Why athletes choke and other reasons the NY Jets break my heart…

Does the postseason really exist? As a Mets, Jets and Islanders fan, it doesn’t seem likely, but rumor has it baseball is still being played, Peyton Manning has one more Super Bowl in him, and the Boston Bruins will NOT win the Atlantic Division. As I sit, simultaneously heartened by headlines like “Islanders improve to 2-0 for first time in 7 years” (NY Post) and haunted by replays of Butt Fumbles past, I’m forced to question why athletes fail to perform to their full potential.

For the sake of argument, let’s chalk Jets’ losses up to choking and not a lack of talent, coaching or general management (indulge me). The concept of choking has been around since at least the 1980s when Roy Baumeister proposed a model for decreased performance under pressure. Since then, psychologists, neurologists and the like have asked why competent people falter in clutch moments, giving rise to two general mechanisms that create “the choke”:

1.   High stress situations that require planning for optimal outcomes decrease the capacity of our long-term (working) memory, lessening our ability to process situations (Otto 2013).

2.   Under pressure, neurons on the left side of the brain involved in analytical thinking fire more frequently than those on the right that control motor skill. As a result, we “overthink” and try to assert conscious control over automatic actions. In these moments, muscle control is lost—a phenomena called focal dystonia or more commonly “the yips” (Linder et al. 2007).

Despite these studies, there is still no clear explanation for why some athletes perform in the clutch, while others flail.

One justification may be that stress has an upside. Stress releases dopamine, a chemical signal, into the prefrontal cortex (front of the brain). Dopamine helps control pleasure and reward centers, and a boost is a good thing; but stress can cause dopamine to flood the prefrontal cortex and disrupt proper function. Some people have enzymes that remove dopamine from the area faster than others. In high stress, high dopamine volume situations, this proves an advantage; on average, however, those with slow-acting enzymes are shown to have higher I.Q.’s (Bronson and Merryman 2013).

Perhaps the NFL will add enzyme analysis to their Wonderlic Test assessment? Or maybe we’re in for a whole new realm of doping? Either way, It’s Tough Bein’ a New York Jets Fan.

New Insight into Proteins and Parkinson's

New research into the role of two enzymes in cell signaling has shed new light on early onset Parkinson’s. While it has been known for a while that two enzymes, PINK1 and PARKIN, are implicated in Parkinson’s, the research of Ordureau et al. has illuminated the specific mechanism of the malfunction.

Parkinson’s is a neurodegenerative disease characterized by mitochondrial malfunction. The mitochondria are a major source of energy in the cell. When the mitochondria are damaged so that they work improperly, they generate chemicals that kill the cell. In a healthy individual, damaged mitochondria are marked for degradation. The degradation keeps the cell healthy.

In Parkinson’s, damaged mitochondria are not properly marked for degradation, causing neuronal cell death. The loss of neurons means that affected individuals are not generating enough of the neurotransmitter dopamine for motor function.

So where do the enzymes PINK1 and PARKIN come into the picture? These enzymes play a crucial role in cell health because they attach the protein ubiquitin to the surface of mitochondria to signal damage and future degradation. In order for a damaged mitochondrion to be degraded, enough ubiquitin must be attached to its surface in order to attract more proteins to break it down. PINK1 identifies damaged mitochondria and attracts PARKIN to them. PARKIN attaches ubiquitin to the mitochondria. The interesting thing about this mechanism is that once ubiquitin is attached to the mitochondria, it further accentuates the role of PARKIN so that even more ubiquitin is attached, ensuring that the damaged mitochondria will be degraded. This is called a ‘feed-forward’ mechanism.

This research is significant because even though PINK1 and PARKIN have been known to play a role in Parkinson’s the specifics of their role are only just now understood. For individuals with early onset Parkinson’s, the dysfunction of PINK1 and PARKIN means that damaged mitochondria are not being degraded, leading to cell death and the progression of Parkinson’s. With more specific details about the way that these two enzyme work, new avenues for treatment can be investigated.

Reference: Ordureau, Alban, et al. 2014 Oct. Quantitative Proteomics Reveal a Feedforward Mechanism for Mitochondrial PARKIN Translocation and Ubiquitin Chain Synthesis. Molecular Cell. http://www.cell.com/molecular-cell/abstract/S1097-2765%2814%2900714-X

Heart Disease and Stress: Men vs Women

A recent study conducted by researchers at the Duke Heart Center was published in the Journal of the American College of Cardiology. This study explored mental stress and the physiological responses of patients with stable heart disease. They concluded that men and women have different cardiovascular and psychological responses to mental stressors, and that physicians need to take this research into account when evaluating and treating patients with cardiovascular disease.

The study looked at 56 women and 254 men that were diagnosed with heart disease and were enrolled in a larger REMIT study. These participants were given three mentally stressful tasks, and then given a treadmill exercise test. Researchers conducted electrocardiography of the heart, took blood samples, and measured blood pressure and heart rate changes.

They were able to conclude that men had a greater change in blood pressure and heart rate due to the mental stress. Conversely, they discovered that women experienced myocardial ischemia, which is a decrease in blood flow to the heart, as well as experiencing increased platelet aggregation, which is how blood clots start to form. Additionally, when compared to men, the researchers saw that women expressed more negative emotions during the mental stress test.

Taken at face value, we can see that both men and women respond physiologically very differently to mental stressors. If physicians do not understand the unique risks for men vs women due to mental stress and how it can affect their on cardiovascular response, then they could be missing a vital component necessary for diagnosing and treating these patients.

The researchers do go on to say that further studies are needed to further understand the sex differences in cardiovascular response. However, I believe that this initial research has provided new understanding about the link between a patient’s sex, mental stress response, and cardiovascular implications. 

References:

http://www.medicalnewstoday.com/articles/283808.php

Is This the Beginning of the End for Injections?

A fear of needles is very real for many people.  Unfortunately, in many cases, injections are the only means of delivering treatments into the blood stream.  Many biopharmaceuticals would be broken down in the GI tract too quickly to be absorbed and utilized by the body and would essentially be wasted if taken as a pill.  The brilliant minds at MIT and Massachusetts General Hospital (MGH) have found a way around this problem.

Researchers have developed a needle coated capsule that effectively delivers drugs into the blood stream through the stomach and intestines.  This delivery system actually delivered insulin more efficiently than a subcutaneous injection in their pig models!  They observed faster and larger drops in blood sugar with these capsules than with the normal injections.

The researchers tested this capsule with insulin but noted that it would be best at delivering “biologics” or biopharmaceuticals, such as antibodies for cancer or autoimmune diseases or vaccines.  The potential benefit to patients is unbelievable.  Imagine if cancer or Rheumatoid Arthritis treatments could be an outpatient procedure that didn’t require four hour infusions.  What if the increased delivery efficiency meant smaller doses and decreased side effects?!

This also has incredible potential for vaccinations in rural areas or third world counties.  A shipment of pills would be much easier to deliver and would require substantially less manpower to administer than the same quantity of medicine administered via injection.   Plus the risk of blood borne pathogens being spread would be drastically reduced.  People all over the world can benefit from new products like this that make healthcare more accessible. 

This is just one step in the ever changing field of medicine, and the progress shows no signs of slowing down.  These same researchers are perfecting their product to even more efficiently deliver drugs and I’m sure other innovations are on their way as well.

References

Trafton A. 2014 Oct 1. New Drug Delivery Capsule May Replace Injections [Internet]. Cambridge(MA):MIT News Office; [cited 2014 Oct 13] . Available from: https://newsoffice.mit.edu/2014/microneedles-drug-delivery-capsule-1001#.VCzXTlrhxrU.reddit

Bionic Eyes

Argus II Bionic Eye:

Good News for Ocular Disorders

Image: Argus II Bionic Eye

Technology appears to be progressing by leaps and bounds on a weekly to daily basis. Especially when it comes to the developing fields of biomedical mechanics, one has to wonder if society has already entered the era of cyborg nanotechnologies. Most recently, this type of technology has been displayed with the ground-breaking invention of the Argus II epiretinal prosthesis, also known as the bionic eye. Its capabilities have profoundly allowed patients suffering from macular degeneration and retinitis pigmentosa to have their eye site restored by enhancing retinal stimulation and spatial resolution in the eye (Cruz et al. 2013). For sci-fi fans and science buffs alike, this is an incredibly exciting breakthrough where science has exceeded the normal limitations of the human body and enhanced it through the implementation of mechanical parts. 

After surgical implantation of the retinal microchip, “the Argus II operates by using a miniature camera mounted in eyeglasses that captures images and wirelessly sends the information to a microprocessor (worn on a belt) that converts the data to an electronic signal and transmits it to a receiver on the eye. The pulses travel to the optic nerve and, ultimately, to the brain, which perceives patterns of light and dark spots corresponding to the electrodes stimulated” (Considine 2013). The Argus II system essentially bypasses the damaged cones and rods in the eye and allows for the electrochemical impulses to proceed down the optic nerve to the brain. 

There have been studies involving transplant patients of the Argus II system that have demonstrated high efficacy rates to the restoration of lost eye site. In one study, 21 subjects were examined 6 months after the implantation and demonstrated a 87% improvement in eye site (Humayun et al.2012). Another study conducted on 28 subjects with the epiretinal implantation device, demonstrated high rates of patients accurately identifying letters and words which was indicative of reproducible spatial resolution (Cruz et al. 2013). Both of these studies help to validate the successful advancements made in biotechnologies involving artificial eye transplants. 

Lastly, with technology progressing at such a fast pace, it’s vital that the ethical systems of modern society stay up to speed with developing biotechnologies. The ethical implications of such technologies should be democratically assessed and laws set in place to protect human civil liberties. I think these kind of nanotechnologies could improve the lives of many who are living with crippling disabilities. On the flip side of that coin, I think it’s also important to critically evaluate the potential repercussions of hybridizing man with machine and what the future consequences will be for generations to come.

References:

Considine, A. [2013 Feb 15]. New bionic eye can make you just like the terminator [Internet]. Motherboard web site [cited in 2014 Oct 13] Available from: http://motherboard.vice.com/en_ca/blog/new-bionic-eye-can-make-you-just-like-the-terminator

Cruz L, Coley BF, Dorn J, Merlini F, Filley E, Christopher P, Chen FK, Wuyyuru V, Sahel J, Stanga P, Humayun M, Greenberg RJ, Dagnelie G. 2013. The Argus II epiretinal prosthesis system allows letter and word reading and long-term function in patients with profound vision loss. The British Journal of Ophthalmology [Internet]. 97(5): 632–636. Available from: http://serach.ebscohost.com/. 

Humayun M, Dorn JD, Ahuja AK, Caspi A, Filley E, Dagnelie G, Salzmann J, Santos A, Duncan J, daCruz L, Mohand-Said S, Eliott D, McMahon M, Greenberg RJ. 2012. Preliminary 6 month results from the Argus II epiretinal prosthesis feasibility study. Engineering in Medicine and Biology Society [Internet]. Available from: http://serach.ebscohost.com/.

Image 2: Argus II (Artificial Retina) 

New Pathway Involved in High Blood Pressure and Therapeutic Implications

A new study has identified a key regulator in the physiological pathway for increasing blood pressure. This hormone, called ouabain, had been identified decades ago, but little was known about how the steroid functioned in our bodies. Researchers from the University of Maryland and the University of Ottawa discovered how ouabain plays a crucial role in raising blood pressure (BP) and contributing to hypertension (high BP).

The central nervous system influences BP through the sympathetic nervous system by controlling the release of several hormones. One of these hormones is angiotensin II (Ang II), which is released by the hypothalamus. It was previously known that increasing Ang II results in an increase of antidiuretic hormone (ADH). ADH increases blood volume, resulting in an increased BP. However, the pathway is more complex with several other hormones involved. Researchers found that Ang II influences the production and release of the steroid ouabain. In a similar way that long-term potentiation works as described in the physiology reading for TBL #1, constant release of Ang II leads to a mechanism involving ouabain and some additional hormones that make arterial myocytes more sensitive to sympathetic stimulation. This leads to increased frequency of arterial constriction and chronic hypertension. So when Ang II levels are high for a prolonged time, circulating ouabain levels are high and lead to a reprogramming of key ion transporters.

The study found that in arterial myocytes, ouabain increases the expression of three membrane pumps involved in sodium and calcium transport. Since ouabain is a steroid, it can diffuse through the plasma and nuclear membrane and directly impact transcription of the genes coding for these pumps. Ouabain also stays in circulation for a long time after it is produced, which allows it to increase the expression of these plasma membrane transport pumps by two to three-fold greater than when ouabain is not in circulation. This change in the protein landscape of the plasma membrane allows the myoctyes to be more easily sympathetically stimulated, leading to contractions occurring more often in arterial smooth muscle.

With this information on the role of ouabain in the sympathetic pathway for increasing BP, therapeutic research can look for a way to block ouabain and its effects. Developing a therapeutic to prevent ouabain synthesis or an antibody to bind and inhibit this steroid should be able to improve the lives of people with hypertension.

References

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183521/pdf/pone.0108916.pdf

http://somvweb.som.umaryland.edu/absolutenm/templates/?a=2903&z=41

Could Sugar Sweetened Beverages Impair Adolescent Brain Development?

When walking into a restaurant a common site to behold is high saturated fatty acid and simple sugar food along with sugar sweetened beverages, also called the “western diet.” Unfortunately, this diet can lead to obesity, Type 2 Diabetes, and cardiovascular disease. Recent research has linked the western diet with spatial memory impairments. However, no study has looked solely at the impact of sugar sweetened beverages on adolescent brain development.

In a study conducted at the University of Southern California, high fructose corn syrup-55 (HFCS-55) and sucrose, the most commonly added sweeteners in the United States, were given to adolescent and adult male rats to determine their impact on hippocampal-dependent spatial memory, metabolism, and neuronal outcomes. Each rat was given either normal water (control), water with sucrose, or water with HFCS-55 for 30 days along with normal water and low-fat chow. After the 30 day sugar diet the rats were placed in a series of mazes to test spatial memory, anxiety effects based on the high sugar diet, and non-hippocampus learning and memory processes. 

Adolescent rats that were given the sugar sweetened beverages showed impaired spatial memory but no effects were found on anxiety or learning and memory processes in other parts of the brain when compared to the controls. Adult rats on the other hand showed no difference between control and experimental groups after placed in the 3 mazes. Plasma insulin levels, liver cytokines, and hippocampal cytokines were also checked using a glucose tolerance test, immunoblotting, and an enzyme-linked immunosorbent assay. As expected higher plasma insulin levels were found in adolescent rats given the sugar sweetened beverages, however, no such changes were discovered in adult rats. Liver cytokines were also higher in adolescent rats on the sugar sweetened beverage diet but, again, no such changes in adult rats were found. Only the HFCS-55 adolescent rats had higher levels of hippocampus cytokine levels while the sucrose adolescent rats and the adult rats showed no difference when compared to the control groups.

This study shows that consuming excess sugar during vital development stages can have adverse effects on cognitive development and metabolic functions but more studies are needed to determine the effect on human adolescents. Until then, soda and other sugar sweetened beverages should be minimally consumed by all age groups but most specifically by adolescents.  

Why antibiotic resistance is a problem?

-Causes?
Antibiotic resistance in bacteria happens when a given antibiotic can no effectively kill or stop the growth of a certain strain of bacteria.  Antibiotic resistance occurs when someone takes an antibiotic and the bacteria that are resistant to the given antibiotic survive.  Essentially the antibiotic exerts a selective pressure on the bacteria, promoting the growth of the strongest or most resistant strain of bacteria.  Bacteria typically obtain resistance via a genetic mutation or get the resistance from another bacterium.

-Increasing rates of use and increasing resistance
Often times patients demand antibiotics when they are sick with the common cold without realizing that an antibiotic would have absolutely no positive impact on their viral infection.  In addition, patients often do not follow the instructions on their prescription and may discontinue an antibiotic as soon as they start feeling better.  This increases the likelihood that the patient will harbor an antibiotic resistant strain.

-Cost of Antibiotics
Antibiotic resistant strains of bacteria require the use of extensive treatments as well as stronger antibiotics such as Levaquin.  Despite being available as a generic, the cost of generic Levaquin, Levofloxacin, is exceedingly high even with prescription coverage.  This puts a significant financial burden on our healthcare system.  Tufts University estimates that the total cost of Antibiotic resistant infections is in the range of 20 billion dollars without considering the corresponding societal costs of missed work and lowered productivity.

-Why should we care?
Do you ever want to get a fecal transplant? I didn't think so.
Antibiotic resistance is an area of increasing concern because infections that were once curable with a simple course of antibiotics are requiring much more extensive course to stop the infection.  This is especially problematic in young children and the elderly.

-What should be done?
Many of the ways to help curb antibiotic resistance rely heavily on the patient taking the antibiotic.  Patients should be sure to follow the instructions on their prescription exactly and not take left over antibiotics when they start feeling sick.  Another key point is that antibiotics should not be prescribed for viral infections.

References
http://www.tufts.edu/med/apua/about_issue/about_antibioticres.shtml
http://www.rxlist.com/antibiotic_resistance-page2/drugs-condition.htm#concern
http://www.tufts.edu/med/apua/consumers/personal_home_5_1451036133.pdf

Stem Cell Research has Unlocked a Potential Cure to Type 1 Diabetes

Science is a beautiful process, a quasi-passing-of-the-intellectual-torch from researcher to researcher, often decades apart, ultimately yielding new translational medicine for a provider's repertoire.  

In the 1920s, diabetes mellitus was a real, pathologic beast and the development of a recombinant DNA protocol to produce synthetic insulin occurred in1978, but did not yield a cure to the disease.  In 2012, Schulz et. al fine-tuned a promising protocol in differentiating human embryonic stem cells (hESC) into glucose-stimulated, insulin-secreting tissue, having the potential for transplantation into Type-1 diabetic patients (2012). A stem cell researcher named Doug Melton has modified and expanded on Schulz's et. al work and has found a way to coax hESC into becoming functional beta cells. 

             

Figure 1 Figure 1a shows the extraction and grow processes of hESC (ES).
Figure 1b illustrates the various protein factors needed to differentiate hESC
(ES) to the subsequent pancreatic endodermal precursor cells (PE).

After 17 years of collaboration, researchers have defined a controlled differentiation process.  hESC are extracted from the inner cell mass of a blastula and implanted on top of a layer of treated embryonic skin cells.  The cells adhere to this layer, divide, and spread over the entirety of the dish producing a pluripotent embryonic cell line (NIH Stem Cell Information, 2014). Melton then subjected these embryonic stem cells to rounds of various transcription and growth factors, which activated differentiation genes that served to demarcate these cells into pancreatic endodermal precursor cells (PE) and later functional beta cells (Schulz et. al, 2014 and Pagliuca, F et. al, 2014). 

The potential for hESCs is undeniable. Significant bioethical debate surrounds the use of hESC in medicine which has postponed the development of this cure.  Many people object to the use of hESC because they are derived from the embryoblast cells of a blastula that may be inculcated with the same rights and dignities of a fully developed fetus (Stein, 2014).  As the future generation of providers, we will have to traverse this morally ambiguous area and decide if stem cell technology is ethically sound.  When do you think life starts?  I would argue that life is defined as any degree of higher cognitive development.

Because Type-1 Diabetes is characterized by autoimmunity of beta cells, Melton made Schulz's work viable by developing a strategy to evade the patient's immune system.  After implantation, the cells are provided a tea-bag-like shield in which they are not degraded, but still activated by intracellular glucose levels, producing insulin that can still diffuse out of the membrane like tea. Now we can push this to clinical trials.

Brilliant!

Figure 2 Figure 2 depicts Beta-like Cells (green) that produce insulin
that form islet clusters reminiscent of the beta islets of the pancreas

 Watch Melton Grow Beta Islet Clusters!


References:

NIH Stem Cell Information. 2014. Stem Cell Basics. NIH Online. [Internet]. Available from: http://stemcells.nih.gov/info/basics/pages/basics5.aspx

Pagliuca, F. Millman, J., Gurtlet, M., Segal, M., Dervort, A., Ryu, J., Peterson, Q., Greiner, D., Melton, D.. 2014. Generation of Functional Human Pancreatic B Cells In Vitro. Cell. [Internet]. Available from: http://hsci.harvard.edu/files/hsci/files/pagliuca_et_al_cell_2014.pdf

Schulz, T., Young, H., Agulnick, A., Babin, J., Baetge, E., Bang, A., Bhoumik, A., Cepa, I., Cesario, R., Haakmeester, C., Kadoya, J., Kell, J., Kerr, J., Robins, A.. 2012. A Scalable System for Production of Functional Pancreatic Progenitors from Human Embryonic Stem Cells. PLOS One. [Internet]. Available from: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0037004#pone.0037004-DAmour1

Stein, R. 09, October, 2014. Scientists Coax Human Embryonic Stem Cells into Making Insulin. NPR Online. [Internet]. Available from: http://www.npr.org/blogs/health/2014/10/09/354708628/scientists-coax-human-embryonic-stem-cells-into-making-insulin


            

    

What do your oral hygiene habits look like? Do you have bad breath?

Are you the kind of person who brushes their teeth once a day, flosses maybe once a month and uses mouthwash maybe every other day? Or are you the person who brushes their teeth at least two times a day, flosses every day and uses mouthwash once a day?

A study from the Journal of Natural Sciences wanted to “determine the prevalence of oral hygiene practices, smoking habits and halitosis among graduate dental students and correlating the oral hygiene practices, oral health conditions to the prevalence of self perceived oral malodor.” Dental conditions such as gingivitis, periodontal disease, gross carious lesions and poor oral hygiene are shown to cause bad breath. Gingivitis is a periodontal disease that is due to the inflammatory response to bacterial build up, known as plaque, around the gums. Gases being produced by bacteria cause bad breath from periodontal disease. The gases emitted are usually sulfur compounds like dimethyl sulfide, methyl mercaptan, hydrogen sulfide and allyl methyl sulfide.  Cavities also lead to bad breath. Cavities are permanently damaged areas of the surface of the teeth that turn into holes. These holes come from plaque build up on teeth and when it is not removed it turns into tartar to calculus. The acids in the plaque damage the enamel covering of the teeth thus causing cavities. Often times, treatment of the dental condition can help eliminate bad breath. An example of this is to remove decay from teeth and get them filled, also known as getting a cavity filled.

A major component to regular health is oral health. So why is it so hard to convince people to take better care of their teeth?  In this study, the undergraduate dental students completed a questionnaire that assessed habit of oral hygiene, such as “brushing, flossing, tongue cleaning, use of mouthwash, self-perception of oral health, awareness of bad breath, timing of bad breath, caries and bleeding gums, dryness of mouth, smoking habits and tongue coating.”

Results found that the women had better oral hygiene habits as compared to men. Men were also shown to have a higher percentage of bad breath as compared to females. This study also found that students who brushed their teeth twice a day, changed their tooth brush after 3 months, used tongue cleaner and used mouth wash had better breath as compared to those who didn’t have as good of oral hygiene habits. Even though females were shown to have better oral hygiene habits, there is still room for improvement in oral health behavior.

Citations:

Setia S, Pannu P, Gambhir RS, Galhotra V, Ahluwalia P, Sofat A. Correlation of oral hygiene practices, smoking and oral health conditions with self perceived halitosis amongst undergradu- ate dental students. J Nat Sc Biol Med 2014;5:67-72.

Katz, D. (2014, January 1). GINGIVITIS. Retrieved January 1, 2014, from http://www.therabreath.com/gingivitis.html

Dental cavities. (2014, October 9). Retrieved October 11, 2014, from http://www.nlm.nih.gov/medlineplus/ency/article/001055.htm