Patrick Tomko – The Early Career Voice

Near the End, and Preparing for a New Beginning

August 2, 2021July 29, 2021 Patrick Tomko

You’ve finally hit that point, where “comps” (comprehensive exams) has been completed. You passed. Now all you have to do is collect data, write it up and present it to your committee. The next challenge is figuring out the time to present the data you collected for the dissertation or thesis. Not to consider the biggest challenge of collecting data that is quality and timely. Thus, there is a few things to consider that might help streamline the PhD journey, or any similar terminal degree.

Thesis/Dissertation Tips

These tips need the context of a “best dissertation/thesis is a done dissertation/thesis”.

Start coming up with ideas for your dissertation/thesis. The ideas evolve, be open to that. Discuss not only with potentially faculty, but also your friends and even family.
Develop a rapport with all the faculty, feel out who may suit you and your journey the best. There is a fit that is needed on both the mentoring and mentee sides of the journey.
Set expectations for yourself and then for your direct report or mentor. This will help ensure efficiency. The mentor has likely been in your shoes before, so he or she may view the initiative and eagerness as a positive.
1. At the same time learn to establish a balance between work and your life. Talk to your mentor about this, he or she likely has valuable input. This is important because the majority of graduate students experiencing anxiety and or depression did not agree with the idea of their advisor being as asset to their career (shown in Figure 1) (Evans et al., 2018).

Figure 1. This figure highlights the graduate students and their experience of depression and anxiety as well as input related to perceived mentorship.
.https://doi.org/10.1038/nbt.4089.

Make sure to back-up all your work. Back it up in more than one spot as well.
It is never too early to start drafting up or writing down and organizing your ideas and concepts.
1. Two sections that you really can get a jump on are the introduction and methods types of sections (Wyllie, 2021).

Future Investigator Tips:

On top of completing the thesis/dissertation, you should really be applying to jobs and considering what would be the next best step for you as a researcher. Dr. Douglas Seals published a very informative manuscript titled “The Academic Biomedical Research Laboratory as a “Small Business”. He provides a perspective that shows biomedical research laboratories providing services to external organizations (Seals, 2021). These services include:

“ -..manuscripts submitted for publication to scientific journals, grant applications submitted to biomedical research funding agencies; and abstracts submitted to professional organizations for presentations” (Seals, 2021).

Dr. Seals viewpoint manuscript is valuable because it highlights the need for developing a network. You learn about the future timelines and the associated potential hurdles. Furthermore, it will help address the a new type of balance, completing the work that you have obtained funding for, and beginning new work from ideas you have formulated. Beyond understanding the dynamics of a laboratory as a small business, developing yourself as a good writer will be something that continues, and a standard that should be set high for yourself.

Find a skill set you would like grow with over time
Look potentially broadening your network.
Understand the importance of treating a lab like a small business.

Below in Figure 2, shows what would be the priorities as a PI through a career. Understanding the frame-work over time can help you determine where you are and where you would like to be as an independent researcher. One of the skills that will need development, will be motivating a variety of people in a variety of ways (Banks, 2021).

https://febs.onlinelibrary.wiley.com/doi/epdf/10.1111/febs.15755

Finally, do your best to continue to find feedback from quality people with the network you established. Research is a process not only for sample and/or population studied, but for you and your development as an independent investigator. Develop patience and diligence.

Reference

Banks, L. (2021). Words of Advice: How to be a good Principal Investigator. The FEBS Journal, 288(13), 3973–3977. https://doi.org/10.1111/febs.15755

Evans, N. R., Shahrokni, R. O., Ferriday, D., Potter, C., Jebb, S. A., Brunstrom, J. M., & Rogers, P. J. (2018). Enhancing meal enjoyment: Evaluating the effects of flavour intensity and hedonic labelling. Appetite, 130, 304. https://doi.org/10.1016/j.appet.2018.05.184

Seals, D. R. (2021). The Academic Biomedical Research Laboratory as a “Small Business.” Journal of Applied Physiology. https://doi.org/10.1152/japplphysiol.00233.2021

Wyllie, D. J. A. (2021). Thesis write-up and manuscript preparation: Related but distinct tasks. The Journal of Physiology, 599(11), 2771–2775. https://doi.org/10.1113/JP281665

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

Atherosclerosis and Osteoarthritis: Understanding the Impact of being Physical Active

June 2, 2021May 27, 2021 Patrick Tomko

Nearly everyone can experience health benefits from being physically active. Simply, brisk walking can be “go to” for a safe and effective tool to improve or maintain current activity levels.

Physical activity continues to be encouraged because of the staggering impact it has on delaying death from all causes (i.e. heart disease).

The Physical Activity Guidelines for Americans report people who are physically active for approximately 150 minutes a week to have a 33 percent lower risk of all-cause mortality. More importantly, these 150 minutes can be spread throughout a 24 hour period. The benefits accumulate (CDC, 2021).

Thus, avoiding a sedentary lifestyle or even prolonged periods of sitting will maintain a healthy vascular system and keep the heart pumping the way you need it. There is evidence showing that as little as 10 minutes of sitting results in changes that impact microcirculation of blood (Vranish et al., 2018). This microcirculation area is the final destination of the cardiovascular system, and ultimately where oxygen is exchanged.

Breaking up the day into brief bouts of activity goes a long way. So those reminders on the fitness trackers, make sure to use them to your advantage. If you have some health goals you want to meet, use physical activity tracking as a supplement to your plan. Walking an additional 1000 steps per day can help lower the risk of all-cause mortality, and cardiovascular disease morbidity and mortality in adults (Hall et al., 2020).

A study published by Wolf et. al. showed that even four-second bouts of intense activity between bouts of sitting can carry benefits that extend into the next day. In a model of 8 hours of inactivity, study participants cycled five times every hour over a 6 hour period. These exercise bouts from the previous day reduced levels of fat in the blood by 31% (Wolfe et al., 2020).

However, not everyone can just get up and move. Individuals that are diagnosed with osteoarthritis of the hip and knee represent one of the leading causes of global disability (Skou et al., 2018). Thus, a group like this will struggle to meet activity guidelines and is likely to share an increased burden of cardiovascular disease risk. The presence of osteoarthritis in a large prospective cohort (1,775) followed over a mean of 8 years showed an increased risk of cardiovascular disease by 27% (Veronese et al., 2018). Determining ways to encourage physical activity even in disabling scenarios/conditions, continues to be a challenge. Magnetic resonance (MR) imaging, one of the most advanced imaging techniques used clinically, could be used to inform physicians how to best to approach this challenge. In a brief review by Liu et. al., MR images were used to visualize lower limbs to aid in the development of biomarker development and/or predict patients with risk to PAD. This could patients who are inactive because of the severity of osteoarthritis (Liu et al., 2019).

Hopefully, we evolve in our approach for activity recommendations and potentially pain management in groups that exhibit disabling conditions like osteoarthritis. I think this brings another point about the pathology of the two conditions and the relatedness. There has been evidence to support a vascular etiology and its ability to predict structural progression of osteoarthritis over 10 years (Jonsson et al., 2019; Wang et al., 2015). There is also data that relates use of statins to treat atherosclerosis and knee osteoarthritis progression (Clockaerts et al., 2012). Recently a nutritional link has been brought to light with Vitamin K and osteoarthritis. Vitamin K is commonly known for its role in blood coagulation (Loeser et al., 2021). Below is the figure Loeser et. al., uses to illustrate vitamin K role in osteoarthritis.

In the next figure below, Findlay 2007, shows how the subchondral vasculature is related to the initiation and/or progression of osteoarthritis. The left side shows healthy articular cartilage and the right side shows some cartilage erosion that may be related to changes due to an occlusion of blood supply.

References:

CDC, 2021. Benefits of Physical Activity [WWW Document]. Cent. Dis. Control Prev. URL https://www.cdc.gov/physicalactivity/basics/pa-health/index.htm (accessed 5.20.21).

Clockaerts, S., Osch, G.J.V.M.V., Bastiaansen-Jenniskens, Y.M., Verhaar, J. a. N., Glabbeek, F.V., Meurs, J.B.V., Kerkhof, H.J.M., Hofman, A., Stricker, B.H.C., Bierma-Zeinstra, S.M., 2012. Statin use is associated with reduced incidence and progression of knee osteoarthritis in the Rotterdam study. Ann. Rheum. Dis. 71, 642–647. https://doi.org/10.1136/annrheumdis-2011-200092

Hall, K.S., Hyde, E.T., Bassett, D.R., Carlson, S.A., Carnethon, M.R., Ekelund, U., Evenson, K.R., Galuska, D.A., Kraus, W.E., Lee, I.-M., Matthews, C.E., Omura, J.D., Paluch, A.E., Thomas, W.I., Fulton, J.E., 2020. Systematic review of the prospective association of daily step counts with risk of mortality, cardiovascular disease, and dysglycemia. Int. J. Behav. Nutr. Phys. Act. 17, 78. https://doi.org/10.1186/s12966-020-00978-9

Jonsson, H., Fisher, D.E., Eiriksdottir, G., Aspelund, T., Klein, R., Gudnason, V., Cotch, M.F., 2019. Hand and knee osteoarthritis are associated with reduced diameters in retinal vessels: the AGES-Reykjavik study. Rheumatol. Int. 39, 669–677. https://doi.org/10.1007/s00296-019-04243-6

Liu, W., Balu, N., Canton, G., Hippe, D.S., Watase, H., Waterton, J.C., Hatsukami, T., Yuan, C., 2019. Understanding Atherosclerosis Through an Osteoarthritis Data Set. Arterioscler. Thromb. Vasc. Biol. 39, 1018–1025. https://doi.org/10.1161/ATVBAHA.119.312513

Loeser, R.F., Berenbaum, F., Kloppenburg, M., 2021. Vitamin K and osteoarthritis: is there a link? Ann. Rheum. Dis. 80, 547–549. https://doi.org/10.1136/annrheumdis-2020-219765

Skou, S.T., Pedersen, B.K., Abbott, J.H., Patterson, B., Barton, C., 2018. Physical Activity and Exercise Therapy Benefit More Than Just Symptoms and Impairments in People With Hip and Knee Osteoarthritis. J. Orthop. Sports Phys. Ther. 48, 439–447. https://doi.org/10.2519/jospt.2018.7877

Veronese, N., Stubbs, B., Solmi, M., Smith, T.O., Reginster, J.-Y., Maggi, S., 2018. Osteoarthristis Increases the Risk of Cardiovascular Disease: Data from the Osteoarthritis Initiative. J. Nutr. Health Aging 22, 371–376. https://doi.org/10.1007/s12603-017-0941-0

Vranish, J.R., Young, B.E., Stephens, B.Y., Kaur, J., Padilla, J., Fadel, P.J., 2018. Brief periods of inactivity reduce leg microvascular, but not macrovascular, function in healthy young men. Exp. Physiol. 103, 1425–1434. https://doi.org/10.1113/EP086918

Wang, Y., Dawson, C., Hanna, F., Fairley, J., Cicuttini, F.M., 2015. Association between popliteal artery wall thickness and knee cartilage volume loss in community-based middle-aged women without clinical knee disease. Maturitas 82, 222–227. https://doi.org/10.1016/j.maturitas.2015.07.010

Wolfe, A.S., Burton, H.M., Vardarli, E., Coyle, E.F., 2020. Hourly 4-s Sprints Prevent Impairment of Postprandial Fat Metabolism from Inactivity. Med. Sci. Sports Exerc. 52, 2262–2269. https://doi.org/10.1249/MSS.0000000000002367

Blood pressure and the consumption of sodium and potassium, which is more important?

April 26, 2021April 22, 2021 Patrick Tomko

Nutrition is one of many lifestyle factors that contribute to cardiovascular disease. Specifically, both sodium and potassium are known to influence the regulation of blood pressure (raising and/or lowering). The dysregulation of blood pressure is related to either too much sodium or little potassium (1-2). Jackson et. al., 2018, surveyed 765 participants to obtain estimates of sodium and potassium intake through 24 hour urine collections. Only about 4.2% dietary sodium intake met the dietary guidelines of less than 2300mg/d, and dietary potassium was reported as 1997 mg/d. The recommended intake for potassium is 4700mg/d. Furthermore, the study highlighted that a 1000-mg-lower level of sodium intake was associated with a –4.4 mmHg level of systolic BP and a 1000-mg higher level of potassium intake a –3.4 mmHg level of systolic BP.

Source: https://ods.od.nih.gov/factsheets/Potassium-HealthProfessional/

Similjanec et al., 2020, showed how dietary potassium could reduce the detrimental effects of sodium on vascular function. The investigators used a 24-hr urine collection and were able to group individuals into a salt-resistant group. Salt resistance was defined as a change of 5 mmHg or less in 24-h mean arterial pressure. In the figure to the left, the authors show how

a potassium-rich diet can mitigate the effects of high dietary sodium on flow-mediated dilation, a technique that shows the strong association of cardiovascular disease risk (3). See figure 3.Thus, adequate consumption of dietary potassium could be protective to many people in the U.S.

Source: https://pubmed.ncbi.nlm.nih.gov/31562419/

Looking at the nutrients together and the impact on health is vital, especially in the case of blood pressure regulation. Similjanec et. al., 2000, results in highlight the need to consider potassium in future investigations for the management of blood pressure and cardiovascular disease risk.

Kogure et al., 200, used an OMRON Healthcare urinary Na/K ratio monitor to look at the urine ratio of Na/K. This handheld self-monitoring device was supported through multiple measurements of the urinary Na/K ratio which were strongly related to home hypertension regardless of the treatment status for hypertension (4). Figure 4 highlights the prevalence of home hypertension over 10 days.

A solid starting spot for keeping your blood pressure in check is to look for some dietary sources you enjoy. Here are some good dietary sources of potassium to add to the diet from the national institute of health’s webpage.

Apricots for the win!

Source: https://ods.od.nih.gov/factsheets/Potassium-HealthProfessional/

References:

1) Jackson, S. L., Cogswell, M. E., Zhao, L., Terry, A. L., Wang, C. Y., Wright, J., Coleman King, S. M., Bowman, B., Chen, T. C., Merritt, R., & Loria, C. M. (2018). Association Between Urinary Sodium and Potassium Excretion and Blood Pressure Among Adults in the United States: National Health and Nutrition Examination Survey, 2014. Circulation, 137(3), 237–246.

2) Smiljanec K, Mbakwe A, Ramos Gonzalez M, Farquhar WB, Lennon SL. Dietary Potassium Attenuates the Effects of Dietary Sodium on Vascular Function in Salt-Resistant Adults. Nutrients. 2020; 12(5):1206.

3) Ras RT, Streppel MT, Draijer R, Zock PL. Flow-mediated dilation and cardiovascular risk prediction: a systematic review with meta-analysis. Int J Cardiol. 2013 Sep 20;168(1):344-51. doi: 10.1016/j.ijcard.2012.09.047. Epub 2012 Oct 4. PMID: 23041097.

4) Kogure, M., Hirata, T., Nakaya, N. et al. Multiple measurements of the urinary sodium-to-potassium ratio strongly related home hypertension: TMM Cohort Study. Hypertens Res 43, 62–71 (2020). https://doi.org/10.1038/s41440-019-0335-2

Alcohol Consumption and Cardiovascular Disease: How much is too much?

March 29, 2021March 25, 2021 Patrick Tomko

Most enjoy sipping on a glass of wine, a beer, or cocktail from time to time on their own, or with a group of others. And in more of these occasions than not, the individual determines how much he or she could or could drink given future plans (e.g. driving a vehicle).

But, why don’t people consider the impact a drink of alcohol consumption could have on their health more?

This is likely because of the recommendations of drinking alcohol in moderation. Alcohol has been shown to have protective effects regarding how we use our fats in our blood (3). There is even data that shows a reduction in the incidence of heart attacks related to alcohol consumption (4).

In 2019, about 26% of people ages 18 and older (29.7 percent of men in this age group and 22.2 percent of women in this age group) reported that they engaged in binge drinking in the past month (1). Binge drinking is 5 or more drinks for men and 4 or more drinks for women in about 2 hours (2). The Dietary Guidelines of 2020-2025 define Alcoholic beverages as the following:

“Adults of legal drinking age can choose not to drink, or to drink in moderation by limiting intake to 2 drinks or less in a day for men and 1 drink or less in a day for women, when alcohol is consumed. Drinking less is better for health than drinking more.”

It is important to define what one alcoholic drink equivalent. About 14 grams (0.6 fl oz) of pure alcohol is one drink, 12 fluid ounces of regular beer (5% alcohol), 5 fluid ounces of wine (12% alcohol), or 1.5 fluid ounces of 80 proof distilled spirits (40% alcohol) (2).

Benefits of Alcohol Consumption Source: https://www.dietaryguidelines.gov/resources/2020-2025-dietary-guidelines-online-materials

Most importantly, what is a moderate amount of alcohol consumption?

A moderate amount is 2 drinks of less a day for men and 1 drink of less a day for women. Okay, what if we drink alcohol above the defined moderation?

Well, the National Institute on Alcohol Abuse and Alcoholism reported that people who drank alcohol two times the gender-specific binge drinking thresholds were 70 times more likely to have an alcohol-related visit to the emergency department. Furthermore, those who consumed alcohol at three times the gender-specific binge thresholds were 93 times more likely to have an emergency department visit.

Perception of a lot and little:

How good are we in determining moderation? In a 2015, a cross-sectionally analysis from the eHeart Health Study dataset had participants answer the following questions (5):

Source: https://www.sciencedirect.com/science/article/pii/S0002914915013533?casa_token=6RqulqCY-doAAAAA:mQDOG8ZbJEp_w4WXk4v7p4cDLT3R3LT8lIzAMQBrUxLx0giLTI0g67EhdTXksWvsLCNAsQ6d

Do you believe alcohol is good for your heart?” – “Yes,”“No,”or“I don’t know.”

You believe alcohol is good for your heart because?” –“ Your doctor told you,” “You learned this in school,” “You learned from reading lay press,” “You learned this from friends, colleagues, or word of mouth, ”or “Other [free text]. Over 5,000 people answered the questions and approximately 30% felt alcohol consumption was health healthy, 39% felt it was unhealthy and 31% were unsure. The majority of the perceptions were related to information retained from the lay press.

The lay press giving us some health guidance! Shocking, I know.

More importantly, it is important to determine the causal effects we see in observational studies. Those are studies that conclude “x” amount of alcohol is related or associated “y” outcome of health. So researchers design studies termed “Mendelian Randomization”. The study looks at genes known to function to look at modifiable (lifestyle) exposure to disease. Larsson et al. published a Mendelian Randomization study in 2020 that investigated the effect of alcohol consumption on 8 cardiovascular diseases (6). The authors found that high alcohol consumption may be causally associated with an increased risk of stroke and peripheral artery disease. Furthermore, the link may occur through blood pressure changes.

Source: https://www.cvphysiology.com/Hemodynamics/H014

Blood pressure changes are controlled by our nervous system. A recent study from Greenlund et al. investigated the effects of night binge alcohol consumption on sleep, morning-after blood pressure, and muscle sympathetic activity (7). Twelve men and ten women were included in this randomized cross-over design. The alcohol had a 1:3 ratio of 95% ethanol mixed orange or cranberry juice. Sounds pretty yummy. The alcohol dose was a 1 g/kg dose for men and a 0.85 g/kg dose for women.. The authors utilize the Valsalva maneuver to observe the changes in blood pressure after the night of binge drinking. The Valsalva maneuver leads to a decrease in heart rate and blood pressure, which then stimulates the sympathetic nervous system and allowing the investigators to examine changes in sympathetic function.

There were increases in resting heart rate the next morning, but blood pressure remained unchanged compared to the fluid control condition. During the Valsalva maneuver, there was a heightened sympathoexcitatory response and a reduced baroreflex response. Furthermore, a night of binge drinking disrupted sleep quality (reduced REM sleep).

Studies that use Mendelian randomization, or have a practical approach of viewing the morning effect effects have significant roles in improving the comprehension of the information received from the lay news. Alcohol consumption is certainly linked with cardiovascular disease. The idea of everything in moderation seems to prevail. However, the amount that is perceived to be a lot person to person varies, making alcohol consumption a known risk to health. People’s perceptions of themselves could change the amount of alcohol consumed in one sitting, which could increase the risk of binge drinking (8).

References

Alcohol Facts and Statistics | National Institute on Alcohol Abuse and Alcoholism (NIAAA) [Internet]. [cited 2021 Mar 14]. Available from: https://www.niaaa.nih.gov/publications/brochures-and-fact-sheets/alcohol-facts-and-statistics
Dietary Guidelines for Americans, 2020-2025 and Online Materials | Dietary Guidelines for Americans [Internet]. [cited 2021 Mar 14]. Available from: https://www.dietaryguidelines.gov/resources/2020-2025-dietary-guidelines-online-materials
Gaziano JM, Buring JE, Breslow JL, Goldhaber SZ, Rosner B, Vandenburgh M, et al. Moderate Alcohol Intake, Increased Levels of High-Density Lipoprotein and Its Subfractions, and Decreased Risk of Myocardial Infarction. New England Journal of Medicine. 1993;329(25):1829–34.
Camargo Jr. CA, Stampfer MJ, Glynn RJ, Grodstein F, Gaziano JM, Manson JE, et al. Moderate Alcohol Consumption and Risk for Angina Pectoris or Myocardial Infarction in U.S. Male Physicians. Ann Intern Med. 1997 Mar 1;126(5):372–5.
Whitman IR, Pletcher MJ, Vittinghoff E, Imburgia KE, Maguire C, Bettencourt L, et al. Perceptions, Information Sources, and Behavior Regarding Alcohol and Heart Health. The American Journal of Cardiology. 2015 Aug 15;116(4):642–6.
Larsson Susanna C., Burgess Stephen, Mason Amy M., Michaëlsson Karl. Alcohol Consumption and Cardiovascular Disease. Circulation: Genomic and Precision Medicine. 2020 Jun 1;13(3):e002814.
Greenlund IM, Cunningham HA, Tikkanen AL, Bigalke JA, Smoot CA, Durocher JJ, et al. Morning sympathetic activity after evening binge alcohol consumption. Am J Physiol Heart Circ Physiol. 2021 Jan 1;320(1):H305–15.
Cromer JR, Cromer JA, Maruff P, Snyder PJ. Perception of alcohol intoxication shows acute tolerance while executive functions remain impaired. Experimental and Clinical Psychopharmacology. 2010;18(4):329–39.

Post-Stroke Cognitive Impairment And Dementia And Risk Factors and Prevention

March 19, 2021March 19, 2021 Patrick Tomko

Dr. Rebecca Gottesman presented on Thursday during the Stroke Conference of 2021. She addressed the past, present, and future related to vascular dementia, mixed dementia, early stroke recovery, and precision medicine.

https://pubmed.ncbi.nlm.nih.gov/30784556/

In the past, the definition of post-stroke dementia was not necessarily uniform. She explains this is related to the term vascular dementia being sort of “tricky”. When classifying dementia you should consider, when you look, where you look, and whom you are looking at?

Many people can have dementia prior to having the stroke, this important when reviewing the prevalence rates after the stroke. Nearly 10% has dementia prior to stroke onset (1).

Dr. Gottesman highlights the need to review mixed pathologies for vascular dementia. The trajectories of onset and recovery vary between people. There can be a decline in cognition, followed by a recovery, then a further decline or an improvement. The Individual-level risk is important in post-stroke dementia.

https://www.ahajournals.org/doi/epub/10.1161/STROKEAHA.117.017319

Dr. Gottesman shared that the same stroke does not affect the person the same way (not every stroke leads to the same outcome). The individual risk profile will help individualize treatments and allow for more precision in medicine. She acknowledges that it is difficult to identify everyone who may have a stroke before they have an actual stroke. The meta-analysis from Oberlin highlights leisure activity as a potential way to reduce post-stroke dementia (2). Near the end of the presentation, Dr. Gottesman suggests we consider the following questions:

1) How do you consider aphasia and other cognitive deficits from the stroke?

2) How much time should pass after the stroke before you call it “dementia”?

3) How do you characterize dementia?

4) How do you characterize the dementia subtype?

5) How might future studies improve post-stroke cognitive outcomes?

We should consider the different prevention approaches due to the number of the different pathologies related to post-stroke dementia.

References

Pendlebury ST, Rothwell PM. Incidence and prevalence of dementia associated with transient ischaemic attack and stroke: analysis of the population-based Oxford Vascular Study. The Lancet Neurology. 2019 Mar 1;18(3):248–58.
Oberlin LE, Waiwood AM, Cumming TB, Marsland AL, Bernhardt J, Erickson KI. Effects of Physical Activity on Poststroke Cognitive Function: A Meta-Analysis of Randomized Controlled Trials. Stroke. 2017 Nov;48(11):3093–100.

Misinformation and being a scientist during the 21st Century

February 25, 2021February 24, 2021 Patrick Tomko

In a recently published paper, Dr. Lykke Sylow shares three challenges for scientists during a time where not only misinformation, but the quantity of misinformation questions what science stands for (1).

Dr. Lykke Sylow is an assistant professor for the department of Nutrition, Exercise and Sports at the University of Copenhagen. Her line of research involves muscle insulin sensitivity, GTPase, exercise cancer cachexia and metabolism. Dr. Sylow shares the following three challenges in a recent publication: 1) Balancing correct interpretation of results with the need for promotion, 2) Schism between the need for fast scientific communication and scientific trustworthiness, 3) Tackling the social media platforms as they take a leading role in how we seek information.

The figure below highlights the incentivization for scientists to promote their research findings, thus the idea of bias comes to mind. This supports challenging circumstances to rely on the public to determine if scientific results are correctly interpreted and translated into a meaningful and comprehensive message (2).

https://doi.org/10.1073/pnas.1317516111

It is important to notice the complexity of the third model and the larger circle of the socio-political context that may often be overlooked.

The next figure below similarly highlights the reliance on the public to balance political and societal concerns with what is shared to them (3). Think about the citizens never-ending exposure to streams of very often contradictory information and/or arguments. Science cannot tackle this age of misinformation alone.

10.1073/pnas.1704882114

I reached out and asked two other scientists for their thoughts about the current state of science and misinformation. Dr. Derek Kingsley is an associate professor at Kent State University in the School of Health Sciences in Kent, OH, US. Dr. Kingsley’s research involved cardiovascular dynamics and outcomes with resistance exercise interventions. His responses are below:

“During times like these it is important to remind scientists to slow down. Good science takes time. It seems that nothing can come quick enough these days, but we all have to remember that is never how science works.”
“When it comes to sifting through information it is important to look for repetitions and commonalities in the data. Science is about repetition. Any experiment should be repeatable, and produce similar findings. Three or four studies do something a little bit different, but the story should generally be the same. If you find a study that stands out as different, then you have to ask the question, why is this one study different?” Dr. Kingsley reminds us that the difference could be strength or a weakness. He stated, “You should probably read more than just one piece of information from one source.”
Finally he finished by stating “Look to understand both sides of the coin.” While commonalities are important, so are differences. Scientists should embrace and understand them. A great argument or point of discussion requires an open-mind, so at the minimum people should be exposed to both sides. This allows them to make a decision supported by the embraced evidence. Remember, this doesn’t make the other side wrong, sometimes it’s just a different perspective.”

Dr. Babajide Ojo is currently a research Fellow at Cincinnati Children’s, in Cincinnati, Ohio, US. His interests are involved with gastroenterology, hepatology, and nutrition. Dr. Ojo is earlier than Dr. Kingsley in his career and shared his thoughts shared below.

He states the first challenge is related to fear. “Misinformation sells and already has a huge following. Breaking through huge following can be a bit scary especially for young scientists trying to establish themselves. Social media is now the number one channel for communicating scientific information to lay audiences. As a scientist with nutrition training, I see the supplement industry as a mess. People spewing a lot of advice on social media that are not backed by repeatable and valid research. My fear is not always about challenging the fake experts, but if I get into it with people on social media for this “good cause”, I worry about my image with my boss, my employer, future employers, and so on. What if some of the big supplement companies have some influence in government regulatory bodies, or with my employer? Unfortunately, this is a real worry for some of my colleagues.”
Dr. Ojo statement reminds us there is little to no reward in academia for science communication to lay audiences. “Why bother? So we decide to focus our time on what pays the bills– the science. This creates a vacuum that the fake experts have capitalized on.”
Finally the third challenge Dr. Ojo states is related to the dearth of mentors. “When you look at senior scientists and achievers in your field, most individuals are where they are at because of science. Therefore, we naturally thread the path of our seniors to achieve that level of excellence in the field.”

Whether it’s remembering your fundamentals like repeatability, or strengths and limitations of a study design, or bringing a concern to help mentorship types of relationships change focus. Dr. Sylow puts misinformation concern best by stating in the article,

“The concern is less about perceptions of consensus, but about what it stands for. If the public are convinced that science is not settled, why would the public weigh scientific facts more heavily than conspiracy beliefs or “alternative facts.”

Misinformation is here to stay, scientists should continue to engage with transparency in the best ways available. You can find Dr. Sylow’s publication in the references below.

Sylow L. Three challenges of being a scientist in an age of misinformation.
Scheufele DA. Science communication as political communication. Proceedings of the National Academy of Sciences. 2014 Sep 16;111(Supplement 4):13585-92.
Drummond C, Fischhoff B. Individuals with greater science literacy and education have more polarized beliefs on controversial science topics. Proceedings of the National Academy of Sciences. 2017 Sep 5;114(36):9587-92.

An MD or PHD, what is the best path for you?

January 27, 2021January 26, 2021 Patrick Tomko

On the American Heart Association Research Committee, you can see 9 of 30 members marked having a Ph.D. Furthermore, you’ll see that all programs the committee members are affiliated with have some medical association.

This example of the committee brings the question “Can an MD do what Ph.D. does?” The short answer is yes. Ph.D.’s may not necessarily have all the training an MD has, so the profession cannot provide exactly the same opportunities. So does the difference lies with patient care? Many PhDs work with MDs, so maybe a Ph.D. can have a similar clinical care experience.

How do people with an MD (Doctor of Medicine) differ from those with Ph.D. (Doctor of Philosophy)? The most common answers are likely:

“MDs make more money.”
“MDs prescribe medications.”
“They’re the real doctors”

Some Differences and Similarities:

PhDs:

On average, about 4-6 years to complete the degree
Purpose – to develop original work
Considered an academic degree
Contribute new theory and knowledge to the field

MDs:

On average, about 4 years to complete the degree, not including residency
Purpose – trained to give patient care
Considered a professional degree
Apply the existing theories and knowledge practically.

Both:

Referred to as Doctors
Both can specialize in fields.
Both perform research and apply for funding

The foundational difference may be related to assuming that Ph.D.s advance knowledge and MDs apply existing knowledge. It is not required for MDs to produce original research, whereas PhDs write up a dissertation (includes original work).

Okay, so obviously the training for doctor degrees are different. But, who is more up-to-date on cutting edge knowledge? Maybe, this sways your opinion?

PhDs are required to do original work, so wouldn’t they be? What about MDs that conduct clinical trials? Do they use cutting edge knowledge?

It begins to get cloudy when you look past the path of earning your MD or Ph.D. Both professions can conduct clinical trials. Both professions can conduct translational related work. Which route is better for you? How do you choose?

The path to the degree prepares you for what is ahead in your career. Hence the obvious difference of original work vs patient-related work. This is how many view it. However, the cloudiness between which path to choose increases when ideas like a specialty in biomedical research come to mind. Acceptance into MD/PhD program absorbs expectations into a research-oriented career. The program is expecting you to make medical advances through your training as a researcher.

Ask yourself “What is the next step after obtaining my terminal degree (MD and Ph.D.)? “

You can pursue research opportunities with just an MD degree. This can occur through a fellowship type of training. Sort of similar to post-doctoral training, an option after completion of a Ph.D.

Overall the training and mentorship past your terminal degree will maximize your opportunities. There is a lot to mull over for choosing a path. Make a Pros and Cons list? Or better yet, maybe just go observe both types of professions? Find a lab to work in or do some volunteering over the summer, Maybe get involved in a big project. Do something that is even just solely preparing materials for a particular procedure. See if you like the environment. I suggest looking beyond obtaining the terminal degree. Look for people you admire and learn their stories. Keep your eyes up to see all the open doors.

Virtual Meeting Preparation and Reflection of Scientific Sessions 2020

December 17, 2020December 17, 2020 Patrick Tomko

As I complete my first virtual meeting of 2020 as a graduate student in science, there was two things I decided to take away from Scientific Sessions 2020. First, there is a specific agenda you could create to help yourself at professional conference meetings. I have some tips on getting involved with the content at the meetings. Second, I want to provide a reminder about the few advantages of virtual meetings.

An Agenda for Professional Conference Meetings:

First you need determine your priorities for attendance. This could be looking at the science specific to your interest that compliments your current work, or engaging in a way where you will communicate with someone outside your current network. Professional meetings have loads of information and dynamics that could create an overwhelming feeling, especially if it is your first meeting as a student. This is the “adulting” component of being a graduate student.

To help with attendance cost, a student should apply for everything. That means any student travel grants, waivers for registration fees, of even finding other agencies that offer to fund “professional development” in students. As frustrating as it can be, plan to be a “penny-pinching patty.” This is part of the goal in prioritizing what you hope to get out of a conference; you need to have the stamina to handle all the sessions you hope to see. This means making sure you eat throughout your entire experience, even if it is virtual.

Second you need to develop general outline for the time frames of the sessions you plan to attend. This is almost like brainstorming what you hope to experience in the scientific sessions you attend at a conference. For me, this year I used the app associated with the American Heart Association meetings. The “AHA” conferences app helped provide reminders and take notes, it’s a virtual planner for your brainstorm session. I found myself on three different occasions changing the sessions I planned to attend virtually. These changes were more related to sessions I was asking others to attend for me, where then I attended a session they could not see in return.

So that brings me to my third point for creating an agenda. Third, a buddy system, which seem obnoxious for scientific conferences. However, if there is an overload of content you want to see and engage with, like I did for this year’s Scientific Sessions, then creating a system to get coverage for all sessions is ideal. Furthermore, this buddy system can lead to an expansion of networks due to attendance of sessions you may not always find yourself becoming involved with.

A Research Tool Box and Advantages of Virtual Meetings:

The main point of research conferences is the presentation of new research in a format that catches attendee interest. Presentations at conferences are typically followed by questions and discussion between presenters and their audience. All of which is was still the framework for virtual scientific conference.

One advantage is no travel and lodging expenses. Most students have to pay out of pocket for travel and lodging at conferences (1). Although, there is nothing that can replace human interaction, there is some light from reduce burden of costs for students in virtual meetings. The stress of affording the expected costs of scientific meetings becomes slightly more manageable. I highlight this because depression and anxiety continue to grow with graduate students. Almost 40% students showed anxiety and depression scores in the moderate to severe range (2). Virtual conferences still allow you connect with others in a different manner. This point is especially important considering the how the pandemic is eroding graduate student mental health. From a current survey of about 4000 U.S. STEM doctoral students , 40% reported symptoms aligning with generalized anxiety disorder and 37% with depression (3).

In addition to the reduced conference expenses, two are three helpful tools for your research conference tool box.

Take breaks and or watch conferences sessions in different environments. Do not be afraid to go outside with the laptop and listen to a session while being in the sun. This can help create a comfortable environment for you to fully immerse yourself in the session.
Get involved on social media for these virtual conferences, it allows for continuing conversation and to expand networks. You can take notes from posts on social media reported by others that you may have missed.

2020 carefully reminds us about the value of human interaction for our lives. We will continue to learn and grow as students, adding to our toolbox. Have a safe, socially distanced, and peaceful holiday.

Malloy J. Stop making graduate students pay up front for conferences. Nature. 2020;13:2020.
Evans TM, Bira L, Gastelum JB, Weiss LT, Vanderford NL. Evidence for a mental health crisis in graduate education. Nature biotechnology. 2018 Mar 6;36(3):282.
Chirikov I, Soria KM, Horgos B, Jones-White D. Undergraduate and Graduate Students’ Mental Health During the COVID-19 Pandemic.

The Final Day (5/5) of AHA Scientific Sessions “Step on the Gas, so you can Hit the Breaks”

November 18, 2020November 18, 2020 Patrick Tomko

In the scientific session titled “Beyond Biomarkers: Inflammation and CVD across the Translational Spectrum”, inflammation was the topic of interest. It is important to note that inflammation has been established as a focus for the development of complications for cardiovascular diseases for some time now. The changes in inflammatory markers have been shown to be predictive of future cardiovascular events. But, do we know what exactly inflammation is? Are the markers we use precise enough to provide meaningful guidance for specific targeted therapies?

Dr. Russell Tracy from the University of Vermont was given the challenging opportunity to open the session in explaining how inflammation in cardiovascular disease works. He starts off by highlighting not just the amount of cells to consider, but all the different types and subtypes. There’s a multitude of pathways linked to inflammation and atherosclerosis. He proposed to focus on the pathophysiology that plays a role over the lifespan. Interestingly, the concept of trained immunity was highlighted as an influencer to the chronic inflammation that is signaled through adipose tissue. Dr. Tracy goes on to share that the inflammatory process could be related to input from multiple small pathways and that adaptative immunity impacts the inflammation research is attempting to characterize (Figure 1).

Figure 1.

Dr. Peter Libby from the Brigham and Women’s Hospital took a shot at addressing why some anti-inflammatory therapies work and then why some do not. He highlighted three studies to keep in mind for attendees: 1) the Canakinumab Anti-inflammatory Thrombosis Outcomes Study or “CANTOS”, 2) the Cardiovascular Inflammation Reduction Trial “CIRT”, and 3) the Colchicine Cardiovascular Outcomes Trial or “COLCOT. CANTOS focused on interleukin-1ß (IL-1ß) and its role in the reduction of rates of recurrent myocardial infarction, stroke, and cardiovascular death among stable patients with coronary artery disease who remain at high vascular risk (1). Canakinumab at a dose of 150 mg every 3 months led to a lower rate of recurrent cardiovascular events (1).

CIRT addressed low-dose methotrexate use among patients with stable coronary artery disease (CAD). The investigation showed low-dose methotrexate does not reduce inflammatory markers or cardiovascular events (2). Dr. Libby quickly pointed out the difference in baseline inflammation between the two populations. Where the CANTOS study already showed some residual inflammation as compared to CIRT.

He went on stating,

“You have to step on the gas to press the breaks.”

The baseline level of inflammation is a characteristic to be more aware of when designing and evaluating drug studies like CIRT.

COLCOT involved the use of Colchicine to decrease the migrations of neutrophils, a white blood cell type that is essential for the resolution of inflammation. Neutrophils are a marker used for cardiovascular risk (4). Colchicine at a dose of 0.5 mg daily showed a significantly lower risk of ischemic cardiovascular events. Dr. Libby summed the presented work up with the slide below addressing residual inflammatory risk (Figure 2).

Figure 2.

He left the attendees with Winston Churchill’s famous quote from London’s Mansion House, just after the British routed Rommel’s forces at Alamein, driving German troops out of Egypt,

“This is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning.”

Referring to the development of targeted anti-cytokine therapies for the treatment of atherothrombosis.

Overall it seems there is an oversimplification of inflammation at times, thus inaccurately conveying the heterogeneity of the processes involved. It is a challenge to accurately assess the mechanisms underlying CVD risk in each patient. More work around specific anti-inflammatory pathway is vital to characterize inflammation and develop targeted therapies that provide a cardiovascular benefit.

References:

Ridker PM, Thuren T, Zalewski A, Libby P. Interleukin-1β inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). Am Heart J. 2011 Oct;162(4):597-605. doi: 10.1016/j.ahj.2011.06.012. Epub 2011 Sep 14. PMID: 21982649.
Ridker PM, Everett BM, Pradhan A, MacFadyen JG, Solomon DH, Zaharris E, Mam V, Hasan A, Rosenberg Y, Iturriaga E, Gupta M, Tsigoulis M, Verma S, Clearfield M, Libby P, Goldhaber SZ, Seagle R, Ofori C, Saklayen M, Butman S, Singh N, Le May M, Bertrand O, Johnston J, Paynter NP, Glynn RJ; CIRT Investigators. Low-Dose Methotrexate for the Prevention of Atherosclerotic Events. N Engl J Med. 2019 Feb 21;380(8):752-762. doi: 10.1056/NEJMoa1809798. Epub 2018 Nov 10. PMID: 30415610; PMCID: PMC6587584.
Tardif JC, Kouz S, Waters DD, Bertrand OF, Diaz R, Maggioni AP, Pinto FJ, Ibrahim R, Gamra H, Kiwan GS, Berry C, López-Sendón J, Ostadal P, Koenig W, Angoulvant D, Grégoire JC, Lavoie MA, Dubé MP, Rhainds D, Provencher M, Blondeau L, Orfanos A, L’Allier PL, Guertin MC, Roubille F. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N Engl J Med. 2019 Dec 26;381(26):2497-2505. doi: 10.1056/NEJMoa1912388. Epub 2019 Nov 16. PMID: 31733140.
Kain V, Halade GV. Role of neutrophils in ischemic heart failure. Pharmacol Ther. 2020 Jan;205:107424. doi: 10.1016/j.pharmthera.2019.107424. Epub 2019 Oct 16. PMID: 31629005; PMCID: PMC6981275.

Modifiable Factors Influence Non-modifiable Factors for Cardiovascular Health?

November 14, 2020November 17, 2020 Patrick Tomko

The scientific community continues its full force swing at reducing cardiovascular disease risk. In the Scientific Session titled “Microbiome in Cardiovascular Disease,” the complexity of accounting for human variation was the theme. The important difference and interactions between non-modifiable (genetics) and modifiable (diet, exercise, smoking, etc..) factors were presented. Dr. Katherine Tucker opened up the session by highlighting work from Thanassoulis et. al., 2012, which identified 13 single nucleotide polymorphisms (SNPs) to generate a genetic risk score (GRS) to predict cardiovascular events and coronary artery calcium (CAC). Single nucleotide polymorphisms are the most common type of genetic variation among people and are used to help quantify the variation in individuals (1). The CAC score comes from a test that quantifies the amount of calcium accumulation in the walls of the coronary arteries. A lower score represents a greater risk and a lower score relates to a lower risk of heart disease. Dr. Tucker went on to explain the genetic risk is influenced by individual environmental factors (i.e. smoking, exercise, and diet) (2). Recent data from the CARDIA study supports this in reporting that, “low-carbohydrate diets at a younger age is associated with an increased risk of subsequent CAC progression, particularly when animal protein or fat are chosen to replace carbohydrates. (3).”

Figure 1 source: https://doi.org/10.1093/nutrit/nux001

The changes in macronutrient content in a diet is related to what happens in the gut. Within the gut, there are trillions of bacteria that make up a microbiome. An individual microbiome modulates the immune system and metabolic processes. The microbiome influence on human health is so pronounced in that it actively reprograms the genome in response to the environment, changing the bacteria phyla ratios that lead to down-stream effects that could influence cardiovascular health (Figure 1) (2). Dietary fiber and prebiotic consumption are two components that modulate the composition of the gut microbiome (Figure 2) (4). Also, there is some great news for you Kombucha fans out there! Fermented foods have some benefits for the gut.

Figure 2. Source: https://doi.org/10.1093/nutrit/nux062

Bhat and Kapila 2017 further highlight diet in a review stating “The composition of the gut microbiota has a tremendous influence on host metabolism.” Perhaps specific dietary interventions can reduce the risk of cardiovascular disease with the focus on obtaining an optimal microbiota composition. Zhang et. al., 2020, showed how detrimental diets with contain highly processed foods can be the bacteria in our gut (Figure 3) (5).

Figure 3. Source: https://doi.org/10.1093/ajcn/nqaa276

To further highlight how much people differ from one another, Dr. Tang from the Cleveland Clinic explained only 37% of the gut is actually shared between twins. In addition, there are significant diurnal variations in response to meals consumed among people. The work presented the relationship between microbiota and trimethylamine (TMA)/trimethylamine–N-oxide(TMAO) generation. Elevated TMAO levels predict major adverse cardiac events like death, myocardial infarction (MI), and stroke (Figure 4) (6). Dr. Tang explained that risk is highest with people who displayed the highest baseline levels of two TMAO precursors choline or L-carnitine, while some may show no risk with higher levels. Dr. Tang emphasized the variation again among individuals.

Figure 4. Source: Tang, W. W., & Hazen, S. L. (2014)

We are only scratching the surface with the modifiable risk factors for heart disease. Specifically, the gut shows an area rich for investigation. The gut microbiota contributes to human physiology and diseases and it is something to be excited about for biomedical researchers.

References:

Thanassoulis G, Peloso GM, Pencina MJ, Hoffmann U, Fox CS, Cupples LA, Levy D, D’Agostino RB, Hwang SJ, O’Donnell CJ. A genetic risk score is associated with incident cardiovascular disease and coronary artery calcium: the Framingham Heart Study. Circ Cardiovasc Genet. 2012 Feb 1;5(1):113-21. doi: 10.1161/CIRCGENETICS.111.961342. Epub 2012 Jan 10.
Mohd Iqbal Bhat, Rajeev Kapila, Dietary metabolites derived from gut microbiota: critical modulators of epigenetic changes in mammals, Nutrition Reviews, Volume 75, Issue 5, May 2017, Pages 374–389, https://doi.org/10.1093/nutrit/nux001
Gao, J. W., Hao, Q. Y., Zhang, H. F., Li, X. Z., Yuan, Z. M., Guo, Y., … & Liu, P. M. (2020). Low-Carbohydrate Diet Score and Coronary Artery Calcium Progression: Results From the CARDIA Study. Arteriosclerosis, Thrombosis, and Vascular Biology, ATVBAHA-120.
Genelle R Healey, Rinki Murphy, Louise Brough, Christine A Butts, Jane Coad, Interindividual variability in gut microbiota and host response to dietary interventions, Nutrition Reviews, Volume 75, Issue 12, December 2017, Pages 1059–1080, https://doi.org/10.1093/nutrit/nux062
Zefeng Zhang, Sandra L Jackson, Euridice Martinez, Cathleen Gillespie, Quanhe Yang, Association between ultraprocessed food intake and cardiovascular health in US adults: a cross-sectional analysis of the NHANES 2011–2016, The American Journal of Clinical Nutrition, https://doi.org/10.1093/ajcn/nqaa276
Tang, W. W., & Hazen, S. L. (2014). The contributory role of gut microbiota in cardiovascular disease. The Journal of clinical investigation, 124(10), 4204-4211.