Neuron length

Neurons are fully differentiated cells arising from the ectoderm which also gives rise to epithelial cells. Functionally neurons are highly specialized to deliver cellular messages from receptor cells to each other or to effector cells. While most neurons are small enough that several thousand could rest on the tip of a dull pencil, some have quite long extensions, or neurites, which may stretch up to a meter in an adult human. However, until recently it was not known what process allowed these neurites (which are primarily located in the spinal regions and are often associated with reflex action and motor activity) to become morphologically different.

A research team from Gumma University led by Assistant Professor Koji Shibasaki and Professor Makoto Tominaga from the National Institute for Physiological Sciences (NIPS) in Japan have identified the TRPV2 receptor on neurons as a mechanical stretch-sensor for helping neurons to develop longer processes. Previously this receptor had been identified as a heat receptor activated in temperatures in excess of 52 degrees Celsius. The research group, however, found activation of this receptor in embryos unexposed to high temperatures, the research group then found that activation of this receptor in developing neurons caused increased growth in axon length (a neurite typically associated with sending signals, dendrites are typically associated with receiving signals and are much shorter and typically more branched). According to Dr. Shibasaki,

We revealed the molecular mechanism why spinal motor and DRG sensory axons can extend such long neurites [sic] toward peripheral tissues. It is really important finding that extending axon can convert mechanical power to electrical energy. I hypothesized that axon outgrowth is regulated by the positive feedback mechanisms through membrane stretch. Now, we can explain why rehabilitation is necessary to improve severe neuronal damage (ex. after traffic accident). The answer could be the activation of TRPV2 by movement of damaged tissue. This molecular mechanism can be applied to neuronal repair, if we can synthesize TRPV2 targeted medication.

This study may provide an answer for how in the future we may be able to foster growth of undamaged neuron processes to replace damaged axons. It is also interesting that when considering neuroscience even the basics of cellular biology such as how neurons begin to differ morphologically are unknown due to the relative youth of this field. There is clearly much more experimental research left to be done before neuroscience may answer some of its larger questions.

Ritalin and neuroplasticity

Nootropics are medications used to increase such diverse mental faculties as cognition, memory, motivation and attention. Perhaps some of the most widely used nootropics by college students are Ritalin, Adderol and the new smart drug of choice, Modafinil. The use and sale of these drugs for non-medicinal purposes is a felony and a further downside of these medications is that both Adderol and Ritalin can be habit forming as found by Martha J. Farah, director at the Center for Cognitive Neuroscience at the University of Pennsylvania as published in the journal Nature. They essentially trigger the brain's reward system (which is the boost in motivation felt by an individual taking either of the two drugs).

According to Eurekalert.org, an online science news abstract service, physicians treat millions of children per year to improve the children's ability to focus. But in addition to aiding in concentration Ritalin accelerates learning. A recent study by Antonello Bonci of the Ernest Gallo Clinic and Research Center and professor of neurology University of California - San Francisco has shown that the mechanism for learning new material that Ritalin fosters involves neuroplasticity. Essentially the drug strengthens connections at the synaptic level and fosters the creation of new synaptic connections, specifically those that involve dopamine pathways.

More research on drugs affecting learning should be performed as it is possible that drugs such as Ritalin may become used for rehabilitation of stroke survivors to facilitate the forming and strengthening of connections. Perhaps when the habit forming nature of these drugs are better understood we may see similar nootropics appearing legally that are as effective as Adderol, Ritalin and Modafinil.

Benefits of video games

It is common for the media to scapegoat violent video games for horrible actions the most obvious being the implication of the first Doom PC game in the Columbine school shootings by Eric Harris and Dylan Klebold who where avid players. Perhaps this is accurate at least for young children based on Albert Bandura's bobo doll experiment in 1961. However, there are positive clinical benefits of video games that are recently developed and are overlooked by the majority of the viewing public and include such diverse uses as neurological treatments and burn rehabilitation.

Cerebral palsy (CP) is an incurable, debilitating neurological condition involving movement and muscle coordination that typically presents in infancy or early childhood and progresses through the life of the individual. CP is treatable, however, and many children with mild conditions may lead near-normal to normal lives. The development of a new treatment for hand function of teenage sufferers of cerebral palsy by professors Burdea and Golomb at Rutgers State University utilizes a commercial available Playstation 3 and gaming glove and a custom designed video game to provide an exercise regimen for improving dexterity and speed. After three months of treatment with the virtual reality telerehabilitation system, participants were able to lift heavy objects (which they previously could not do) and had "varying improvement in such activities as brushing teeth, shampooing, dressing, and using a spoon." After a period of 10 months, one participant was able to open a heavy door. This system while it takes time to build coordination and muscle strength has led to a greater standard of living in teenage patients suffering from CP.

Another example of a clinical benefit of video games is a specially-designed system designed for burn rehabilitation. In this system, burn victims are introduced into a virtual reality world that revolves around a game much in the manner of a biathlon. The patients rehabilitate their injured arms by aiming a gun and shooting flying targets as they move down a virtual world of whites and blues. The significance of this is the choice of colors as the brain is tricked into believing that it is in a cold environment and pain from burns (even third degree burns) are reduced or eliminated.

These examples make me wonder what other ways medicine can adapt items from popular culture to benefit patients.

Four good musical acts

Several blogs ago, I introduced several jazz musicians and groups that are worth listening to. I thought that for this installment I would make some suggestions concerning rock and metal genres. Much of the music we hear by artists in these domains (I use domain rather than genre to describe a class of music due to the latter's increased specificity, I intend a broader looser terminology) is rather formulaic and typically has little dynamic and emotional range. Increasingly it is also mass-market based rather than showing a true depth of musicianship. This is not to say that certain musical acts who have wide spread appeal are necessarily bad, or that acts that are Indie and have a very small fan base are good. Rather the statement was to illustrate that much of today's music is more heavily influenced by what Theodor Adorno terms the "culture industry" which determines sales rather than the artistry of the group. This being said I would like to introduce some groups that break free and perform music as an art and not a job.

1. Vampire Weekend - The first self-titled album by this group was very good. I did not enjoy the second album Contra as much. The act uses a typical rock instrumentation but also incorporates a keyboardist, strings and winds (the latter two are only occasionally used). The style hearkens back to early rockers such as the Beatles although modern African pop rhythms and baroque styles also figure predominantly in their sound. This group has gained some popularity recently.
2. Mastodon - The prog metal group Mastodon has appeared on the Guitar Hero franchise of video games (but as with Vampire Weekend I knew about them before they were popular). Many of their earlier recordings have very mythological foci supported by the tribal drumming. Perhaps the most interesting ability they posess is their great rhythmic sense, consider that the instrumental "Bladecatcher" on Blood Mountain is in 7/8 time as opposed to the typical 4/4 or 12/8 of rock and metal.
3. Pelican - Along the same lines as Mastodon is Pelican. Much of what I have stated about Mastodon is true for Pelican except with regards to vocals. Pelican is an entirely instrumental group (due to my like of instrumentals, this was the selling point for me to purchase and EP they released).
4. TSO - If you haven't heard of Trans-Siberian Orchestra then I truly am sorry. They are the only Rock Opera to go platinum and includes guitarist Al Pitrelli of Megadeath and keyboardist Rober Kinkel (session player for The Who, Aerosmith, Genesis...). Their latest album, Night Castle, is a concept album like many of their previous recordings but it also includes covers of "The Nutrocker" by ELP and "O Fortuna" by Carl Orff. The latter is without a doubt one of the most dramatic pieces of opera literature composed to date and it sounds amazing with guitar distortion (I think Orff would have called for it had he not composed Carmina Burana in 1935). Perhaps the most beautiful (and angsty) piece on the act's album is "Believe." It would be nearly impossible to dislike this song.
   

Hopefully I have provided a few more artists and groups for you to research if you haven't heard them. I believe that these groups, despite their popularity in three of the four cases, have great artistry. I wish that more music on the air would be the caliber of these performances. I suppose I will just have to continue digging for more music to find their equals.

The ThermoMed

Leishmaniasis is a parasitic infection by Leishmania parasites and is encountered worldwide and affects roughly 2 million people per year. The disease may present in one of two forms: cutaneous, which involves sores that the CDC has described as volcano shaped, and visceral, which includes hepatosplenomegaly, anemia, fever and weight loss. Both infections by Leishmania parasites are treated with intravenous Pentostam which is manufactured by GlaxoSmithCline. Pentostam has several drawbacks, firstly it is only given on a named-patient basis by the CDC so it is unusually hard to obtain for patients, there is also widespread resistance to the drug (by not by Leishmania), and it must be administered intravenously by slow diffusion which takes approximately five minutes during which the patient must also undergo cardiac monitoring. Typically this disease is relatively unknown to Americans, however, recently it has been illustrated that it is a threat to both citizens of Texas and to American soldiers in Iraq as a vector of Leismania, the sandfly, is native to both locations.

Considering the problems associated with Pentostam it is relieving that a very simple procedure shows promising signs of treating leishmaniasis. The journal PloS Neglected Tropical Diseases recently published an article by Naomi Aronson and her team at the Uniformed Services University of the Health Sciences and Walter Reed Army Medical Center which found that simple heat therapy was as effective as a 10-day course of Pentostam. Also the patients treated with the device by Thermosurgery Technologies based in Pheonix, Arizona received one single session of treatment as opposed to the 10 treatments with Pentostam. The ThermoMed device also is able to treat skin cancers, HPV worts, fibromas and other skin diseases.

The ThermoMed by Thermosurgery Technologies provides several major advantages over the traditional anti-parasitic Pentostam for cutaneous leishmaniasis. While Pentostam will remain the major medication for the sufferers of visceral leishmaniasis, this device will become indispensable for dermatologists offices and hospitals. One wonders what other dermatologic problems may be addressed by these units.

Silent mutations in metastatic brain cancer

Cancer researchers in Croatia found in one case study of a metastatic brain lesion removed from a 49-year old man suffering from lung carcinoma found that the metastatic lesion contained a silent point mutation in the adenomatous polyposis coli gene (APC). The point mutation was located in the 15th exon of the gene and eliminated an adenine base from the sequence CCA-G (the hyphen indicates separation between codons - sets of three bases) to CCG. Since translation involves sets of specific nitrogen bases coding for a specific amino acid, a single point mutation may affect which amino acid is coded for and may prevent the functioning of larger proteins if an incorrect amino acid is coded for. However both CCA and CCG codons both code for proline so any proteins synthesized from this gene would be in tact.

The importance of this study lies in that the mutation was only found in the DNA of the cancer tumors and not of the patient. The authors state that this "may indicate an important regulatory element change at the DNA level," meaning that although point mutations are generally characterized as non-pathogenic, this change could alter regulatory functions such as splicing. Essentially, even though the DNA sequence looks the same except for one base, that one base may make the exon non-functional. This is the case of the metastatic lesion which shows no proteins produced by the APC gene.

The primary reason I found this study interesting was that by saying that silent point mutations do matter, this study challenges mainstream thought in genetics. It shows how far we are away from understanding human genetics despite the enormous growth in this field. If we are to understand cancer perhaps we should take a closer look at our fundamental ideas of genetics, perhaps as in the case of silent mutations we are grossly oversimplifying a truly complex problem.

Job shadowing

Yesterday I was involved for the first time in the process of job shadowing an individual. I always felt slightly left out whilst in high school as I felt myself to be the only person in the top 10% of my class who had not done so at least once., but at the time I felt that I had no idea what I truly wanted to do so any job shadowing I could have done would most likely have been a waste of my, and the individual's I was shadowing, time. As you have seen from my posts (and my first paper), I have an interest in the field of infectious disease, a subspecialty of internal medicine. I contacted my academic adviser to request that I be able to follow Dr. Esguerra of St. John's Medical Center from 8:00 am yesterday morning until 1:00 pm that evening. I felt that this would be a very good opportunity to observe a typical day's case load and gain insight into the field of infectious disease (ID) that might sway me in the direction of ID as a future career.

During this time I observed Dr. Esguerra make visit five patients (much of the morning was spent traveling between floors as I quickly learned an ID doctor's cases span roughly six flights of stairs). I learned quickly that I have been completely mistaken about the realm of ID and the patients seen in the field. I realized the severity of drug resistant bacteria, but I didn't truly realize that the majority of patients that an infectiologist would see are not cases of parasitic infection by organisms like nematodes and botfly larvae, but rather severe bacterial infection of critically ill patients. Many of these patients will continue to be treated for at least 2 months on IV antibiotics even after they are discharged and several of the patients I saw were in the ICU and despite the lowering fevers in response to antibiotic treatments I read on the chart, there was little hope.

I had always relegated the most depressing cases in medicine to be those seen by oncology/hematology physicians or genetic medicine physicians. I think after seeing an ID physician's typical day treating the sickest patients in the ICU and throughout the hospital, I think that I was mistaken.

There are very few ID specialists in the US now despite the greater risk of drug-resistant bacteria, reduction in the amount of immunizations and rapid transportation between countries that spreads disease due to travelers' negligence to take simple precautions. I thought that I might be able to find a niche in this gap, but after seeing what I did, I am not so sure. It seemed to me that death followed ID more than recovery. I am grateful for the opportunity to have this experience but I feel that I am leaning less and less towards this career and I know that the first patient I saw in the ICU will haunt me for the rest of my life.