seat). One thing I have omitted that I got scooped on was the VIP parking. It cost you a $20 extra but honestly I think it worth the investment (I will explain later).
So here I was, quickly taking the road after work toward New Mexico. The good thing about entering the state is switching to Mountain Time, saving me one hour. The venue was at the Isleta Amphitheater, just near the airport. It is nicely located out of town to avoid the nuisance, but also well designed for a concert event. The thing I was not anticipating was the queue. A damn long queue, bumpers to bumpers.

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A good 2-miles at slow speed, with sellers selling you some bootleg tees along the road. Later on, Bruce announced we were about 15’000 fans up to the Hill to attend that event. Nice! But it was also a nice opportunity to enjoy the desert landscape of New Mexico. Albuquerque gives you the desert and the mountain skyline to enjoy. Neat!

 

Arrived at the parking spot, it took me another 30-40 minutes to finally reach the stage. I basically missed the whole Ghost performance but was not a big loss. I already saw them las October as the main act and second the recent turmoil with Tobias Forge and his former bandmates put me a bit into cold feet.
Of course, the ritual was at the march booth to grab an official Iron Maiden tee and find my place. I can tell, the Isleta venue is very well organized place, well designed. The only caveat? The parking! A good 20 minutes walk in, 20 minutes walk out. You don’t want to get stuck in traffic on the return thus you have to leave the event early. This is why I think investing $20 for the VIP parking worth its weight of pesos.
Iron Maiden like their stage and you can feel it by the details they put in the decoration.

The A/V was good, so even with a fairly-priced ticket you could enjoy the show. Sure the pit has its added value, but such as its price ticket. Bruce definitely knows how to pull the show. It was great! Bruce knows how to nurture the fans and likes it! I have captured some videos on my Phone (note to myself: invest in a iPhone with a bigger capacity next time!)

The only piece of criticism (that other people also mentioned) is that Iron Maiden played a good half of the show titles from the current album. Its an okay album but you know there are way much better songs in Maiden repertoire. There were some oldies played (Children of The Damned, Powerslave…..) and the classic “awesome” ones (Fear of The Dark, Iron Maiden, Number of the Beast…..) but you know feel a bit hunger. Bruce clearly stated once he is against playing classics in concert, leaving it to tribute bands. The complete setlist can be found here:

http://www.setlist.fm/setlist/iron-maiden/2017/isleta-amphitheatre-albuquerque-nm-13e4ddf9.html

I left by the beginning of the encore, in order to save being stuck in traffic but also I was exhausted from a long day. It was amazing to see how Iron Maiden transcend generations (like a Dad came with his teenage son and his 3-4 years old son. Seeing the little one brandishing his horns was cute!). I was amazed by the Latin-American fanbase that came in force, I don’t see that much Latin-American in my local gigs but I guess Mexican fans came in force and Latin folks know their metal very well.

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If you have a chance to attend an Iron Maiden concert in town, go on. Their metal is very accessible and it is impressive to see 40 years later the band has still the vigor and the charm live, reminding me why I loved Iron Maiden at the first place.

 

 

[Music/Metal] Happy 4th of July!

As living in the US, it is for me now part of the tradition to celebrate the 4th of July. Happy 4th of July! Time for me to share my favorite US metal bands that are in my disc library. This is my very personal list, so please don’t comment asking why I have not have a certain band in my list. There are likely two reasons: either they went under my radar or they simply did not click with me in terms of my musical taste. I have been running this redundant post for two years now, so I will spare you the blabla and let you jump to the list :). Here we go, sorted by alphabetical list:
* Aria Flame (ex-Dendura, MI) – Gothic Metal: https://www.facebook.com/ariaflameworld/
* Beyond Forgiveness (CO) – Gothic/Folk Metal. If you are looking for a US minstrels and troubadours having the vibes of medieval folk metal (something like a Blind Guardian or Haggard), this is your inn to stop on your journey: https://www.facebook.com/beyondforgivenessmetal/
* Destiny Beard (MI, PA) – Gothic Metal:https://www.facebook.com/Destinibeardmusic/
* The Ditch & The Delta (UT) – Sludge Metal: https://www.facebook.com/theditchandthedeltaslc/
* Evanescence (AR) – Gothic Rock: https://www.facebook.com/Evanescence/
* Exalt The Throne (TX) – Melodic Death, they are having their final gig on July 29th, I gonna miss them :(. https://www.facebook.com/exaltthethroneofficial/
* Faytree (GA, OH) – Melodic Death: https://www.facebook.com/faytreeband/
* In This Moment (CA) – Metalcore. Check their old stuff (first three albums), that was some promising band that unfortunately lost their vibe for few years now: https://www.facebook.com/officialinthismoment/
* Kamelot (FL) – Power Melodic Metal. Come on, should I introduce Kamelot? https://www.facebook.com/kamelotofficial/
* Mercy Isle (MI) – Gothic Metal. A very interesting US-Dutch collaboration, making them a sort of spinning free electron: https://www.facebook.com/MercyIsle/
* Metallica (CA) – Thrash Metal. Because who does not have a Metallica album in their disc library. 35 years and still running! https://www.facebook.com/Metallica/
* Midnight Eternal (NY) – Power Melodic Metal. What if Dragonforce and Nightwish had a child? Midnight Eternal would be its name: https://www.facebook.com/MidnightEternal/
* Red Beard Wall (TX) Sludge Metal. Ever wondered how doom metal would sound with a flavor of Southern music, with elements of punk and death metal? It has a name: sludge metal and my first exposure was through Red Beard Wall. It came out of nowhere like a meteor and crashed into the local metal scene in Yellow City. If you are living in the High Plains or South Plains, check them out: https://www.facebook.com/redbeardwall/
* Rozamov (MA) Sludge/Doom Metal. That was some of the best surprise this spring, allowing me to discover this sub-genre of doom metal blended with Southern tunes, punk and death metal. https://www.facebook.com/Rozamov/
* Santa Marta (UT) – Gothic Metal. The next project of Mary Zimmer (ex-Ottoman Empire/Luna Mortis, ex-The White Empress). Check it out and keep eye on it. https://www.facebook.com/SantaMartaBand/
* Scarlet Canary (CO) – Metal/Rock: https://www.facebook.com/ScarletCanary/
* Seven Kingdoms (FL) – Melodic Power Metal. There is something running in Florida water but it makes their Melodic Power Metal
* Slayer (CA) – Thrash Metal. Slayer still slaying, not even an ounce of their brutal tempo was left over the years. This is where I had to disagree on Floor Jansen, nothing beats a mosh pit or an album from Slayer as a catharsis vector. If you don’t know what to expect from Slayer, go attend one of their gigs with Lamb of God and Behemoth. Not for the choir singer though: https://www.facebook.com/slayer/
* Thyshade (CO) – Symphonic Metal. One of my discovery last winter and one of the best US soprano vocals: https://www.facebook.com/thyshadeofficial/