The Biology of Preeclampsia

What is Preeclampsia? 
Preeclampsia is a complication during pregnancy associated with high blood pressure (greater than 140/90 mmHg). Possible associated complications can include damage to the liver and kidneys, fluid retention, and swelling. Preeclampsia may be related to problems with the placenta and thus, may impair fetal growth and lead to preterm birth or even a stillbirth (if the placental abruption leads to heavy bleeding in the mother). Offsprings of mothers who had preeclampsia are at a higher risk for long-term health issues such as learning disorders, epilepsy, blindness, and cerebral palsy.

The Biochemistry of Preeclampsia
While the exact cause of preeclampsia has yet to be determined, a study found significant alterations in the metabolites in the first-trimester serum of women destined to develop late preeclampsia. Particularly, there were anomalies in the branch chain amino acids (valine, leucine, and isoleucine), glycolysis, gluconeogenesis, and ketone body metabolic pathways. A study found increased levels of glucose and glycerol with perturbations of lipid metabolism. These observed changes indicate abnormal lipid metabolism, which is implicated in the pathogenesis of late preeclampsia. Moreover, valine, leucine, and isoleucine were found to be significantly upregulated in first-trimester serum samples. These amino acids play a large role in carbohydrate synthesis and fat synthesis and are implicated in predicting future insulin resistance that can be observed in the development of PE. In general, the observed differences (increased glucose and levels of certain amino acids) indicates that an increased BMI might be related to the development and progression of preeclampsia. Furthermore, this study indicates that analysis of the first-trimester serum of those with late-onset preeclampsia shows an increased pyruvic acid concentration and lactate. This suggests a disturbance in glycolysis and gluconeogenesis because hypoxia and oxidative stress are features of preeclampsia.

Sociodemographic Risks
Apart from genetic influences, another major risk for the development of preeclampsia involves social factors. Women with a lower socioeconomic background may be associated with poor prenatal care and nutritional deficits, which can increase the risk of disturbances in glycolysis and gluconeogenesis and by proxy, preeclampsia.

Bahado-Singh, Ray O., et al. “Metabolomic Determination of Pathogenesis of Late-Onset Preeclampsia.” The Journal of Maternal-Fetal & Neonatal Medicine, vol. 30, no. 6, 2016, pp. 658–664., doi:10.1080/14767058.2016.1185411.K, R., Gandhi, S., & Rao, V. (2014). Socio-Demographic and Other Risk Factors of Pre Eclampsia at a Tertiary Care Hospital, Karnataka: Case-Control Study. Journal of Clinical and Diagnostic Research : JCDR, 8(9), JC01–JC04. http://doi.org/10.7860/JCDR/2014/10255.4802

Do we live in a simulation?!?!

Most people don't realize just how fast technology is evolving, so let me put things into prospective for you. In November of 1972, the video game Pong was released. Two bars on a screen and a dot to bounce between them. This simple technology captivated the world, as we had never seen anything like it. News flash, 1972 was only FORTY SIX YEARS AGO. In the grand scheme of things, this is a minuscule amount of time. In 2002, I remember my math teacher telling me I needed to know long division because "I wasn't just always going to have a calculator in my pocket." LOL okay Mrs. Yelverton. Now I can literally pull out my phone and say "OK Google" and a pizza will show up where ever I am in under an hour. I think it's safe to say long division is the least of my worries as long as as I have my Google phone in my pocket, which is always. In 2002, however, no one saw this coming. Heck, remember in 2007 when the first iphone was released? The camera was amazing, the phone operated seamlessly at high speeds, and the whole thing seemed unreal. If you tried using the first iphone today, you would laugh at the terrible camera quality and be frustrated with how long things take to load. Remember, that was just over ten years ago. So the question is, what will the next ten years bring that will make us laugh at our current technology? Or even just five years since the growth has been more than exponential? We currently have virtual reality Occulus Go goggles that are very realistic (and I could have my Google phone deliver me a pair right now for $199.99) but while you are wearing the goggles, you are aware that it isn't reality.....but in forty six years? Is it possible we could have graphics processors so powerful that they process data that is indistinguishable from reality? The artificial intelligence so powerful that the creations in the simulation could not even tell they were just a simulation? What if humans have already created this, and we are just in one of those "games" or "simulations" RIGHT NOW!?
I assure you, I am not crazy to think this. Here is a video of Elon Musk, the closest person we have to real life Iron Man, explaining this theory and why he believes it.
https://www.youtube.com/watch?v=xBKRuI2zHp0
Mr. Musk isn't the only brilliant mind to talk about this, as Neil deGrasse Tyson and other famed physicists have mentioned the possibility as well.
Is quantum mechanics just computer code? Is the Big Bang just when our masters flipped the on switch? After watching the video, could any of you now consider this as a reasonable possibility?

Instagram and Medicine

Yesterday my brother posted an instagram picture of him at a walk for Mysthenia Gravis, the autoimmune disorder we learned in physiology. I had only just learned of this disease a few days ago, and here was my brother - a geologist in Seattle - posting about raising awareness for MG.

One of his co-workers suffers from this condition and his caption was "MG is an autoimmune disorder that breaks down the communication between nerves and muscles. Build awareness! And eat beautiful burritos".  I saw in his comments, his friends talking about how they'd never heard of MG before.

The power of social media has huge implications in educating (with facts and with fake news) large amounts of people. I find out about a lot of cool new medical interventions and technologies from instagram through "insiderscience" and many other medical instragram accounts. I also weirdly follow a lot of other female physicians' so that I can read about their journeys throughout their training. Doctor offices have their own instagram handles to entice new patients and I'm wondering how this will play out in the next few years. You can even watch surgical procedures on instagram!

Will instagram still be as popular as it is today? Can we catalog medical diseases in easily digestible photo packages with hashtags and accounts like Instagram for future specialties that are regulated and factual? Instagram educates specialists and laymen alike- but what are the limits? What are the precautions? 10 years ago, practices HAD to have websites to be considered legitimate. Is Instagram the new website?

A quick pubmed search of "instagram AND medicine" produced only 71 articles as of today, October 2, 2018. Most of the titles also had the words "millenials."

Give us free flu shots!

Who's ever gotten the flu?

I have . . . the one and only time being when I was in college and it wiped me out for 2 weeks.

Since then, I've gotten a flu shot every year. I've also never paid for a flu shot because they were given for free from school, through my employer, or through my volunteer organizations.

I noticed a few signs around Regis advertising for free flu shots on one morning only, "Saturday September 29th from 9am - 2pm or until supplies run out". I was shocked.That is not nearly good enough to safeguard a large community of close quartered individuals.

According to a recent NPR article, the National Foundation of Infectious Disease found that between 8 and 39 percent of college students get the flu vaccine. Despite being a high risk group for getting and spreading the virus, why is this happening?

Last year's flu strain called H3N2 yielded the deadliest flu season in over 40 years. In 2017, there were a reported 80,000 flu related deaths in the US. A flu shot can save a life, yet why aren't college students, the supposedly most educated population cohort, protecting themselves?

What are some of the reasons that some of you have or haven't gotten your flu shot yet?

Here are some juicy FYIs I learned from the news article:

1. Although the vaccines don't offer complete protection, the CDC estimates that the risk of illness is reduced by about 40 - 60%. IF you do catch the flu, your illness is likely to be milder with less major complications.
2. You can't catch the flu from getting the vaccine. If you are among the tiny percent of people who have fever or get sick chronologically after your shot - it's a reaction to the shot or you've caught another unrelated strain. This seems to be a huge misconception that I hear all the time.
3. Pregnant mothers can safely get the flu vaccine which transfers across the placenta and protects the baby for around 6 months post-partum.
4. TL;DR: GET YOUR FLU SHOT. Or petition Regis to make a more significant effort in providing free vaccines to all Regis members.

Reference:

Aubrey, A. (2018, October 1) Think You Don't Need A Flu Shot? Here Are 5 Reasons to Change Your Mind. NPR (https://www.npr.org/sections/health-shots/2018/10/01/652140517/think-you-dont-need-a-flu-shot-here-are-5-reasons-to-change-your-mind)

Clinical trials in Africa and developing nations. Is it ethical..?

Clinical trials are crucial to discovering new medicines and therapies for diseases that plague humanity.  The clinical trial process is very long, and often expensive.  So, in order to speed up the process and/or decrease costs, many pharmaceutical companies run the trials in developing nations in Africa, Asia, and Latin America.  In 2013, all of the major pharmaceutical companies were present in Africa alone (1).  In 2015, about 40% of the clinical trials were taking place in these developing countries (1).  Trials in developing countries can be very controversial.  However, there are certain places in the world where specific diseases are present.   For instance, there is a much higher prevalence of HIV/AIDs in Africa in comparison to rest of the world (2).  So, it would be logical to have clinical trials located in countries where the majority of the disease is located.  With this in mind, there are certain steps that the pharmaceutical companies must take in order to establish an ethical clinical trial, even in Africa.  The National Institutes of Health (NIH), which is a research center and an agent of the U.S. Department of Health, is not required to provide trial participants compensation for treatment of research-related injury (2).  Many people in Africa and developing countries do not have access to health care, let alone insurance to pay for an injury caused by a clinical trial.  Although there is not a requirement for compensation, many PIs in the research studies provide medical care and treatment for the patients with a research related injury (2).  Not having adequate funding for treatments is just one ethical concern of doing clinical trials in developing nations.

References:

11. Puppalwar, G., Mourya, M., Kadhe, G., & Mane, A. (2015). Conducting clinical trials in emerging markets of sub-Saharan Africa: Review of guidelines and resources for foreign sponsors. Open Access Journal of Clinical Trials, 23. doi:10.2147/oajct.s77316

22. Mamotte, N., Wassenaar, D., & Singh, N. (2013). Compensation for research-related injury in NIH-sponsored HIV/AIDS clinical trails in Africa. Journal of Empirical Research on Human Research Ethics, 8(1), 45-54. doi:10.1525/jer.2013.8.1.45

Pros and Cons to Weight Loss Surgery in Mexico

It is a part of our responsibility as future healthcare providers to be informed on trending healthcare procedures, so we can have informative discussions with patients in our future practice. To avoid expensive surgeries that most often U.S health insurances won’t cover, many U.S citizens have chosen to have surgeries done abroad. Oftentimes, due to lower wages and lower cost to the same surgical equipment, Mexico is the top choice. Weight loss surgeries include lap band, gastric sleeve, and gastric bypass surgeries. A lap band is a silicone band place around the hiatal end of the stomach, designed and adjusted to limit food intake. This device is connected to a port that is placed under the skin for future adjustment accessibility. A gastric sleeve procedure is the removal of about 80% of the stomach, leaving behind a tube-shaped stomach about the size of a banana, and is a powerful weight loss method. Gastric bypass includes the rejoining of the hiatal end of the stomach to the jejunum of the small intestines, bypassing the stomach, and duodenum of the small intestine. A lap band procedure can cost from $3,000-$6,500 in Mexico compared to $9,000-$22,000 in the U.S. A gastric sleeve procedure can cost $4,000-$9,000 in Mexico and in the U.S prices can range from $10,000-$31,500. A gastric bypass surgery can cost $6,500-$11,000, and the U.S cost comparison at $19,000-$35,000. Included in these cost estimates is anesthesia, medications before and after the procedure, operating room costs, preoperative evaluations, dietary guideline instruction, transportation, and follow up care for the lap band procedure. The largest concern for most people interested in surgery abroad is the doubt in finding a highly-skilled surgeon, which is very possible if you know how to look. Most complications occur from lap band surgery in both short term and long-term complications, and cause malfeasance to the patient. Overall, the cost alone could motivate someone to seek surgery abroad, and the relative skill of surgeons that can be found in Mexico is comparable to surgeons in the states, which is considered beneficence to the patient. In contrast, patients give up legal rights when they travel abroad for surgery and things go south during the procedure, no pun intended. The support patients have post surgery might be better if their procedure is done in the U.S. but if a patient is confident they can control themselves to strict dietary changes without external aid, they could potentially save thousands of dollars in Mexico. Average Cost of Gastric Bypass Surgery. (2017, October 03). Retrieved from https://www.obesitycoverage.com/insurance-and-costs/how-much/average-laparoscopic-gastric-bypass-prices Average Cost of Lap Band Surgery. (2017, October 03). Retrieved from https://www.obesitycoverage.com/insurance-and-costs/how-much/average-lap-band-prices Prices for gastric sleeve surgery by state. (2017, October 03). Retrieved from https://www.obesitycoverage.com/insurance-and-costs/how-much/average-cost-of-gastric-sleeve-surgery/gastric-sleeve-cost-2015/ Weight Loss Surgery In Mexico – A Candid Look. (2018, January 09). Retrieved from https://www.obesitycoverage.com/weight-loss-surgery-in-mexico-a-candid-look/

A Silver Lining for Prostate Cancer Patients

My albeit short career in medical research has haphazardly and ironically kept me focused on your friend and mine—the prostate. More specifically, I have been driven to look at the possible biochemical processes underlying prostate cancer as well as the physical science behind our contemporary treatments of this particular malady. As a result, I can discuss the biggest points regarding our current standard of care for prostate cancer in the U.S. 

Prostate cancer is currently noted as having the third highest rate of mortality amongst all other cancers, where 1 in 4 men are likely to experience the disease in their lifetime.¹ While there are clearly many contributing factors to development of the disease, a general lack of biochemical knowledge has made cancer screening one of our societies only first lines of defense; and our screening just isn’t that great. As you might know, males over the age of 50 are recommended to have PSA screenings, which seeks to identify the concentration of an antigen in the patient’s blood. It’s minimally invasive, and doesn’t pose a significant risk to patients, but the practice can have an astounding 75% false-positive rate. This means that for every four men who are told they have an irregularly elevated PSA level, only one ends up with a diagnosis for prostate cancer.² The vilifying factor is that the majority of individuals who’s lab results demonstrate elevated PSA are then referred to have a prostate biopsy, which is an invasive and costly procedure that requires anesthetics. 3 out of 4 men who receive these biopsies do not need them.

Luckily, new diagnostic tools are in development and the overall prognosis for prostate cancer, if caught early (low-risk), is quite good. Because of a reliably evident drop in prostatic zinc concentrations prior to any other external symptoms, a great deal of research is underway to create effective imaging tools to screen men’s prostatic fluid.³ My own thesis project focused on developing a contrast agent to be used with standard MRI that chelates with zinc and measurably affects the intensity of generated images. This has been safely demonstrated in mouse models.⁴ Hopefully, the practice will soon emerge on a broader stage following further investigation. Likewise, with improvements to modern chemotherapy and radiation treatments, the 10-year post-treatment rate of patients having no evidence of disease has reached upwards of 95% for patients with low-risk diagnoses—especially within the population that receives high dose rate (HDR) brachytherapy, an option that limits temporary radiation to affected tissues.⁵ So I feel confident in saying that, while current practices for prostate cancer could be improved, the future of it’s diagnosis and treatment is looking optimistic. 

(1)     Siegel, R. L.; Miller, K. D.; Jemal, A. Cancer Statistics, 2018. CA. Cancer J. Clin.2018, 68(1), 7.

(2)     Wolf, A. M.; Wender, R. C.; Etzioni, R. B.; Thompson, I. M.; Amico, A. Vd; Volk, R. J.; Brooks, D. D.; Dash, C.; Guessous, I.; Andrews, K.; et al. American Cancer Society Guideline for the Early Detection of Prostate Cancer Update 2010. Cancer Journal, The2010,60(2), 70.

(3)     Costello, L. C.; Franklin, R. B. The Clinical Relevance of the Metabolism of Prostate Cancer; Zinc and Tumor Suppression: Connecting the Dots. Mol. Cancer2006, 5, 17.

(4)     Clavijo Jordan, M. V.; Lo, S.-T.; Chen, S.; Preihs, C.; Chirayil, S.; Zhang, S.; Kapur, P.; Li, W.-H.; De Leon-Rodriguez, L. M.; Lubag, A. J. M.; et al. Zinc-Sensitive MRI Contrast Agent Detects Differential Release of Zn(II) Ions from the Healthy vs. Malignant Mouse Prostate. Proc. Natl. Acad. Sci.2016, 113(37), E5464.

(5)     Hauswald, H.; Kamrava, M. R.; Fallon, J. M.; Wang, P.; Park, S.; Van, T. High-Dose-Rate Monotherapy for Localized Prostate Cancer : 10-Year Results. Int. J. Radiat. Oncol. Biol. Phys.2016,94(4), 667.