Arnica and a scientist’s frustrations

angry-1372523 - CopyWhen you’re the only scientist in the family you get asked the weirdest things. Actually, I’m not the only one, but the other one is a chemist and he’s mostly asked about astrophysics stuff, so he doesn’t really count, because I am the one who gets asked about rare diseases and medication side-effects and food advice. Never mind that I am a neuroscientist and I have professed repeatedly and quite loudly my minimum knowledge of everything from the neck down, all eyes turn to me when the new arthritis medication or the unexpected side-effects of that heart drug are being brought up. But, curiously, if I dare speak about brain stuff I get the looks that a thing the cat just dragged in gets. I guess everybody is an expert on how the brain works on account of having and using one, apparently. Everybody, but the actual neuroscience expert whose input on brain and behavior is to be tolerated and taken with a grain of salt at best, but whose opinion on stomach distress is of the utmost importance and must be listened to reverentially in utter silence [eyes roll].

So this is the background on which the following question was sprung on me: “Is arnica good for eczema?”. As always, being caught unawares by the sheer diversity of interests and afflictions my family and friends can have, I mumbled something about I don’t know what arnica is and said I will look it up.

This is an account of how I looked it up and what conclusions I arrived to or how a scientists tries to figure something out completely out of his or her field. First thing I did was to go on Wikipedia. Hold your horses, it was not about scientific information but for a first clarification step: is it a chemical, a drug, an insect, a plant maybe? I used to encourage my students to also use Wikipedia when they don’t have a clue what a word/concept/thing is. Kind of like a dictionary or a paper encyclopedia, if you will. To have a starting point. As a matter of fact Wikipedia is an online encyclopedia, right? Anyway, I found out that Arnica is a plant genus out of which one species, Arnica Montana seems to be popular.

Then I went to the library. Luckily for me, the library can be accessed online from the comfort of my home and my favorite pajamas in the incarnation of PubMed or Medline as it used to be affectionately called. It is the US National Library of Medicine maintained by the National Institutes of Health, a wonderful repository of scholarly papers (yeah, Google Scholar to PubMed is like the babbling of a two-year old to the Shakespearian sonnets; Google also has an agenda, which you won’t find on PubMed). Useful tip: when you look for a paper that is behind a paywall in Nature or Elsevier Journals or elsewhere, check the PubMed too because very few people seem to know that there is an obscure and incredibly helpful law saying that research paid by the US taxpayers should be available to the US taxpayer. A very sensible law passed only a few years ago that has the delightful effect of having FREE full text access to papers after a certain amount of months from publishing (look for the PMC icon in the upper right corner).

I searched for “arnica” and got almost 400 results. I sorted by “most recent”. The third hit was a review. I skimmed it and seemed to talk a lot about healing in homeopathy, at which point, naturally, I got a gloomy foreboding. But I persevered because one data point does not a trend make. Meaning that you need more than a paper – or a handful – to form an informed opinion. This line of thinking has been rewarded by the hit No. 14 in the search which had an interesting title in the sense that it was the first to hint to a mechanism through which this plant was having some effects. Mechanisms are important, they allow you to differentiate speculation from findings, so I always prefer papers that try to answer a “How?” question as opposed to the other kinds; whys are almost always speculative as they have a whiff of post factum rationalizations, whats are curious observations but, more often than not, a myriad factors can account for them, whens are an interesting hybrid between the whats and the hows – all interesting reads but for different purposes. You want to publish in Nature or Science? Design an experiment that answers all the questions. Gone are the days when answering one question was enough to publish…

Digressions aside, the paper I am covering today sounds like a mechanism paper. Marzotto et al. (2016) cultured a particular line of human cells in a Petri dish destined to test the healing powers of Arnica montana. The experimental design seems simple enough: the control culture gets nothing and the experimental culture gets Arnica montana. Then, the authors check to see if there are differences in gene expressions between the two groups.

The authors applied different doses of Arnica montana to the cultures to see if the effects are dose-dependant. The doses used were… wait, bear with me, I’m not familiar with the system, it’s not metric. In the Methods, the authors say

Arnica m. was produced by Boiron Laboratoires (Lyon, France) according to the French Homeopathic pharmacopoeia and provided as a first centesimal dilution (Arnica m. 1c) of the hydroalcoholic extract (Mother Tincture, MT) in 30% ethanol/distilled water”.

Wait, what?! Centesimal… centesimal… wasn’t that the nothing-in-it scale from the pseudoscientific bull called homeopathy? Maybe I’m wrong, maybe there are some other uses for it and becomes clear later:

Arnica m. 1c was used to prepare the second centesimal dilution (Arnica m. 2c) by adding 50μl of 1c solution to 4.95ml of distilled ultra-pure water. Therefore, 2c corresponds to 10−4 of the MT”.

Holy Mother of God, this is worse than gibberish; this is voluntary misdirection, crap wrapped up in glitter, medieval tinkering sold as state-of-the-art 21st century science. Speaking of state-of-the-art, the authors submit their “doses” to a liquid chromatograph, a thin layer chromatograph, a double-beam spectrophotometer, a nanoparticle tracking analysis (?!) for what purposes I cannot fathom. On, no, I can: to sound science-y. To give credibility for the incredulous. To make money.

At which point I stopped reading the ridiculous nonsense and took a closer look at the authors and got hit with this:

“Competing Interests: The authors have declared that no competing interests exist. This study was funded by Boiron Laboratoires Lyon with a research agreement in partnership with University of Verona. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.”

No competing interests?? The biggest manufacturer of homeopathic crap in the world pays you to see if their product works and you have no competing interest? Maybe no other competing interests. There were some comments and replies to this paper after that, but it is all inconsequential because once you have faulty methods your results are irrelevant. Besides, the comments are from the same University, could be some internal feuding.

PLoS One, what have you done? You’re a peer-reviewed open access journal! What “peers” reviewed this paper and gave their ok for publication? Since when is homeopathy science?! What am I going to find that you publish next? Astrology? For shame… Give me that editor’s job because I am certain I can do better.

To wrap it up and tell you why I am so mad. The homeopathic scale system, that centesimal gibberish, is just that: gibberish. It is impossible to replicate this experiment without the product marketed by Boiron because nobody knows how much of the plant is in the dose, which parts of the plant, what kind of extract, or what concentration. So it’s like me handing you my special potion and telling you it makes warts disappear because it has parsley in it. But I don’t tell you my recipe, how much, if there anything else besides parsley in it, if I used the roots or only the leaves or anything. Now that, my friends, it’s not science, because science is REPLICABLE. Make no mistake: homeopathy is not science. Just like the rest of alternative medicine, homeopathy is a ruthless and dangerous business that is in sore need of lawmakers’ attention, like FDA or USDA. And for those who think this is a small paper, totally harmless, no impact, let me tell you that this paper had over 20,000 views.

I would have oh so much more to rant on. But enough. Rant over.

Oh, not yet. Lastly, I checked a few other papers about arnica and my answer to the eczema question is: “It’s possible but no, I don’t think so. I don’t know really, I couldn’t find any serious study about it and I gave up looking after I found a lot of homeopathic red flags”. The answer I will give my family member? “Not the product you have, no. Go to the doctors, the ones with MDs after their name and do what they tell you. In addition, I, the one with a PhD after my name, will tell you this for free because you’re family: rub the contents of this bottle only once a day – no more! – on the affected area and you will start seeing improvements in three days. Do not use elsewhere, it’s quite potent!” Because placebo works and at least my water vial is poison free.

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Reference: Marzotto M, Bonafini C, Olioso D, Baruzzi A, Bettinetti L, Di Leva F, Galbiati E, & Bellavite P (10 Nov 2016). Arnica montana Stimulates Extracellular Matrix Gene Expression in a Macrophage Cell Line Differentiated to Wound-Healing Phenotype. PLoS One, 11(11):e0166340. PMID: 27832158, PMCID: PMC5104438, DOI: 10.1371/journal.pone.0166340. ABSTRACT | FREE FULLTEXT PDF 

By Neuronicus, 10 June 2017

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100% Effective Vaccine

A few days ago I was reading random stuff on the internet, as is one’s procrastination proclivity, catching up after the holiday, and I exclaimed out loud: “They discovered an 100% effective Ebola Vaccine!”. I expected some ‘yeay’-s or at least some grunts along the lines of ‘that’s nice’ or ‘cool’. Naturally, I turned around from my computer to check the source of unaccustomed silence to the announcement of such good news or, at least, to make sure that everybody is still breathing and present in the room. What met my worried glare was a gloom face and a shaking head. That’s because news like that are misleading, because, duh, it finally dawned on me, there is no such thing as ‘100% effective vaccine’.

And yet…, and yet this is exactly what Henao-Restrepo et al. (2016) say they found! The study is huge, employing more that 10 000 people. Such a tremendous endeavor has been financed by WHO (World Health Organization) and various departments from several countries (UK, USA, Switzerland, South Africa, Belgium, Germany, France, Guinea, and Norway) and, I’m assuming, a lot of paid and unpaid volunteers. I cannot even imagine the amount of work and the number of people that made this happen. And the coordination required for such speedy results!

The successful vaccine in rodents and non-human primates, called the recombinant, replication-competent, vesicular stomatitis virus-based vaccine expressing the glycoprotein of a Zaire Ebolavirus (rVSV-ZEBOV) has been taken to the Republic of Guinea and rapidly administered to volunteers who were in contact with somebody that had Ebola symptoms. And their contacts. I mean the contacts and the contacts of contacts of the Ebola patient. Who were contacted by the researchers within 2 days of a new Ebola case based on the patient’s list of contacts. And of contacts of contacts. Is not that complicated, honest.

After vaccinations, the “vaccinees were observed for 30 min post-vaccination and at home visits on days 3, 14, 21, 42, 63, and 84” (p.4). Some volunteers received the vaccine immediately, others after 3 weeks. No one who received the vaccine immediately developed Ebola, which lead the researchers to claim that the vaccine is 100% effective. Only 9 from the delayed vaccination group developed Ebola within 10 days of vaccination, but the researchers figured that these people probably contacted Ebola prior to the vaccination, since the disease requires typically about 10 days to show its ugly  horns.

So this is great news. Absolutely great. Even if, as always, I could nitpick thorough the paper, squabble over the “typically” 10-day incubation period, and cock an eyebrow at the new-fangled ring vaccination design as opposed to the old-fashioned placebo approach. Even after these minor criticisms this is – I repeat – GREAT NEWS!

P.S. Don’t ever say that the UN didn’t do anything for you.

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Reference: Henao-Restrepo AM, Camacho A, Longini IM, Watson CH, Edmunds WJ, Egger M, Carroll MW, Dean NE, Diatta I, Doumbia M, Draguez B, Duraffour S, Enwere G, Grais R, Gunther S, Gsell PS, Hossmann S, Watle SV, Kondé MK, Kéïta S, Kone S, Kuisma E, Levine MM, Mandal S, Mauget T, Norheim G, Riveros X, Soumah A, Trelle S, Vicari AS, Røttingen JA, Kieny MP. (22 Dec 2016). Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!). Lancet. pii: S0140-6736(16)32621-6. doi: 10.1016/S0140-6736(16)32621-6. PMID: 28017403 [Epub ahead of print] ARTICLE | FREE FULLTEXT PDF | Good Nitpicking in The Conversation

By Neuronicus, 18 January 2017

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Don’t eat snow

Whoever didn’t roll out a tongue to catch a few snowflakes? Probably only those who never encountered snow.

The bad news is that snow, particularly urban snow is bad, really bad for you. The good news is that this was not always the case. So there is hope that in the far future it will be pristine again.

Nazarenko et al. (2016) constructed a very clever contraption that reminds me of NASA space exploration instruments. The authors refer to this by the humble name of ‘environmental chamber’, but is in fact a complex construction with different modules designed to measure out how car exhaust and snow interact (see Fig. 1).

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Fig. 1 from Nazarenko et al. (2016, DOI: 10.1039/c5em00616c). Released under CC BY-NC 3.0.

After many experiments, researchers concluded that snow absorbs pollutants very effectively. Among the many kinds of organic compounds soaked by snow in just one hour after exposure to fume exhaust, there were the infamous BTEX (benzene, toluene, ethylbenzene, and xylenes). The amounts of these chemicals in the snow were not at all negligible; to give you an example, the BTEX concentration increased from virtually 0 to 50 and up to 380 ug kg-1. The authors provide detailed measurements for all the 40+ compounds they have identified.

Needles to say, many these compounds are known carcinogenics. Snow absorbs them, alters their size distributions, and then it melts… Some of them may be released back in the air as they are volatile, some will go in the ground and rivers as polluted water. After this gloomy reality check, I’ll leave you with the words of the researchers:

“The accumulation and transfer of pollutants from exhaust – to snow – to meltwater need to be considered by regulators and policy makers as an important area of focus for mitigation with the aim to protect public health and the environment” (p. 197).

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Reference: Nazarenko Y, Kurien U, Nepotchatykh O, Rangel-Alvarado RB, & Ariya PA. (Feb 2016). Role of snow and cold environment in the fate and effects of nanoparticles and select organic pollutants from gasoline engine exhaust. Environmental Science: Processes & Impacts, 18(2):190-199. doi: 10.1039/c5em00616c. ARTICLE | FREE FULTEXT PDF 

By Neuronicus, 26 December 2016

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Soccer and brain jiggling

There is no news or surprise that strong hits to the head produce transient or permanent brain damage. But how about mild hits produced by light objects like, say, a volley ball or soccer ball?

During a game of soccer, a player is allowed to touch the ball with any part of his/her body minus the hands. Therefore, hitting the ball with the head, a.k.a. soccer heading, is a legal move and goals marked through such a move are thought to be most spectacular by the refined connoisseur.

A year back, in 2015, the United States Soccer Federation forbade the heading of the ball by children 10 years old and younger after a class-action lawsuit against them. There has been some data that soccer players display loss of brain matter that is associated with cognitive impairment, but such studies were correlational in nature.

Now, Di Virgilio et al. (2016) conducted a study designed to explore the consequences of soccer heading in more detail. They recruited 19 young amateur soccer players, mostly male, who were instructed to perform 20 rotational headings as if responding to corner kicks in a game. The ball was delivered by a machine at a speed of approximately 38 kph. The mean force of impact for the group was 13.1 ± 1.9 g. Immediately after the heading session and at 24 h, 48 h and 2 weeks post-heading, the authors performed a series of tests, among which are a transcranial magnetic stimulation (TMS) recording, a cognitive function assessment (by using the Cambridge Neuropsychological Test Automated Battery), and a postural control test.

Not being a TMS expert myself, I was wondering how do you record with a stimulator? TMS stimulates, it doesn’t measure anything. Or so I thought. The authors delivered brief  (1 ms) stimulating impulses to the brain area that controls the leg (primary motor cortex). Then they placed an electrode over the said muscle (rectus femoris or quadriceps femoris) and recorded how the muscle responded. Pretty neat. Moreover, the authors believe that they can make inferences about levels of inhibitory chemicals in the brain from the way the muscle responds. Namely, if the muscle is sluggish in responding to stimulation, then the brain released an inhibitory chemical, like GABA (gamma-amino butyric acid), hence calling this process corticomotor inhibition. Personally, I find this GABA inference a bit of a leap of faith, but, like I said, I am not fully versed in TMS studies so it may be well documented. Whether or not GABA is responsible for the muscle sluggishness, one thing is well documented though: this sluggishness is the most consistent finding in concussions.

The subjects had impaired short term and long term memory functions immediately after the ball heading, but not 24 h or more later. Also transient was the corticomotor inhibition. In other words, soccer ball heading results in measurable changes in brain function. Changes for the worst.

Even if these changes are transient, there is no knowing (as of yet) what prolonged ball heading might do. There is ample evidence that successive concussions have devastating effects on the brain. Granted, soccer heading does not produce concussions, at least in this paper’s setting, but I cannot think that even sub-concussion intensity brain disruption can be good for you.

On a lighter note, although the title of the paper features the word “soccer”, the rest o the paper refers to the game as “football”. I’ll let you guess the authors’ nationality or at least the continent of provenance ;).

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Reference: Di Virgilio TG, Hunter A, Wilson L, Stewart W, Goodall S, Howatson G, Donaldson DI, & Ietswaart M. (Nov 2016, Epub 23 Oct 2016). Evidence for Acute Electrophysiological and Cognitive Changes Following Routine Soccer Heading. EBioMedicine, 13:66-71. PMID: 27789273, DOI: 10.1016/j.ebiom.2016.10.029. ARTICLE | FREE FULLTEXT PDF

By Neuronicus, 20 December 2016

Scientists don’t know the risks & benefits of science

If you want to find out how bleach works or what keeps the airplanes in the air or why is the rainbow the same sequence of colors or if it’s dangerous to let your kid play with snails would you ask a scientist or your local priest?

The answer is very straightforward for most of the people. Just that for a portion of the people the straightforwardness is viewed by the other portion as corkscrewedness. Or rather just plain dumb.

Cacciatore et al. (2016) asked about 5 years ago 2806 American adults how much they trust the information provided by religious organizations, university scientists, industry scientists, and science/technology museums. They also asked them about their age, gender, race, socioeconomic status, income as well as about Facebook use, religiosity, ideology, and attention to science-y content.

Almost 40% of the sample described themselves as Evangelical Christians, one of the largest religious group in USA. These people said they trust more their religious organizations then scientists (regardless of who employs these scientists) to tell the truth about the risks and benefits of technologies and their applications.

The data yielded more information, like the fact that younger, richer, liberal, and white people tended to trust scientists more then their counterparts. Finally, Republicans were more likely to report a religious affiliation than Democrats.

I would have thought that everybody would prefer to take advice about science from a scientist. Wow, what am I saying, I just realized what I typed… Of course people are taking health advice from homeopaths all the time, from politicians rather than environment scientists, from alternative medicine quacks than from doctors, from no-college educated than geneticists. From this perspective then, the results of this study are not surprising, just very very sad… I just didn’t think that the gullible people can also be grouped by political affiliations. I though the affliction is attacking both sides of an ideological isle in a democratic manner.

Of course, this is a survey study, therefore a lot more work is needed to properly generalize these results, from expanding the survey sections (beyond the meager 1 or 2 questions per section) to validation and replication. Possibly, even addressing different aspects of science because, for instance, climate change is a much more touchy subject than, say, apoptosis. And replace or get rid of the “Scientists know best what is good for the public” item; seriously, I don’t know any scientist, including me, who would answer yes to that question. Nevertheless, the trend is, like I said, sad.

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Reference:  Cacciatore MA, Browning N, Scheufele DA, Brossard D, Xenos MA, & Corley EA. (Epub ahead of print 25 Jul 2016). Opposing ends of the spectrum: Exploring trust in scientific and religious authorities. Public Understanding of Science. PMID: 27458117, DOI: 10.1177/0963662516661090. ARTICLE | NPR cover

By Neuronicus, 7 December 2016

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Amusia and stroke

Although a complete musical anti-talent myself, that doesn’t prohibit me from fully enjoying the works of the masters in the art. When my family is out of earshot, I even bellow – because it cannot be called music – from the top of my lungs alongside the most famous tenors ever recorded. A couple of days ago I loaded one of my most eclectic playlists. While remembering my younger days as an Iron Maiden concert goer (I never said I listen only to classical music :D) and screaming the “Fear of the Dark” chorus, I wondered what’s new on the front of music processing in the brain.

And I found an interesting recent paper about amusia. Amusia is, as those of you with ancient Greek proclivities might have surmised, a deficit in the perception of music, mainly the pitch but sometimes rhythm and other aspects of music. A small percentage of the population is born with it, but a whooping 35 to 69% of stroke survivors exhibit the disorder.

So Sihvonen et al. (2016) decided to take a closer look at this phenomenon with the help of 77 stroke patients. These patients had an MRI scan within the first 3 weeks following stroke and another one 6 months poststroke. They also completed a behavioral test for amusia within the first 3 weeks following stroke and again 3 months later. For reasons undisclosed, and thus raising my eyebrows, the behavioral assessment was not performed at 6 months poststroke, nor an MRI at the 3 months follow-up. It would be nice to have had behavioral assessment with brain images at the same time because a lot can happen in weeks, let alone months after a stroke.

Nevertheless, the authors used a novel way to look at the brain pictures, called voxel-based lesion-symptom mapping (VLSM). Well, is not really novel, it’s been around for 15 years or so. Basically, to ascertain the function of a brain region, researchers either get people with a specific brain lesion and then look for a behavioral deficit or get a symptom and then they look for a brain lesion. Both approaches have distinct advantages but also disadvantages (see Bates et al., 2003). To overcome the disadvantages of these methods, enter the scene VLSM, which is a mathematical/statistical gimmick that allows you to explore the relationship between brain and function without forming preconceived ideas, i.e. without forcing dichotomous categories. They also looked at voxel-based morphometry (VBM), which a fancy way of saying they looked to see if the grey and white matter differ over time in the brains of their subjects.

After much analyses, Sihvonen et al. (2016) conclude that the damage to the right hemisphere is more likely conducive to amusia, as opposed to aphasia which is due mainly to damage to the left hemisphere. More specifically,

“damage to the right temporal areas, insula, and putamen forms the crucial neural substrate for acquired amusia after stroke. Persistent amusia is associated with further [grey matter] atrophy in the right superior temporal gyrus (STG) and middle temporal gyrus (MTG), locating more anteriorly for rhythm amusia and more posteriorly for pitch amusia.”

The more we know, the better chances we have to improve treatments for people.

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unless you’re left-handed, then things are reversed.

References:

1. Sihvonen AJ, Ripollés P, Leo V, Rodríguez-Fornells A, Soinila S, & Särkämö T. (24 Aug 2016). Neural Basis of Acquired Amusia and Its Recovery after Stroke. Journal of Neuroscience, 36(34):8872-8881. PMID: 27559169, DOI: 10.1523/JNEUROSCI.0709-16.2016. ARTICLE  | FULLTEXT PDF

2.Bates E, Wilson SM, Saygin AP, Dick F, Sereno MI, Knight RT, & Dronkers NF (May 2003). Voxel-based lesion-symptom mapping. Nature Neuroscience, 6(5):448-50. PMID: 12704393, DOI: 10.1038/nn1050. ARTICLE

By Neuronicus, 9 November 2016

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The FIRSTS: The Name of Myelin (1854)

One reason why I don’t post more often is that I have such a hard time deciding what to cover (Hint: send me stuff YOU find awesome). Most of the cool and new stuff is already covered by big platforms with full-time employees and I try to stay away of the media-grabbers. Mostly. Some papers I find so cool that it doesn’t matter that professional science journalists have already covered them and I too jump on the wagon with my meager contribution. Anyway, here is a glimpse on how my train of thought goes on inspiration-less days.

Inner monologue: Check the usual journals’ current issues. Nothing catches my eye. Maybe I’ll feature a historical. Open Wikipedia front page and see what happened today throughout history. Aha, apparently Babinski died in 1932. He’s the one who described the Babinski’s sign. Normally, when the sole of the foot is stroked, the big toe flexes inwards, towards the sole. If it extends upwards, then that’s a sure sign of neurological damage, the Babinski’s sign. But healthy infants can have that sign too not because they have neurological damage, but because their corticospinal neurons are not fully myelinated. Myelin, who discovered that? Probably Schwann. Quick search on PubMed. Too many. Restrict to ‘history”. I hate the search function on PubMed, it brings either to many or no hits, no matter the parameters. Ah, look, Virchow. Interesting. Aha. Find the original reference. Aha. Springer charges 40 bucks for a paper published in 1854?! The hell with that! I’m not even going to check if I have institutional access. Get the pdf from other sources. It’s in German. Bummer. Go to Highwire. Find recent history of myelin. Mielinization? Myelination? Myelinification? All have hits… Get “Fundamental Neuroscience” off of the shelf and check… aha, myelination. Ok. Look at the pretty diagram with the saltatory conduction! Enough! Go back to Virchow. Does it have pictures, maybe I can navigate the legend? Nope. Check if any German speaking friends are online. Nope, they’re probably asleep, which is what I should be doing. Drat. Refine Highwire search. Evrika! “Hystory of Myelin” by Boullerne, 2016. Got the author manuscript. Hurray. Read. Write.

Myelinated fibers, a.k.a. white matter has been observed and described by various anatomists, as early as the 16th century, Boullerne (2016) informs us. But the name of myelin was given only in 1854 by Rudolph Virchow, a physician with a rich academic and public life. Although Virchow introduced the term to distinguish between bone marrow and the medullary substance, paradoxically, he managed to muddy waters even more because he did not restrict the usage of the term mylein to … well, myelin. He used it also to refer to substances in blood cells and egg’s yolk and spleen and, frankly, from the quotes provided in the paper, I cannot make heads or tails of what Virchow thought myelin was. The word myelin comes form the Greek myelos or muelos, which means marrow.

Boullerne (2016) obviously did a lot of research, as the 53-page account is full of quotes from original references. Being such a scholar on the history of myelin I have no choice but to believe her when she says: “In 1868, the neurologist Jean-Martin Charcot (1825-1893) used myelin (myéline) in what can be considered its first correct attribution.”

So even if Virchow coined the term, he was using it incorrectly! Nevertheless, in 1858 he correctly identified the main role of myelin: electrical insulation of the axon. Genial insight for the time.

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I love historical reviews of sciency stuff. This one is a ‘must-have’ for any biologist or neuroscientist. Chemists and physicists, too, don’t shy away; the paper has something for you too, like myelin’s biochemistry or its birefringence properties.

Reference: Boullerne, AI (Sep 2016, Epub 8 Jun 2016). The history of myelin. Experimental Neurology, 283(Pt B): 431-45. doi: 10.1016/j.expneurol.2016.06.005. ARTICLE

Original Reference: Virchow R. (Dec 1854). Ueber das ausgebreitete Vorkommen einer dem Nervenmark analogen Substanz in den thierischen Geweben. Archiv für pathologische Anatomie und Physiologie und für klinische Medicin, 6(4): 562–572. doi:10.1007/BF02116709. ARTICLE

P.S. I don’t think is right that Springer can retain the copyright for the Virchow paper and charge $39.95 for it. I don’t think they have the copyright for it anyway, despite their claims, because the paper is 162 years old. I am aware of no German or American copyright law that extends for so long. So, if you need it for academic purposes, write to me and thou shall have it.

By Neuronicus, 29 October 2016

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Drink before sleep

Among the many humorous sayings, puns, and jokes that one inevitably encounters on any social medium account, one that was popular this year was about the similarity between putting a 2 year old to bed and putting your drunk friend to bed, which went like this: they both sing to themselves, request water, mumble and blabber incoherently, do some weird yoga posses, cry, hiccup, and then they pass out. The joke manages to steal a smile only if someone has been through both situations, otherwise it looses its appeal.

Being exposed to both situations, I thought that while the water request from the drunk friend is a response to the dehydrating effects of alcohol, the water request from the toddler is probably nothing more than a delaying tactic to postpone bedtime. Whether there may or may not be some truth to my assumption in the case of the toddler, here is a paper to show that there is definitely more to the water request than meets the eye.

Generally, thirst is generated by the hypothalamus when its neurons and neurons from organum vasculosum lamina terminalis (OVLT) in the brainstem sense that the blood is either too viscous (hypovolaemia) or too salty (hyperosmolality), both phenomena indicating a need for water. Ingesting water would bring these indices to homeostatic values.

More than a decade ago, researchers observed that rodents get a good gulp of water just before going to sleep. This surge was not motivated by thirst because the mice were not feverish, were not hungry and they did not have a too viscous or a too salty blood. So why do it then? If the rodents are restricted from drinking the water they get dehydrated, so obviously the behavior has function. But is not motivated by thirst, at least not the way we know it. Huh… The authors call this “anticipatory thirst”, because it keeps the animal from becoming dehydrated later on.

Since the behavior occurs with regularity, maybe the neurons that control circadian rhythms have something to do with it. So Gizowski et al. (2016) took a closer look at  the activity of clock neurons from the suprachiasmatic nucleus (SCN), a well known hypothalamic nucleus heavily involved in circadian rhythms. The authors did a lot of work on SCN and OVLT neurons: fluorescent labeling, c-fos expression, anatomical tracing, optogenetics, genetic knockouts, pharmacological manipulations, electrophysiological  recordings, and behavioral experiments. All these to come to this conclusion:

SCN neurons release vasopressin and that excites the OVLT neurons via V1a receptors. This is necessary and sufficient to make the animal drink the water, even if it’s not thirsty.

That’s a lot of techniques used in a lot of experiments for only three authors. Ten years ago, you needed only one, maybe two techniques to prove the same point. Either there have been a lot of students and technicians who did not get credit (there isn’t even an Acknowledgements section. EDIT: yes, there is, see the comments below or, if they’re missing, the P.S.) or these three authors are experts in all these techniques. In this day and age, I wouldn’t be surprised by either option. No wonder small universities have difficulty publishing in Big Name journals; they don’t have the resources to compete. And without publishing, no tenure… And without tenure, less research… And thus shall the gap widen.

Musings about workload aside, this is a great paper, shedding light on yet another mysterious behavior and elucidating the mechanism behind it. There’s still work to be done though, like answering how accurate is the SCN in predicting bedtime to activate the drinking behavior. Does it take its cues from light only? Does ambient temperature play a role and so on. This line of work can help people that work in shifts to prevent certain health problems. Their SCN is out of rhythm and that can influence deleteriously the activity of a whole slew of organs.

scn-h2o-copy
Summary of the doi: 10.1038/nature19756 findings. 1) The light is a cue for suprachiasmatic nulceus (SCN) that bedtime is near. 2) The SCN vasopressin neurons that project to organum vasculosum lamina terminalis (OVLT) are activated. 3) The OVLT generates the anticipatory thirst. 4) The animal drinks fluids.

Reference: Gizowski C, Zaelzer C, Bourque CW. (28 Sep 2016). Clock-driven vasopressin neurotransmission mediates anticipatory thirst prior to sleep. Nature, 537(7622): 685-688. PMID: 27680940. DOI: 10.1038/nature19756. ARTICLE

By Neuronicus, 5 October 2016

EDIT (12 Oct 2016): P.S. The blog comments are automatically deleted after a period of time. In case of this post that would be a pity because I have been fortunate to receive comments from at least one of the authors of the paper, the PI, Dr. Charles Bourque and, presumably under pseudonym, but I don’t know that for sure, also the first author, Claire Gizowski. So I will include here, in a post scriptum, the main idea of their comments. Here is an excerpt from Dr. Bourque’s comment:

“Let me state for the record that Claire accomplished pretty much ALL of the work in this paper (there is a description of who did what at the end of the paper). More importantly, there were no “unthanked” undergraduates, volunteers or other parties that contributed to this work.”

My hat, Ms. Gizowski. It is tipped. To you. Congratulations! With such an impressive work I am sure I will hear about you again and that pretty soon I will blog about Dr. Gizowski.