PANDAS, and not the furry kind...

Most, if not all, of us have likely had strep throat as children or even as adults caused by that pesky microorganism known as group A streptococcus. Hopefully all of us listened to our physicians and took every last antibiotic as prescribed and then went about our lives just as before, but for some this doesn't seem to be how things work out. Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS), aside from being a mouth-full, was given its name by Susan Swedo in the 90's while studying other disorders associated with untreated group A infections, and is believed to be the cause behind behavioral cognitive changes seen in some children following strep infections (Zamzow, 2019). Particularly, those thought to be suffering from PANDAS express tics, and obsessive-compulsive behaviors as well as a dampening of motor functions, anxiety, and developmental regression (Hesselmark & Bejerot, 2017).

So what is thought to be happening in these few individuals that are unfortunate enough to develop these symptoms? We aren't entirely sure, which is why some in the medical community still discount the existence of PANDAS all together, but in recent years researchers have come a little closer to an explanation. The culprit, they think, is our own immune system being overzealous resulting in postinfectious autoimmunity resulting in neuroinflammation (Swedo et al., 2017). Surprisingly our good friend the NMDA receptor could have something to do with it! Researchers recently discovered that "rouge antibodies" attack these receptors causing seizures, and in 2018 these antibodies were discovered to attach to a large number of receptors in the basal ganglia which is associated with voluntary motor movement, learning, cognition, and emotion (Zamzow, 2019).

As it currently stands however, there is still a lot to learn about PANDAS before we can know exactly what causes it, or whether it even exits at all as some argue since it is incredibly difficult to link a streptococcal infection, which clears quickly, to symptoms that may not develop until a few months after. For now, patients believed to be suffering PANDAS are treated with immunomodulatory therapy, where a healthy individuals antibodies are infused to deactivate the patients own (Swedo et al. 2019). This treatment also accompanies psychotherapy and antibiotic treatment. But wait... should we be treating patients that no longer have an active infection with antibiotics?! This is definitely an ethical question for concern considering what we already know about the rampant overuse of antibiotics and the "super-bugs" that its brought about. More importantly, immunomodulatory therapies also failed to show any results that bested the placebo they were tested against (Zamzow, 2019). This begs the question of whether these treatments should continue to be administered to individuals considering they have a disorder that some argue doesn't even exist and has no clear etiology.


Original article:
https://www.sciencenews.org/article/strep-throat-infections-brain-ocd-anxiety-mental-illness-kids


Works Cited:

Biomarkers for diagnosis of Pediatric Acute Neuropsychiatric Syndrome (PANS) – Sensitivity and specificity of the Cunningham Panel. Hesselmark, Eva et al. Journal of Neuroimmunology, Volume 312, 31 - 37.

Swedo, S. E., Frankovich, J., & Murphy, T. K. (2017). Overview of Treatment of Pediatric Acute-Onset Neuropsychiatric Syndrome. Journal of child and adolescent psychopharmacology, 27(7), 562–565. doi:10.1089/cap.2017.0042

Zamzow, R. (2019, August 26). How strep throat may spark OCD and anxiety in some kids. Retrieved September 30, 2019, from https://www.sciencenews.org/article/strep-throat-infections-brain-ocd-anxiety-mental-illness-kids.

A Trip to Better Health

Although clinical research involving psychedelics showed great promise over 60 years ago when it began, false information peddled by the media and throughout popular culture framed many of these plant-based chemicals as drugs of abuse or even as the cause of rebellions. As a result, the clinical studies evaluating their potential for good dried up as the drugs became tightly regulated and funding for research became increasingly scarce.

Fortunately, studies began to re-emerge around the 1990’s and this time the potential of these substances could no longer be ignored. Part of what is great about these unique substances is that they can be administered in animal models, allowing us to not only gain greater insight into their efficacy as a method of treatment, but they also help us to learn more about the mechanisms that may be underlying these various mental/emotional disorders.

For example, repeated administration of LSD activates feel-good receptors in the front of our brains, which eventually leads to their down-regulation—making us more sensitive to future feel-good moments (Buckholtz et al., 1990). Post-mortem brain samples of people with major depression showed an increase in these same receptors (Shelton et al., 2008), and mice genetically engineered to have a low amount of these receptors showed a significant decrease in anxiety-like behavior (Weisstaub et al., 2006). This research along with many other studies suggests that LSD could really help people with depression and anxiety disorders!

Currently, the theory is that these receptors may normally play a role in modulating the activity of other brain structures like the amygdala (Weisstaub et al., 2006), which is known for its function in fearful memory-associations (this part of the brain tends to be enlarged in people with PTSD for example (Kuo et al., 2012)), so if down-regulating these receptors can cause a decrease in the bad mojo feelings that come from the amygdala, this could lead to some promising avenues for treating a disorder that we still don’t really understand.

Right now the goal of this research is to break the stigma that these drugs currently hold so that we can finally pursue some novel (and promising!) approaches to the many mental/emotional disorders that are currently plaguing our society. Also by deepening our understanding of the underlying mechanisms of these disorders, we can seek to develop other effective treatments that have less psychoactive symptoms, potentially allowing us to treat even more people.

References:

Buckholtz NS, Zhou DF, Freedman DX, Potter WZ. (1990) Lysergic acid diethylamide (LSD) administration selectively downregulates serotonin2 receptors in rat brain. Journal of Neuropsychopharmacology. 137-148

Kuo JR, Kaloupek DG, Woodward SH. (2012). Amygdala Volume in Combat-Exposed Veterans With and Without Posttraumatic Stress Disorder: A Cross-sectional Study. Archive of General Psychiatry. 69(10),1080–1086. doi:10.1001/archgenpsychiatry.2012.73

Shelton, R.C., Sanders-Bush, E., Manier, D.H., & Lewis, D.A. (2008). Elevated 5-HT 2A receptors in postmortem prefrontal cortex in major depression is associated with reduced activity of protein kinase, A. Journal of Neuroscience. 158,1406-1415

Weisstaub, N.V. et al. (2006). Cortical 5-HT2A receptor signaling modulates anxiety-like behaviors in mice. Journal of Science. 313, 536-540

Needle or Knife? Platelet-rich Plasma as an alternative to surgery

Treatment of hip labral tears are a fairly new (and controversial) topic in the world of orthopedics. Somewhere between 20-50% of hip and groin pain in adults is caused by hip labral tears. The current conversation mostly revolves around the balance between invasiveness and recovery time. In my opinion, the procedure is dependent on the patient.

I am in a unique position in which I can compare both methods from personal experience. In September of 2018, I underwent an arthroscopic hip labral repair for an acute anterior labral tear in my right hip, in which the surgeon first shaved off the bone spurs on my femoral head and then reattached my labrum to my acetabulum. I was cleared to play 7 months later.

In June 2019, I was diagnosed with a similar labral tear in my left hip. This time I consulted a doctor that specialized in non-surgical orthopedic techniques. He suggested a platelet-rich plasma injection that would hopefully kickstart my own body's healing process. Although it wouldn't heal my labrum entirely, the injection would ease my symptoms enough to allow me to play through the season.

During the outpatient procedure, I first had blood drawn from my arm which was centrifuged to isolate the plasma. The medical assistant then added calcium chloride to initiate the release of growth factors from the platelets, and then that solution was injected directly into my hip joint using ultrasound imaging. The whole process took less than an hour, and I walked out of the appointment with no assistance (albeit a slight limp). I was cleared to play 6 weeks later.

At first, the pain improved. This relief unfortunately only lasted a few weeks until my symptoms returned in full force. So, I am meeting with my surgeon soon to schedule my second hip surgery to repair my labrum once and for all. 

Between the two procedures, my outcome was better after hip arthroscopy. However, I trust the evidence that there are instances in which PRP has been very successful. I wish I had been one of those for whom PRP could have been a miracle cure, but I have full confidence that I will have the same success in my left hip after arthroscopic labral repair as I had in my right hip.

Kraeutler, M. J., Garabekyan, T., & Mei-Dan, O. (2016). The use of platelet-rich plasma to augment conservative and surgical treatment of hip and pelvic disorders. Muscles, ligaments and tendons journal, 6(3), 410–419. doi:10.11138/mltj/2016.6.3.410

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5193533/#

Numbing the Effects of Cancer

Growing up, I remember the first weekend of October meant a lot of pink during NFL games as October is breast cancer awareness month. It is estimated that 1 in 8 women and 1 in 883 men will develop breast cancer during their lifetime (“U.S. Breast Cancer Statistics,” 2019). Unfortunately, these statistics may not come as a surprise to many, but they do exemplify the importance of increasing the awareness for breast and associated cancers. Continued research efforts should be undertaken to better understand the many forms of breast cancer and possible treatments for the disease.

One such research study published findings in September on the effects that the local anesthetics ropivacaine and levobupivacaine have on triple-negative breast cancer and melanoma (Castelli et al., 2019). The study was inspired by preliminary research indicating that anesthetics improve the conditions of cancer patients after surgery (Castelli et al., 2019). With this logic, it is possible that local anesthetics could be combined with radiation and chemotherapy in the treatment of cancer.  

Results from the experiments indicate that both ropivacaine and levobupivacaine reduce the viability of the cancerous cells, but both drugs did not have an equal effect on each cancer type. At a concentration of 50 micromolar, levobupivacaine reduced the cell viability of both types of cancer by 50% at 24 hours (Castelli et al., 2019). At the same concentration of 50 micromolar, ropivacaine reduced the viability of triple-negative breast cancer by 50% at 24 hours but did not have the same influence on melanoma (Castelli et al., 2019).  

Reducing the viability of cancer cells by the application of local anesthetic provides a unique approach to aid the currently used treatments for cancer. The results provide promise and a pave pathway for more research into the use of local anesthetics for the treatment of cancer. What other anesthetics can be used and what combinations of anesthetics can give the most promise in reducing cancer cell viability? Hopefully in time, more answers will become available and the rates of breast cancer can be reduced.

        Castelli, V., Piroli, A., Marinangeli, F., d’Angelo, M., Benedetti, E., Ippoliti, R., Zis, P., Varrassi, G., Giordano, A., Paladini,A., Cimini, A. (2019). Local anesthetics counteract cell proliferation and migration of human triple-negative breast cancer and melanoma cells. Journal of Cellular Physiology, 0(0). https://doi.org/10.1002/jcp.29236 

        U.S. Breast Cancer Statistics. (2019, February 13). Retrieved October 4, 2019, from Breastcancer.org website: https://www.breastcancer.org/symptoms/understand_bc/statistics

When the Wolff Runs Away with Your Heart

My father is one in 20,000. One whose heart has the habit of getting away from him, of contracting offbeat. Wolff Parkinson White Syndrome cases are found in less than 20,000 US citizens per year and is only discovered through thorough heart exams or a presence of symptoms. My father's case was a more extreme one, born with an extra electrical pathway in his heart, when he grew anxious his heart beat had an extra dub in it. I remember him often having to lay on the ground and wait for his heart to slow and fix its own rhythm. Most children born with this condition never realize they have it simply due to the fact the extra electrode never fires. In the case of my father, he decided to have surgery done to remove the extra pathway. Inserting a small camera into a vein within his thigh, the surgeon traveled up to his heart, location the pacemaker cells of that specific electrical pathway and cauterized it. For the most part, his palpitations stopped, the electrode only trying to fire when he undergoes extreme anxiety but no longer causing an irregular heart beat. This syndrome is rarely fatal but I do have to say, the surgery helped my dad do the things he wanted to do like play baseball with us kids or ride his bicycle over twenty-five miles a day.

BANG for your (workout) buck?

BANG energy drinks have recently become popular in our everyday world, specifically in the fitness industry. Originally, the company impressed its audience with promises of a healthy energy supplement. The fitness world exploded with support for this new drink, a phenomenon known as the BANG revolution. With the drink containing creatine, it makes sense that health-nuts would craze over it. But is this drink really a 'bang for your buck'?

Containing both creatine and caffeine, the drink is actually a dangerous mixture. According to the FDA, it is safe to consume up to 400mg of caffeine per day. A single can of BANG contains 300mg, almost reaching the average healthy person's daily maximum! Mix that with the other active ingredients of BANG, such as creatine, and you could have a problem. Creatine is used to shorten your muscle relaxation time, helpful in high-intensity workouts. Caffeine is used during endurance workouts. Recent research shows that consuming creatine and caffeine at the same time may decrease both of their effectiveness because you are confusing your body, as both ingredients are meant to create opposite effects. With that in mind, it has been found that drinking BANG is actually decreasing your workout worth (Lindberg, 2019).

On another note, the long-term effects of BANG in your system are alarming. It takes around 12 hours for all traces of caffeine to exit your system, finally allowing your body to return to homeostasis (Ding, 2019). Repetitively placing this much caffeine in your body could lead to long-term problems including increased heart rate and blood pressure, and decreased fertility and digestion. There are also reports of failed drug tests due to the consumption of energy drinks, raising the question of if it is worth it to drink them in hopes of a better workout (Ding, 2019).

As with all things, BANG is not necessarily bad for you (even with its intimidating warning label on the can directly stating the negative effects of drinking high amounts of caffeine). What matters is drinking them in moderation. BANG doesn't seem to be living up to its hype of being a healthy workout supplement, but that doesn't mean it can't be an occasional pick-me-up on your tired mornings.


References

Ding, E. (2019, June 2). Are Bang Energy Drinks bad for you? (studies revealed). Retrieved October 1, 2019, from https://reizeclub.com/bang-energy-drinks-good-bad/.

Lindberg, S. (2019, September 12). Can I Take Caffeine While Taking Creatine? Retrieved October 1, 2019, from https://www.livestrong.com/article/540935-can-i-take-caffeine-while-taking-creatine/.

Lie Detector Tests: Physiology and Ethics

Have you ever watched Love Island? It’s truly a horrible reality TV show based from the UK but it makes for a quality binge-watch. I recently watched an episode where the people on this show undergo a lie detector test in their relationships and wondered, what exactly is the mechanism to detect deception? This led me on my journey to find some interesting literature about established neural connections linked to deception, meaning that there might be some credibility to these lie detector tests.

The most common lie detection test we can think of is the polygraph which is actually utilized in security screenings and interrogation by the US Department of Defense (Cook & Mitschow, 2019). It detects deception-induced stress in the autonomic nervous system (ANS) like heart rate, blood pressure, respirations, and even perspiration (Cook & Mitschow, 2019). However, it is up to the individual jurisdictions to allow polygraph evidence into the court and Colorado is one of the few states that actually allows it.

However, there are other physiological tests for lie detection. Ofen et al. conducted a study using fMRI to scan brain activity while participants lied or told the truth about their own personal experiences or beliefs. They found that both the frontal and parietal cortex showed higher activation when participants lied, demonstrating that there is some detectable connection when they are conjuring up a lie (Ofen et al., 2017). The frontal and parietal cortexes, as we know, are involved in cognitive thinking and decision making, which makes sense when we have to think up something other than the truth on the fly. However, they also found that different areas of the brain were activated based on the content of the lie, either personal experience or an opinion (Ofen et al., 2017). This shows that although there are correlations to the brain during deception, those connections could be blurred by the kind of lie the person is telling which introduces a myriad of conflicting factors if we want to actually implement this.

Let’s discuss the implications of this. Asking about personal experiences and beliefs is useful in court cases for witness testimonies but does that mean we need a fMRI machine in every courtroom? Let’s also consider that these findings do not really prove anything. These findings are variable and based on the context of the lie and these regions of the brain may just be activated because of the individual’s own logical thinking independent of the lie (Ofen et al., 2017). This does provide more insight in mapping the human brain, but even that has not been achieved in its entirety. There's still so much we don't know about our brain so are lie detection tests a means of closing that knowledge gap? Are they even relevant today?

Cook, L. G., & Mitschow, L. C. (2019). Beyond the Polygraph: Deception Detection and the Autonomic Nervous System. Federal practitioner : for the health care professionals of the VA, DoD, and PHS, 36(7), 316–321.

Ofen, N., Whitfield-Gabrieli, S., Chai, X. J., Schwarzlose, R. F., & Gabrieli, J. D. (2017). Neural correlates of deception: lying about past events and personal beliefs. Social cognitive and affective neuroscience, 12(1), 116–127. doi:10.1093/scan/nsw151