Cough Syrup to Treat Phantom Limb? Really?

        Phantom Limb Pain (PLP) is a common problem in patients following an amputated extremity. PLP is the sensation of pain that a patient experiences in a limb following removal. It is estimated that 45-85% of amputees experience some degree of phantom limb sensation following amputation (Kuffler, 2018). Patients typically experience PLP in the first month following surgery and again at one-year post-op. Typically, this pain dissipates over time, but some patients continue to experience intense pain chronically. PLP affects patients physically and mentally and often inhibits rehabilitation. The cause of this neuropathic pain is not entirely understood. Some research has associated the presence of neuromas, which are growths of sensory nerve fibers, at the site of amputation (Ramachadran et al., 1998). These neuromas may form from nerve endings that are severed during the amputation. Prior research has led to the belief that some of the pain associated with PLP is due to the nerves continuing to produce action potentials (Ramachadran et al., 1998). However, other possible explanations have been made to describe the cause, including brain changes, dorsal horn changes, and epigenetics.

Presently, there is no standard treatment for PLP. Non-medication therapies are used, including mirror box therapy, with varying levels of success. A few treatments that healthcare professionals may trial for PLP patients include local anesthetics like lidocaine administered into the spinal canal, NSAIDs, antidepressants, anticonvulsants, and opioids (Kuffler, 2018). However, non-traditional treatment approaches have been studied too. Intriguingly, dextromethorphan, also known as Robitussin, has been used to treat PLP. Dextromethorphan is an N-methyl-D-aspartate (NMDAR) antagonist, which has been found to be successful in treating neuropathic pain, by preferentially binding to the NMDA receptor, which is a hypothesized mechanism of the pain. Another NMDAR antagonist is ketamine, which carries increased cognitive and CNS side effects. In a small 3-week study in 2002, PLP patients who received dextromethorphan experienced relief of PLP symptoms at doses of 120 and 180 mg, without significant side effects, compared to the control group (Abraham et al., 2002). Additionally, a study was performed in 2014, testing the efficacy of low-dose dextromethorphan on post-surgical pain in mice. It showed improved behavior and cognitive function in treatment of hyperalgesia following surgery (Morel et al., 2014). Despite the promising results in these small studies, there have been few studies to date testing the efficacy of dextromethorphan for the treatment of PLP. Dextromethorphan, when taken in therapeutic doses, is unique in that it may treat recurrent PLP without the risks associated with opioids or ketamine. However, further expansion of clinical studies is necessary to determine if dextromethorphan is an effective treatment for PLP.

 

Abraham, R., Marouani, N., Kollender, Y., Meller, I., & Weinbroum, A. A. (2002). Dextromethorphan for phantom pain attenuation in cancer amputees: A double-blind crossover trial involving three patients. The Clinical Journal of Pain, 18(5), 282–285. https://doi.org/10.1097/00002508-200209000-00002

Kuffler, D. P. (2018). Coping with Phantom Limb Pain. Molecular Neurobiology, 55(1), 70–84. https://doi.org/10.1007/s12035-017-0718-9

Morel, V., Pickering, G., Etienne, M., Dupuis, A., Privat, A.-M., Chalus, M., Eschalier, A., & Daulhac, L. (2014). Low doses of dextromethorphan have a beneficial effect in the treatment of neuropathic pain. Fundamental & Clinical Pharmacology, 28(6), 671–680. https://doi.org/10.1111/fcp.12076   

Ramachandran, V. S., & Hirstein, W. (1998). The perception of phantom limbs. The D. O. Hebb lecture. Brain: A Journal of Neurology, 121 ( Pt 9), 1603–1630. https://doi.org/10.1093/brain/121.9.1603

Possible new drug to treat hypertrophic cardiomyopathy?

 

Will Listening to the LoFi Girl Improve Your Test Scores?

Believe it or not, studying is a common activity for us students and we tend to do these things for long periods of times, especially if you are a MSBS student. Everyone has their different studying techniques and environments that they prefer. Some like dead silence, isolated in their room, others love coffee shops where there is a ton of activity around. A common thing people like to do while studying or doing work , is to listen to music. Many studies have investigated whether listening to music has affected learning and memory, and the results vary. 

This study tested college students’ memories while listening to either pop music, classical music, or silence. The results demonstrated that college students recall more content after listening to pop music or silence during study when compared to classical music (Mensink, M., Dodge, L., 2014). The researcher believed that classical music had negative effects because the students were not used to this type of music and found it more distracting than pop music. The results from their study also showed that silence compared to music showed significant results. This suggests that the auditory environment potentially limits the student’s ability to study. 

Another study compared background music with and without lyrics to determine if it affected work performance. Background music with lyrics had a greater effect on attention performance compared to that without lyrics.  They also found that background music increases work satisfaction (Shih, N., Huang, H., 2012). 

Looking at all of these studies, it seems that more research is needed to determine whether it is beneficial to listen to music while studying. It seems that listening to music while studying is very personal and results vary from each person. From personal experience I believe listening to lofi or soft background music at low volume, that does not have lyrics keeps me focused! What do you guys think about background noise while you study for your exams? 

Shih, Y. N., Huang, R. H., & Chiang, H. Y. (2012). Background music: effects on attention performance. Work (Reading, Mass.), 42(4), 573–578. 

Mensink, C., M., Dodge, L. (2014). Music and memory: effects of listening to music while studying in    college students. University of Wisconsin. http://digital.library.wisc.edu/1793/77348.

Fruit fly and new Alzheimer's Disease mechanism

 Researchers at the Tokyo Metropolitan University have presumably discovered a new mechanism by which tau aggregation causes Alzheimer's Disease (AD). According to the researchers, their primary focus was on the MARK4 (microtubule affinity regulating kinase 4) enzyme and some mutation is occurring that induces dysfunction of this enzyme. It is phosphorylating tau at sites Ser 262 and Ser 356. As you may imagine, when tau is working correctly it serves as a component of the neuronal cytoskeleton. MARK4's job is to keep the microtubules from disassembling at a constant rate. Therefore, a mutation in this enzyme can have drastic effects on microtubule structure affinity, and intern, you begin to see the characteristic aggregation of these proteins that are seen in AD.  

Essentially what the team did was they introduced a genetically modified MARK4 enzyme into the fruit fly (drosophila) which had several chemical mutations via functional groups. What they noticed was that the mutated MARK4 caused an even greater effect of misfolding and aggregation of tau proteins. Not only that but it also made it a whole lot easier for the tau to aggregate in the first place. 

As for my thoughts, MARK4 is not just known to act on tau but other proteins as well. The researchers do mention this so it is very great research indeed but it almost feels as though what is the point. It is a smaller mechanism of action for tau aggregation due to hyperphosphorylation. I do believe this insight to be somewhat substantial but you also have to take into account that this was done in a fruit fly model. I would say that until the same results can be seen in mouse model neurons or if we can find this mechanism in post mortem AD patients, it is not a huge breakthrough in AD neurodegeneration. 

AD certainly is a difficult condition to study and unfortunately, no treatments have been found. There are just too many proteins that are affected and as I have come to realize, usually within neurological research, new questions arise that take into account a whole new brain structure or region and before you know it, questions are answered with more questions. 

My final thought is that since there is no clear treatment, would you be inclined to go through an AD risk-associated gene screening? 

Oba, T., Saito, T., Asada, A., Shimizu, S., Iijima, K. M., & Ando, K. (2020). Microtubule Affinity Regulating Kinase 4 with an Alzheimer’s disease-related mutation promotes tau accumulation and exacerbates neurodegeneration. Journal of Biological Chemistry, jbc.RA120.014420. https://doi.org/10.1074/jbc.RA120.014420

ADHD a Risk Factor For Diabetes Mellitus

    Attention‐deficit/hyperactivity disorder is a neurodevelopmental disorder with childhood-onset and usually lasts into adulthood. A study done by Xu et al. (2020), looked at the association between ADHD and diabetes in adulthood in the United States. They analyzed 52,821 adults with a weighted mean age of 45.5 years and found that 1,642 of these participants had a diagnosis of ADHD and 4,631 of them had a diagnosis of diabetes. Additionally, the researchers adjusted for a variety of factors and found that there was no significant association between age, sex, race/ethnicity, or obesity status (Xu et al., 2020). This means that the association between ADHD and adult diabetes mellitus was significant and was independent of age, sex, and BMI. So what? These findings are important for two reasons. One, early screening for diabetes among those with a diagnosis of ADHD might be an important intervention to consider. Two, encouraging healthy lifestyles in children is important, but it might be even more important to those diagnosed with ADHD. 

    Why is it that ADHD is a possible risk factor for diabetes in adulthood? Could it have something to do with the physiology of those with ADHD or could it have something to do with the behaviors due to ADHD? Further research is needed to assess the mechanisms behind this association. 

    Finally, this association can be looked at under an ethical lens. At what point is knowing this association beneficial versus harmful? If the association is high and the diagnosis of ADHD is correct, one can take early measures and screening to prevent or prolong diagnosis of diabetes in adulthood. However, if ADHD is incorrectly diagnosed, negative implications that come with diagnosis may affect the person with a diagnosis unnecessarily as substantial controversy regarding correct diagnosis exists (Ford-Jones, 2015). What are your thoughts? 

References:

Ford-Jones, P. C. (2015). Misdiagnosis of attention deficit hyperactivity disorder: ‘Normal behaviour’ and relative maturity. Paediatrics & Child Health, 20(4), 200-202. doi:10.1093/pch/20.4.200

Xu, G., Liu, B., Yang, W., Snetselaar, L. G., & Jing, J. (2020). Association of attention‐deficit/hyperactivity disorder with diabetes mellitus in US adults. Journal of Diabetes. doi:10.1111/1753-0407.13107

Can Weight Training Decrease Your Risk of Cancer?

Physical exercise has been known to provide many health benefits such as improved cardiovascular health and overall physical function, reduced blood pressure, and bone and muscle development (Mazzilli, Matthews, Salerno, & Moore, 2019). Have you heard that muscle-strengthening activities such as weight lifting and resistance training can lower your risk of cancer?

A national cohort study was recently used to explore the relationship between weight training and the risk of the ten most common cancer types. According to the National Institutes of Health (NIH)-American Association of Retired Persons (AARP) Diet and Health Study, the ten most common types of cancer include colon, kidney, bladder, breast, lung, non-Hodgkin lymphoma, pancreatic, prostate, rectum, and melanoma. The purpose of this study was to determine the cancers associated with weight training and if there were any correlations between sex, age, and BMI. It was determined that participants who engaged in weight lifting had a significantly lower risk of colon cancer and nearly significantly lower risk for kidney cancer than those who do not engage in weight lifting (Mazzilli, Matthews, Salerno, & Moore, 2019). The researchers in this study believe that the benefits of physical activity could reflect a decreased risk of cancer through several biological mechanisms. They proposed that strength training promotes increased muscle gain and strength, which is important for maintaining glucose homeostasis (Mazzilli, Matthews, Salerno, & Moore, 2019). If a person has trouble maintaining glucose, this could be correlated with an increased risk of colon cancer. Additionally, strength training is a major activator of a regulator for cell growth and metabolism called mTOR (Mazzilli, Matthews, Salerno, & Moore, 2019). In cancer patients, mTOR is often not regulated properly and can be associated with cancer progression.

 

This particular study claims to have found a correlation between weight training and risk for different types of cancer. However, the researchers acknowledged that their study was the first prospective study to truly assess this correlation and that they relied on self-reported data from their participants. Therefore, can it be assumed that if you weight train, you can actually decrease your risk of colon or kidney cancer? Ultimately, we have the autonomy to choose whether we want to exercise, but if there is a little bit of evidence it might decrease your risk of cancer… would you increase how often you engage in muscle-strengthening activities?

Mazzilli, K. M., Matthews, C. E., Salerno, E. A., & Moore, S. C. (2019). Weight Training and Risk of 10 Common Types of Cancer. Medicine & Science in Sports & Exercise, 51(9), 1845-1851. doi:10.1249/mss.0000000000001987

Mo Hotta Mo Betta

Have you ever wondered why you can eat a raw habanero with no problem while your friends and family think you’re crazy? Genetics just might be on your side (or against you depending on how you look at it). The gene TRPV1 is a heat-gated ion channel that is expressed in most heat-sensitive nociceptive neurons (Mckemy, 2011). It also is a receptor for capsaicin which is the active chemical in spicy peppers. Capsaicin binds to TRPV1 receptors sending a signal to the brain which is interpreted as heat and if it is activated enough, is interpreted as pain. The crazy part is that massive neuronal calcium influxes triggered by topical exposure to sufficient concentrations of capsaicin is potentially cytotoxic, which triggers a reflex down-regulation of TRPV1 activity. This means that the neurons become less responsive when TRPV1 is exposed to capsaicin resulting in analgesic effects (Mccarty et al., 2015).

  

That still does not explain why some people can tolerate spicier foods than others. Well, it is thought that some people just have less TRPV1 receptors (Törnwall et al., 2012). This means that when they eat that raw habanero, some capsaicin binds the receptors that are available, resulting in neuronal impulses that might only be interpreted as heat. Others with more receptors will get more neural impulses that will be interpreted as pain. It is also thought that you can desensitize these receptors overtime by eating more spicy food more frequently (Crane, 2015). There is also some research suggesting that those with thrill-seeking personalities just might like spicy foods because it is fun (Byrnes et al., 2013). 

Byrnes, N. K., & Hayes, J. E. (2013). Personality factors predict spicy food liking and intake. Food Quality and Preference, 28(1), 213-221. doi:10.1016/j.foodqual.2012.09.008

Crane, B. (2015, February 23). To Enjoy Spicier Food, Train Your Nervous System. Retrieved October 13, 2020, from https://www.theatlantic.com/health/archive/2015/02/learning-to-handle-spicy-food/385606/

Mccarty, M. F., Dinicolantonio, J. J., & O'keefe, J. H. (2015). Capsaicin may have important potential for promoting vascular and metabolic health: Table 1. Open Heart, 2(1). doi:10.1136/openhrt-2015-000262

Mckemy, D. D. (2011). A spicy family tree: TRPV1 and its thermoceptive and nociceptive lineage. The EMBO Journal, 30(3), 453-455. doi:10.1038/emboj.2010.350

Törnwall, O., Silventoinen, K., Kaprio, J., & Tuorila, H. (2012). Why do some like it hot? Genetic and environmental contributions to the pleasantness of oral pungency. Physiology & Behavior, 107(3), 381-389. doi:10.1016/j.physbeh.2012.09.010

Endochondral Ossification only occurs in fetuses, right?

Nope. Well maybe not exactly endochondral ossification, but a very similar mechanism. Let me explain...Researchers at Stanford have recently come up with a way to regenerate cartilage in the joints of mice. Typically, if one wanted to regenerate cartilage they would drill tiny microfractures into the tissue which would promote the damaged cartilage to create fibrocartilage. While this is new tissue covering the bone, according to the co-author on the paper Dr. Chan, it is not the same. The fibrocartilage that results is primarily in the form of scar tissue, does not have the elasticity of natural cartilage, and degrades relatively quickly.

So how does it work? The researchers had the idea to stimulate the tissue to act like it is going to start forming bone again, but then stop it at the cartilage phase (this is my endochondral ossification analogy). To do so, they start with the same first step of drilling small microfractures into the damaged cartilage tissue then add a molecule called "bone morphogenetic protein 2" (BMP2). BMP2 initiates the formation of bone at these microfracture sites. Next, in order to stop the process midway through the bone development they add a signal blocking molecule called "vascular endothelial growth factor" (VEGF) which halts the development at the cartilage stage. BAM! You've got a product that resembles natural cartilage in its mechanical properties, unlike the scar tissue-like fibrocartilage. Furthermore, the mice had improved mobility in their previously-arthritic joints and a reduction in pain (not sure how they objectively measured this).

While the researchers have not taken to human trials yet, they did implant human tissue into mice and were able to see very similar outcomes. While they plan to start human trials soon, they are hopeful for a fast-moving clinical period, as both BMP2 and VEGF are already FDA approved for use in other treatments. Dr. Longaker, the other co-author, reports that their goal is to address arthritic joints and rejuvenate that cartilage before the condition comes to the point of full joint replacements.

References:

Murphy, M. P., Koepke, L. S., Lopez, M. T., Tong, X., Ambrosi, T. H., Gulati, G. S., Marecic, O., Wang, Y., Ransom, R. C., Hoover, M. Y., Steininger, H., Zhao, L., Walkiewicz, M. P., Quarto, N., Levi, B., Wan, D. C., Weissman, I. L., Goodman, S. B., Yang, F., Longaker, M. T., … Chan, C. (2020). Articular cartilage regeneration by activated skeletal stem cells. Nature medicine, 26(10), 1583–1592. https://doi.org/10.1038/s41591-020-1013-2

https://med.stanford.edu/news/all-news/2020/08/Researchers-find-method-to-regrow-cartilage-in-the-joints.html

Axon Regeneration as a Treatment

Anatomy can wait, get some sleep!

     During my third year at Regis, I was fortunate enough to take a biochemistry class with one of my favorite teachers: Dr. Stacy Chamberlain. She teaches undergraduate biochemistry and if you have never met her, you can meet her in the chemistry suite on the third floor of the science building, she is awesome!! All fangirling aside, the reason I mention her is because she told us a story that I will not forget, and from which I learned a valuable lesson; Dr. Chamberlain is one of the happiest, healthiest, most active, most resilient and genuinely fun people I have met, and depsite all of this she is still pre-diabetic (and let me tell you that this REALLY pisses her off!). 

    Dr. Chamberlain continued on to tell us (after she fumed about how pissed she really was) that it all traced back to her habits in college. She would stay up all hours of the night studying and stressing about her school work. In total she averaged a whopping 3-4 hours fo sleep a night, if she managed to get even that. Albeit, she did incredibly well in college and is reaping the benefits from it now, but she is also dealing with the unforseen consequences. It does not matter how active or how healthy a lifestyle she is living now, due to her wacky sleep habits for such a prolonged amount of time (all 4 years of college!!) she is pre-diabetic, and her doctors say that she will most likely be indefnitely. 

   Sleep is very important. Not only does it feel oh so good to hit the pillow and let the day melt away, but it is also the time for our bodies to repair and restore itself. According to a study done to assess the relationship between sleep deprivation and type 2 diabeties, it is nsuggested that a minimum of eight hours of sleep per night is needed for metabolism to work normally (Al-Abri, et. al., 2016). Insufficient sleep throws your hormones out of proportion. With prolonged sleep deprivation, less insulin will be released after meals and staying awake increases your cortisol levels. These combined hormonal imbalances result in too much glucose staying in the bloodstream, which increases the risk for type 2 diabetes. 

   The moral of the story is this program is already a little bit stressful and our cortisol levels are already most likely higher than normal. Not only because this is a rigourous program but COVID-19 on top of it (yeesh!). Keeping as much balance in our hormones is beneficial to us and getting an adequate amount of sleep is vital. I implore you to take care of yourselves and one another. Anatomy can wait, get some sleep! We can study some more in the morning. (:

References:

Al-Abri, M. A., Jaju, D., Al-Sinani, S., Al-Mamari, A., Albarwani, S., Al-Resadi, K., Bayoumi, R., Hassan, M., & Al-Hashmi, K. (2016). Habitual Sleep Deprivation is Associated with 
Type 2 Diabetes: A Case-Control Study. Oman medical journal, 31(6), 399–403. https://doi.org/10.5001/omj.2016.81

https://www.sleepfoundation.org/articles/link-between-lack-sleep-and-type-2-diabetes

Can the Manipulation of Gene Expression Slow Muscle Atrophy?

As we advance in age, our muscles undergo atrophy, meaning they experience a reduction in strength and size. This is known as sarcopenia and is a natural occurrence in the aging process (Buford et al., 2010). Other factors such as diet, lack of physical activity, and disease can increase the rate of muscle atrophy (Buford et al., 2010). This is because increased muscle disuse increases the rate of protein degeneration past the rate of muscle synthesis (Hunter & Kandarian, 2004). Research also suggests that restricting the completion of the Akt growth pathway, a pathway involved in muscle growth, in muscles may further enhance muscle atrophy (Hunter & Kandarian, 2004). The Akt pathway utilizes kinases (proteins that transfer phosphate to other molecules) that are active during increased levels of protein synthesis but remain dephosphorylated during decreased levels of protein synthesis (Hunter & Kandarian, 2004). A recent study also suggests that muscle atrophy may be able to be directly manipulated by using specific proteins known as transcription regulators. Transcription regulators control a process called transcription, which is an ongoing process of making RNA from DNA; this RNA will then be used to make proteins in a process called translation. Research suggests that the removal of the expression of either 2 genes that code for these specific regulators results in the inhibition of decreased muscle size in mice (Hunter & Kandarian, 2004). The expression of these genes can be masked and unmasked by transcription regulators, resulting in the activation and deactivation of muscle atrophy. This mechanism of controlling gene expression is known as epigenetic, which involves manipulating gene expression without changing the genetic code of DNA. The expression of our genes is regulated in this way for many of our bodily processes. The epigenetic regulation of muscle atrophy could prove to be an important finding. Pharmaceuticals could be developed to promote these changes, and thus slow the degeneration of aging muscles. This could lead to a much easier transition into late adulthood considering that the loss of strength could prove detrimental to the way of life for most individuals. The generation of these drugs would be justified by the ethical value beneficence because we would be improving the livelihoods of others. It is also important to follow nonmaleficence so as to not promote a drug that could be harmful. Hopefully this study is the start of creating effective treatments to slow aging. References: Buford, T. W., Anton, S. D., Judge, A. R., Marzetti, E., Wohlgemuth, S. E., Carter, C. S., Leeuwenburgh, C., Pahor, M., & Manini, T. M. (2010). Models of accelerated sarcopenia: critical pieces for solving the puzzle of age-related muscle atrophy. Ageing research reviews, 9(4), 369–383. https://doi.org/10.1016/j.arr.2010.04.004 Hunter, R.B. & Kandarian, S.C. (2004). Disruption of either the Nfkb1 or the Bcl3 gene inhibits skeletal muscle atrophy. The Journal of Clinical Investigation, 114(10). doi.org/10.1172/JCI21696.

Vaccinate your children

     To vaccinate or not to vaccinate our children has become a very controversial topic in recent years and in my opinion I think it is very important to vaccinate and protect our children. Children are helpless and vulnerable creatures and it is our duty to protect them as much as possible. I know with my children I will be vaccinating them with the suggested vaccination to ensure protection.

An article I came across looked into outbreaks of diseases, specifically measles and pertussis, to determine whether or not vaccinated people got the disease in comparison to non-vaccinated people. What they found was mostly significant with regards to measles. They found that in 1416 cases of measles more than half (56.8%) of the unvaccinated population for measles contracted this disease. Many of these cases were eligible for vaccination, but were intentionally unvaccinated (Phadke et. al., 2016).

    Another study focused on influenza and the effects it would have on total illness rates in the US if our children are vaccinated for influenza. They found that if only 20% of our children are vaccinated that it would decrease the total contraction rate by 46% and if it was 80% coverage for influenza it would decrease by 91% (Weycker et. al., 2005). These data are very significant and are important to notice. If we can just vaccinate our children, we wouldn't only be protecting them, but we would also be protecting millions of other Americans. 

References: 

Phadke VK, Bednarczyk RA, Salmon DA, Omer SB. Association Between Vaccine Refusal and Vaccine-Preventable Diseases in the United States: A Review of Measles and Pertussis. JAMA. 2016 Mar 15;315(11):1149-58. doi: 10.1001/jama.2016.1353. Erratum in: JAMA. 2016 May 17;315(19):2125. Erratum in: JAMA. 2016 May 17;315 (19):2125. PMID: 26978210; PMCID: PMC5007135.

Weycker D, Edelsberg J, Halloran ME, Longini IM Jr, Nizam A, Ciuryla V, Oster G. Population-wide benefits of routine vaccination of children against influenza. Vaccine. 2005 Jan 26;23(10):1284-93. doi: 10.1016/j.vaccine.2004.08.044. PMID: 15652671.

    

Women and ADHD

     My whole life I've had issues with hyperactivity and the inability to stay focused. I never realized it was an issue until I got into high school and small tasks were hard to accomplish because my attention span was so short. Luckily, my mom is a doctor and decided to test me for ADHD as the possible reason. However, a lot of other girls struggle with ADHD and are not given the tools for diagnosis or referred for treatment, unlike men who are more likely to be referred. Furthermore, I had heard that women with ADHD are less likely to be diagnosed than men and so I decided this was an interesting topic to research. 

    The first article I came across called ADHD in women a "hidden disorder" since the symptoms are less obvious and also other existing conditions/disorders are different in woman than in men which makes it hard to diagnose (i.e. anxiety and/or substance disorders) (Patricia Quinn, 2005). Also women have a tendency for fluctuating hormones which also muddies the picture as to whether ADHD is the cause of the symptoms, or if it is another disorder, or even a mix.  

    Additionally, I found another article which illustrated how there are varying symptoms between males and females and this is why men are usually more likely to be diagnosed. It was said that women are more predominately inattentive than men and that women have lower self-efficacy and poorer coping strategies, higher rates of depression and anxiety, but have lower aggressive behaviors (Julia Rucklidge, 2010). Just like in the previous article, these other factors can sometimes make it difficult for women to be diagnosed as easily as men and this is a possible reason as to why we see a higher percent of males with ADHD than woman. 

    Finally, more research is necessary to help further diagnosis and detect symptoms in adolescence, so that these men and women can understand what is going on and have a treatment plan earlier on in life, to hopefully prevent these other disorders from occurring, or possibly ease the severity. This was an interesting topic to research for me since I do have ADHD and I think it is very important that more women get this diagnosis, so that they can fully understand what is going on with them and not feel like something is innately wrong with them. 

References:

Patricia O. Quinn, Treating adolescent girls and women with ADHD: Gender‐Specific issues (2005),  

https://doi.org/10.1002/jclp.20121

Rucklidge JJ. Gender differences in attention-deficit/hyperactivity disorder. Psychiatr Clin North Am. 2010 Jun;33(2):357-73. doi: 10.1016/j.psc.2010.01.006. PMID: 20385342.

Video Games: Violent or Valuable?

Video games of today have become a mainstream source of entertainment and stress relief for millions. The video game industry is among the lucrative businesses in the world. Technological advancements, social media, and the internet have continued to boost the popularity and pervasiveness of video games in society. Many continue to believe that video games cause gun violence and increase aggression (Hollingdale & Grietemeyer, 2014). However, video games have been shown to enhance problem-solving, social interactions, and provide an outlet for stress-relief (Choi et al., 2020). Video games are becoming more steeped in our lives and the world we live in. Contrary to popular belief, there are various benefits to playing video games.

First-person shooters (FPS) are one of the most popular types of video games on the market. These FPS and other violent games are often credited with causing gun violence. While playing violent games has been shown to increase aggression, there is little to research on the connection between video games and mass violence (Hollingdale & Grietemeyer, 2014). In fact, other studies have shown that video games can improve cognitive function such as problem-solving and attention (Choi et al., 2020). Media and new technologies have now made it possible to integrate video games into schools for learning purposes. Perhaps more importantly, video games offer a safe outlet for stress. A study among medical school students, some of the most stressed individuals in society, showed that playing video games can help relieve stress and increase overall well-being (Goswami & Salvi, 2020). Research has shown that playing video games can stimulate the release of the neurotransmitter dopamine (Koepp et al., 1998). Video games are not as harmful as many parties may like to believe. This is not to say that video games do not have their drawbacks and like all things, everything should be done in moderation. As games continue to play an integral part in modern lifestyles we must conduct more research to determine how video games affect us.

Choi E, Shin S, Ryu J, Jung K, Kim S. and Park M. (2020). Commercial video games and cognitive functions: Video game genres and modulating factors of cognitive enhancement. Behavioral and Brain Functions, 16, 1. doi:http://dx.doi.org.dml.regis.edu/10.1186/s12993-020-0165-z

Goswami, G., & Salvi, S. (2020). Video gaming, physiological responses, and well-being in medical students: An essence of intrigue way of learning. National Journal of Physiology, Pharmacy and Pharmacology, 10(6), 468-472. doi:http://dx.doi.org.dml.regis.edu/10.5455/njppp2020.10.03067202025032020

Hollingdale, J., & Greitemeyer, T. (2014). The effect of online violent video games on levels of aggression. PLoS One, 9(11) doi:http://dx.doi.org.dml.regis.edu/10.1371/journal.pone.0111790

Koepp, M. J., Gunn, R. N., Lawrence, A. D., Cunningham, V. J., & al, e. (1998). Evidence for striatal dopamine release during a video game. Nature, 393(6682), 266-8. doi:http://dx.doi.org.dml.regis.edu/10.1038/30498

 

 

Achy Joints and the Inevitable Threat of Aging; Mortality of Sepsis in Patients With Rheumatoid Arthritis

    .A wonderful woman was born in 1945 on a small farm far from the lights of the city. On this farm, hard work was not only necessary but also an ingrained trait that carried with this woman throughout the rest of her life. Despite being diagnosed with Rheumatoid Arthritis [RA] at the young age of 25 this woman continued to work, and raise kids living to the age of 76. However, the disease attacking her joints caused chronic pain, and the medication only gave her terrible side effects. This woman was my Grandmother and her strength and grit she had for life despite her condition, still inspires me today. RA is an autoimmune disease that attacks the joints of the patient and comes with an increased risk of infections due to the prematurely aged immune system, or due to the immunosuppressant treatment for the disease (D. Scott 2010). In comparison to the general population,  the mortality risk of infections has increased 2-6x. Furthermore, population-based studies show an increased risk for admission to an intensive care unit (ICU) in patients with RA compared to the general population (with a hazard ratio [HR]: 1.65, 95% confidence interval [CI]: 1.50-1.83). (M. Krasselt, 2020). Overall it was seen that the second most common reason for ICU admission in patients with RA (after ischemic cardiovascular diseases) are infections. this was concluded from the observations collected by Rheumatology, Medical Department III—Endocrinology, Nephrology and Rheumatology, University Hospital of Leipzig, Leipzig, Germany, and the Medical Intensive Care Unit, University Hospital of Leipzig, Leipzig, Germany. 

    In the most recent study published this year in the Journal of Intensive Care Medicine, there was a retrospective analysis done through the University Hospital of Leipzig. The study looked at RA patients older than 18 admitted into the ICU  with sepsis between  February 2006 - January 2019, in comparison to non-RA patients admitted sepsis to the ICU within the same time frame (M. Krasselt, 2020). The study analyzed the hospital's epidemiological data and clinical outcome using Sequential Organ Failure Assessment (SOFA) and the Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score II (SAPS II) (M. Krasselt, 2020). Although Septic shock was more often diagnosed among patients with RA, 65.3% versus (non-RA) 29.4%,  gave a significant P-value = .0006.  In bivariate analysis, septic shock was significantly more frequent in non-surviving patients with RA (P = .001) this was also true for vasopressor use (P = .007). Lastly, the in-hospital mortality was significantly higher in patients with RA than among controls (42.9% vs 15.7%, P = .0016) (M. Krasslet, 2020).

    However, as impressive this study outcome is I am disappointed in the sample size in which they chose to use for the analysis. By only using their own data at the university hospital and not reaching out to more hospitals for data to include for their analysis I believe the authors have an error in their experimental planning. Also only analyzing their own school from which the data is collected from this can serve as a conflict of interest as well since the reputation of the institution can be affected as well from the study. There needs to be data from various hospitals in the same time frame because not all hospitals are run the same way and may have differences in their ICU patient procedures, doctors, environments, etc. These are aspects that may change the way RA patients with sepsis or non-RA patients recover and provide further room to question the sepsis mortality. So why is this important to understand? Well, as a future doctor I strive to find the best knowledge to provide my best care and instruction to my future patients based on reputable science.  

M. Krasselt, MD, C. Baerwald, MD, Ph.D., S. Petros, MD, Ph.D., and O. Seifert, MD, Ph.D. 2020 Mortality of Sepsis in Patients With Rheumatoid Arthritis: A Single-CenterRetrospective Analysis and Comparison With a Control Group: Journal of Intensive Care Medicine. Published April 6, 2020, https://doi.org/10.1177/0885066620917588

D. Scott, F. Wolfe, T. Huizinga. 2010 Rheumatoid Arthritis: The Lancet. 2010 Sep 25;376(9746):1094-108. DOI: 10.1016/S0140-6736(10)60826-4. PMID: 20870100.

G. Ngian. 2010 Rheumatoid Arthritis: Aust Fam Physician. 2010 Sep;39(9):626-8. PMID: 20877764.

The Very Real Effects of a Broken Heart

 Working as a medical assistant in a heart and vascular clinic I have seen many instances of heart failure. These often involve the heart being overworked or blockages in the coronary arteries. In such instances we are able to diagnose the cause and treat the underlying condition.  Every now and then though, we see an instance of Takotsubo cardiomyopathy which is also known as Broken Heart Syndrome. Takotsubo cardiomyopathy is strange in that it is hard to diagnose for certain but one thing that most cases have in common is that ventriculograms of the heart have a very distinctive vase like shape with a round bottom and a narrow neck. A Takotsubo is an instrument used for catching octopuses which looks very similar to a vase (Akashi et. al., 2008).

Takotsubo is an acute form of cardiomyopathy or heart failure that is caused directly by stress. It occurs predominantly in post-menopausal women after sudden exposure to a large stress whether physical or mental. As you can probably guess this stress is usually caused by the death of a loved one but it can also be caused by abuse, high work load or even extreme disasters. The amount of cases of Takotsubo substantially increased after the Niigata Earthquake in elderly women (Sato et. al., 2006). The good news is that this is not a permanent form of heart failure. As a matter of fact in most cases it will reverse itself after a couple weeks, meaning if the person is being treated for heart failure with appropriate precaution they should go back to living a full life (Akashi et. al., 2008). Now for the bad news, any person who has experienced this stress induced heart failure is likely to develop this again. When discussing with patients about Takotsubo especially close to the time of the incident, the doctors I work with suggest avoiding places that may cause the recurrence of symptoms. This raises a conundrum as many patients are unable to avoid these areas whether it is the house of loved one or a favorite spot. How can we make it so that the patient can continue with their life yet also not end up back in the hospital? Some doctors leave these patients on heart failure medications indefinitely until much more time has passed than needed but medications can get expensive and insurances don't like to pay if they don't have to. I digress discussions about the difficulty of insurance is a talk for another time and probably a different class.

References:

Akashi YJ, Goldstein DS, Barbaro G, Ueyama T. Takotsubo cardiomyopathy: a new form of acute, reversible heart failure.Circulation. 2008; 118:2754–2762. doi: 10.1161/CirculationAHA.108.767012

Sato M, Fujita S, Saito A, Ikeda Y, Kitazawa H, Takahashi M, Ishiguro J, Okabe M, Nakamura Y, Nagai T, Watanabe H, Kodama M, Aizawa Y. Increased incidence of transient left ventricular apical ballooning (so-called “Takotsubo” cardiomyopathy) after the mid-Niigata Prefecture earthquake. Circ J. 2006; 70: 947–953.

The Effects of Psychotropic Medications on Mortality Rate

As someone who struggles with mental illness, I was interested in how antipsychotics, antidepressants, and mood stabilizers affect physical health. The mortality rate in people with severe mental illnesses such as schizophrenia, bipolar disorder, and major depressive disorder is 2-3 time higher (10-15 years difference) as compared to the general population (Correll et al., 2015). This statement made me wonder if the increase in mortality rate is caused by unhealthy lifestyle choices, by the medications used to treat these diseases, or by some other factor unaccounted for. According to the World Health Organization, cardiovascular disease is the leading cause of death among people with severe mental disorders yet, heart disease is also the leading cause of death in the general population. Therefore, why do people with mental illness have a higher mortality rate? 

One reason for an increase in mortality rate in individuals with severe mental illnesses is due to unmonitored antipsychotic medications. These medications can cause severe weight gain and as we all know; weight gain can lead to cardiovascular complications. (World Health Organization, n.d.) People with schizophrenia have a 2.8-4.4 fold increase in the likelihood of being obese and individuals with major depression or bipolar disorder have a 1.2-1.7 fold increase in the likelihood of being obese (Correll et al., 2015). Personally, I have tried various antipsychotics, mood stabilizers, and antidepressants and based on my own experience I can say with 100% certainty, that weight gain is a common side effect of these medications. Knowing and understanding the potential side effects of these medications has allowed me to better cope with the idea that people like me have an increase in mortality rate as I can combat this with a healthy diet and a regular exercise routine in order to live a normal, healthy life. 

            

Correll, C., Detraux, J., Lepeleire, J., & Hert, M. (2015, June). Effects of antipsychotics, antidepressants and mood stabilizers on risk for physical diseases in people with schizophrenia, depression and bipolar disorder. PubMed Central (PMC). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471960/

 

World Health Organization. (n.d.). Premature death among people with severe mental disorders. WHO | World Health Organization. https://www.who.int/mental_health/management/info_sheet.pdf?ua=1

 

 

Vape Use and COVID-19

The use of electronic cigarettes has been highly controversial, especially because of their widespread use by adolescents. While they can provide the opportunity for cigarette smokers to cut back on nicotine, without ingesting tobacco or tar, e-cigarettes and vapes have become as easily accessible vice for teenagers and adolescents. As FDA restrictions increase, and companies such as JUUL have been sued due to their advertising to teenagers specifically, there is no doubt that e-cigarettes can be extremely harmful when misused. Few studies of long-term effects have been conducted, due to the fact that vaping is a relatively new phenomenon. However, in recent years, there has been a rise in numbers of adolescents entering emergency rooms with acute respiratory distress, macular degeneration, and other forms of e-cigarette and vaping-associated lung injuries (Rice et al., 2020). 

 

A current and damaging belief is that young people are at a significantly lower risk for being seriously affected by COVID-19; yet, data shows that those who vape are at an elevated risk (potentially as much as 5x, compared to those who have never vaped) for experiencing COVID symptoms such as coughing, fever, and difficulty breathing (Digitale, 2020, Gaiha et al., 2020). Additional studies suggest that among those who have been infected with COVID, those with a history of smoking were twice as likely to show disease progression (Gaiha et al., 2020). 

 

This research highlights the necessity to increase education about the dangers of vaping for all age groups, but adolescents in particular. As a group of mainly future healthcare professionals, in the age of anti-vaping campaigns instead of anti-smoking ones, we are presented with this challenge: how can we warn our peers of these dangers? One way is to look at vaping through the COVID-19 perspective. Vaping, like smoking, can be a social activity. Sharing vapes provides coronavirus an easy access to the airway. And remember- if you are smoking or vaping, you aren’t wearing a mask. 

 

 

References

 

Digitale, Erin. “Vaping Linked to COVID-19 Risk in Teens and Young Adults.” News Center, 11 Aug. 2020, med.stanford.edu/news/all-news/2020/08/vaping-linked-to-covid-19-risk-in-teens-and-young-adults.html.    

Gaiha, S. M., Cheng, J., & Halpern-Felsher, B. (2020). Association Between Youth Smoking,     

Electronic Cigarette Use, and COVID-19. Journal of Adolescent Health, 67(4), 519–523.       

https://doi.org/10.1016/j.jadohealth.2020.07.002

Patanavanich, R., & Glantz, S. A. (2020). Smoking Is Associated With COVID-19 Progression: A 

Meta-analysis. Nicotine & Tobacco Research, 22(9), 1653–1656. https://doi.org/10.1093/ntr/ntaa082

Rice, S. J., Hyland, V., Behera, M., Ramalingam, S. S., Bunn, P., & Belani, C. P. (2020). Guidance on the Clinical Management of Electronic Cigarette or Vaping-Associated Lung Injury. Journal of Thoracic Oncology. https://doi.org/10.1016/j.jtho.2020.08.012

 

The Heart Pounding Affects of Pregnancy

I was raised an only child by a single mother, this ofcourse means my mother and I are incredibly close. With that being said, the thought of losing her is understandably difficult to imagine and so her story regarding her "brush with death" post my birth always invokes significant fear in me. 

Two days after I was born my mother felt as though she'd been "hit by a truck", so my grandmother drove her to the hospital. She had two different nurses come in and take her blood pressure, both could not believe the readings they were receiving and left my mother for another opinion. On the third trip, her OBGYN came in and took the reading himself. He immediately made her lie down on her left side and said he felt as though he was speaking to a ghost, for her blood pressure was so high he genuinely couldn't believe she was still alive, nonetheless able to walk around and function normally. The reality of this situation is pregnancy-induced hypertension (PIH) affects 7-10% of all pregnancies in the United States (Granger et al, 2001). At a day and age where the question of abortion with regards to the mother's health is still highly controversial, I believe this to be a highly concerning topic. The study specifically looks at the mechanisms for which hypertension occurs in pregnant women and how these abnormal physiological changes occur in contrast to those that occur naturally during pregnancy. As expected, there are numerous physiological changes that occur in women during pregnancy to adapt to and support the embryo being developed. Some of these include: maternal cardiac output and blood volume increases by approximately 40% to 50% (Lindheimer, 1995) and elevations occur in renal plasma flow and glomerular filtration by a rate of approximately 30% to 40% (Hytten, 1974). In women who develop PIH however, these changes do not occur, or they occur at highly abnormal rates. This article mentions the challenges associated with performing mechanistic studies in pregnant women that could provide further answers regarding cause and treatment of PIH, however some potential mechanisms have been suggested in it. A new approach to reducing uteroplacental perfusion conducted on gravid rats after 14 days of gestation suggested arterial pressure could be increased in pregnant hypertensive rats to reflect that of normal pregnancy levels, however this study also indicates that this pregnancy-induced hypertension is associated with proteinuria (elevated protein levels in the urine), reductions in renal plasma flow and glomerular filtration rate, and a hypertensive shift in the pressure natriuresis (excretion of sodium through urine) relationship (Granger et al, 2001). There is also substantial evidence showing NO levels are highly elevated under normal pregnancy conditions, but inhibited in instances of PIH which thus has significant affects on the renal vasodilatation of pregnant women. At this point it appears the mechanism for which PIH occurs in pregnant women remains quite questionable due to the numerous abnormal conditions that appear to occur, however I feel this is very important to understand in the obstetrics field at this point in time. 

Article: Granger JP, Alexander BT, Bennett WA, Khalil RA. Pathophysiology of pregnancy-induced hypertension. In: American Journal of Hypertension [Internet]. Elsevier Inc.; 2001 [cited 2020 Oct 5]. p. 178S-185S.

Available from: https://academic.oup.com/ajh/article/14/S3/178S/205336

References:

Baylis C, Suto T, Conrad K: Importance of nitric oxide in control of systemic and renal hemodynamics during normal pregnancy: studies in the rat and implications for preeclampsia. Hypertens Pregnancy 1996;15:147–169.

Granger JP, Alexander BT, Bennett WA, Khalil RA. Pathophysiology of pregnancy-induced hypertension. In: American Journal of Hypertension [Internet]. Elsevier Inc.; 2001 [cited 2020 Oct 5]. p. 178S-185S.

Khalil RA, Crews JK, Novak J, Kassab S, Granger JP: Enhanced vascular reactivity during inhibition of nitric oxide synthesis in pregnant rats. Hypertension 1998;31:1065–1069.

Lindheimer MD, Katz AI: Renal physiology and disease in pregnancy, in Seldin D.W. and Giebisch G. (Eds). The Kidney: Physiology and Pathophysiology. 2nd ed. Raven Press: New York, 1992. 3371–3431.

Molnar M, Suto T, Toth T, Hertelendy F: Prolonged blockade of nitric oxide synthesis in gravid rats produces sustained hypertension, proteinuria, thrombocytopenia, and intrauterine growth retardation. Am J Obstet Gynecol 1994;170:1458–1466.

Epigenetics and Heart Disease

 

Researchers have recently found epigenetic applicability to establishing a patient’s cardiovascular risk.  Methylation, the epigenetic modification investigated in this study, is a mechanism utilizing the transfer of methyl groups onto the cytosine of specific DNA sequences. These methyl groups then allow for the recruitment of other proteins involved in down regulating gene expression or interfere with binding of transcription factors necessary to promote gene expression. This epigenetic modification is reversible and can be heavily influenced by environmental factors (Moore et. al.)

Prior to the study in question, only small cohorts had been evaluated for CPG island methylation status correlated with estimating one’s cardiac risk.  This study utilized blood DNA samples from multiple cohort studies in both the United States and Europe to evaluate epigenome-wide modification of leukocytes in cardiovascular disease. Areas that were associated with coronary heart disease were in found genes that play a part in calcium regulation, coronary artery calcified plaque, and kidney function. Additionally, Mendelian randomization analysis showed a causal effect of DNA methylation in regulatory regions, both in non-coding RNA and genes that play a role in normal cellular structure and function. These findings highlight the clinical utility of methylation states, as well as identifying less-emphasized pathways in calcium regulation and kidney function that may significantly contribute to coronary heart disease. This could lead to new therapeutic targets, new prevention strategies, and novel diagnostic tools.

 

Agha, G., Mendelson, M. M., Ward-Caviness, C. K., Joehanes, R., Huan, T., Gondalia, R., Salfati, E., Brody, J. A., Fiorito, G., Bressler, J., Chen, B. H., Ligthart, S., Guarrera, S., Colicino, E., Just, A. C., Wahl, S., Gieger, C., Vandiver, A. R., Tanaka, T., Hernandez, D. G., … Baccarelli, A. A. (2019). Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease. Circulation, 140(8), 645–657. https://doi.org/10.1161/CIRCULATIONAHA.118.039357

 

Moore, L. D., Le, T., & Fan, G. (2013). DNA methylation and its basic function. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 38(1), 23–38. https://doi.org/10.1038/npp.2012.112