Laptops and cancer...

So I decided to do a slightly interesting post for my last blog. Recently I read an article claiming that laptop use can lead to testicular cancer (I heavily doubted its validity, but thought it interesting). Testicular cancer is fairly rare, but is the most common form of cancer in 15 to 34 year olds (this subset of the population rarely gets any cancer). Much of the supposed "research" that has been done is merely interviewing young business professionals who use laptops frequently during long flights. Of course, the ones interviewed are in the upper range of the most effected population range. While searching on the internet for this topic I stumbled upon this article which mentions hematologist and oncologist Timothy M. Kuzel of Northwestern's Feinberg School of Medicine. According to the article Kunzel states that he felt that any relationship between testicular cancer is highly debatable: "We’re not seeing an epidemic of 50-year-old businessmen with testicular cancer." That is to say one would also expect elevated levels of all laptop users. There aren't.

So as to whether we men should be worried about holding our laptops away from, ahem, ourselves when we use them, the answer, like that of cell phone usage and brain tumours is no. This area should definitely be watched as carcinogens and radioactivity may act slowly depending on dosage, but for the moment, I am not particularly worried.

Blinking neurons

Perhaps I am a little too nerdy, however, when I read this article from the Max Planck Society. Anyone who has a biology lab has probably performed a genetic transformation lab. Essentially a plasmid (circular strand of DNA) is transferred from one organism (the standard to use in bio classes is called the PUC8 plasmid) into a bacteria which has been heatshocked. Inserting the plasmid will change the bacteria so that it expresses proteins that grant it such properties as antibiotic resistance and the ability to break down lactose into galactose and glucose (this latter property is used to identify the bacteria that take up the plasmid, the breakdown creates a blue product). In addition proteins such as green flourescent protein (GFP) plasmids are added for the same reason (GFP is actually common, look for the green GloFish next time you're at a pet store). These techniques are useful as they can allow macroscopic visualization of microscopic events.

The specific type of GFP (along with another unnamed flourescent protein) used for this study is known as "Cameleon" and it is a GFP molecule that is activated by calcium. Essentially calcium binds to the protein and causes the flourescent molecules to approach each other and change color. As neurons are involved in calcium signaling, the application of cameleon to neurons will allow neuroscientists to observe neuronal signaling in realtime without microelectrodes for stimulation and voltage measuring. When a neuron is activated, calcium concentrations generally raise and the color of the neuron will alter.

According to the study:

These new advances, using light to study the brain, provide us with a unique opportunity to investigate how memories are formed and lost and, furthermore, when and where nerve cell activity patterns become altered as in the case of aging and also in neurological diseases such as Alzheimer’s disease, Parkinson’s disease and schizophrenia.

This is a very unique new technique with diverse applications and it will be most interesting what may discovered with its use in time.

More on vitamin D

Last week I spoke of some recent benefits mentioned for consumption of milk and the ill effects of vitamin D deficiency along with several alternate sources of vitamin D. While scanning Eurekalert.org's science news service I came across yet another article concerning the ill effects of deficient levels of vitamin D on patients suffering from multiple sclerosis (MS). MS is a debilitating neuromuscular-immune disorder which involves immune cells attacking the body's own oligodendrocytes (also known as Schwnn cells when located in the peripheral nervous system) which possess the primary function of insulating axons. This causes the loss of signal from the brain to the muscle.

According to a University of Buffalo study published in the American Academy of Neurology, "(l)ow vitamin D levels may be associated with more advanced physical disability and cognitive impairment in persons with multiple sclerosis." The 236 participants' blood serum for total vitamin D (D2 and D3) along with active vitamin D byproducts. According to the study "(r)esults showed that only seven percent of persons with secondary-progressive MS showed sufficient vitamin D, compared to 18.3 percent of patients with the less severe relapsing-remitting type." This indicates that there is a possible correlation between vitamin D levels and severity of neurodegeneration in MS. When controlling for both season (Winter is associated with lower levels of vitamin D) and depression (which is also associated with lowered vitamin D levels), this relationship still held true.

Little is currently known about vitamin D's relation to cognitive development or degeneration. What is known is that vitamin D levels are associated with increased risk for MS and that low levels may be implicated in worse prognosis for MS. As I have stated many times before, we do not know enough about these severe neurological diseases and much work is yet to be done in order to prevent and fine treatments for these conditions.

Artificial scents and flavors

I just exited from my final lab in Organic Chemistry II (with some elation I must add) in which I was to identify one of four unknown organic compounds using a slew of laboratory procedures. I chose the first compound and proceeded to waft the scent of the compound (this really is a bad idea considering many organic compounds can be highly toxic and/or carcinogenic but it is very quick for identification of a class of compounds). I knew that I had picked a relatively simple compound to identify as it smelled (at least to me) like licorice flavoring in taffy or jelly beans and peppermint (which is a most delicious scent combination by the way).

Whenever we purchase orange soda, perfume or cologne the flavors and scents that we admire are not compounds that are necessarily found in fruits or musk, but rather organic chemicals. Specifically most of these are derived from aptly named aromatic compounds typically derived from benzine, the most studied of aromatics. For instance, my compound was determined to be ethyl benzoate which is a flavoring and scent most often associated with Ylang Ylang and tobacco essences. In wine alone over 200 flavor components are due to organic aromatics, in simple coffee over 800 are present. The interactions of these compounds with taste receptors give rise to the highly complex sensations of taste associated with these beverages.

Perhaps our Organic classes would be more beneficial to the student if they aided theory with practical and intriguing uses and qualities of aromatic compounds. I for one find it more interesting that such simple variations on a simple molecule like benzine can create so many diverse scents and flavors. I most certainly will be able to identify an aromatic ester by its smell.

Drink more milk and enoy the summer

Vitamin D is a group of fat-soluble secosteroids (which is similar in structure to a steroid but involves the breaking of one of a steroids cyclic rings) that are commonly found in fish, eggs and milk. In addition sunlight helps facilitate synthesis in the human body which is thought to be enough to prevent deficiencies. However, fewer individuals are meeting the necessary allotment of time outside to aid vitamin D synthesis and deficiency is becoming a potential problem. According to the National Institutes of Health Dietary Supplement fact sheet the minimum daily requirement for Vitamin D intake is 200 IU (5 mcg), several dietary guidelines recommend 400 IU (10 mcg). For reference, to meet these guidelines 4 glasses of non-fat or low-fat milk would need to be consumed (more of higher fat content milk) or it is suggested by the Mayo clinic that merely 10 minutes in direct sunlight would suffice to prevent deficiency. One would assume that these requirements would be easy to meet (I should mention that one must be careful with vitamin D intake, as I stated earlier it is fat-soluble - it can easily be built up to toxic levels if one is not careful and consumes too many sources of it).

Apparently not. A study described on Eurekalert's online science news website stated that Vitamin D intake levels are so startingly low that "current deficiency levels prompted the American Academy of Pediatrics to double the vitamin D recommendations for children and teens." Half of adolescents, according to the study, are deficient in Vitamin D. It seems to be well-known that Vitamin D and calcium intake will help prevent osteoporosis and other bone problems (primarily in women), but there are other benefits of Vitamin D that are quite beneficial. Studies have correlated adequate Vitamin D intake levels with lower levels of diabetes, hypertension, heart disease and certain cancers. In addition the immune system also benefits from adequate Vitamin D levels (so if you want to prevent catching a bacterial infection, you should perhaps opt for some yogurt over antibacterial soaps).

This being said I think I think it is a pretty simple task to drink another glass of milk per day and spend a few minutes outside. It most certainly will pay off later down the road when we are at risk for all manner of chronic diseases.

Stroke after cardiac bypass

I was perusing Eurkealert.org and came across this interesting study relating cardiac bypass procedures to stroke.

A cardiac bypass involves using existing blood vessels from the patient in order to build an alternate route for blood to flow through around a blockage which are caused primarily by the buildup of fat and cholesterol. In order to prevent organ damage in the patient undergoing a bypass, the body is cooled and subsequently been rewarmed. For years approximately 5% of cardiac bypass patients wake up post surgery with a significant loss of motor activity or speech; to this date few explanations why this correlation of bypass surgery with stroke would occur exist.

Stroke is caused by a disruption to the blood supply of the brain restricting both glucose and oxygen supplies. The brain requires much of the oxygen and glucose in the body in order to function and a disruption of blood flow robs the brain of its nourishment causing cellular death. A recent study from Johns Hopkins may have pinpointed this correlation between stroke and cardiac bypass surgery to the procedure of cooling and rewarming the body in order to prevent organ damage. According to the study blood flow and pressure were recorded for "127 patients undergoing standard, lengthy cardiac bypass surgery during which they spent two hours on a heart-lung machine that circulated their blood for them" and "(e)leven patients undergoing shorter bypass operations were kept at normal body temperature throughout and served as a control group." Of the 127 test subjects 7 suffered from stroke and 1 suffered from a transient ischemic attack which is considered a harbinger for future stroke. None of the control groups suffered an attack of any kind.

While this study does suffer from a minuscule control group, it does help point that the rewarming technique may somehow interfere with the autoregulation mechanism that helps to prevent damage to the brain from blood pressure fluctuation. Currently the research team for the study is developing a near-infrared monitoring device for cardiac bypass surgeries to display blood flow in real-time allowing surgeons to alter blood pressure in order to protect the brain from risk of stroke.

Chloride channels and epilepsy

According to the Mayo Clinic, epilepsy is "a disorder that results from the generation of electrical signals inside the brain, causing recurring seizures." The symptoms of seizures vary drastically, some patients may simply blankly stare for a few moments while others may convulse. In order for a diagnosis of epilepsy, one lone seizure is not sufficient. Statistically speaking, approximately 1 person out of 100 will experience at least one seizure in their lifetime and for 7 out of 10 persons experiencing multiple seizures (epilepsy), no cause may be found. It is clear that due to the risk of death and injury from seizures due to drowning, falling, burning, car accidents and complications in pregnancy, much work must be done to determine specific causes of epilepsy (it is currently believed that oxygen starvation during the natal and prenatal periods may contribute as well as simple differences in brain structure).

A new study by the Max Planck Institute of Neurobiology (I find it interesting that many biomedical facilities were named after physicists, not that this is incorrect as all biological processes seem to arise from conglomerations of quantum physical interactions; still it seems more appropriate for an institute of neurobiology to be named in honor of a neurologist, neuroscientist, psychiatrist or psychologist) has studied the physiology of the chloride channel ClC-2 which has been implicated in a relation to epilepsy and seizures. A prevailing theory of the function of the Clc-2 channel is that as the amount of functioning ClC-2 channels decrease, the more likely the neuron will be activated (its excitability increases due to the greater intracellular concentration of negatively charged chloride ions. However in mice with genetically malformed ClC-2 channels were no more susceptible to seizures than the healthy controls. More confusing is that despite this lack of susceptibility of mice with dysfunctional ClC-2 channels, the neurons lacking the channels were still more excitable than the normal neurons. The answer to this conundrum is actually quite elegant; as the neurons lack ClC-2 on excitatory neurons (which can signal other neurons and lead to actions, or seizures), so do inhibitory neurons (which will lead to nonaction, or help prevent seizures).

It is proposed in this study that while ClC-2 channel presence is implicated in excitability, it may still be implicated in epilepsy. Protein channels may be opened or closed due to presence of chemicals that both naturally (neurotransmitters, hormones , etc.) and unnaturally (medications, drugs, etc.) occur in the brain. It is proposed that the neurons can alter the structure of the ClC-2 neuron in order to alter its excitability (essentially a normal neuron with mitigating factors can act as though it was a dysfunctional neuron as compared to the study described above).

Clearly, we know little about the neurobiological basis of epilepsy and some of what we have discovered is complex and confusing. We need to carry out more research both on the cellular, molecular and clinical scales in order to determine the pathophysiology of these neurological diseases. Neuroscience is a young field, and as V. S. Ramachandran describes, every science must enter into an experimental phase before it can answer its primary question. Neuroscience, it appears is still in it's experimental stage.

Anti-oxidants and cirrhosis

I have always been particularly fond of dark chocolate. My brother is in the habit of purchasing extremely high cacao level chocolates for my tasting (my last was a 95% cacao chocolate bar which is nearly solid cacao, it was quite delicious). Much recent work in nutritional health centers on the effect of anti-oxidants and their benefits to the body. This is unsurprising since oxidizing agents have severe effects on the human body including the breaking of the DNA backbone rendering cellular processes non-functional.

A recent presentation at the International Liver Congress 2010 (sounds like a riveting engagement) enumerated the effects of dark chocolate which like blueberries, red wine and acai berries are high in anti-oxidants. According to the clinical study, dark chocolate liquid meals which contained 85% cacao (a very good percentage as far as taste is concerned I must add) at 0.55 grams/kilogram of the patients body weight were administered to patients suffering from end stage liver disease. The patients receiving the treatment showed improvement in post-prandial (after eating) hepatic blood pressure. High liver blood pressure is associated with blood vessel rupture in cirrhotic patients and by administering a source of anti-oxidants as a nutritional supplement, such as dark chocolate, these problems may be avoided.

I believe that we should be more aware of the benefits of anti-oxidant rich foods, and perhaps it is prudent for American physicians to begin considering recommendations for patients at risk for cirrhosis (alcoholics, college students, etc.) to increase their intake of anti-oxidant rich foods. I certainly would not complain about being told to eat some dark chocolate after meals to help prevent cirrhosis.

Nicotine and intensive care

As of 2007, 19.8% of Americans smoked (a decrease from 20.8% in 2006) according to the CDC's Morbidity and Mortality Report. Withdrawal from nicotine due to cessation of smoking can have several complications that provide difficulty for cessation of use including irritability, concentration difficulties, fatigue, insomnia and gastrointestinal problems among other complaints.

In addition to these effects of nicotine withdrawal, a recent study published in Critical Care, a BioMed Central open access journal, has shown that nicotine withdrawals can cause "serious agitation in intensive care patients." This study found that patients suffering from nicotine withdrawal were more likely to remove their catheters and tube, require anti-psychotic medication, physical restraints or sedatives. In fact the patients suffering from nicotine withdrawal were twice as likely to become agitated as non-nicotine patients.

The purpose of this test was more to provide grounding for later testing of nicotine replacement therapy (NRT) in the case of intensive care patients. This is a particularly sensitive area within the emergency community as NRT has been associated with higher mortality rates. However, due to the harm caused by patients suffering from nicotine withdrawal, it seems prudent to see whether NRT actually does affect mortality rates (this has not been scientifically proven). If NRT is viable for treatment of patients then hospitals can address the difficulties associated with nicotine withdrawal in a critical care setting.

For watchers of medical television hows...

There was a dearth of interesting new studies on Eurekalert.org for the past few days so I have decided to do something different and write about a (semi) rare neurovisceral genetic disorder. Acute intermittent porphyria (AIP) is a disease caused by buildup of heme precursors (the oxygen carrying component of hemoglobin in red blood cells among other things) in the liver. These two compounds, delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) can cause nonspecific symptoms including severe abdominal pain, paraesthesia (tingling in the arms and legs), paralysis and psychosis. These attacks may be infrequent and between attacks the patient may feel very healthy.

This laundry list of symptoms makes AIP particularly difficult to diagnose. However, there is a tell-tale sign that can lead to quicker diagnosis. ALA and PBG are excreted in urine and during an acute attack urine may be red or purple in color (this is not in itself definitive enough for a diagnosis of AIP and urine tests for the levels of PBG and ALA must be performed).

It is estimated the 1 in 20,000 people carry the defective gene for AIP, however, due to some unknown reason only 10% of those with the defective gene express it. For those 1 in 200,000 AIP can be a serious risk as infections, medications, smoking, alcohol and other drugs can all trigger an acute attack.

As of now there isn't an approved cure or treatment for AIP (liver transplants have been done and show promising signs of curing the disease, but are highly unfeasible in most cases). However, just as in the case of phenylketonurics, simple lifestyle compensations such as limiting alcohol and smoking, treating infections rapidly, and watching food intake can allow patients with AIP to have a normal life.

New method of treatment for migraine

Chances are you have probably had to use a nasal medication or saline solution sprays for alleviation of allergy symptoms or coughing. Generally these sprays have tow problems: drip-out (yes, this is actually a scientific term) and an unpleasant taste. A recent development in order to combat these problems has been worked upon by OptiNose. This innovative nasal drug administration system can deliver a dry powder form of the medication.

However, it was not this particular innovation that I found interesting (I don't have a problem with normal nasal sprays). Typically, medication dosed intranasally treats cough and allergy problems, however, a recent study published in Cephalgia has shown that a dry nasal treatment for migraines reduces migraine pain after two hours in 57% patients (20 mg dose) and 54% (10 mg dose). 25% of those given placebo treatments also had alleviated pain in 2 hours making the finding statistically significant.

As migraines affect more than 28 million Americans a year (mostly women) I think it is very important that more research be done into the pathophysiology of migraines. In addition new medications such as intranasal treatment in addition to knowledge of risk factors for migraines will greatly reduce the effect of this problem.

Diagnostic Imaging and shorter stays

Computed tomography (CT) and magnetic resonance imaging (MRI) are diagnostic imaging studies that have been used for screening purposes in preventative medicine and to supplement previous imaging techniques such as x-rays (CT actually is a high level of x-ray radiation that is simply shot from different angles with the resulting images superimposed to form a three dimensional structure) and ultrasonography.

The Journal of the American College of Radiology has recently published a study that links these diagnostic tests with shorter hospital stays (this, I thought was rather common sense - the more tests that are performed, the quicker the diagnosis can be found and treatment performed). The catcher to this study, however, is that on average healthcare costs have been found to be reduced as the costs of CT and MRI are lower than that of inhospital stays (the decrease in costs will only be possible if testing is performed early before hospitalization can occur). These inpatient costs account for roughly 18% of total healthcare insurance premiums paid and have been increasing by 8% annually. It seems prudent to test earlier rather than later when such diagnostic imaging as abdominal CTs and neurological MRIs are necessitated.

It is important for diagnosis to be rapid and efficient in the field of medicine for the patient and as CT and MRI scans reduce both the time of stay in the hospital and thus the cost of inpatient care, it is essential to perform diagnostic imaging studies as quickly as possible when they are thought necessary (this is not to say that they should be administered more frequently, this will increase the cost of care and of cancer for the patient). Hopefully, this practice will become more prevalent.

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.

Monsters inside me

I tend to dislike Animal Planet, most of the people shown on the channel either treat their animals barbarically as in the animal cops style shows, or are pamper their pets to the point of inducing me to cringe or become nauseous. There is one series that I enjoy watching on this channel, however. I have always been drawn to medical reality series such as Mystery Diagnosis and wildlife documentaries such as Planet Earth so the conjunction of these two genres is certainly one of interest to me. I am writing of the series Monsters Inside Me which is entering its second season (unfortunately a season only has 6 episodes). The series focuses on the interaction of humans and their parasites. Past episodes have covered bed bugs (which are horribly nasty in their reproductive habits), strongyloides worms (I recently adopted one of the on The Parasite Pet Shop online) and botflies (they can inject their eggs into a human as host, the maggots can even infect the human head).

Animal Planet has also been kind enough to include 34 clips from this series on their website along with several other extras relating to the series such as the aforementioned Parasite Pet Shop where you can adopt a slightly more friendly version of several featured parasites. Perhaps a little stranger (and I think slightly humorous) are the parasite wallpapers and the email address to contact the show if you have been infected and would like to be on the second season (I think casting for this would be much easier than any other show, go to Indonesia, walk around barefoot and go home and be treated for an infection from strongyloides).

The next time you are channel surfing and you see a show entitled Monsters Inside Me maybe you should take a look. You'll be surprised by what you learn. I for one will never eat unwashed lettuce, will always thoroughly search any hotel room I am staying at and think twice before walking outside without Off or without shoes.

bio.Diaspora

The Vancouver Olympics allowed researchers Dr. Kamran Khan at St. Michael's Hospital in Toronto and Dr. John Brownstein of the Informatics Program at Children's Hospital Boston a chance to study disease patterns by using the epidemiological informatics programs bio.Diaspora and HealthMap (the global disease alert map) to track global air traffic patterns helping to control and alert cities and countries of emerging infectious diseases. For the 2010 Olympics, the two researchers found that nearly two-thirds of all international travelers came from 25 cities. The infectious disease patterns of these cities are currently being monitored on an hourly basis.

When considering a contagious infectious disease, perhaps the worst thing humans can do is meet in large groups in small areas. As Dr. Khan puts it,

(m)ass gatherings can potentially amplify and disperse infectious disease threats globally because they can draw millions of people from around the world into a single space....By enabling our two systems to communicate in real-time, we are exploring new ways to generate actionable intelligence to organizers of mass gatherings.

This junction of infectious disease, epidemiology, biostatistics public health and other fields will compliment greatly the medical preparation for large events by identifying the possible sources of infection and narrowing the differential diagnosis of possible infections. It is hoped that through this furthered knowledge disease transfer may be slowed or even prevented in the cases of mass gatherings like the Vancouver Olympics.

Lester Bowie

A while ago I wrote a blog about jazz musicians whose music would be a good starting point for fans of more popular music. However, there are many musicians that do to their eccentricity are not such good starting points. Once one begins listening to more diverse types of music, though, many of these more eccentric jazz musicians open up new avenues for understanding music.

Wednesday while driving home from my Biomedical Ethics class I turned my radio to PSU's NPR station on 89.9 FM. I instantly recognized the first song being played. It was the jazz standard "I only Have Eyes for You" and it was being performed by Lester Bowie's Brass Fantasy. If you have heard Lester Bowie once, then you will always be able to recognize his playing. To any song he performs, whether a standard or a funk song (Lester has even done a cover of the 70's song "Oh What a Night"), Lester brings a degree of playfulness that is seldom heard in music. Through his half valved playing, grunts, fluttering and squeals he never took himself seriously.

Perhaps we should have more musicians in the mainstream of the music industry like Lester Bowie. We have pop stars like John Mayer who break down on stage and rappers like Kanye West and 50 Cent who slander each other through the news and it grates on me how these are our models for a musician while Lester Bowie will never be. Perhaps we as a people will start being more critical of our role models in music, but with the present news industry I am doubtful.

Copper on the brain

Copper is the third most abundant transition metal in the human body after iron and zinc and is used as a cofactor in enzymes such as cytochrome c oxidase and dopamine b-monooxygenase. However, too much copper can be highly toxic leading to cognitive deterioration and palsy and can be fatal. In order to control the amount of copper, cells are able to regulate uptake and are also able to excrete copper. Dysfunction of enzymes controlling levels of calcium have been linked to diseases such as Wilson's and buildup of copper has also been indicated in studies of neurodegenerative diseases such as Alzheimer's.

A recent article in Neurochemistry International (the abstract only is viewable here) sought to study how copper was absorbed in astrocytes as these cells are involved in clearing residue from the synapse between neurons. It was suggested by this study that understanding how copper homeostasis is thrown off during certain diseases during their progression may lead to a better understanding of the diseases themselves. This study hints that we should focus more on the astrocyte with the concluding statement that astrocytes may be responsible for the protection of neurons by uptaking copper by several different methods (astrocytes themselves seem fairly copper stable).

In neuroscience it has been stated that 99% of the research has been focused on 1% of the brain (the neurons). There has been some research lately to correct this overemphasis. However, if we are to understand highly complex disease such as Alzheimer's, we must look from all aspects of the problem including cells we normally ignore such as the astrocyte.

The blancmange

Thus far I have written about two of my passions, medicine and music. I chose for this installment to venture into other territory, food. I have been expanding my cooking skills of late and stumbled onto a very simple and elegant dessert, the blancmange. A blancmange (pronounced bləˈmɑnʒ) is essentially a dairy gelatin. When coupled with honey and good dessert cheeses and topped with a fresh fruit mixture a blancmange is one of the most palatable desserts I have eaten and I have had my fair share.

The blancmange recipe I use is a variation on one that I found on Epicurious.com. Some important changes to the method of cooking and specific types of ingredients are of importance. This is a straight forward recipe and I will note the only difficult points when they arise. Perhaps this may be of use to impress someone on Valentine's Day.

Ingredients

• 1 1/4 cups cold skim milk

• 1 tbs powdered gelatin
• 1 cup half-and-half
• 6 oz. goat cheese
• 2 oz. mascarpone, white stilton or other dessert cheese
• 1/4 cup honey
• 2 tbs white honey
  
• 2 tsp vanilla extract

• fresh fruit
• powdered sugar
• balsamic vinegar

Directions

Pour the skim milk into a double boiler (best choice so as to not curdle later) or a saucepan. Sprinkle contents of the unflavored gelatin over the milk and let sit for about 10 minutes. Bring the milk to a simmer and whisk until the gelatin dissolves. The only difficulty in the recipe comes here, you must let the milk cool enough so that the goat cheese will not denature and the honey (which contains mostly fructose) will not break down. Goat cheese and honey are both very unstable with temperature (which is why it seems that when honey is added to hot tea it takes large amounts to reach the desired sweetness) so the milk should be warm, not hot. At this point the rest of the blancmange ingredients should be whisked in (the half-and-half, cheeses, honeys, and vanilla). After the ingredients dissolve completely transfer the mixture to ramekins or miniature cake or bundt pans that have been sprayed with cooking spray (martini glasses work as well). Cover the pans or glasses with plastic wrap and refrigerate for 4 hours. To make the topping for the blancmanges mix equal amounts of powdered sugar and a sweet balsamic vinegar (about two tablespoons of each) and add in the fresh fruit.

I hope that this recipe may be of use. I always enjoy making it.

Noninvasive neurosurgery

Tumors in the central nervous system (CNS) pose a major challenge despite advances in cancer treatment due to risks of radiotherapy and neurosurgical resection. Chemotherapy is difficult due to the low permeability of the blood-brain barrier and for chemotherapy to be undertaken Ommaya reservoirs are typically implanted which requires a neurosurgical procedure. Less invasive treatments are needed. The most recent development is a modification of thermal ablation to suit the CNS.

The University Children's Hospital Zurich has performed the first human clinical trials utilizing a low frequency ultrasound machine (700 kHz as opposed to 1 to 4 MHz) and a hemispherical shape. These design changes address the problem of overheating. Magnetic resonance imaging (MRI) is also utilized for quantitative temperature measurement. To further reduce the risk of overheating the scalp is actively cooled. The treatment was performed on three patients with otherwise inoperable gliobastomas (primary malignant brain tumors).

The article states that TcMRgFUS (I think a better acronym may be in order, it's a little less concise than PET or CT) may be an alternative to radiosurgery or a treatment option for patients with recurrence after radiotherapy and may offer a larger benefit with brain tumors such as metastases or benign tumors with clearly defined boundaries. I hope that other hospitals or universities will be able to replicate the results from this study. If so we may have a much needed noninvasive method of treating brain tumors.

America's music

It would be difficult to find a person who believes that they know something about music who did not say that jazz is an art music or perhaps more derogatorily a highbrow music. This may indeed be the case, you can't dance particularly well in 20/8 time like some music by the Mahavishnu Orchestra or sing along with an improvisation (perhaps I should take that back, I have been known to do that with songs I love in the genre). However, even if jazz is an art music that is no barrier to its popularity. For example, consider Johann Pachelbel's "Canon in D Major," Pink Floyd's Dark Side of the Moon album or even Trans-Siberian Orchestra rock operas. All three are art music, are widely popular and do not have a binding genre.

I am going to suggest some groups or musicians that I feel deserve much more attention than they currently have. Some of these names are well known in the realm of jazz or are well-known in general, yet I very seldom meet someone who has actually listened to them.

1. Miles Davis - The first name (in my opinion) in jazz. He encompassed every genre from the 1940s to the 1990s and originated a few of them. His Kind of Blue album is a very nice starting point.
   
2. John McLaughlin - He has performed with Miles and his best work was with the group the Mahavishnu Orchestra and in the group the Trio of Doom (blame the bass player Jaco Pastorius of the trio for that name).
3. Bill Frisell - A newer guitarist who has played hardcore jazz and thrash jazz with John Zorn in the group Naked City and folk and country influenced jazz on albums where he is the leader.
4. Marcus Miller/Victor Wootin - Both are electric bass players and the play together with another bassist in the SMV group. On their own the former plays more smooth and funk oriented jazz and the latter plays incredibly difficult solo bass music.
   

Jazz is a very diverse genre and as one of the United States only art forms that was formed with little outside influence it deserves more listening than it is given. It would be nice to see a few albums by groups like the Bad Plus and the Mahavishnu Orchestra placed in the Rock/Pop section for once.

PVC7 vaccine benefits and problems

Pneumococcal meningitis is one of several forms of acute purulent meningitis and is caused by Streptococcus pneumoniae, a normal inhabitant of the upper respiratory tract in humans and can be detected in 5% to 70% of the population (seasonal differences and age play as factors in this wide range), that passes through the blood-brain barrier and into the subarachnoid space followed by neutrophils (white blood cells). The pediatric pneumococcal conjugate vaccine (PCV7) which is recommended for use in children aged 5 and younger and immunizes the child for seven strains of pneumococcal bacteria has been found to reduce the incidence of pneumococcal meningitis.

However, before we celebrate this new vaccine we may want to consider the troubling findings also reported in this study. PVC7 immunizes as stated above for th seven most common types of pneumococcal bacteria in humans. The various strains not immunized for by PCV7 have increased 60.5% from the 1998-1999 period to 2004-2005. Also penicillin resistant strains have increased from 19.4% to 30.1% between 2003 and 2005. Due to our widespread use of broad-spectrum antibiotics we have increased drug-resistant bacteria in uncommon organisms as well so as we eliminate the common bacteria through methods such as immunization, other strengthened bacteria will fill the vacant niche. Dr. Harrison author of the study in collaboration with the Johns Hopkins Bloomberg School of Public Health stated:

PCV7 has been highly successful in preventing pneumococcal meningitis, but it remains a very serious and deadly disease. Of the patients in our study, 8 percent of children and 22 percent of adults died. These findings indicate the need to continue to explore new methods of prevention with a special emphasis on strains that are not covered by PCV7 and strains that are drug resistant. Next-generation vaccines are in development and patients and physicians need to avoid unnecessary use of antibiotics.

We must be more vigilant in our use of treatment and we must consider potential problems of treatment such as the overuse of antibiotics leading to drug-resistant strains of bacteria and of vaccines leaving us open to infection by other non-covered microorganisms.

Vaccination

Parental refusal of vaccination has been increasing in recent years. Allegations have been raised that vaccination may lead to autism, sudden infant death syndrome (SIDS), multiple sclerosis (MS), bovine spongiform encephalopathy (mad cow) and schizophrenia among other ailments. Do any of these claims stand up to empirical evidence? No. There has been no correlation in any of these disease to studies sampling children who were vaccinated against those whose parents refused for them to be vaccinated. Indeed diagnosis of autism has increased despite rejection of vaccinations. The rates of measles, mumps, pertussis and tetanus are rising and unsurprisingly in the populations of unvaccinated children.

There are several questions that we should consider about vaccinating our children. Are side-effects of vaccination adequate when compared to the risks of contracting the illness later in life? This is the most easily argued case for refusal of vaccination, perhaps an individual feels that a risk of a potentially contracting fatal infectious disease later in life is less than the risk of any side-effects to the vaccine. I am disinclined to agree but this is a judgement of opinion, not of fact. However, this raises the question of proxy in medicine as well. Is the parent always the best person to determine what the best decision for the child is as the child cannot make a decision to the previous question? I would be inclined to believe that the parent who refuses vaccination may not have the child's best interest in mind and instead their own but once again I cannot object as this is a judgement of opinion.

The question, however, that does allow a definite answer concerns whether vaccination only affect the child? If vaccination only endangers the child to a possible later infection then vaccination should be the decision of the parents. Vaccination does not. It places risks upon all others with compromised or weak immune systems. The elderly, the young and those with immunodeficiency diseases are all susceptible to any child who may have contracted a disease easily prevented by immunization regardless of whether the other individual may have been vaccinated or not. Failing to vaccinate can cause the death and suffering of many, this cost far outweighs any cost of adverse reactions to the child.

When we consider vaccinating our children we have two choices: either we accept the possibility of reactions to vaccines and attempt to protect the child and those around her through immunizations despite their risks or we act selfishly and risk both the child and those around her with compromised immune systems. I hope that we are brave enough to all choose the former.

Overusing antibiotics

If you enter Reynold’s Hall on the campus of Missouri Southern State University you are likely to see gallon-sized dispensers of hand sanitizer and the restrooms are outfitted with antibacterial soaps. Indeed it is difficult to find non-antibiotic soaps or detergents in most locations. With the scare from H1N1 hand sanitizers can be seen in the entrances of retail outlets and restaurants. One must also note the extent to which antibiotics are prescribed for minor ailments by physicians and the misuse of antibiotics by patients; however, the medical industry is not the sole problem with the emergence of stronger strains of bacteria. An estimate by the UCS suggests that nearly 70% of all antibiotics in the United States are given to healthy livestock including pigs, cattle and poultry (it is suggested that this either counteracts or gives the illusion to counteract unsanitary conditions related with industrial agriculture.

There is a great cost to this excessive use of broad-spectrum antibiotics. A recent survey by bioMerieu and a study by the University of Pennsylvania School of Medicine highlight this cost. According to bioMerieu, sepsis (fatal between 20% and 35% of cases) and septic shock (fatal in 40% to 60% of cases) are increasing in prevalence and are being diagnosed in much younger patients. From an economical perspective this has led to an increase of $5 billion per annum. The University of Pennsylvania recently illustrated that the use of broad-spectrum antibiotics over extended periods of time can lead to dangerous secondary infections by displacing the balance between the immune system and beneficial bacteria in the gastrointestinal tract preventing the bacteria from essentially priming the immune system to respond to other more potent infections.

Infections are a societal problem and have beset human civilizations since their foundations. With many breakthroughs in technology due to human ingenuity costs of bacterial infection were incurred (consider the spread of syphilis, or Treponema pallidum to Europe with the introduction of the boat to the new world or the invention and implementation of air conditioning units which foster an environment conducive to Legionella pneumophila, the bacteria responsible for a nationwide scare during the United States bicentennial). In recent years we have become paranoid. We are shown cases of avian flu, H1N1, MRSA and VRSA and we proceed to wash and bathe with antibiotics and spray or wipe antibiotics on our counters and tabletops and in doing so we are breeding the very organisms we fear. Killing an advertised 99.9% of all bacteria on surfaces we leave 0.1% remaining that are possibly resistant to antibiotics.

What is my recommendation? Leave antibacterial soaps and other products for places they are needed: medical and veterinary facilities. Overuse of antibiotics that stems from our fears of being ill has created a cycle leading to the growth of more dangerous organisms, a growth so quick that quantum effects have been implicated in its mechanism. The next time you hear a news article or see a television report of the dangers of any infection consider that a study by the University College Hospital, London found that simple hand washing was more effective in preventing the spread of bacteria than isolation.