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February 23, 2024 BlogResearch in General

180 years ago, a doctor in the Austrian Empire conducted a radical experiment that has saved millions of children but cost him his life. This shocking, ground-breaking experiment involved doctors washing their hands. I know, I know, it sounds ridiculous, but doctors not only didn’t wash their hands back then, they were opposed to the very idea so much that the researching doctor was institutionalized and beaten to death. In this article, we’ll explore the history of handwashing, how they came up with the experiment, why people weren’t washing their hands in the first place, why the experiment worked, and how modern hand washing works. Then, we’ll dive into some nitty-gritty science.

Handwashing is old. Like, it’s really old. We have good evidence of soap from nearly 3000 years ago. Handwashing as a ritual before meals is in Abrahamic religious texts. It was recorded in ancient Egyptian and Greek civilizations and is even practiced by raccoons. But this was superficial handwashing, mostly meant to get rid of visible dirtiness because we hadn’t discovered germs yet. Instead, ideas of how disease spread were based on things like miasma – the stinkiness of a dirty thing.

Ignaz Semmelweis was a physician who, in the 1860s, got a residency in a maternity ward. In those days things were separated by gender, so there were two clinics. One was attended by male doctors and one by female midwives. Dr. Semmelweis noted that people died in the male-run clinic at a rate 300% higher than in the midwife-run clinic. He was appalled and wrote that women would have better outcomes giving birth in the street than in the hospital. The primary disease causing all the deaths was childbed fever, now known as (pew-er-per-al) puerperal fever. Luckily, Dr. Semmelweis had a shocking (shocking!) insight. He theorized that perhaps the fact that the doctors would do autopsies before going to the maternity ward was causing some of the “cadaverous particles” to infect the patients. He got this idea when a fellow doctor cut himself during an autopsy and subsequently died of childbed fever. Dr. Semmelweis concluded that doctors should wash their hands in chlorinated water upon entering the maternity clinic! Within a year the death rate plummeted from ~10% to under 2%.

Unfortunately, doctors were reluctant to change their ways. The theory that doctors could be killing their patients was seen as offensive and came with the implication that doctors were unclean, which went against the class system of the era. He was reluctant to release his findings, but when he did they were dismissed and his reputation was ruined. In his book Die Aetiologie, der Begriff und die Prophylaxis des Kindbettfiebers, he is racked with guilt. He was committed to an insane asylum where he was beaten to death by the orderlies within weeks under suspicious circumstances. It would be decades before germ theory gave an explanation for Semmelweis’s findings and brought them back into the public consciousness. He would never know how many millions of children and mothers he saved.

In Dr. Semmelweis’s day, they used chlorinated water to wash their hands. Let’s dive into modern-day hand washing. How does washing hands work? Why do we need to wash our hands, even if they look clean? Are there better ways to wash hands? Is hand sanitizer just as good? To start, let’s look at the skin as an immune organ. The skin is awesome. It’s our biggest organ and is the primary defense against invading germs; the tiny microorganisms like bacteria, fungi, and viruses. The skin has three major defense mechanisms. Our immune cells fight organisms that get too close for comfort and our skin hardens and sloughs off, taking bacteria and viruses with it. Before either of those, potential attackers have to deal with the skin microbiome. It turns out our skin isn’t just a cool canvas for tattoos but is an entire ecosystem for thousands and millions and billions of teeny little friends that make a living harvesting our sweat or whatever. Three important genera of bacteria take up the bulk of what we call the resident flora: cutibacterium, staphylococcus, and corynebacterium. These three coat our skin and enhance the immune protection skin gives us. They are commensal organisms, which is kind of like the mob. We give them food and shelter, and they promise to (mostly) do us no harm. They are called “residents” because they live with us our whole lives. They colonize our skin, making it hard for other invaders (called transient flora) to get a foothold. The defense mechanisms they have for themselves work well against the transient flora. In addition, they break down cholesterols we emit into free fatty acids which keep our skin a little acidic, killing invaders. They tend to reside deeper in the skin layers than transient bacteria, are less likely to cause infection, and are harder to remove.

This is exactly where handwashing shines. Transient flora, like MRSA, multidrug-resistant gram-negative bacteria, Vancomycin-resistant Enterococci, and “cadaverous particles” tend to be closer to the outer layers of skin and are easier to remove. Effective hand-washing removes the transient flora but keeps the residents intact. Even more effective than just soap and water are antibacterials. These attack the transients in creative ways, degrading the cell walls, DNA, and proteins. Hand sanitizer is effective at destroying many bacteria and can be applied frequently and without a sink. So next time you wash your hands between visiting the morgue and the maternity ward, think of Dr. Semmelweis and thank him for his experimental vision!

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

Listen to the article here:


Boyce, J. M. (2021). Hand hygiene, an update. Infectious Disease Clinics, 35(3), 553-573.

Edmonds-Wilson, S. L., Nurinova, N. I., Zapka, C. A., Fierer, N., & Wilson, M. (2015). Review of human hand microbiome research. Journal of dermatological science, 80(1), 3-12.

Skowron, K., Bauza-Kaszewska, J., Kraszewska, Z., Wiktorczyk-Kapischke, N., Grudlewska-Buda, K., Kwiecińska-Piróg, J., … & Gospodarek-Komkowska, E. (2021). Human skin microbiome: Impact of intrinsic and extrinsic factors on skin microbiota. Microorganisms, 9(3), 543.

Semrnelweis, I. (1861). Die Aetiologie, der Begriff und die Prophylaxis des Kindbettfiebers, C. A. Hartleben’s Verlag-Expedition, Translated by K. Codell Carter. Madison, 1983

Widmer, A. F. (2000). Replace hand washing with use of a waterless alcohol hand rub?. Clinical infectious diseases, 31(1), 136-143.


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Alzheimer’s Dementia, often shortened to AD, is abjectly terrible. People with the disease lose memories, language, and the ability to function by themselves. It was first described over a hundred years ago by Dr. Alzheimer,  and there has been startlingly little progress in treating the disease since. Alzheimer’s disease is a dementia characterized by two kinds of brain deposits: amyloid plaques and tau tangles. It’s the most common type of dementia. Dr. Alzheimer also noticed the distinct presence of extra cholesterol in the brain, which we will return to.

We have few medications that are approved to help with Alzheimer’s. Even these don’t cure the disease but instead slow its progress. This indicates a fundamental lack of a good model for how the disease starts or progresses. The first big hypothesis for Alzheimer’s was the cholinergic hypothesis; that there is a paucity of a neurotransmitter called acetylcholine causing the damage. Unfortunately, drugs that increase acetylcholine don’t stop the disease progression. The second big hypothesis, the one that is currently in vogue, is the amyloid cascade hypothesis. According to this theory an amyloid precursor known as amyloid beta (Aβ) is the cause of Alzheimer’s. This makes a lot of sense, as Aβ is the main component of amyloid plaques and people with a genetic predisposition to make extra Aβ tend to get Alzheimer’s (called familial Alzheimer’s). There are a few inconsistencies in this hypothesis: the distribution of Aβ doesn’t match how bad the disease is, and risk factors that increase Aβ don’t match those of Alzheimer’s. To make matters worse, in spite of decades of research, over 99% of clinical research studies targeting Aβ have failed to bring a medication to market.1 

Enter the Lipid Invasion Model. This is a new hypothesis developed in 2021 to explain the root cause of Alzheimer’s dementia. The basic idea is that the barrier between the brain and the rest of the body degrades, which allows cholesterols and free fatty acids to “invade” the brain and cause damage. The less basic idea is the rest of this article.

To begin, let’s discuss the barrier between the brain and the body, aptly called the Blood Brain Barrier. The barrier is made up of the blood vessels of the brain. These are special blood vessels with unique properties. The cells that make up the walls of the blood vessels, called epithelial cells, are joined together with tight junctions that keep small charged particles from getting past. These epithelial cells are dotted with special transporters that only let in certain nutrients. Other brain cells called pericytes and astrocytes surround the epithelial cells (on the brain side) and keep out stragglers. This allows the brain to maintain the environmental conditions that it needs to function. Instead of letting a free flow of blood to cells, the blood brain barrier only lets in specific amounts of specific nutrients. One of the key items that is restricted by the blood brain barrier is lipids.

“Lipids” is another name for fats. In the body they perform several vital functions, and in the brain they are critical. Even though the brain is only 2% of the body’s weight, it contains nearly a ¼ of the body’s cholesterol. It uses this for cell repair, creating synapses (learning), releasing communication particles, and for coating neurons to increase the speed of thought. The two lipids relevant to this discussion are cholesterol and free fatty acids. These are energy-dense particles that don’t dissolve in watery liquids like blood. Instead, they need to hitch a ride to be transported through the bloodstream. In the brain, cholesterols and free fatty acids must be transported in small, dense, protein-rich particles called lipoproteins. In the body, lipoproteins come in many different sizes (including low-density lipoproteins, known as LDL). In addition, free fatty acids can be transported in a different protein called albumin. Part of the blood brain barrier’s job is to keep these two systems of transporting lipids separate.

The Lipid Invasion Model postulates that this separation system fails. When this happens the brain can’t handle the extra lipids. Free fatty acids in particular have a detrimental effect. They cause oxidative stress that can result in cell damage and change the energy regulation of neurons, causing problems, and activating immune receptors causing an inflammatory response. Inflammation can result in astrocyte cells producing extra cholesterol, making the problem worse. On top of this, excess lipids in the brain are thought to limit the ability of neurons to grow and cause the amnesia typical of Alzheimer’s. Finally, excessive lipids may cause the brain to create amyloid beta, the precursor to the stereotypical amyloid plaques.

So what goes wrong with the blood brain barrier? Scientists think the barrier degrades over time. Those tight junctions loosen, the transporters let in too many items, or items of the wrong type, and different proteins on the surface of epithelial cells disrupt the barrier. Additionally, microbleeds in the brain let unrestricted blood flow through and interact without the epithelial cells’ consent. The barrier lets the wrong type of materials cross, including lipids. In Alzheimer’s patients, we see free fatty acids and non-brain-native lipoproteins (including the risky APOE4) spread through the brain. The risk factors for blood brain barrier damage are eerily similar to those of Alzheimer’s dementia:

  • Aging is the number one risk factor
  • Brain trauma (CTE from football has similar symptoms)
  • High blood pressure
  • Stress
  • Lack of sleep
  • Smoking
  • Drinking
  • Obesity
  • Diabetes
  • Genetic differences
  • Amyloid beta – that’s right, Aβ disrupts the blood brain barrier in a cruel feedback loop

So what can we do with this new hypothesis? The most important step is to research it! I need to reiterate that this is only a hypothesis. It’s still only a few years old, and there is no experimental data verifying the veracity of this very vivacious version of Alzheimer’s. There is some early evidence the lipid invasion model may have merit; people on lipid-lowering statin medication have significantly lower rates of Alzheimer’s. If experimentation verifies the hypothesis, we may see new methods of targeting Alzheimer’s, hopefully with a much higher success rate!

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

Listen to the article here:


Chaves, J. C., Dando, S. J., White, A. R., & Oikari, L. E. (2023). Blood-brain barrier transporters: An overview of function, dysfunction in Alzheimer’s disease and strategies for treatment. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 166967.

1Cummings, J. L., Morstorf, T., & Zhong, K. (2014). Alzheimer’s disease drug-development pipeline: few candidates, frequent failures. Alzheimer’s research & therapy, 6(4), 1-7.

Hu, Z. L., Yuan, Y. Q., Tong, Z., Liao, M. Q., Yuan, S. L., Jian, Y., … & Liu, W. F. (2023). Reexamining the Causes and Effects of Cholesterol Deposition in the Brains of Patients with Alzheimer’s Disease. Molecular Neurobiology, 60(12), 6852-6868.

Jick, H. Z. G. L., Zornberg, G. L., Jick, S. S., Seshadri, S., & Drachman, D. A. (2000). Statins and the risk of dementia. The Lancet, 356(9242), 1627-1631.

Rudge, J. D. A. (2022). A new hypothesis for Alzheimer’s disease: The lipid invasion model. Journal of Alzheimer’s Disease Reports, 6(1), 129-161.

Rudge, J. D. A. (2023). The Lipid Invasion Model: Growing Evidence for This New Explanation of Alzheimer’s Disease. Journal of Alzheimer’s Disease, (Preprint), 1-14.

Wang, H., Kulas, J. A., Higginbotham, H., Kovacs, M. A., Ferris, H. A., & Hansen, S. B. (2022). Regulation of neuroinflammation by astrocyte-derived cholesterol. bioRxiv, 2022-12.

Xiong, H., Callaghan, D., Jones, A., Walker, D. G., Lue, L. F., Beach, T. G., … & Zhang, W. (2008). Cholesterol retention in Alzheimer’s brain is responsible for high β-and γ-secretase activities and Aβ production. Neurobiology of disease, 29(3), 422-437.


February 9, 2024 BlogHolidays

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If there’s one thing I learned in elementary school… well, it was probably how to read. But if there’s one thing I learned every year around this time, it’s that Valentine’s Day isn’t just for lovers but for friends and classmates, too. Valentine’s Day is the time of year we celebrate the most special people in our lives – and it’s a good time to investigate the health effects of love and social relationships.

Love is a curious word. I love my wife and child, but also my cats, parents, siblings, friends, cookies, pizza, and ice cream. While some of my loves are potentially dangerous (or so my blood pressure tells me), my love of friends, family, and community might keep me alive – or at least balance the carbs. Studies have shown that maintaining social relationships can lower the rate of all-cause mortality: love literally increases your lifespan. This has been suspected for centuries and can be seen anecdotally in extreme examples with hermits, but it has been causally validated in recent years. Multiple studies in several countries have found that those with healthy social relationships are around half as likely to die over a given time span than isolated people. These relationships included marriage, contact with friends and family, and participation in communities like church, and other formal and informal groups. But how could our social lives affect our health? And what is the scientific definition of love anyway?

Love is… hard to define. One of the best ways to describe love is as a motivation system. It’s not only an emotion because it lasts much longer and shapes how we act over long periods of time. Instead, it’s the part of our personality that recognizes our need for social relationships to survive and reproduce. A skillful lone person can survive in the wilderness or on a deserted island for a while, but they will have trouble if they break an arm or try to have children without anyone else around. We need each other, and one of the parts that ensures we will act prosocially is love. So what’s that look like inside the brain?

Experiments show that a brain on love has a few hallmarks. The brain activates the reward system and parts of the cortex (medial insula, anterior cingulate cortex, hippocampus). The reward system encourages us to keep loving others and boosts dopamine, which makes us feel good, raises our desire, and acts in an almost addictive way similar to cocaine. The brain also lowers the activation of the amygdala, which is responsible for fear, the sympathetic “fight or flight” response, and chemicals like cortisol. Love also deactivates parts of the brain associated with social judgment, assessing other people’s intentions, and “negative emotions” like sadness. Serotonin is also suppressed, which may lead to obsessive symptoms similar to OCD. Love is both addictive and obsessive!

Two hormones are released by the hypothalamus: oxytocin and vasopressin. Oxytocin is known as the “love hormone” and increases attachment and bonding. It’s released in romantic love and during childbirth. It is thought to help mothers bond with babies. Vasopressin also increases bonding and attachment while affecting blood pressure and the kidneys. This gives a clue as to how love can be healthy.

In most developed nations (including the USA), the biggest causes of death aren’t from infectious diseases but from chronic ones. Diseases like heart disease are exacerbated by stress and stress hormones like cortisol and those of the sympathetic nervous system. Studies have shown that animals with social relationships have fewer ulcers and neurotic conditions and have lower blood pressure. Social support is able to mitigate stress and its negative effects. Love also has positive effects on the big picture of how we run our lives, giving us meaning, coherence, and promoting healthy behaviors like self-improvement and getting enough sleep (after college at least).

So this Valentine’s Day, tell those around you that you love them. Appreciate the relationships and communities you are a part of and activate those obsessive and addictive parts of your brain on something healthy. It’s elementary, really.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

Listen to the article here:


Cuzzo, B., Padala, S. A., & Lappin, S. L. (2023). Physiology, vasopressin. In StatPearls [Internet]. StatPearls Publishing.

House, J. S., Landis, K. R., & Umberson, D. (1988). Social relationships and health. Science, 241(4865), 540-545.

Seshadri, K. G. (2016). The neuroendocrinology of love. Indian journal of endocrinology and metabolism, 20(4), 558.

Zeki, S. (2007). The neurobiology of love. FEBS letters, 581(14), 2575-2579.


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I have two cats. They seem pretty smart, there’s definitely something going on in their minds. Unfortunately, I can’t see inside their thoughts, so it is hard for me to know just how capable they really are. Weirdly, this isn’t just a problem with cats, but people too. Many of us have the ability to talk, type, sign, or draw, but even with our most precise communication methods, it is impossible to find out what’s actually going on up there. The modern form of this problem was clearly explained in the 1960’s by the founders of cognitive psychology, the study of how people think.

Cognition is a challenging field to study because even with imaging technologies that can look inside the brain, like MRIs and CAT scans, we can’t ever really know how a person is thinking. We can study the inputs and outputs, we can study how neurons fire, and we can look at the overall state of the brain, but the individual subjective experience escapes us. An example of subjective experience is color. Our experiences of color can be altered by external factors like tinted sunglasses, cataracts, and eye deformities, but we can also change it just by staring at a bright color for a long time, being out in the sun and coming inside, or even through the language we use to describe colors! Cognition is an interesting area of study but has real-world consequences.

One of the challenges with the complexity of cognition and our subjective experience is gauging the presence and severity of mental decline. Unlike diabetes, where we can measure the amount of glucose in the blood, with mental decline and dementia, we have to rely on tests of cognition to measure how well or poorly someone performs cognitive tasks. The benchmark Mini Mental State Exam (MMSE) is the most widely used tool. MMSE is a relatively short (5-15 minute), untimed set of 20 questions that measure 11 domains of cognition:

    • Orientation to time/place
    • Word retention
    • Attention/calculation
    • Word recall
    • Naming
    • Repetition
    • Comprehension
    • Reading
    • Writing
    • Drawing

The MMSE can be repeated to track changes over time. The test alone is not a diagnostic tool; a low score does not confirm mental decline and further testing would be needed. Further, age and education level can also lead to lower scores. A high score, however, is unlikely in patients with dementia. This makes the MMSE a great tool for screening patients and quickly assessing patients who fear they may be slipping cognitively.

Now, they need to make one for cats based on meows and mice.

ENCORE Research Group provides complimentary Mini Mental State Examinations (MMSE) at designated research locations for individuals over the age of 60 who are worried about experiencing memory loss beyond what is considered age-appropriate.

Those locations include:
Jacksonville Center for Clinical Research       (904) 730-0166
Fleming Island Center for Clinical Research       (904) 621-0390

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

Listen to the article here:


Yoo, S. G. K., Chung, G. S., Bahendeka, S. K., Sibai, A. M., Damasceno, A., Farzadfar, F., … & Flood, D. (2023). Aspirin for Secondary Prevention of Cardiovascular Disease in 51 Low-, Middle-, and High-Income Countries. JAMA, 330(8), 715-724.

Esenwa, C., & Gutierrez, J. (2015). Secondary stroke prevention: challenges and solutions. Vascular health and risk management, 437-450.

American Heart Association News. (April 4, 2019). Proactive steps can reduce chances of second heart attack. American Heart Association.

American Heart Association. (2022). 5 ways to lower your risk of a second heart attack. American Heart Association.

Karlin, R., Wojcik, S., Kang, S. (2024).  Preventing a second heart attack. University of Rochester Medical Center Rochester.

de Jong, M., van der Worp, H. B., van der Graaf, Y., Visseren, F. L., & Westerink, J. (2017). Pioglitazone and the secondary prevention of cardiovascular disease. A meta-analysis of randomized-controlled trials. Cardiovascular diabetology, 16(1), 1-11 .


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One of the most important tasks for researchers is to make sure the experiment we are running is accurately assessing the intended variable. Because of this, each study has specific inclusion and exclusion criteria, which determine who can qualify to participate. An example would be needing a diagnosis of severe asthma for a study testing a new asthma medication. Usually, criteria include age, relevant medical diagnoses or histories, and exclude major health events such as cancer, heart attack, or stroke. Recently (as of the writing of this article), however, we have seen a notable uptick in the number of cardiovascular studies that allow or even require a previous heart attack or stroke as an inclusion criterion. This is because there are several medications or devices being studied that hope to lower the recurrence of these events.

Heart attack and stroke are often two sides of the same coin. In both cases, blood flow to part of the organ is lowered or stopped, and the affected tissue is damaged or dies. You might be familiar with the term Major Adverse Cardiovascular Event (MACE), which encompasses various cardiovascular issues, including heart attack and stroke. Most people survive their first incident, but 20-25% of people have more than one. According to the American Heart Association, about 1 in 5 people who have had a heart attack will suffer from (or experience) a second one within five years. Each heart attack or stroke comes with a chance of lowered quality of life, disability, or death, so preventing further events is critical.

One of the biggest problems with preventing a second heart attack or stroke is the myriad of causes of these conditions. Any prolonged insult to the cardiovascular system can lead to a heart attack or stroke. The risks, then, include a sedentary lifestyle, poor diet, obesity or excess weight (especially around the midsection), high blood pressure, high cholesterol, uncontrolled diabetes, smoking, stress, alcohol, and drugs. The solutions to these disparate causes can also spread far and wide. For this reason, the two most important ways to reduce the risk of a second heart attack or stroke are to talk to a medical professional and take prescribed medications.

A medical professional can look at the underlying condition of individuals and determine which factors likely had the biggest impact. They may recommend cardiac rehabilitation and specific medications to address underlying conditions and prevent recurrence. Targeting specific, relevant causes with medications, such as anticoagulants like warfarin, antiplatelets like aspirin, and cholesterol-lowering medications like statins, can reduce the risk of resurgence by up to 70%! Doctors may also recommend medications to help with diabetes or blood pressure and/or surgical procedures to fix structural problems with the cardiovascular system. Managing the risk factors that caused the first heart attack or stroke can reduce the likelihood of a second (or third). On top of this, changes to lifestyle and diet can have a significant impact, lowering the chance of a second event by almost a third. Add a reduction in smoking, alcohol, and drugs for an even greater effect.

Beyond standard medical advice, two additional interventions may help. The first is support. Family, friends, and others who have experienced heart attacks and strokes can help make the recovery process more bearable and lower anxiety and stress (which are risk factors in themselves!). Finally, clinical trials may help. Indeed, the inclusion of previous heart attacks or strokes in clinical research inclusion criteria indicates an increased recognition that indirect influence can induce repeated injury to the heart and brain. In short, research studies are looking at new ways to lower the incidence of a second heart attack or stroke by targeting underlying conditions with new medications and new methods of treatment. This is invariably a great idea. Only YOU (and your doctor (and maybe a clinical research coordinator)) can prevent secondary strokes and heart attacks.

At the time of this writing, ENCORE Research Sites have several studies for people who have had a previous heart attack or stroke. Call your local office to explore research options for you.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

Listen to the article here:


Yoo, S. G. K., Chung, G. S., Bahendeka, S. K., Sibai, A. M., Damasceno, A., Farzadfar, F., … & Flood, D. (2023). Aspirin for Secondary Prevention of Cardiovascular Disease in 51 Low-, Middle-, and High-Income Countries. JAMA, 330(8), 715-724.

Esenwa, C., & Gutierrez, J. (2015). Secondary stroke prevention: challenges and solutions. Vascular health and risk management, 437-450.

American Heart Association News. (April 4, 2019). Proactive steps can reduce chances of second heart attack. American Heart Association.

American Heart Association. (2022). 5 ways to lower your risk of a second heart attack. American Heart Association.

Karlin, R., Wojcik, S., Kang, S. (2024).  Preventing a second heart attack. University of Rochester Medical Center Rochester.

de Jong, M., van der Worp, H. B., van der Graaf, Y., Visseren, F. L., & Westerink, J. (2017). Pioglitazone and the secondary prevention of cardiovascular disease. A meta-analysis of randomized-controlled trials. Cardiovascular diabetology, 16(1), 1-11 .


January 19, 2024 BlogUlcerative Colitis

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The immune system is awesome, but overwhelming. It’s filled with billions of cells and quintillions of proteins. There are neutrophils, dendritic cells, antibodies, B cells, macrophages, lymphoid cells, lymphocytes, the complement system, and more! Instead of trying to understand the whole thing, let’s narrow our focus down to just one type of cell, the T cell, and just one variant, T-helper 17, or Th17.

T-cells are a type of white blood cell and are about the size of a red blood cell. They are adaptive, which means they change in response to threats. These cells start as virgin (or naïve) cells and transform into a specialized version when danger is detected. T-cells can be divided into two parts: killers and helpers. Killers are good at killing other (hopefully bad) cells, while helpers activate other cells and amplify immune responses. The cell we’re focusing on, Th17, is a type of helper cell, but a special one.

Th17 was first identified in 2005, but scientists have rapidly learned loads about it. It is particularly good at helping the body fight unusual attackers like fungi and certain bacteria. When activated, it releases a powerful signaling chemical that increases inflammation and recruits other white blood cells, telling them to come and fight. In addition, it can assist in tightening the spaces between our border cells to keep invaders out. When the body detects unknown particles, cells release signaling molecules. When a T-helper cell encounters the right mix of these molecules, it transforms into the rallying Th17 captain which sounds the alarm.

Unfortunately, all that shimmers is not silver. Th17 can certainly be useful in some circumstances, but it can be dangerous when activated by the wrong signals. In many of these cases, Th17 cells tell white blood cells to go nuts and attack anything that moves (or doesn’t move), but without a clear opponent, they just attack whatever’s around and cause an autoimmune response. Th17 has been implicated in diseases like experimental autoimmune encephalomyelitis (EAE), arthritis, and inflammatory bowel diseases (IBD) like Ulcerative Colitis. Let’s look at ulcerative colitis as an example.

Ulcerative colitis is an inflammatory bowel disease where the immune system attacks benign bacteria or food particles. The causes aren’t clear, but part of the problem is a thinning of the mucus and separation of border cells that line the intestines. Many signaling molecules called interleukins (abbreviated IL-) are released in the disease state, including three important ones for Th17. These are IL-1β, IL-6, and IL-23 (write this down for the quiz at the end). The first two activate Th17, and that’s when IL-23 can turn it into a problem. In the presence of IL-23, Th17 sends wild signals and can cause the autoimmune problems listed above, including ulcerative colitis. Also, remember how Th17 helps tighten the spaces between border cells? It turns out that in the presence of IL-23 this function doesn’t work properly and the borders stay open, letting in more particles that the body attacks with inflammation.

Scientists have been trying to find ways to solve the problems caused by Th17 since long before it was even known to exist. In the past, a treatment for something like ulcerative colitis might have been limited to restricting your diet. Currently, anti-inflammatory medications, steroids, and/or surgeries are used. Those are all big solutions bound to affect many other parts of the body and immune system. Now that Th17 has been identified as an occasional dirty traitor, researchers are instead targeting this specific cell to hopefully stop it from being activated incorrectly. With luck, we can help the T-helper cell to help us instead of unhelping us.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Kałużna, A., Olczyk, P., & Komosińska-Vassev, K. (2022). The role of innate and adaptive immune cells in the pathogenesis and development of the inflammatory response in ulcerative colitis. Journal of clinical medicine, 11(2), 400.

Sender, R., Weiss, Y., Navon, Y., Milo, I., Azulay, N., Keren, L., … & Milo, R. (2023). The total mass, number, and distribution of immune cells in the human body. Proceedings of the National Academy of Sciences, 120(44), e2308511120.

Tesmer, L. A., Lundy, S. K., Sarkar, S., & Fox, D. A. (2008). Th17 cells in human disease. Immunological reviews, 223(1), 87-113.

Wu, B., & Wan, Y. (2020). Molecular control of pathogenic Th17 cells in autoimmune diseases. International immunopharmacology, 80, 106187.


January 12, 2024 BlogHeart Failure

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Heart failure is when the heart doesn’t pump enough blood throughout the body. This doesn’t mean instant death, but the body starts wearing out around the edges. People with heart failure might feel short of breath and tired because there’s not enough oxygen reaching the brain and cells. Ankles and lower extremities might start swelling because the heart is unable to pull all of the blood up out of our legs. Sufferers understandably have trouble exercising. So what’s going on? Can anything be done about it?

Heart failure is an enormous problem. Tens of millions of people worldwide suffer from it, including at least 6 million Americans. It is the most common cause of hospitalization for adults over 65, and causes many repeat hospitalizations. Heart Failure severely reduces the quality of life, and comes with a high mortality rate. 

The causes of heart failure are numerous and can be difficult to identify; anything that impairs the heart’s ability to pump or deliver oxygen can be a contributing factor. Risk factors include:

  • Coronary artery disease
  • Smoking
  • Obesity
  • High blood pressure
  • Diabetes
  • Age
  • Liver problems
  • Kidney problems

To understand how these conditions may contribute to heart failure, we should first dive wholeheartedly into how the heart works. The heart is a muscle. It squeezes about once a second in a coordinated fashion. This squeezing pushes blood to and from the lungs, and to and from the body. We generally don’t get new heart muscle cells as adults. Instead, in order to react to changes in the needs of the body the heart cells themselves can grow (enlarge), as can the structure around and between the cells. A healthy heart may get stronger and more efficient in response to exercise or pregnancy A weakened heart, on the other hand, might change its structure by enlarging in response to stress, hormone changes, inflammation, and/or the risk factors listed above. These changes can result in a reduction of the amount of capillaries that supply the heart with blood, as well as fibrosis, chemical changes, and changes in the metabolism and organization of heart cells. But why would the heart do this? Is it rebelling against us? Is it something I said?

The heart loves us with its whole… self. It changes because it is trying its hardest and can’t manage to do it alone. When the heart senses it isn’t functioning properly, it may undergo cardiac hypertrophy. Cardiac is Greek (and Latin (and French)) for heart. Hyper- indicates an excessive amount, and -trophy is from the Greek word for nourishment, which in this case means growth. Cardiac hypertrophy is the excessive thickening or lengthening (or both) of the heart muscle. In pathological heart disease, scientists think this is initially an adaptive response. The heart attempts to compensate for dysfunction by increasing the size of the heart tissue. This works for a bit, right up until it doesn’t. Eventually, blood vessels can no longer reach all of the heart tissue. As a result, important chemicals like nitrous oxide are not produced and delivered to cells, connective tissue grows and stiffens, hormones get out of balance, and damaging inflammation occurs.

These maladaptive signs of heart failure give evidence as to why it’s so dangerous. Each of these responses to a stressed heart can also cause damage and restructuring of the heart. Inflammation is a great example. Consistent inflammatory chemicals in the body can spur the heart into a stress response that results in structural changes, which in turn may cause inflammation that spreads to other parts of the body. Similarly we can look at hormones like angiotensin, which regulate blood pressure by affecting how narrow your blood vessels are. An excess of angiotensin can narrow blood vessels and cause the heart to work harder, leading to thickening of the tissue. However, when the stiff tissue doesn’t pump blood efficiently the body responds by releasing more angiotensin in an attempt to help blood move through the body. Regardless of the initial cause, when the heart can’t keep up with the demands of the body, heart failure occurs.

So what can be done? Luckily, this problem has attracted some of the best minds on the planet (like our very own Dr. Michael Koren). Standard treatments aim to improve the quality of life and heart function in patients while reducing the incidence of hospitalization and mortality. Four classes of medications make up the standard of care (SOC) for heart failure:

  • Those that affect angiotensin, such as
      • Angiotensin converting enzyme inhibitor (ACE-inhibitor)
      • Angiotensin II receptor blocker (ARB)
      • Angiotensin receptor neprilysin inhibitor (ARNI)
  • Beta blockers, which block stress hormones and help the heart relax
  • Mineralocorticoid receptor antagonists (MRAs), which block the hormone aldosterone
  • Sodium/glucose cotransporter 2 (SGLT2) inhibitors, which affect a host of cardiac functions

These SOC medications, though effective in many patients, are not perfect. While they tend to target and counteract the effects of wayward hormones,  they do not address underlying heart dysfunction or the changes to heart structure occurring beneath it all. There are many new medications that target a host of new mechanisms for fighting the scourge of heart failure. These include targeting the inflammation pathways or simulating the effects of relaxin. Relaxin is a natural hormone with many effects, including recycling extra structural material in the heart and increasing the efficiency of heart muscle at the tissue level. With luck (and the help of excellent, well-read volunteers like yourself), we can turn heart failure into heart success.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Groenewegen, A., Rutten, F. H., Mosterd, A., & Hoes, A. W. (2020). Epidemiology of heart failure. European journal of heart failure, 22(8), 1342-1356.

Lopaschuk, G. D., & Verma, S. (2020). Mechanisms of cardiovascular benefits of sodium glucose co-transporter 2 (SGLT2) inhibitors: a state-of-the-art review. Basic to Translational Science, 5(6), 632-644.

Murphy, S. P., Kakkar, R., McCarthy, C. P., & Januzzi Jr, J. L. (2020). Inflammation in heart failure: JACC state-of-the-art review. Journal of the American College of Cardiology, 75(11), 1324-1340.

Pandey, K. N. (2008). Emerging roles of natriuretic peptides and their receptors in pathophysiology of hypertension and cardiovascular regulation. Journal of the American Society of Hypertension, 2(4), 210-226. 

Shimizu, I., & Minamino, T. (2016). Physiological and pathological cardiac hypertrophy. Journal of molecular and cellular cardiology, 97, 245-262.

Xie, Y., Wei, Y., Li, D., Pu, J., Ding, H., & Zhang, X. (2022). Mechanisms of SGLT2 inhibitors in heart failure and their clinical value. Journal of Cardiovascular Pharmacology, 10-1097.


January 4, 2024 BlogResearch in General

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Last month, the US Food and Drug Administration approved two gene-editing therapies to treat sickle cell disease. This made national news in a way few drug approvals have, but why? What’s the big deal, and why should we care?

Sickle cell disease is an inherited genetic disease affecting around half a million babies globally every year. People affected by sickle cell disease have genes that create malformed red blood cells that carry oxygen. These malformed cells become curved like a crescent moon (or a sickle), which results in poor oxygen delivery. Even worse, the curved cells can clump together into clots, which restrict blood flow and cause pain, organ damage, and/or death. Because it is genetic and there has been no known cure, it ranks consistently within the top 20 deaths of children. The disease is most prevalent in people of African descent, and globally the highest concentration of sufferers is in sub-Saharan Africa.

Sickle cell disease is a result of problems with genetic mutation and malformed cells, which makes it very hard to target with traditional medicine. In spite of this, innovative researchers have developed two promising treatments for sickle cell disease. These use our own cells to help cure the disease – instead of an oral, topical, or injected medication. These are both gene therapies, where the genetic code of the patient is altered. This is an understandably touchy topic. Gene-editing is different from other medical procedures in that it may be inherited: your genes are passed to your children after all! The benefit of starting gene therapy with sickle cell disease is that we are starting with mutated genes. The mutated sickle-cell-creating genes will already be passed to any children, so fixing the mutations is likely to have better outcomes. I think of it like CPR. With CPR, you are starting with a person who isn’t breathing and has no circulation; you can’t really get any worse than that. With sickle cell gene therapy, as long as the gene-editing tools are specific and target the correct genes it is hard to do worse than one of the top killers of children worldwide. So what are the therapies that were approved?

The first, Lyfgenia, is a gene-additive therapy. It uses a modified virus that can’t reproduce to infect cells and add new DNA. The virus, a lentivirus, delivers special RNA to the cells, which our cells incorporate into the DNA strand when they copy it. This genetic code tells the cells to make a different kind of hemoglobin – the protein in red blood cells that carries oxygen. This hemoglobin is a particular type that prevents sticking to the walls of bloodstreams. Note that viruses already deliver RNA that gets encoded into our genes all the time. A 2022 study looked at a protein and found that almost 10% of the human genome may be from viruses.

The second therapy, Casgevy, is gene-editing in the most fundamental way. It uses a technology called CRISPR/Cas9 to cut and change pieces of our DNA. While our DNA may be around 10% viral, bacteria have much smaller genomes, and viral insertion of new DNA is a proportionally bigger problem. To combat this, some bacteria have a gene-editing system that can find and remove bits of wayward code. This system was adapted by very smart scientists into a gene-editing tool we can use to find and correct mutations in our genetic code. The process is pretty intense. Blood stem cells are removed from the body, then the CRISPR-Cas9 system edits them outside the body. The modified cells are reinserted into the bone marrow, where they will reproduce and turn into everyday functioning red blood cells. This is mind-blowing.

Of course, there is controversy surrounding these therapies. One of the biggest is really unrelated to sickle cell disease, but instead to the very idea of gene-editing. This use of gene therapy in sickle-cell is hard to contest: we’re starting with mutated DNA in blood cells that can kill children. The what-ifs about adding new functionality like laser eyes or super strength get a lot of press and can make us question what it means to be human at a fundamental level. The second big problem is inequality. Could gene-editing be used to make a two-tiered system of wealthy people with great eyesight and perfect skill while poor people suffer? It very much looks like that, as Lyfgenia and Casgevy are both amazingly expensive, somewhere between 2-3 million dollars for treatment. But then, if we can permanently stop sickle cell for a person and all of their descendants, it may be worth it.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Food and Drug Administration. (December 8, 2023). FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease

Milone, M. C., & O’Doherty, U. (2018). Clinical use of lentiviral vectors. Leukemia, 32(7), 1529-1541.

Frank, J. A., Singh, M., Cullen, H. B., Kirou, R. A., Benkaddour-Boumzaouad, M., Cortes, J. L., … & Feschotte, C. (2022). Evolution and antiviral activity of a human protein of retroviral origin. Science, 378(6618), 422-428.

Thomson, A. M., McHugh, T. A., Oron, A. P., Teply, C., Lonberg, N., Tella, V. V., … & Hay, S. I. (2023). Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000–2021: a systematic analysis from the Global Burden of Disease Study 2021. The Lancet Haematology.


December 29, 2023 BlogClinical TrialsHolidays

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This year has been exciting for clinical research. Our ENCORE sites completed 65 clinical trials (studies), and the FDA approved 66 new medications and vaccines nationwide. There is a long time between when a research organization or site, such as ours, completes a study and when a medication is ready for FDA review. Out of the 66 new medications or vaccines that were approved this year, ENCORE sites conducted seven of those clinical trials. That means all of you fantastic research volunteers helped get seven new medications or vaccines to market! In this article, we’ll review this year’s approvals and what they mean.

Three new vaccines that received FDA approval this year had trials at ENCORE sites. Arexvy and Abrysvo were both approved for the treatment of Respiratory Syncytial Virus (RSV) in adults. This disease hospitalizes 177 thousand adults over 65 each year and causes over ten thousand deaths. Arexvy was the first vaccine approved against RSV in adults, and Abrysvo is intended for both prevention and treatment of RSV and is approved for use in pregnant women. Arexvy was studied at the Westside Center for Clinical Research and Abrysvo at Nature Coast Clinical Research – Crystal River. Ixchiq is the world’s first vaccine to be approved for Chikungunya. Chikungunya is spread to people by infected mosquitoes and causes fevers and joint pain. St. Johns Center for Clinical Research participated in two phase III clinical trials for Ixchiq.

Two more ENCORE-researched medications approved this year were the first of their kind. Vowst has become the first medication to become FDA-approved for the treatment of C. difficile, also known as C. diff. C. difficile is a major health threat and causes colon inflammation. ENCORE Borland Groover Clinical Research investigated Vowst in the ECOSPOR trials. Veozah (fezolinetant) is the first non-hormonal treatment for moderate to severe vasomotor symptoms in women with menopause. These symptoms include hot flashes and night sweats, and Veozah targets the temperature centers of the brain to help with these symptoms. Three ENCORE research sites participated in the SKYLIGHT trials to investigate Veozah, Fleming Island Center for Clinical Research, St. Johns Center for Clinical Research, and Nature Coast Clinical Research – Crystal River.

Two medications were approved, which may help with established diseases. Rinvoq (upadacitinib) is a daily pill for those with Crohn’s disease, an autoimmune disorder. Rinvoqwas the first oral treatment for Crohn’s disease to be approved. It was studied at ENCORE Borland Groover Clinical Research. Inpefa (sotagliflozin) has been approved as a daily pill to reduce cardiovascular death, hospitalization, and urgent heart failure by 33% in patients with heart failure. It was studied at the Jacksonville Center for Clinical Research.

We at ENCORE Research Group are very excited about a year of amazing approvals. It validates the hard work and effort of all of our research staff and doctors, and – most importantly – it goes to show just how important our patient volunteers are! With the help of these heroes, we have new and effective options to help with six different diseases. Many thanks to everyone who has participated in any of our clinical trials, and we’ll see you next year!

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Abbvie. (18 May, 2023). U.S. FDA Approves RINVOQ® (upadacitinib) as a Once-Daily Pill for Moderately to Severely Active Crohn’s Disease in Adults.

Astellas. (13 May, 2023). Astellas’ VEOZAHTM (fezolinetant) Approved by U.S. FDA for Treatment of Vasomotor Symptoms Due to Menopause.

GSK plc. (3 May, 2023). US FDA approves GSK’s Arexvy, the world’s first respiratory syncytial virus (RSV) vaccine for older adults.

Lexicon Pharmaceuticals. (26 May, 2023). Lexicon Announces FDA Approval of INPEFA™ (Sotagliflozin) for Treatment of Heart Failure.

Schneider, M., Narciso-Abraham, M., Hadl, S., McMahon, R., Toepfer, S., Fuchs, U., … & Wressnigg, N. (2023). Safety and immunogenicity of a single-shot live-attenuated chikungunya vaccine: a double-blind, multicentre, randomised, placebo-controlled, phase 3 trial. The Lancet.

Seres Therapeutics, Nestle Health Science. (26 April, 2023). Seres Therapeutics and Nestlé Health Science Announce FDA Approval of VOWST™ (fecal microbiota spores, live-brpk) for Prevention of Recurrence of C. difficile Infection in Adults Following Antibacterial Treatment for Recurrent CDI.

Velena SE. (10 November, 2023). Valneva Announces U.S. FDA Approval of World’s First Chikungunya Vaccine, IXCHIQ®.

U.S. Food & Drug Administration. (27 November, 2023). 2023 Biological License Application Approvals.

U.S. Food & Drug Administration. (19 December, 2023).  Novel Drug Approvals for 2023.


December 22, 2023 BlogHolidays

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The holidays are a time for giving. We give gifts, hugs, support, unsolicited advice, and time. Of those, time can make the most significant difference to society at large if we provide it in the form of volunteering. Over 1 in 4 Americans volunteer their time. To count as volunteering, one has to freely choose to do the activity (no getting volun-told) and it should be altruistic. There are different categories of volunteering broken down into self-oriented and other-oriented. Self-oriented volunteering involves some kind of personal benefit, like potential career advancement. Other-oriented volunteering is instead focused on helping others in areas like health, education, religious groups, and youth development. Regardless of the category, any volunteering is good volunteering. Anyone who volunteers knows that besides helping others, it also gives you a warm fuzzy feeling inside, but did you know that fuzzy feeling might help keep you alive?

Before we get into studies and possible health benefits, we must cover caveats. Studying the effects of volunteering on the body and brain is hard. You literally can’t force people to volunteer, so most of our information comes from observational studies. This is where researchers will follow people over time and compare those who volunteer to those who don’t. This can give us some great data, but it’s hard to know if volunteering is the cause or the effect. A senior citizen with a painful condition who works 60 hours a week will probably volunteer less than a healthy retiree (clinical research tries to mitigate these needs by providing compensation for time and travel to help make volunteering easier). Good studies therefore compare people with similar health, economic, and other factors in an attempt to isolate any effects volunteering has.

With that in mind, volunteering seems to be associated with great outcomes. It appears to be associated with improvements in depression and life satisfaction. In a 14-year study of those above 60, a 2016 study found a reduced risk of cognitive decline due to volunteering. Most amazingly, a 2013 meta-analysis, which looked at the results of 40 other studies, found a 22% reduction in death! Even when taken with a McDonald’s french fry of salt, these results are very promising. But what’s going on to make this happen? There are no definite answers, but three suspected ones:

  • Physical activity: volunteering usually requires people to get up and move. This is particularly helpful for those whose social networks are shrinking
  • Social interaction: volunteering uses the social parts of your brain. Increasing these has been shown to increase survivability by up to 50%
  • Prosocial behavior: volunteering increases our social networks, which act as reinforcement systems for health

How can we gain these benefits? By volunteering, of course! Food banks, schools, refugee services, and youth development programs can always use volunteers. The internet is a great place to look for opportunities to grow your social networks and help others. Clinical research is another great way to volunteer. One of the biggest draws for clinical research volunteers is knowing that the medicines they help research can help future generations. Today’s trials can help pave the way for medications and procedures that may persist into the future. This holiday season, if you can, volunteer and give the gift that keeps on giving.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Holt-Lunstad, J., Smith, T. B., & Layton, J. B. (2010). Social relationships and mortality risk: a meta-analytic review. PLoS medicine, 7(7), e1000316.

Infurna, F. J., Okun, M. A., & Grimm, K. J. (2016). Volunteering is associated with lower risk of cognitive impairment. Journal of the American Geriatrics Society, 64(11), 2263-2269.

Jenkinson, C. E., Dickens, A. P., Jones, K., Thompson-Coon, J., Taylor, R. S., Rogers, M., … & Richards, S. H. (2013). Is volunteering a public health intervention? A systematic review and meta-analysis of the health and survival of volunteers. BMC public health, 13(1), 1-10.

Kwon, S. J., van Hoorn, J., Do, K. T., Burroughs, M., & Telzer, E. H. (2023). Neural representation of donating time and money. Journal of Neuroscience, 43(36), 6297-6305.

Webster, N. J., Ajrouch, K. J., & Antonucci, T. C. (2021). Volunteering and health: The role of social network change. Social Science & Medicine, 285, 114274.


December 15, 2023 BlogCholesterol

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Fats are necessary for survival. In the body, we call them lipids. They are needed to build the borders of our cells, create molecules and hormones, coat important neurons in the brain, protect and insulate our organs, store energy between meals, and perform many other vital functions. Lipids are fats, which don’t play well with water; think Spongebob and Squidward (or oil and water). Lipids need to be transported through the bloodstream by proteins. Lipids attach to these proteins to make lipoproteins (lipid + protein). Triglycerides are the most common type of lipid found in the body. They are used as energy for muscles and are stored in fat cells. They are transported in very low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), and gut-produced chylomicrons. Cholesterols are needed for parts of our cells and are some of the building blocks of hormones, bile acids, and enzymes. Important types of cholesterol lipoproteins include low-density lipoproteins (LDL), high-density lipoproteins (HDL), and Lipoprotein(a) (Lp(a)). Our body stays healthy in part by maintaining a healthy balance of these lipids and lipoproteins.

Keeping the balance of lipids is critical to our health. When it is out of whack, we experience dyslipidemia. Dys meaning “bad,” lipid- indicating the lipids, or fats, and -emia meaning “presence in blood”. Dyslipidemia, or bad lipid presence in blood, is when the lipids in the blood are out of balance. This condition is unsettlingly common — one of every three American adults 20 years or older has dyslipidemia. Any imbalance falls under this description, but the most common and dangerous types in the USA are high LDL cholesterol, low HDL cholesterol, and high triglycerides. The prefix hyper- means “high,” so high cholesterol is called hypercholesterolemia (high cholesterol presence in blood); high triglycerides are hypertriglyceridemia (high triglyceride presence in blood); and a combination of both is simply called combined dyslipidemia. Some people suffer from hypolipidemia (low lipid presence in the blood), but it is much rarer in the USA.

Because dyslipidemia is defined and diagnosed with a blood test, the underlying causes can vary, unlike conditions such as sickle cell anemia or chicken pox. Primary causes are genetic, where you inherit a risk factor. This might look like elevated Lp(a) levels, which are heavily influenced by genetics. Secondary causes are anything that may alter lipid levels, including diabetes, obesity, an unhealthy diet high in triglycerides, and lack of exercise. Regardless of the cause, the effects can be deadly. The biggest, most obvious problem is atherosclerotic cardiovascular disease (ASCVD), when cholesterols, fats, and other materials build up on the inside of our blood vessels. These buildups, called plaques, can block blood flow to the heart, brain, or other parts of the body, potentially causing heart attack, stroke, and/or pain in the body and limbs.

With these outcomes in mind, solutions are critical. As with almost every non-infectious disease, some of the best methods for preventing complications are a healthy lifestyle. A diet high in vegetables, fruits, and whole grains may help. Keeping calorie counts low and moderate-to-vigorous exercise is also recommended, if possible. Beyond lifestyle, medications have helped many people. Statins like Lipitor are typically the first line of defense. They are the most widely prescribed class of drugs in the world, though not everyone can tolerate them. They inhibit an enzyme called HMG-CoA reductase. Statins can lower LDL levels by slowing the cholesterol-making process. PCSK9 is another important enzyme in the creation of cholesterol. PCSK9 inhibitors target this enzyme to help reduce cholesterol if statins aren’t working. Bempedoic acid and icosapent ethyl may also help reduce the amount of cholesterol the liver makes. Ezetimibe (uh·zeh·tuh·mibe) reduces the amount of cholesterol absorbed. Beyond lowering lipid levels, other medications may help reduce the risk of cardiovascular disease. Finally, if medications aren’t tolerated or effective enough, blood plasma can be removed, cleaned outside the body, and pumped back in using a process called plasmapheresis.

Fats may be necessary for survival, but too many in the bloodstream can be deadly.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Berberich, A. J., & Hegele, R. A. (2022). A modern approach to dyslipidemia. Endocrine Reviews, 43(4), 611-653.

Feingold, K. R. (2015). Introduction to lipids and lipoproteins.

Pappan, N., & Rehman, A. (2023). Dyslipidemia. In StatPearls [Internet]. StatPearls Publishing.

Pokhrel, B., Yuet, W. C., & Levine, S. N. (2017). PCSK9 inhibitors.


December 8, 2023 BlogDiabetes

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Type 2 Diabetes is a worldwide growing pandemic. Globally, around 425 million people have type 2 diabetes; that’s more than the entire US population. Almost 10% of Americans have type 2 diabetes, which is characterized by the body’s inability to regulate blood sugar (glucose). Uncontrolled high blood glucose levels can have severe long-term effects, impacting the cardiovascular system, brain function, and overall mortality. Because of the increased dangers associated with diabetes, there are a myriad of medications that target this disease. Unfortunately, these can be difficult to adhere to and usually require a daily activity like a pill, blood strip testing, and/or exercise. The more intensive and difficult these steps are (for instance, taking three pills a day vs one), the less likely people will be able to follow through. Additionally, though the medications can effectively reduce blood sugar levels and the risk of complications, they do not target the underlying disease. Medications may need to be increased or changed if the disease progresses. So, what is the underlying disease profile?

The big picture causes of type 2 diabetes include genetics, diet, exercise, and overall weight. Inside the body, these risk factors and habits manifest as cellular changes. The most significant change that takes place is called insulin resistance. Insulin is an important hormone that helps your body manage blood sugar; when cells are resistant to insulin, they can’t adequately respond to high blood sugar. This is the key indicator of type 2 diabetes. Many medications attempt to correct insulin resistance by replicating or replacing chemicals involved in the insulin pathway – including insulin itself in advanced cases. These have been a significant boon to many patients, but what if we could go deeper?

One of the changes many people see is in the intestines. The part of the intestines connected to the stomach is called the duodenum. The duodenum is short but important. It regulates the release of  hormones like glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP), both disrupted in insulin resistance. Scientists have found evidence that people with type 2 diabetes have increased duodenum tissue; a process called hypertrophy. Tissue removal in these patients may positively affect type 2 diabetes.

One of the most successful therapies for type 2 diabetes is bariatric (weight loss) surgery that bypasses some or all of the duodenum. These surgeries have been shown to have an immediate and long-lasting effect on people with diabetes. Studies have found that A1C levels, which measure blood sugar, are completely back to normal range in patients who have had these surgeries at a rate five times higher than people on medication alone. It is thought that by bypassing or removing the duodenum, the hypertrophic cells stop interfering with the insulin process, and insulin resistance decreases or is outright reversed! Also, since surgery is a one-time deal, the adherence problems of pills and other daily activities are reduced or eliminated.

Unfortunately, surgery is invasive, intensive, painful, and somewhat risky (10-20% have complications). Additionally, removing parts of the duodenum can result in malabsorption of nutrients. To solve this, researchers have devised a new investigative procedure for tackling type 2 diabetes. Instead of cutting the body open and removing, adding, or rearranging the intestinal tract, a new approach called the Revita system is being tested. This system revolves around a catheter that moves into the duodenum and ablates, or removes, the top layer of hypertrophic duodenum tissue. Early studies have shown that by targeting just the hypertrophic tissue, the duodenum will heal and retain its function while blood sugar normalizes. This is an exciting potential alternative to normal bariatric surgery for people with type 2 diabetes.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Cummings, D. E., Overduin, J., & Foster-Schubert, K. E. (2004). Gastric bypass for obesity: mechanisms of weight loss and diabetes resolution. The Journal of Clinical Endocrinology & Metabolism, 89(6), 2608-2615.

Jacobsen, S. H., Olesen, S. C., Dirksen, C., Jørgensen, N. B., Bojsen-Møller, K. N., Kielgast, U., … & Madsbad, S. (2012). Changes in gastrointestinal hormone responses, insulin sensitivity, and beta-cell function within 2 weeks after gastric bypass in non-diabetic subjects. Obesity surgery, 22, 1084-1096.

Rubino, F., Forgione, A., Cummings, D. E., Vix, M., Gnuli, D., Mingrone, G., … & Marescaux, J. (2006). The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes. Annals of surgery, 244(5), 741.

Rubino, F. (2008). Is type 2 diabetes an operable intestinal disease? A provocative yet reasonable hypothesis. Diabetes care, 31(Supplement_2), S290-S296.

Schauer, P. R., Bhatt, D. L., Kirwan, J. P., Wolski, K., Aminian, A., Brethauer, S. A., … & Kashyap, S. R. (2017). Bariatric surgery versus intensive medical therapy for diabetes—5-year outcomes. New England Journal of Medicine, 376(7), 641-651.

Theodorakis, M. J., Carlson, O., Michopoulos, S., Doyle, M. E., Juhaszova, M., Petraki, K., & Egan, J. M. (2006). Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP. American Journal of Physiology-Endocrinology and Metabolism, 290(3), E550-E559.

Wickremesekera, K., Miller, G., Naotunne, T. D., Knowles, G., & Stubbs, R. S. (2005). Loss of insulin resistance after Roux-en-Y gastric bypass surgery: a time course study. Obesity surgery, 15(4), 474-481.

van Baar, A. C., Holleman, F., Crenier, L., Haidry, R., Magee, C., Hopkins, D., … & Bergman, J. J. (2020). Endoscopic duodenal mucosal resurfacing for the treatment of type 2 diabetes mellitus: one year results from the first international, open-label, prospective, multicentre study. Gut, 69(2), 295-303.


December 1, 2023 BlogImmune System

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This article was requested by an ENCORE community member. We do not currently have a study enrolling for this topic.

The immune system is huge, complex, critical for life, and dangerous. It is good for us, protecting us by fighting infections and cancer; but there is a dark side: the inflammation it uses to fight can cause damage, it can overreact to cause autoimmune diseases, and its vigilance against invaders is what makes organ transplants difficult. The immune system is specialized in destroying cells and viruses. One of the most important features of the immune system is its ability to differentiate between cells we want and cells we don’t (including cancer cells!). However, when things go wrong, they can go very wrong. This may happen with autoimmune diseases like lupus or rheumatoid arthritis. Things may also go wrong when the immune system attacks transplanted organs; like a heart or liver. In these cases, we turn to immunosuppressant drugs. These do just what their name implies: they suppress the immune system. How they actually go about suppressing is very complicated, and requires a quick look at the immune system in general.

A very, VERY simplified version of the immune system and how it responds over time

The immune system can be divided into two major pieces, the innate and adaptive immune systems. There is overlap, as some cells have multiple functions. The innate immune system is made of cells that attack any invader they sense. These get activated immediately when we have infections or wounds and are like big, blunt weapons in their killing. The innate immune system includes monocytes, mast cells, macrophages, neutrophils, and eosinophils. These white blood cells ingest and eat perceived threats and cause inflammation. Inflammation helps bring in the complement system, a horde of mindless proteins that aim to attack invaders. If infections are not stopped immediately, dendritic cells activate the adaptive immune system. This is made up of T cells, B cells (including plasma cells), and antibodies. Throughout all this, cytokines like interferon and interleukin modify the immune system and are used for communication. Immunosuppressant drugs tend to target either the immune system at large or specific aspects of it, like T cells.

-mab   Monoclonal antibody
-cept   Targets receptor molecules
-mib    Inhibits protein breakdown mechanisms

A quick guide to what the endings of some drugs mean

T cells are special cells that detect, remember, and fight against invaders. When they misidentify healthy cells as invaders, things get out of control quickly. Certain medications, like cyclosporin, tacrolimus, and voclosporin target the T cell’s ability to detect “dangerous” particles – like a transplanted organ. Others, such as Abatacept and Belatacept downregulate the ability of T cells to respond effectively. These tend to cause high blood pressure and associated problems.

B cells are critical for producing deadly antibodies. They also act as memory cells to ensure future infections are dealt with quickly. The two ways to deal with wayward B cells are by destroying them or limiting their ability to differentiate. Rituximab, ocrelizumab, ofatumumab, and veltuzumab target B cells for destruction, while bortezomib targets specialized plasma cells that spew antibodies at a rate of 2000 per second. By lowering the number of B cells they cause less autoimmune damage. Targeting B cell differentiation limits their functionality with medications like belimumab and atacicept, but comes at the expense of reducing some cell signals and possible pneumonia.

Free-floating proteins are critically important to the immune system. The complement system is composed of quintillions (!!!) of tiny proteins that act autonomously to hamper invaders. Eculizumab targets a specific protein that helps activate the destructive powers of the complement system. Cytokines are different but equally important proteins. They are the communication particles used by the immune system. Corticosteroids are broad immunosuppressant anti-inflammatory drugs. They reduce the activity of the immune system, slow fluid flow that causes inflammation, interfere with cytokines, and inhibit immune cell production. They can be effective, but the effects are not specific to the immune system and can cause problems with “virtually every system in the body” (Barshes, 2004). Major side effects include bone problems like osteoporosis, skin changes, obesity, diabetes, and neurologic changes. Advanced medications like basiliximab, anikara, and rilonacept target only specific cytokines, with hopefully reduced side effects that may be flu-like.

Finally, two medication classes reduce B and T cell counts through unique mechanisms. Polyclonal antibody immune globulins are additional antibodies that are given at high doses. These seem to overwhelm the immune system, depleting white blood cell counts and keeping it from attacking itself. These are potent but come with severe side effects that feel like getting sick: hives, fever, headaches, and even heart attacks. Alemtuzumab is a medication that targets proteins found outside B and T cells and targets them for death. This has the expected side effects of fever, nausea, etc.

Each class of medication targets a different part of the immune system. This means some may be more useful in some situations, and some may not work at all in some instances. Please note that all medications should be discussed with a medical professional who is aware of your unique medical history; don’t make medical choices based on an internet article! Further, we’ve mentioned some of the bigger, or more general side effects of these medications, but each has many more that should be considered before use. We’ve also left off the most important side effect of all: these suppress the immune system! Patients on these medications are more prone to infection, cancers, and dangerous particles in the body. They are dangerous and should not be taken lightly. Instead, prudence demands that taking an immunosuppressant medication be weighed against the alternative. In the case of a critical organ transplant, like a heart, it’s a no-brainer. Each situation is unique and should be discussed with your medical team.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Barshes, N. R., Goodpastor, S. E., & Goss, J. A. (2004). Pharmacologic immunosuppression. Front Biosci, 9(1-3), 411-420.

Claeys, E., & Vermeire, K. (2019). Immunosuppressive drugs in organ transplantation to prevent allograft rejection: Mode of action and side effects. Journal of immunological sciences, 3(4).

Dettmer, P. (2021). Immune: A journey into the mysterious system that keeps you alive. Random House. 

Nicholson, L. B. (2016). The immune system. Essays in biochemistry, 60(3), 275-301.

Wiseman, A. C. (2016). Immunosuppressive medications. Clinical journal of the American Society of Nephrology: CJASN, 11(2), 332.


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Low back pain affects some 60-90% of people at some point in their lives. Most cases resolve within a few months, but sometimes, a more sinister condition lies underneath. When the cause of pain is nerve root irritation, the condition is called lumbosacral radiculopathy. Lumbosacral describes where this pain occurs: in the lumbar (lumbo- lower back) and –sacral (back of the hip) area. This is part of the spinal cord and contains the nerves that control and sense pain in the hips and legs. Radiculopathy describes the problem. Radiculo- comes from the Greek radix, indicating the root of the nerve. Pathy is from the Greek patheia and means suffering or pain. Together, it is clear what lumbosacral radiculopathy is: lower back pain originating from a nerve root. Though low back pain is common, lumbosacral radiculopathy affects only around 3-5% of the population. It is more common in males, but occupation plays a bigger role than sex.

Lumbosacral radiculopathy is defined through the presentation of pain and where it is located. This presentation is usually back pain but may radiate into the legs. People describe the pain as electric, burning, and/or sharp. Untreated, it can affect sleep, mood, and your ability to function. In general, the nerve root is aggravated through either compression or inflammation, but the underlying causes are diverse. Degenerative spine conditions, including disc herniation, spondylolisthesis, and spinal stenosis, cause lumbosacral radiculopathy when nerves are physically crushed or pinched by parts of the spinal column. Injury and tumors can also cause parts of the nerve to be pinched. Alternatively, the nerve root can become inflamed from infection, vascular conditions, and injury.

Before we move into treatments, it is important to understand how nerves work. A nerve is a cell or group of cells called neurons that communicate information through electricity. Individual cells gather information from one end and fire an “action potential.” This is an electrical and physical event. Cells open special holes called ion channels that let charged particles (usually sodium and calcium) into the cell. Some ion channels are activated by mechanical stress, proteins, and chemical neurotransmitters, but many are activated by electricity! When enough charged ions cross the channels, other electricity-dependent ion channels start rapidly opening, letting in a rush of charged particles and causing the whole cell to “fire.” At the distant end of the neuron, chemical neurotransmitters are released, and the signal can move to other cells.

An illustration of a neuron opening ion channels and firing an action potential

Treatments for lumbosacral radiculopathy vary widely but can be grouped into conservative (non-surgical) and surgical. Initial conservative treatments include exercises, education, and NSAID anti-inflammatory medications like ibuprofen. More intensive therapies may consist of antidepressants and anticonvulsants, which modify how the neurons communicate. Other than injected steroids, these are all systemic treatments, meaning they affect the whole body and can come with a host of side effects. Surgical therapy options are invasive and can come with risks as well as pain. The “gold standard” surgery is a laminectomy with discectomy, where parts of the vertebrae and disc are removed. This has been shown to be safe, but improvements to symptoms and function – especially in the long term – are dubious. The goal in most lumbosacral radiculopathy cases is to stay with conservative treatments as long as possible.

Luckily, scientists are always on the prowl for new treatments. Remember the ion channels? It turns out not all ion channels are created equal. One type of ion channel, NaV 1.8, transports the common ion sodium. This channel is only found in peripheral pain neurons – like those that may be aggravated in lumbosacral radiculopathy. This ion channel has been shown to be necessary for pain neurons to fire their action potential. Medications that can shut down this ion channel may be able to relieve the symptoms of lumbosacral radiculopathy, hopefully without wide-ranging side effects. Ridiculous as it sounds, relief for lumbosacral radiculopathy may be near.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Alexander, C. E., & Varacallo, M. (2017). Lumbosacral radiculopathy.

Berry, J. A., Elia, C., Saini, H. S., & Miulli, D. E. (2019). A review of lumbar radiculopathy, diagnosis, and treatment. Cureus, 11(10).

Clark, R., Weber, R. P., & Kahwati, L. (2020). Surgical management of lumbar radiculopathy: a systematic review. Journal of general internal medicine, 35, 855-864.

Hsu, P. S., Armon, C., & Levin, K. (2017). Acute lumbosacral radiculopathy: Pathophysiology, clinical features, and diagnosis. Waltham, MA: UpToDate Inc.

Kuijer, P. P. F., Verbeek, J. H., Seidler, A., Ellegast, R., Hulshof, C. T., Frings-Dresen, M. H., & Van der Molen, H. F. (2018). Work-relatedness of lumbosacral radiculopathy syndrome: review and dose-response meta-analysis. Neurology, 91(12), 558-564.

Renganathan, M., Cummins, T. R., & Waxman, S. G. (2001). Contribution of Nav1. 8 sodium channels to action potential electrogenesis in DRG neurons. Journal of neurophysiology, 86(2), 629-640.


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Previously, we explored how the character trait of gratitude can have long-lasting impacts on our health and well-being. Unfortunately, character traits are internal and can be hard to change. Thankfully, scientists are a creative lot and have been working for decades attempting to find out how to increase gratitude. Note that the following methods are still experimental; positive results have been found, but the sample sizes have been relatively small. These interventions have shown increased psychological well-being in the form of increased happiness and satisfaction, as well as fewer depressive symptoms in adults. Please note that this is not a substitute for professional psychological or medical help! Instead, these are interventions that may have positive effects when adhered to. The interventions are: Gratitude journaling, Gratitude letters, Mental subtraction, and Experiential consumption.

Gratitude journaling is easy and effective; you just write down things you are thankful for. Various methods have been studied, including the amount (3-5 things) and the frequency (daily or weekly) of journaling. The most effective method I’ve seen is to write three things you are grateful for that happened on the same day. Generally, people wrote a sentence or two about each event. Keeping it limited to daily events helps keep this task from becoming stale. In addition, writing the causes of those events seems to help make the results long-lasting. In one study, a week of gratitude journaling led to increased measures of happiness for the next six months. The idea behind gratitude journaling is that by focusing on the positives, we reinforce those mental pathways and make it more likely that we think about positive things.

Gratitude letters are a little more intense than gratitude journaling. In this task, participants write a letter to someone who has been particularly kind to them but hasn’t been properly thanked before. Ideally, the letter should be hand-delivered for maximum effect. By showing gratitude to others, participants had higher scores associated with gratitude themselves. This one is a particularly tactile activity, which may be helpful to some. The effects of this intervention were shown to last over a month on average.

Mental subtraction is an interesting intervention. In this activity, participants imagined and wrote about a positive event that occurred in their lives and what their lives would be like had the event never taken place. Alternatively, participants were asked to describe how a positive event was surprising to them, forcing them to think of ways it may not have occurred. This was shown to have positive effects on people’s mental state. By looking at the ways things may not have occurred, it might make people more grateful that they occurred at all.

Experiential consumption is an interesting “intervention.” When looking at habits of what people buy, scientists have found that spending money on experiences (trips, music events, etc.) seems to increase people’s happiness and gratitude more than buying tangible items (furniture, clothes, etc.).The thinking behind why experiences may be beneficial is that they are more personal and intrinsic. Experiences are less likely to be compared to others, more likely to be incorporated into who you are, and more likely to be social. Material items are easy to compare to others and unlikely to make lasting impacts on how you see yourself. In addition, ownership is defined as exclusive use, making it an inherently antisocial state.

These methods of increasing our gratitude may not be the end-all of increasing our happiness, but they are a good start. We have a few tips to increase the success rate of these interventions. First, a desire for self-improvement helps a lot. If you want to be more thankful this season, it will make each of these tasks easier. Second, expectations matter. The benefits of these interventions may not change your life, but they are pretty sure to improve how you feel about it; plus, they are basically no-risk (unless your experiential consumption is skydiving). Finally, it is easier to follow through on engaging activities. Things like writing the causes of a thankful event may help keep things engaging and fun, making you more likely to complete the task. Feel free to modify these as needed to keep yourself engaged and having fun with them. Hopefully, these ideas help increase your gratitude this Thanksgiving season. Thank you, as always, for reading!

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

Listen to the article here:


Allen, S. (2018). The science of gratitude (pp. 1217948920-1544632649). Conshohocken, PA: John Templeton Foundation.

Dickens, L. R. (2017). Using gratitude to promote positive change: A series of meta-analyses investigating the effectiveness of gratitude interventions. Basic and Applied Social Psychology, 39(4), 193-208.

Enmons, R. A., & McCullough, M. E. (2003). Counting blessings versus burdens: An experimental investigation of gratitude and subjective well-being in daily life. Journal of Personality and Social Psychology, 84(2), 377-389.

Geraghty, A. W., Wood, A. M., & Hyland, M. E. (2010). Attrition from self-directed interventions: Investigating the relationship between psychological predictors, intervention content and dropout from a body dissatisfaction intervention. Social science & medicine, 71(1), 30-37. 

Kaczmarek, L. D., Kashdan, T. B., Kleiman, E. M., Baczkowski, B., Enko, J., Siebers, A., … & Baran, B. (2013). Who self-initiates gratitude interventions in daily life? An examination of intentions, curiosity, depressive symptoms, and life satisfaction. Personality and Individual Differences, 55(7), 805-810. 

Koo, M., Algoe, S. B., Wilson, T. D., & Gilbert, D. T. (2008). It’s a wonderful life: Mentally subtracting positive events improves people’s affective states, contrary to their affective forecasts. Journal of personality and social psychology, 95(5), 1217. 

Renshaw, T. L., & Olinger Steeves, R. M. (2016). What good is gratitude in youth and schools? A systematic review and meta‐analysis of correlates and intervention outcomes. Psychology in the Schools, 53(3), 286-305. 

Seligman, M. E., Steen, T. A., Park, N., & Peterson, C. (2005). Positive psychology progress: empirical validation of interventions. American psychologist, 60(5), 410.

Walker, J., Kumar, A., & Gilovich, T. (2016). Cultivating gratitude and giving through experiential consumption. Emotion, 16(8), 1126.


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Clinical research has many benefits. There are the obvious ones, like a stipend for time and travel and the potential benefits of an investigational medication, but also more esoteric benefits, like increased quality of care, attention from medical staff, and knowledge about the conditions people face. We recently had a chance to talk with one of our repeat patients, Brendle, who will walk us through her clinical research experience and why she keeps signing up for more studies.

“I’ve learned so much,” she stated. One of the big benefits of clinical research is the knowledge gained through experience. Brendle said “Dr. Koren explains things so well.” Not only do patients get access to podcasts from Dr. Michael Koren and articles from our knowledgeable staff, but they also get a lot of direct face-to-face time with medical professionals and support staff. Transparency is key in clinical research, so we spend a lot of time talking through the full medical history of every patient. We also make sure everyone understands the science, risks, benefits, and process of a trial before enrolling. We typically schedule an hour or two for patients to talk through medical history, medications, and the specifics of a clinical trial before enrolling. Compare this to a typical doctor’s visit with a wait time of 15-30 minutes and only 10-20 minutes of time with a doctor and it’s easy to see why people like Brendle enjoy the clinical trial experience so much. Imagine how many complications could be avoided if primary care practices were able to spend an hour with each patient before prescribing a new medication!

Of course, medications and procedures are the major benefit most people think of when it comes to clinical research. Participants rank risks and benefits as the most important information before participating. The importance of understanding the potential risks of investigational medications or procedures should not be taken lightly. We ensure that patients are given the information needed to make well-informed decisions. Obviously, potential benefits are different in every study. Registry studies only collect information, and the benefit is in drug development down the road (and compensation). Phase 3 studies, in contrast, can have long-lasting effects on biological markers of health.

Brendle notes, “when I first came here, my Ejection Fraction (EF) was only 10%. Now it’s up!” This information is exactly what we want to know for statistical analysis, but the real-world consequences can be even better. Brendle continues, “I could only go from the bed to the couch and back, but now I can do much more.” Amazingly, it’s possible that benefits like this may be realized even when a patient is given a placebo. Not only is the placebo effect real, but the increased attention from doctors and medical staff makes sure we catch any health changes as soon as they happen.

Brendle finished up her chat with us saying “This is the best experience. I am thankful to get into studies.” We are very thankful for patients like Brendle – and you, dear reader – who help push science forward by volunteering for clinical trials!

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Business Wire, (March 22, 2018). 9th annual vitals wait time report released

CISCRP, (2021). Perceptions and insights study 2021. 

Tai‐Seale, M., McGuire, T. G., & Zhang, W. (2007). Time allocation in primary care office visits. Health services research, 42(5), 1871-1894.


November 3, 2023 BlogHolidays

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The long-dead philosopher Cicero once said, “There is no quality I would rather have, and be thought to have, than gratitude. For it is not only the greatest virtue, but is the mother of all the rest.” Gratitude is when we are thankful and appreciate kindness, people, and the world around us. It goes beyond a quick emotion. When we get a thoughtful or meaningful gift, it makes us happy, but that feeling may only stay with us short term. The long-term nature of gratitude is what makes it powerful. Simple appreciation can change into a general mood, and with enough gratitude, our personality can change (hopefully for the better). If we live a life choosing gratitude, we feel happy when we get gifts, but also at smaller things. The long-term personality trait associated with gratitude can increase positive emotions, leave us satisfied, and may help decrease envy, anxiety, and depression.

Persistent personality traits are a neat thing. They affect our mood and emotional response to everyday things. Gratitude as a personality trait increases the intensity (amplitude) and duration of positive thankful emotions and makes it easier to feel thankful. It also increases the number of other people you feel thankful for (like being appreciative that your sister’s cousin’s best friend’s thrash metal band got a record deal). This happens because personality traits indicate that the brain has specific structures and wiring paths built over time. With gratitude, we can see that these changes are in a few key areas of the brain: those responsible for social bonding, perspective-taking, moral judgment and decision-making, and the reward system. They aren’t just emotional areas; they include intentional and calculated parts of the brain that help change our overall outlook. Overall, brain areas increased by gratitude are prosocial; they promote good social behaviors like friendship.

Being thankful is great for making friends and feeling good, but it may also have health benefits! Psychological effects include increased positive emotions, satisfaction, and spirituality as well as decreased indicators of depression, anxiety, and envy. Gratitude-filled people also tend to be more empathetic, forgiving, helpful, and supportive. This makes sense; recognizing good things focuses our attention on more good things. Thankfully, gratitude may also affect our physical health! Measuring gratitude is difficult, so take the following with a grain of salt. Beneficial biomarkers of health measured by people with high gratitude include improved inflammation, diastolic blood pressure, heart rate, and A1C (blood sugar). These are associated with some pretty serious conditions like asthma, cardiovascular disease, and the effects of diabetes. It is unclear how feeling thankful can cause all of these changes, but it may be due to eating and sleeping habits. Gratitude has been linked with lowering dysfunctional eating habits and with improving sleep quality. A good diet is always important, but a good night’s sleep may be even more important for gratitude. So this November, let’s all be thankful for the ability to feel thankful!

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

Listen to the article here:


Allen, S. (2018). The science of gratitude (pp. 1217948920-1544632649). Conshohocken, PA: John Templeton Foundation.

Boggiss, A. L., Consedine, N. S., Brenton-Peters, J. M., Hofman, P. L., & Serlachius, A. S. (2020). A systematic review of gratitude interventions: Effects on physical health and health behaviors. Journal of Psychosomatic Research, 135, 110165.

McCullough, M. E., Emmons, R. A., & Tsang, J. A. (2002). The grateful disposition: a conceptual and empirical topography. Journal of personality and social psychology, 82(1), 112.


October 26, 2023 BlogHolidays

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Boo! This Halloween many of us will dress as spooky things, visit houses with creepy decorations, go into haunted houses, watch scary movies, and enjoy other horror-related entertainment. But being scared kinda sucks. Why do many of us actively subject ourselves to being scared on purpose?

One of the big draws of scary things is dichotomy: the contrast between two ideas that can’t both be true. When we watch a scary movie, we are safe in a theater, but feel the danger and emotion as if we were ourselves being chased by a shark with a knife (or whatever). In a haunted house we may get an even more visceral experience, as our neighbor jumps out at us with a rubber knife in his realistic shark costume. Knowing we are safe makes our brains bounce back and forth between danger and safety. Another big pull of Halloween scares is that they rely on expectations. Most of us would be pretty upset to come home and find a giant spider and some skeletons on our bed. But when given the proper context and expectation, we can be excited and find scary decorations fun and exciting.

Fear is the major emotion at play here, but what is fear? Our emotions can be roughly divided along two lines: valence and amplitude. Valence describes the positive or negative quality of an emotion and amplitude is how strong the emotion is felt. In this organization scheme, fear has a negative valence and a high amplitude, it makes us feel bad and we feel it strongly. On top of this, amplitude seems a little more persistent than valence, so there is a delay period where we still feel excited but can change from a negative to positive valence. So fear with the right context (such as a haunted house or scary movie) makes us switch between the negative valence of fear and the logical knowledge that we are safe.

We can look inside the brain to get a better understanding of what’s happening. There are two competing pathways that activate with fear, depending on the distance to danger. The midbrain pathway activates for close, immediate threats. It is the “fight or flight” response to fear. The frontal cortex is for threats that are further away and is in charge of planning and strategizing. With spooky halloween fears, these two systems are in direct opposition. Trying to overcome the midbrain pathway is hard, but rewarding. We are also rewarded when successfully surviving a scary situation. When we conquer our fear we have the high amplitude of fear combined with the positive valence of relief. So this Halloween, indulge in a little emotional hijacking and enjoy your fear a little bit!

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Anders, S., Lotze, M., Erb, M., Grodd, W., & Birbaumer, N. (2004). Brain activity underlying emotional valence and arousal: A response‐related fMRI study. Human brain mapping, 23(4), 200-209.

Dewey, J. (1894). “The theory of emotion: I: Emotional attitudes”. The Psychological Review. 1(6), 553–569.

Nummenmaa, L. (2021). Psychology and neurobiology of horror movies. PsyArXiv.


October 20, 2023 BlogResearch in General

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It was the best of me, it was the worst of me. There are two versions of your dear author: the one who loves cookies, pizza, and video games and the one who loves surfing, cycling, and roasted vegetables. In a stroke of complete luck, I live at the beach where exercise and healthy living are trendy and encouraged. That wasn’t always the case, however. When I was younger, I went to college in Indiana. There was no beach, I had no bike, everyone had a computer, and my meal plan included unlimited pizza. Unsurprisingly, these two versions of myself have very different health outcomes. One lifestyle is associated with heart attacks, diabetes, and obesity, while the other isn’t. Which version makes it through to the end isn’t just determined by self-discipline and genetics but heavily by the community you are in.

Things that contribute to your health outcomes are called determinants of health. These include your genetics, behavior, and medical care, but also the physical place you spend time and social factors. The determinants of health aren’t insulated; they interact and influence each other. That last one is properly termed Social Determinants of Health (SDOH). These are the daily interactions with people and the area around you, but also the bigger systems that influence these interactions. Examples of the social determinants of health include:

  • Availability of quality food
  • Income 
  • National economic stability
  • Housing quality
  • Access to healthcare
  • Community

It was easy to see these social determinants at work during the pandemic. The “Quarantine 15” was a real phenomenon where somewhere around 48% of people in America gained weight. People were stressed, jobs and income were unstable, healthcare access was limited, exercise options dropped, and – importantly – many of us lost our community connections. Luckily, with the pandemic calming down, we are presented with opportunities to shore up our social determinants of health.

With the pandemic as a reference, we can see that social determinants of health are subject to very big forces. To improve the social determinants of health in our area, we would ideally look at inequality, structural biases, macroeconomic conditions, and government policy. On the personal level, the most productive changes we can make (other than moving halfway across the country) are at the community level. This includes your family, friends, neighbors, and people you interact with and share common ground with, such as those in a book club or church. From a healthcare perspective, “community” determines who you talk to when sick, who checks in on you, who cooks food when you have a newborn, who takes you to the doctor when you can’t drive, and so on.

Luckily, your community can expand. When you join a clinical trial at one of our ENCORE Research Group sites, you don’t just gain access to cutting-edge research, you gain a community that is committed to health. We partner with other groups, perform community outreach, and write extremely well-written, clever, and funny articles for your inbox weekly. On top of this, when enrolled in a clinical trial, we need to monitor your health and stay in touch.  We look for what will help your specific situation and if you miss an appointment we reach out to make sure you are ok. ENCORE stands for Encouraging COmmunity Research and Education, it’s right there in our name!

Staff Writer / Editor Benton Lowey-Ball, BS, BFA
With contributions from Stacey Lowey-Ball, BA Anthropology

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Khubchandani, J., Price, J. H., Sharma, S., Wiblishauser, M. J., & Webb, F. J. (2022). COVID-19 pandemic and weight gain in American adults: A nationwide population-based study. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 16(1), 102392.

Artiga, S., & Hinton, E. (2018). Beyond health care: the role of social determinants in promoting health and health equity. Kaiser Family Foundation, 10.

Baciu, A., Negussie, Y., Geller, A., Weinstein, J. N., & National Academies of Sciences, Engineering, and Medicine. (2017). The Role of Communities in Promoting Health Equity. In Communities in Action: Pathways to Health Equity. National Academies Press (US).

Centers for Disease Control and Prevention. (8 December, 2022). Social determinants of health at CDC. U.S. Department of Health & Human Services.


October 13, 2023 BlogDry EyeEyes

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The eyes are the windows to the soul. But what happens when those windows don’t get properly cleaned? They might get scratchy, stingy, blurry, and discolored. Dry eye disease is when tears don’t adequately lubricate the eye. Symptoms include scratchy burning or stinging in the eyes, red eyes, sensitivity to light, and blurry vision. This disease affects 5%-30% of the world population and is more common in women and those above 50 years old. Dry eye is a multifactorial disease, meaning multiple things may have a hand in causing it. To understand what might be going wrong, we first have to understand a little about how the eye works.

The eye is lubricated by a 3-layered film called the tear film on the outside. That’s tear like near, not tear like hair. The layers, from inner to outer, are the mucus layer, aqueous (water) layer, and lipid (oil) layer. These aren’t hard, distinct layers, but each has a separate purpose. The mucus layer is secreted by goblet cells located on the surface of the eye and lubricates it. The aqueous (water) layer is secreted by the lacrimal gland and keeps everything clean. It is susceptible to evaporation, which is where the lipid (oil) layer plays a part. The lipid layer is oily, which resists evaporation and is secreted by meibomian glands on the edge of the eyeball. Together, these layers act like a crew of window washers to keep the eye lubricated and clean.

Don’t let all the vocabulary make you googly-eyed: the lacrimal gland, goblet cells, and meibomian glands just produce different types of eye fluids. They work together to produce the tear film, but they don’t work alone. The brain receives moisture signals from the eye and sends signals to the glands to keep the eye moist. The eyelids spread the tear film and help prevent evaporation. Finally, the surface of the eye itself needs to be clean and healthy. Together, these components make up the lacrimal functional unit. Disruptions to this system are the cause of dry eye disorder. Problems can be divided into broad categories, but each can overlap and lead to problems with other parts of the lacrimal functional unit.

Problems can originate in the nerves to and from the brain. These can become inflamed or attacked by immune cells such as with Sjogren’s syndrome. When the nerves from the brain to the lacrimal gland are disturbed, tear production might be reduced. When the sensory nerves from the eye to the brain are disrupted, the brain doesn’t know to tell the lacrimal glands to secrete tears and keep the tear film intact. Nerve response can also be disrupted permanently by long-term contact lens use and temporarily by laser surgery. The cells of the eye itself can also be damaged. Epithelial (surface) cells need to interface smoothly with the tear film. The aqueous (water) layer can be deficient – you may not produce enough tears. This can be due to inflammation and autoimmune problems (as above), obstructed glands, nerve damage, and more. Medicines like antihistamines, beta-blockers, and diuretics can also reduce the aqueous layer. Allergies can cause dry eye, so the fact that antihistamines can cause it too is deeply eye-ronic. Finally, tears may evaporate too quickly. This is called tear instability or evaporative dry eye and is usually due to a problem with the oil layer. Other evaporative problems include eyelid problems, gland dysfunction, decreased blinking, vitamin A / omega-3 deficiency, and environmental problems (like wind and smoke). 

To help with dry eye we can look at three methods: environmental, surgical, and medical. Environmental relief can be found by avoiding dry, dusty, and smoky air while ensuring you get enough vitamin A and Omega-3. Surgical blocking of the drainage tear duct can keep moisture on the eye surface longer. Medical solutions include different types of eye drops. Some mimic tears, and some deliver medicine. For severe and chronic problems, there are two major medications: cyclosporine and nerve growth factor (NGF). Cyclosporine is an immunosuppressive drug that can relieve inflammation in the nerves and glands. Nerve growth factor is an amazing medical category that can regenerate damaged nerve fibers and can heal surface epithelial cells. With new clinical trials on the horizon, we can peer through the window to new relief for dry eyes!

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Lemp, M. A., & Foulks, G. N. (2007). The definition and classification of dry eye disease. Ocul Surf, 5(2), 75-92.

Mantelli, F., Massaro‐Giordano, M., Macchi, I., Lambiase, A., & Bonini, S. (2013). The cellular mechanisms of dry eye: from pathogenesis to treatment. Journal of cellular physiology, 228(12), 2253-2256. 

National Eye Institute. (April 8, 2022). Dry Eye. National Institute of Health


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Electricity is essential for most modern-day activities. We use it for lights, air conditioning, and watching cat videos. We also use it to keep our hearts beating. Electricity coordinates the heart and causes it to contract into its familiar wub-dub. Why do we need electricity in the heart, and what can we do when the zips don’t zap properly?

Shockingly, we’ll start with a broad overview. The heart is an organ made of several billion cells. These are organized into many structures, including chambers. There are two small upper chambers called atria, which is the plural word for the left atrium and right atrium. There are also two large lower chambers called ventricles, which are again separated into left and right. The set on the left pumps fresh, oxygenated blood from the lungs to all the cells in the body. The set on the right pumps deoxygenated blood to the lungs to get more oxygen. It is a little strange to describe the heart only as a series of chambers, as the actual structure of the heart is a giant, very strong, coiled muscle. In order for muscles to contract and produce power, electricity is needed. Electricity tells the muscles they need to move. In most of the body, the electrical signals for muscles to contract are delivered by the brain. The heart is a little different.

The heart is involuntary, meaning we have no direct control over when it beats. We can send signals to the heart by breathing deeply or jumping, but the electrical signal that tells the heart to beat comes from within the heart itself. Near the top is a collection of cells called the sinoatrial (SA) node. Here resides a group of cells called pacemaker cells. These cells produce a small electrical zippy zappy signal around once per second. This signal rapidly amplifies and spreads throughout the atria, causing them to contract. This spreading comes out like a wave, which allows all the atrial muscle cells to contract in a big, coordinated manner. Soon after, the signal travels through the atrioventricular (AV) node into the ventricles, propagating outward. This takes a fraction of a second, so we hear wub-dub instead of just one big beat. This also gives blood time to travel from the atria to the ventricles, ensuring it goes correctly.

This system is pretty amazing, but it’s not foolproof. Many things can go wrong. The electrical signal might be disrupted, the heart might be too slow, or it might beat at a bizarre rhythm. When this happens, the heart pumps less efficiently than it needs to, and sometimes can’t pump enough blood for oxygen to get around the body. Unlike a heart attack, where heart cells die immediately, electrical problems can often be alleviated. When the electricity in our heart doesn’t behave correctly, we can put in artificial electricity.

When the heart’s pacemaker cells aren’t successfully sending coordinated signals to the whole heart, an artificial cardiac pacemaker (often just called a pacemaker) can be implanted. Temporary pacemakers may sit outside the body, but permanent ones are installed inside our body cavities. These are made of materials our bodies don’t find threatening, like titanium. They can be attached to the heart through wires called leads, mounted on the heart surface, or inside the heart muscle. Each patient will have electrical problems in specific areas; maybe the pacemaker cells aren’t working properly, or maybe electricity can’t travel to the ventricles, or maybe it can’t cross from the left to the right side. Because of this, pacemakers can attach to either an atrium, a ventricle, or to both ventricles.

Because the electrical problems are so varied, artificial pacemakers have many different patterns for firing. Artificial pacemakers don’t just cause beating; they also detect it. Little electrodes can tell when the heart has fired, and internal circuitry can measure this against when the cardiologist thinks a beat should have happened. Most will detect when a shock is needed and fire on demand, but some fire all the time. Pacemakers can respond to changes in heart rate, can sense abnormal rhythms, and have special modes for things like surgery. On top of all of this, medical professionals can often remotely monitor artificial pacemakers and adjust the pacemaker’s programming without surgery! This can be used to make sure heart rhythms stay ideal, but can also help alleviate the side effects of artificial pacemakers, which include chest pain, dizziness, fatigue, and shortness of breath. Pacemakers are amazing wonders of the modern era. As time goes on, scientists are developing new and more specific programs to zap the heart without zapping our fun. It’s nice to know that when you watch a video of a funny cat falling off the dresser, electricity makes your heart happy inside and out.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Buckberg, G. D., Nanda, N. C., Nguyen, C., & Kocica, M. J. (2018). What is the heart? Anatomy, function, pathophysiology, and misconceptions. Journal of cardiovascular development and disease, 5(2), 33.

Lak, H. M., & Goyal, A. (2020). Pacemaker types and selection.

Sundnes, J., Lines, G. T., Cai, X., Nielsen, B. F., Mardal, K. A., & Tveito, A. (2007). Computing the electrical activity in the heart (Vol. 1). Springer Science & Business Media.


September 29, 2023 BlogResearch in General

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You may have heard the news; earlier this month an FDA committee unanimously concluded that phenylephrine, a common decongestant, doesn’t work. What does this mean? Why is it still on shelves? Is it poison? Should I throw my medicine away? Is the FDA a scam!? What’s the point of science if they change the rules?!?

We’ll address the last two questions first. Good science is a process of change. It’s not definitive; just our best, evidence-based guess at how to predict what will happen given current best experimentation and data. As we get more data of better quality the conclusions drawn by scientists change. To be clear, when scientists update their conclusions this is good and means science is working. It means we are getting more accurate information through better practices and updated information. New technology plays a big part in this. Think of it like maps. The first explorer to document an area may have a hand-drawn map outlining the major features. Later cartographers may come along and refine the map, making it more accurate and filling in the details. Their map may show a landmark in a different, more accurate position. This doesn’t mean the original mapmaker was malicious, or that maps don’t work, but instead that we can update our information to have a more accurate view of the world.

Back to the issue at hand, let’s find out what we’ve learned. On September 11th and 12th, 2023, the Non-prescription Drug Advisory Committee reviewed the results of several clinical studies which looked into the effectiveness of oral phenylephrine at lowering nasal congestion (stuffy nose). These studies measured symptoms in hundreds of patients who took phenylephrine and/or a placebo sugar pill in controlled environments. These studies found, by and large, that the decongestant was not significantly better than the placebo at providing relief. It should be noted that in the studies, most patients found relief from both phenylephrine and the placebo! It should also be noted that participants had few or no adverse reactions to the studies, though some had headaches. In response, the committee concluded that phenylephrine is not effective at providing relief when compared with a placebo; the drug doesn’t work.

So what does this mean for me? First, note that this is an advisory committee. They provide independent advice to the FDA, but do not make policy. In the near term nothing has changed. The FDA will likely take a while to make any policy changes and may have public input. Additionally, the clinical trials did not find the medication dangerous, just ineffective. This means phenylephrine isn’t dangerous at the recommended doses; you don’t need to throw it away (unless it’s expired!). It also means that a phase-out period will probably be slow, because there isn’t a danger to the public beyond wasting money on a medicine that works no better than a placebo.

Finally, how did this happen? How did a medication that doesn’t work get past the FDA? The answer is that while oral phenylephrine doesn’t seem to provide relief, inhaled phenylephrine continues to show effectiveness! When the oral form was approved in the 1970s, scientists thought around 30% of the medication would be absorbed in the gut. It has come to light that around 1% of the decongestant medication is actually available for our body to use when taken orally. From this, it follows that we would need to take much higher doses to get significant relief, which comes with increased side effects – including to the heart! On top of this is the completely fascinating finding in 2015 that placebos are getting better. A meta-study of several placebo-controlled clinical trials found that the effects of medications stayed the same, but the effect of placebos has been increasing over time! Some scientists believe this may be because we expect medications to do more, so the placebo is more effective! This means that when clinical trials are repeated, medications have a more difficult time showing effectiveness versus placebo. Think of our map-makers. That same landmark may have been perfectly mapped by cartographers, but tectonic plates can still cause it to slowly shift position. Lucky for us this means that new medicines brought to market are virtually guaranteed to be more effective than if they were introduced last century!

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Division of Nonprescription Drugs 1 (DNPD1), Division of Inflammation and Immune Pharmacology (DIIP), Office of Clinical Pharmacology (OCP), Division of Epidemiology II (DEPI-II). (September 11, 2023). Efficacy of Oral Phenylephrine as a Nasal Decongestant. U.S. Food & Drug Administration.

U.S. Food & Drug Administration. (September 14, 2023). FDA clarifies results of recent advisory committee meeting on oral phenylephrine. U.S. Food & Drug Administration.

Meltzer, E. O., Ratner, P. H., & McGraw, T. (2015). Oral phenylephrine HCl for nasal congestion in seasonal allergic rhinitis: a randomized, open-label, placebo-controlled study. The Journal of Allergy and Clinical Immunology: In Practice, 3(5), 702-708.

Meltzer, E. O., Ratner, P. H., & McGraw, T. (2016). Phenylephrine hydrochloride modified-release tablets for nasal congestion: a randomized, placebo-controlled trial in allergic rhinitis patients. Annals of Allergy, Asthma & Immunology, 116(1), 66-71.

National Library of Medicine. (March 3, 2011). Safety Study Comparing Phenylephrine HCL Extended Release Tablets 30 mg and Placebo (Study CL2007-07)(P07529)(COMPLETED).  U.S. Department of Health and Human ID NCT00874120.

Tuttle, A. H., Tohyama, S., Ramsay, T., Kimmelman, J., Schweinhardt, P., Bennett, G. J., & Mogil, J. S. (2015). Increasing placebo responses over time in US clinical trials of neuropathic pain. Pain, 156(12), 2616-2626.


September 21, 2023 BlogInfluenzaVirus

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Though it’s still warm and beautiful out, winter looms on the horizon. Winter in Florida can be good: a time for family, biking and outdoor exercise, bigger waves for surfing, and tasty foods. Winter can also be bad: a time for cold, wetsuits, fruitcakes, and the flu. So what is the flu, how does it work, and why does it take after my extended family and only visit us in the cooler months?

The seasonal flu is caused by the flu virus, properly called Influenza, and more properly a type of orthomyxoviridae (there will be a test at the end). There are three categories of influenza viruses that infect humans, conveniently named influenza A, B, and C. These are distinct from each other in some critical ways, one being how easily they change the proteins on the outside of the virus. Viruses are tiny little packets of DNA or RNA that are contained in a little pouch. The pouch has special proteins called antigens on the outside that help it invade target cells. The proteins are also one of the key ways our immune system detects and fights these viruses. Influenza A changes these rapidly, influenza B changes slowly, and influenza C is stable, undergoing little or no change over time.

Influenza A and B viruses undergo a process called antigenic drift. This is when the surface proteins change a little bit at a time. The changes can cause incremental “improvements” to the virus, allowing it to evade our immune system and infect cells more easily. These changes are fast enough that over the course of a year your body may not be able to recognize the virus and you may get the flu year after year, but slow enough that you probably won’t get it twice in the same season – especially with a vaccine. Influenza A can also undergo antigenic shift, which is like the antigenic drift on overdrive. This is like when your dad shaves his beard for the first time in 20 years: same thing underneath but different enough you have trouble recognizing him. When this happens your body can’t recognize the virus as dangerous and previous antibodies and vaccines provide little or no aid. Because of this Influenza A has been responsible for all flu pandemics.

Why is it seasonal though? Well, it’s not seasonal everywhere. In some tropical and subtropical areas, the flu follows the rainy season and comes twice a year. In some tropical areas the flu is present year-round. This provides a clue; it’s the weather! Strangely, it might actually be our response to changing weather that is the progenitor of a flu season. Influenza viruses spread through the air. This is bad news for us in that they spread easily from person to person, but also means they are affected by the weather more than things that may be spread by fluids or insects. Temperature and relative humidity are the two biggest factors. Cool, dry air gives influenza viruses a better chance for infecting us. The virus is more stable in droplets, more of them are shed, and the droplets might stay in the air longer as they evaporate. Our defensive capabilities are decreased in the cold – anyone with a dry throat can attest to this. The protective mucus layer in our airway is decreased and the innate immune system isn’t as efficient. To make things worse, in the winter we spend more time indoors.

In the industrialized world, including America, we spend almost no time outdoors. A 2001 study found that we spend around 87% of our time in buildings and 6% in cars. This varies heavily by where you work, but most of us spend almost our whole lives in buildings with recirculated, conditioned air. In the winter, heated air is drier, which promotes influenza virus stability. As we walk into and out of buildings our throats are dry and inefficient at removing viral particles. This creates ideal conditions for Influenza to infect and spread during the winter.

So what can we do? Get vaccinated of course! Every year scientists work hard to produce vaccines that will target the most likely versions of influenza to emerge during the winter. Antigenic drift is taken into account and vaccines will (hopefully) protect against the likely minor antigenic changes between production of the vaccine and emergence of flu season. New mRNA vaccines shorten the time between production and deployment of vaccines based on the current dominant strain, increasing their effectiveness. All flu vaccines available in the USA are quadrivalent, meaning they protect against two strains of influenza A and two strains of influenza B. So don’t forget to get a flu vaccine, spend time with the family, and go outside!

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases (NCIRD). (12 December, 2022). How flu viruses can change: “drift” and “shift”. U.S. Department of Health & Human Services.

Couch, R. B. (1996). Orthomyxoviruses. Medical Microbiology. 4th edition.

Klepeis, N. E., Nelson, W. C., Ott, W. R., Robinson, J. P., Tsang, A. M., Switzer, P., … & Engelmann, W. H. (2001). The National Human Activity Pattern Survey (NHAPS): a resource for assessing exposure to environmental pollutants. Journal of Exposure Science & Environmental Epidemiology, 11(3), 231-252.

Lowen, A. C., & Steel, J. (2014). Roles of humidity and temperature in shaping influenza seasonality. Journal of virology, 88(14), 7692

Moriyama, M., Hugentobler, W. J., & Iwasaki, A. (2020). Seasonality of respiratory viral infections. Annual review of virology, 7, 83-101.


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I recently went to a dessert party. That’s a party where everyone brings a dessert. I, naturally, arrived with cookies while others brought cakes and pies. Surprisingly, there was one attendee who presented a bowl of berries, another who showcased a sweet potato casserole, and a third who simply brought avocado with a dash of salt. Do these all count as desserts? What is a dessert? A word that was clear at the outset was quickly confusing in how broad it was. Unfortunately, that confusion can also happen with medical terms. Take cardiovascular disease. It’s got something to do with the heart, but sometimes it includes strokes in the brain. So what is cardiovascular disease?

Cardiovascular” is a word made of two component parts: cardio- means “heart” and vascular indicates blood vessels. Together, cardiovascular disease is that which affects the heart and/or blood vessels. The heart and blood vessels carry oxygen to the cells and keep them alive. Since we’re made of cells, keeping them alive is pretty important. Therefore, the heart and blood vessels are also quite  important, and cardiovascular disease can be dangerous if not managed. 

Cardiovascular disease is more common than apple pie in the United States. Data from the CDC show that nearly HALF of adults over 20 have some form of cardiovascular disease. With a prevalence that high, it’s no surprise that cardiovascular disease is the leading cause of death in America and around the world. Unfortunately, as noted above, the exact definition of “cardiovascular disease” is very broad. In researching this article you are currently reading, I consulted the World Health Organization, the American Heart Association, and the National Institute of Health (part of the CDC). These organizations listed the various diseases included in cardiovascular disease, and only agreed on two conditions:

    • Coronary artery disease – when the blood vessels to the heart are narrowed by plaques
    • Cerebrovascular disease including stroke – where the vessels to be brain are blocked

Other diseases that at least two agreed on include:

    • Arrhythmia – an irregular heartbeat
    • Congenital heart defects – heart defects occurring from birth
    • Heart attack – also called a myocardial infarction, where the blood flow to the heart is blocked
    • Hypertension – high blood pressure

Though all these diseases may seem different, they are all part of the same system. Narrow blood vessels to the heart or brain cause oxygen loss. This narrowing can be caused by plaque formed when cholesterol lodges in the vessel wall.  If some of this plaque dislodges, it can lead to heart attacks and strokes. Irregular heartbeats and heart attacks can lower the amount of blood (and oxygen!) delivered around the body. Hypertension stresses the whole system and can lead to heart attack, stroke, and damage to other organs like the kidneys. Additionally, they may have similar risk factors, outcomes, and treatments.

There is a genetic component to cardiovascular disease. This is evident with congenital heart defects, which occur during development. It is also evident looking at who is at risk of developing cardiovascular disease. African Americans are at the highest risk, while people who identify as Hispanic have the lowest risk. Big modifiable risks include cholesterol, smoking, and hypertension (which is itself a form of cardiovascular disease!). Other risks include diabetes, being overweight, poor diet, low exercise, alcohol consumption, and low sleep. Research is ongoing into the cycle of mental health and cardiovascular disease as well. Mood and anxiety disorders, PTSD, and chronic stress can cause direct damage to the cardiovascular system while simultaneously increasing behaviors that compound the danger, including smoking and failing to take medicines.

Lowering the modifiable risks above is, unsurprisingly, one of the best ways to fight cardiovascular disease. Managing cholesterol, blood pressure, and diabetes can help. Cutting smoking and lowering alcohol intake can make a big difference. Getting help with mental health (and getting a good night’s sleep) may help your heart relax as well. Maintaining a healthy weight through a good diet and dynamic exercise is vital. Unfortunately, without management, cardiovascular disease is more like a desert than a dessert: it can kill you.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Centers for Disease Control and Prevention. (July 19, 2021). Coronary artery disease (CAD). U.S. Department of Health and Human Services.

 National Center for Chronic Disease Prevention and Health Promotion, Division for Heart Disease and Stroke Prevention. (May 15, 2023). About heart disease. U.S. Department of Health and Human Services.

American Heart Association. (May 31, 2017). What is cardiovascular disease?

Tsao, C. W., Aday, A. W., Almarzooq, Z. I., Alonso, A., Beaton, A. Z., Bittencourt, M. S., … & American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. (2022). Heart disease and stroke statistics—2022 update: a report from the American Heart Association. Circulation, 145(8), e153-e639.

National Heart, Lung, and Blood Institute. (n.d). Heart and vascular diseases. U.S. Department of Health and Human Services. Accessed on September 12, 2023.

The World Health Organization. (June 11, 2021). Cardiovascular diseases (CVD).


September 8, 2023 BlogLupus

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What happens when the things that are supposed to keep us safe turn against us? In fiction, this is usually posed as some big, world-ending problem like artificial intelligence going off the rails and killing everybody. In nonfiction, this question is hashed out in the world of autoimmune diseases. 

Systemic Lupus Erythematosus (SLE) is an autoimmune disease that typifies an entire cluster of autoimmune diseases , known as “lupus-associated”. These include rheumatoid arthritis, systemic sclerosis (scleroderma), Sjogren’s syndrome, and more. These diseases tend to spread though different parts of the body, which is why many have “systemic” in the name. 

Systemic lupus erythematosus is a chronic and progressive autoimmune disease. Chronic indicates that it is long-lasting, and progressive means that the disease can change over time, usually by getting stronger and more severe. It is much more prevalent in racial and ethnic minorities, and 90% of sufferers are women. These statistics immediately give us clues as to the nature of SLE and autoimmune diseases: they have a genetic component. People from different parts of the world have different packages of genes, but why are women so susceptible? 

Genes are part of our DNA, the code that describes what we are. Specifically, they are sections of code that describe how to build a protein. Each gene has instructions for a single protein, and changes to the genetic code can result in changes to the protein that it’s supposed to build. Genes aren’t randomly distributed in the DNA code; they are located on chromosomes. We have 23 chromosomes that we get from our mother and 23 from our father. Most are the same size, but the X and Y sex chromosomes look different. The X chromosome, attributed to females, contains 800-900 genes while the Y chromosome, attributed to males, contains only 50-60 genes! It is thought that a genetic component of autoimmune diseases may be found on the X chromosome. 

The immune system is made of cells that have specific proteins they use to identify invaders, send alert signals, and attack. A huge class of signaling molecules is called hormones. Many of these are proteins. One class of immune hormone proteins is interleukins. When there are too many of these, they are in the wrong place, or they have changed in some way the immune system can go haywire and attack healthy cells. 

Autoimmune diseases like SLE are complex. The immune system gets out of whack due to multiple conditions acting together. Affected people have a genetic predisposition: their DNA has code that makes it likely to produce dangerous levels or types of interleukins. This isn’t a foregone conclusion, however. An environmental stimulus is needed to start the autoimmune process. This can be airborne particles like silica or cigarette smoke, drugs including contraceptives, viruses, and even sunlight! When the genetic primer is lit, the immune system misidentifies what is good and bad and can explode on healthy cells.

Like many autoimmune diseases, SLE has a cycle of remission and relapse; people have symptom-free periods, and periods of increased symptom activity. Symptoms may be low on the disease scale, including pain, fatigue, and a rash on the face. This rash may be exacerbated by UV light, appearing on the nose and cheeks where we get sun. This takes on the classic “butterfly rash” shape associated with SLE. Higher on the disease scale is damage to organs like the kidneys, heart, lungs, bloodstream, gut, and nervous system. When it is widespread it can also cause skin and joint disease, including arthritis. Severe cases can lead to hospitalization and death. 

So what can we do about autoimmune diseases like SLE? Each patient is different, each disease is different, and doctors have to balance the effects of medications against side effects. In general, the most obvious preventative step for autoimmune diseases is something that calms the immune system down. Antimalarials like hydroxychloroquine decrease immune activity and are often a preventative step. During flare-ups, a targeted anti-inflammatory like a glucocorticoid may be used. If these fail, doctors may prescribe immunosuppressant drugs or monoclonal antibodies. Specific organ maintenance, like treating liver and kidney problems can help alleviate damage, and doctors can also recommend procedures that work directly on our bloodstream. The future may hold promise for new medications that target specific parts of the autoimmune disease pathway. Keep your eyes open for new clinical trials aimed at helping those with autoimmune diseases like SLE.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Ameer, M. A., Chaudhry, H., Mushtaq, J., Khan, O. S., Babar, M., Hashim, T., … & Khan, O. S. (2022). An overview of systemic lupus erythematosus (SLE) pathogenesis, classification, and management. Cureus, 14(10).

Angum, F., Khan, T., Kaler, J., Siddiqui, L., & Hussain, A. (2020). The prevalence of autoimmune disorders in women: a narrative review. Cureus, 12(5).

Barber, M. R., Drenkard, C., Falasinnu, T., Hoi, A., Mak, A., Kow, N. Y., … & Ramsey-Goldman, R. (2021). Global epidemiology of systemic lupus erythematosus. Nature Reviews Rheumatology, 17(9), 515-532.

Mackay, I. R. (2009). Clustering and commonalities among autoimmune diseases. Journal of autoimmunity, 33(3-4), 170-177.


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I remember learning in biology that we’re made out of cells. That’s true, but not all the way true. We’re also made out of the stuff in between cells This stuff is called the extracellular matrix. Extracellular means outside of the cells and matrix in this context means the environment that is occupied. Though the extracellular matrix isn’t a dystopian cyberworld made by robots, it can be dangerous if parts of it start getting out of control. Systemic sclerosis, a type of scleroderma, is a disease that results in excess material being deposited in the extracellular matrix, causing body-wide problems.

Systemic sclerosis is a rare, chronic, and progressive autoimmune disease. It affects women in their 60s, though men and African Americans have the worst outcomes from the disease. Around one in four people with systemic sclerosis also have another autoimmune disease. The biggest risk factor for systemic sclerosis is family history; and genetics. It is thought that some people have a genetic predisposition to the disease and that environmental factors cause it to “kick on.”

As an autoimmune disease, systemic sclerosis is complex. It may present differently in each patient who has it. One of the easiest ways to differentiate types is by how it affects skin. Sclerosis comes from Greek and means to harden or a tumor. Systemic sclerosis is hard, tumor-like skin that affects the whole body (or system). There are three categories based on how widespread the condition is. Systemic Sclerosis sine scleroderma is when skin is unaffected, though fingers may experience discoloration. Limited cutaneous systemic sclerosis is, as the name suggests, limited. The skin on the fingers and face is affected. It tends to progress slower and may be less dangerous. Diffuse cutaneous systemic sclerosis is quite the opposite. It is diffuse, meaning it spreads far and wide. It may affect the arms and legs up to knees and elbows, the chest, stomach area, and back. It progresses quickly and is associated with poorer outcomes.

Beyond the hardening of the skin, there are other symptoms, and (unsurprisingly) none are great. Patients may experience:

  • Pain
  • Joint abnormalities
  • Itching
  • Fatigue
  • Digestive issues
  • Heart, lung, and kidney problems
  • Psychological problems like anxiety and body image concerns

All of these can be annoying and painful, but many are very dangerous. Systemic sclerosis, in fact, is the most deadly of all rheumatic diseases. Let’s dig into how systemic sclerosis works to find out why.

As stated before, systemic sclerosis is an autoimmune disease. Some environmental factors like smoke, alcohol, viruses, solvents, or chemicals activate our epithelial cells. Epithelial cells interact with the outside world and are located on the skin, in our lungs and digestive tract, and around organs. The cells send out danger signals in the form of cytokines. There are several cytokines, but one of the most prevalent in this system is type 1 interferon (IFN). If this were The Matrix these guys would be the Agents, good at getting rid of unwanted intruders but dangerous when they get out of control. They are usually sent out in viral infections and put the immune system into a general state of alert. When there are too many cytokines, they start causing damage that needs to be repaired. The body responds to high IFN in a couple of ways: alerting immune cells, starting inflammation, and – in people with systemic sclerosis, by activating fibroblasts. Fibroblasts make the connective tissue between cells (you may see where this is going). These guys go into overdrive and spew extra collagen, elastin, and other connective tissues between cells. They try to repair damage from the cytokines, but the excess tissue signals problems and creates a deadly feedback loop.

When this is bad enough, normal cells are replaced by this dense tissue in the extracellular matrix. The skin on the fingers and toes thickens, and the vascular (circulatory) system starts getting crushed. Small blood vessels called capillaries die. The tissue around your vital organs thickens and causes damage. The body can’t deliver enough oxygen to organs, which is bad. If this happens to the blood vessels of the lungs, it’s even worse. The thickening on the fingers, toes, arms, legs, and face may be debilitating, but the real danger is what’s happening inside.

So what can be done? Doctors can try to treat the symptoms and complications to keep people comfortable. They may treat vascular, skin, kidney, arthritic, and gastrointestinal problems. If the lungs are affected, specific monoclonal antibodies may be prescribed. Some patients also find that general immunosuppressors help, but these can come with myriad side effects. The best bet for patients is to discover and treat systemic sclerosis early, before damage spreads, if possible. Medications may slow the decline, possibly until the disease becomes stable. On the horizon, clinical researchers are looking at medications that may cut the feedback loop and help patients break free from the matrix.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Harrison, D. G., Coffman, T. M., & Wilcox, C. S. (2021). Pathophysiology of hypertension: the mosaic theory and beyond. Circulation research, 128(7), 847-863. 

Myat, A., Redwood, S. R., Qureshi, A. C., Spertus, J. A., & Williams, B. (2012). Resistant hypertension. Bmj, 345.

Sarafidis, P. A., Georgianos, P., & Bakris, G. L. (2013). Resistant hypertension—its identification and epidemiology. Nature Reviews Nephrology, 9(1), 51-58.


August 24, 2023 BlogBlood Pressure

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What do Star Wars, Nazi-occupied France, and surge protectors have in common? We root for the resistance to win! But what if the resistance is evil and bad? Meet resistant hypertension. This little devil is a special, particularly damning form of hypertension that resists medications. Not just one or two medications, either! Resistant hypertension avoids at least three separate medications of three separate types (called classes)! 

Resistant hypertension is when blood pressure remains over 140/90 mmHg while seated, even when the patient is taking the maximum tolerated dose of three or more different classes of hypertension medications. It can damage the heart, eyes, and kidneys and lead to heart attack, stroke, end-stage renal disease, and death. It can be caused by a narrowing of the veins, but the prevalence isn’t narrow at all. It affects 6-9 million Americans, with the highest incidence in Black males. A few conditions are associated with resistant hypertension, including diabetes, obesity, and chronic kidney disease.

To understand how this disease works, we must first understand how blood pressure works. Blood pressure is controlled by three main components: heart rate, volume pumped, and blood vessel size. This may seem like a simple system, but each of these three components are affected by a myriad of body systems. Think of it like trying to maintain peace in the middle east. It might seem like you could balance the needs of religion, economics, tradition, and foreign influence, but it turns out: no. Other big actors in the blood pressure realm include the brain and kidneys. The brain directs other organs how to act and the kidneys regulate the fluid in the bloodstream (which we call blood). On top of these big organs, blood pressure is affected by interconnected systems, genes, inflammation, salt, even the bacteria in our gut! One of the biggest systems involved with blood pressure is the Renin-Angiotensin-Aldosterone System, or RAAS (or RAS). This system involves the kidneys and uses hormones to regulate blood pressure. It relies on a few key hormones and enzymes, and is also affected by other systems like the natriuretic peptide system and the brain.

In hypertension, one or more of these systems no longer functions properly. We have four major classes of medication to help get the body back on track. Long-acting calcium channel blockers (CCB) reduce the amount that the heart and arteries can contract, relaxing the system. Angiotensin is a hormone that causes blood vessels to narrow. Angiotensin-converting enzyme inhibitors (ACEI) block angiotensin from being made and angiotensin receptor blockers (ARB) block it from acting on blood vessels. Finally, diuretic medications remove water and salt from the blood, lowering the volume of fluid that the heart pumps. Each of these medications targets the body in slightly different ways. Different medications work better for some people, and side effects may present differently. A good doctor will look for a blood pressure medication (or two (or three (or more))) that brings blood pressure to healthy levels without too many side effects.

When we do not achieve healthy blood pressure levels even at the maximum tolerated dose of three or more medications we have resistant hypertension. Patients with resistant hypertension are at a higher risk of major cardiac events because they can’t get blood pressure under control with available medications. Prolonged high blood pressure leads to damage throughout the cardiovascular system.

So what can be done? The best first step is to lower modifiable risks. This is actually a good first step for literally anything that is dangerous. Weight loss is a good opening move if you are obese. Lowering alcohol and salt intake may help. Talking to a doctor about any medications or conditions that may be raising blood pressure is important. Finally, clinical trials may be underway to look for specialty medications that target those with resistant hypertension. Hopefully we can find a way to crush resistance without succumbing to the dark side of the force (or becoming nazis).

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Harrison, D. G., Coffman, T. M., & Wilcox, C. S. (2021). Pathophysiology of hypertension: the mosaic theory and beyond. Circulation research, 128(7), 847-863. 

Myat, A., Redwood, S. R., Qureshi, A. C., Spertus, J. A., & Williams, B. (2012). Resistant hypertension. Bmj, 345.

Sarafidis, P. A., Georgianos, P., & Bakris, G. L. (2013). Resistant hypertension—its identification and epidemiology. Nature Reviews Nephrology, 9(1), 51-58.


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Most of us have experienced standing up and feeling a little light-headed. This is caused by gravity pulling blood into the legs, causing the brain to run a teensy bit dry. Within a few seconds, the vessels in the legs tighten and push blood out, and the heart pumps it up to the brain so we can forget where we left our glasses. For some people, it’s not quite as simple – or as harmless. Between 500 thousand and 3 million Americans, mostly women between 15 and 50 years of age, suffer from Postural Orthostatic Tachycardia Syndrome, or POTS. Postural means it relates to your position. Orthostatic comes from the Greek for “upright” and “to stand.” Tachy- means fast, and -cardia refers to the heart; together, tachycardia means the heart is beating excessively fast. Syndrome actually means a group of symptoms happening together, which is an important part of POTS. Together, Postural Orthostatic Tachycardia Syndrome (POTS) is an abnormal increase in high heart rate when standing up from a lying position.

POTS has two aspects that occur together: tachycardia when standing and orthostatic intolerance. Tachycardia is a very high heart rate. With POTS, this is defined as 30 beats per minute (BPM) more than normal (40 in children) or a BPM of 120 or more. Orthostatic intolerance means the patient can’t stay upright without experiencing symptoms. Symptoms include:

  • Lightheadedness and fainting
  • Blood pressure changes
  • Shaking
  • Trouble concentrating
  • Nausea
  • Trouble exercising
  • Coldness in legs
  • Chest pain
  • SOB (shortness of breath)
  • Cold, red/blue discoloration of legs

As alluded to earlier, POTS occurs because of gravity. When we stand up, around 2 cups (500mL) of blood falls into our lower body, and we must push and pull it back out. Baroreceptors in the cardiovascular system detect the change in blood pressure and kick the autonomic nervous system (which does things automatically) into action. The brain rapidly sends signals to redistribute blood (especially to get more blood up to the brain!) Blood vessels push out blood. They constrict, squeezing blood out and providing less space to pool up. The heart pulls blood up. If not enough blood is coming up, it beats faster to try to help. With POTS, the autonomic system breaks down somewhere, and the heart starts beating out of control to try to help.

POTS is a syndrome, not a disease. This is significant because syndromes like POTS can have many causes and can be hard to precisely parse into perfunctory pieces. Any part of the system described above can be out of whack and potentially cause POTS. The brain might not receive proper signals or might not send signals in a helpful way. Our ability to squeeze blood vessels might be compromised. We might have hormone imbalances, sensitivities, or changes. The amount of blood or salt in the body might be too low. Some people find their blood pressure decreases slightly with POTS, but some find that their blood pressure increases! Conditions that can cause these differences vary widely. Small vessel muscles can weaken, pregnancy, surgery, and trauma may cause POTS, and autoimmune or infectious diseases can affect things. Genetics, diabetes, and poisoning from alcohol, heavy metals, or chemotherapy may also be implicated. The common factor is that the heart tries very hard to pump blood to the brain and doesn’t think it’s succeeding. In cases where it does fail, the brain goes into standby mode, and we faint.

With all of these possible mechanisms, no solution to POTS can hope to work for everyone. Treating underlying causes is a good start, if applicable. Beyond that, each case is unique, and sufferers must talk with a medical professional to find a solution that works for them. There are no approved medications for POTS, but a doctor may prescribe something off-label that could work in a specific case. Non-medicinal remedies include drinking more water (soda does NOT count), eating more salt, and compression leggings. These should go to the waist to avoid blood pooling about the knees. The best long-term solution is physical conditioning – exercise. This can be very difficult in severe cases of POTS as it can cause exercise intolerance. A good goal is around 20-30 minutes of aerobic exercise three times a week. As with all lifestyle and medication changes, talking to a medical professional is a good idea. With POTS and its varied causes, signs, and symptoms, it is critical.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Dysautonomia International, (2019). Postural Orthostatic Tachycardia Syndrome.

Grubb, B. P. (2008). Postural tachycardia syndrome. Circulation, 117(21), 2814-2817.

Olshansky, B., Cannom, D., Fedorowski, A., Stewart, J., Gibbons, C., Sutton, R., … & Benditt, D. G. (2020). Postural orthostatic tachycardia syndrome (POTS): a critical assessment. Progress in cardiovascular diseases, 63(3), 263-270. 

Raj, S. R. (2006). The postural tachycardia syndrome (POTS): pathophysiology, diagnosis & management. Indian pacing and electrophysiology journal, 6(2), 84.


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I remember the early days of COVID-19, everything was new and scary and dangerous and no one knew what was going on. It seemed to be very dangerous for two groups of people, those of advanced age and those who were immunocompromised. Vaccines rolled out, testing became easy, and things have calmed down quite a bit. But corona isn’t all limes on the beach, as any virus, it’s still dangerous for people who are immunocompromised. What does this term mean, who are the immunocompromised, and is there anything they can do in the new reality of COVID-19?

Immunocompromised is a broad term. It indicates that a person’s immune system cannot generate an appropriate response to infection. When bacteria or viruses make it inside these people’s bodies, they cause much more damage and are very hard to control. The immune system is very, very complicated, so there are many ways a person can become immunocompromised. We can generally lump these into two categories: primary and secondary immunodeficiency.

Primary immunodeficiency means the condition is built-in to the body; it’s genetic. Primary immunodeficiencies are fairly rare, with <0.1% of the population experiencing them. The rest of the almost 3% of people who have immunodeficiencies have secondary immunodeficiencies.Infectious diseases (such as HIV), malnutrition, age, surgery, environmental stress, and immunosuppressive drugs can all cause secondary immunodeficiency. Immunodeficiency affects millions of Americans. Women are twice as likely as men to have immunodeficiency; it is most common in white Americans and those aged 50-59. Nearly 3% of the population – over 9 million Americans – are suspected to have immunodeficiency. 

Unfortunately, immunodeficiency can greatly reduce a person’s ability to deal with a COVID-19 infection. The most obvious problem is that immunocompromised people are more susceptible to severe symptoms. A disproportionate amount of people who are hospitalized for COVID-19 are immunocompromised. Immunodeficiency doesn’t compromise, it packs a double-whammy. Those with a weak immune system also find vaccines less effective! In fact, 44% of people who had “breakthrough” cases (where they were vaccinated but still hospitalized) were immunocompromised. This is because the body is unable to produce enough protective antibodies for the body to be protected – a process called seroconversion.

Seroconversion is when antibodies are able to be detected in the blood. With vaccines, successful seroconversion indicates that the body is protected and has the equipment necessary to put up a good fight against the COVID-19 virus. When vaccinated against COVID-19, people with healthy immune systems showed seroconversion rates of 99%. The type of immunocompromisation affects how well vaccines produce seroconversion. People with solid tumor cancers, such as breast, colon, prostate, and lung cancer show seroconversion rates of 92%. Immune-inflammatory disorders like lupus, primary biliary cholangitis, psoriasis, and rheumatoid arthritis have seroconversion rates reduced to 78%. Vaccine effectiveness in people with blood cancers such as lymphomas, myeloma, and leukemia drops to 64%. Those with organ transplants have to be on strong immunosuppressive drugs to avoid organ rejection and because of this they have the lowest rates of seroconversion, only 27%.

Some factors of immunocompromisation. Adapted from Chinen, J., & Shearer, W. T. (2010).

So what can immunocompromised people do to protect themselves against COVID-19? A lot of the same things as people who are immunocompetent! High quality masks and respirators can help. Avoiding crowds and indoor areas with poor ventilation is a must. Washing hands with soap and water is critical, though hand sanitizer is a good second option. Immunocompromised people who contract COVID-19 should contact their doctor or other healthcare provider right away. Isolating and using masks to prevent the spread is always a good idea. Immunocompromised people may also keep infections from getting out of control if their medical provider recommends an antiviral medication or convalescent plasma. Of course, the best way to avoid getting sick with COVID-19 is through prevention, including vaccines. A 27% seroconversion rate is much better than 0% after all. And there may be more hope for immunocompromised people, as new vaccines are being developed to serve this community.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Boyle, J. M., & Buckley, R. H. (2007). Population prevalence of diagnosed primary immunodeficiency diseases in the United States. Journal of clinical immunology, 27, 497-502.

Chinen, J., & Shearer, W. T. (2010). Secondary immunodeficiencies, including HIV infection. Journal of Allergy and Clinical Immunology, 125(2), S195-S203.

Harpaz, R., Dahl, R. M., & Dooling, K. L. (2016). Prevalence of immunosuppression among US adults, 2013. Jama, 316(23), 2547-2548.

National Institute of Health. (July 21, 2023). Special considerations in people who are immunocompromised. COVID-19 Treatment Guides,

Parker, E. P., Desai, S., Marti, M., Nohynek, H., Kaslow, D. C., Kochhar, S., … & Wilder-Smith, A. (2022). Response to additional COVID-19 vaccine doses in people who are immunocompromised: a rapid review. The Lancet Global Health, 10(3), e326-e328.

SY, L. A. W., SC, C. L. L., & Muthiah, L. M. (2021). Efficacy of COVID-19 vaccines in immunocompromised patients: A systematic review and meta-analysis. medRxiv.


August 4, 2023 BlogFibromyalgia

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Pain isn’t fun. So why do we feel it then? Because it is a learning mechanism. When I burn myself tasting boiling soup I quickly pull the spoon away, blow on it, and learn not to do that again until tomorrow. Pain is useful, but what about when it’s not? Fibromyalgia is a condition where the body’s sensitivity to pain has increased beyond the useful range. Instead of keeping you from stopping damaging activities, it can stop people from performing healthy ones. It is a complex, poorly understood disease.

Fibromyalgia affects between 2-8% of the world population, somewhere around 500 million people worldwide. It mostly affects women and onset is usually between 30 and 35 years of age. Risk factors include being female, experiencing trauma, infections, diabetes, inflammatory diseases, neurological and psychiatric disorders, genetics, and oxidative stress. Major symptoms include:

  • Sleep difficulty, including insomnia and sleep that doesn’t make you feel rested
  • Cognitive dysfunction
  • Mood changes, such as anxiety and depression
  • Fatigue
  • Gut changes
  • Muscle stiffness
  • Joint stiffness

Fibromyalgia is hard to diagnose because it doesn’t have physical symptoms that we know how to detect. Doctors look for pain that has been spreading for three or more months. A rheumatologist (a doctor who specializes in inflammatory diseases), may provide the diagnosis. 

How does fibromyalgia work? It is multifactorial, meaning there are several possible causes that all lead to the same result. Because of this, looking at individual causes may not be helpful. Instead, according to Dr. Siracusa, fibromyalgia “…is thought to represent the degradation of the autonomic nervous system in a failed attempt to adapt to a hostile environment” (Siracusa, 2021). The autonomic nervous system is the part which controls involuntary activity, like heart rate and digestion. This theory holds that as this system breaks down from repeated or constant stresses to it; it eventually fails to interpret pain signals in a useful way. Some of these stresses may include:

  • Increased inflammation
  • Immune system changes, including in the brain
  • Genetic differences
  • Psychosocial changes, including depression, anxiety, and sleep disorders
  • Hormonal changes, including to stress hormones
  • Stress

We will digress here to talk about some of the controversy and problems with fibromyalgia. It is hard to diagnose, doesn’t leave good molecular clues, and is hard or impossible to see. This has led to widely proliferated discounting of the symptoms, even by medical professionals. This is unacceptable. I have heard that fibromyalgia is “in their head.” Even if true, this doesn’t mean it’s any less real! Chronic and sensitized pain is debilitating. Having acquaintances and medical professionals dismiss debilitating symptoms can be devastating.

With any change in how we sense the world, there are changes in the body and brain. With fibromyalgia, the most likely culprit of change is the pain system. This system, called the nociceptive system, becomes high strung, firing willy-nilly. There are changes to neurotransmitter levels, molecules that lessen pain, and nerve fibers associated with pain. Many of these changes occur in the peripheral nervous system; the nerves outside of the brain and spinal cord. There are also changes to overall brain structure, which may lead to pain when at rest. Central sensitization is a term for a state of increased pain sensitivity. Repeated injury or pain can cause sensitization, where the nerves that send pain signals fire more easily and at inappropriate times. We are just beginning to see the differences in how the brain fires using MRI and fMRI (functional magnetic resonance imaging) technology.

What can be done about fibromyalgia? There are no cures, but there may be some methods to find a modicum of relief. Education is the first piece of the puzzle. Understanding what fibromyalgia is and that it tracks changes in your body can help you understand what is going on. One of the stressors to the pain system is stress and anxiety. Along with education, psychotherapy may provide some relief. Fitness can also help, and is particularly helpful when a patient has received dismissive medical advice in the past. Some patients experience a reduction in symptoms with a low glutamate diet. This is NOT a low gluten diet. Glutamate is a neurotransmitter that is a possible culprit for some nociceptive changes. Low glutamate diets are specific, quite restrictive diets that should be discussed with a dietitian. MSG, aspartame, protein concentrates, smoke flavoring, and more are all restricted on this diet. Finally, some fibromyalgia patients find relief with medication. Some specific anti-nociceptive neurotransmitter medications seem to help, as do other specific brain-altering medications. Some patients find relief with medical marijuana or prescription opioids, though side effects may not be worth it. Across the board, NSAIDs, such as ibuprofen (motrin, advil), aspirin, and naproxen (aleve) do NOT seem to provide relief. Talking to a medical professional is a good idea before making changes to your medical routine or diet. Hopefully this article helps with the education aspect of relief, and hopefully sufferers can find more as well!

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Holton, K. F., Taren, D. L., Thomson, C. A., Bennett, R. M., & Jones, K. D. (2012). The effect of dietary glutamate on fibromyalgia and irritable bowel symptoms. Clin Exp Rheumatol, 30(6 Suppl 74), 10-7.

Kandel, E. R., Schwartz, J. H., Jessell, T. M., Siegelbaum, S., Hudspeth, A. J., & Mack, S. (Eds.). (2000). Principles of neural science (Vol. 4, pp. 472-479). New York: McGraw-hill.

Sagy, I., Bar-Lev Schleider, L., Abu-Shakra, M., & Novack, V. (2019). Safety and efficacy of medical cannabis in fibromyalgia. Journal of clinical medicine, 8(6), 807.

Siracusa, R.; Paola, R.D.; Cuzzocrea, S.; Impellizzeri, D. Fibromyalgia: Pathogenesis, Mechanisms, Diagnosis and Treatment Options Update. Int. J. Mol. Sci. 2021, 22, 3891.


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Medical terminology can be hard to understand. Much of it is in Latin, some is in Greek, several words are named after people, and terminology can change. Sometimes that change is a good thing, though. In June 2023 a collaboration of hundreds of experts in liver disease released new names for the liver diseases previously known as Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH).

Adapted from Rinella, M. E., et al., 2023

Under the broad category of Steatotic Liver Disease (SLD) we now have Metabolic dysfunction Associated Steatotic Liver Disease (MASLD), which can progress to Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Metabolic Alcohol-associated Liver Disease (MetALD, which is MASLD and increased alcohol intake). This change was made for many reasons. The terms “non-alcoholic” and “fatty” may have been confusing, stigmatizing, or inaccurate. People who are not overweight may still have the disease, and those with the disease may still be consuming alcohol. Finally, naming a disease after what it isn’t (“nonalcoholic…”) is less than ideal.

The new system describes the same symptoms but with more specific language. Steatosis is the accumulation of fat inside of cells and the disease is caused by changes in the metabolic system; how our cells change food into energy. A critical change has also been made with the adoption of the new term MetALD. MetALD describes people who have MASLD, but who still consume some alcohol. Alcohol affects the disease progression, but metabolic disruptions do as well. Hence, a term was developed to describe this overlap.

These terms were planned and adopted by an international group of clinical researchers, scientists, educators, industry experts, and patient advocates. The American Association for the Study of Liver Disease (AASLD), European Association for the Study of the Liver (EASL), Asian Pacific Association for the Study of the Liver (APASL), and Asociación Latinoamericana para el Estudio del Hígado (ALEH) made up most of the participants and have ensured widespread adoption of the new terminology

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Rinella, M. E., Lazarus, J. V., Ratziu, V., Francque, S. M., Sanyal, A. J., Kanwal, F., … & NAFLD Nomenclature consensus group. (2023). A multi-society Delphi consensus statement on new fatty liver disease nomenclature. Annals of Hepatology, 101133. 


July 21, 2023 BlogLiverNASH

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Nonalcoholic Steatohepatitis, or NASH, has no approved medications available for treatment. This isn’t because the disease is safe, however. NASH can lead to cell death, cells going rogue, collagen accumulation, fibrosis, cirrhosis, and liver cancer. One problem with treating NASH is that it is a multifactorial disease, meaning there are many possible causes that all lead to the same outcome. The current best methods for treating NASH are exercise, weight loss, and treating other conditions that may contribute. We will discuss scientifically backed information regarding these treatment options, but it is critical that any medical advice be discussed with your doctor. NASH has many many causes and affects a lot of body systems. Medical professionals that may be involved in NASH treatment include your primary care physician, a hepatologist, dietitian, endocrinologist, cardiologist, and others. Every person is an experiment of one, and your specific circumstances may contraindicate one or all of the methods discussed below. Talk to your doctor. 

Weight loss is the go-to method of treating NASH. A combination of diet and exercise is the best method to achieve weight loss. This ensures fewer calories enter the body than exit it, and that the body is burning weight from fat instead of from muscle. Losing weight very rapidly can be dangerous, so be conscientious of your body’s overall health (and speak with a professional!) Research has shown that reducing weight by as little as 5% (12.5 lbs for a 250 lb person) can help improve steatosis, the fat buildup in the liver. Losing 7% or more (17.5 lbs for a 250 lb person) also shows a reduction in inflammation and improved health of liver cells. When patients, particularly obese patients, lose 10% of their body weight (25 lbs for a 250 lb person) the structural liver changes known as fibrosis start to regress or stabilize. For NASH patients of a normal weight, they may see results when losing as little as 3-5% of body weight.

Exercise is a great way to lose weight, but studies have shown that exercise can help your liver even when you aren’t losing weight. The exact mechanisms for how this works are complex and not fully known. Scientists have found that exercise helps make the body more sensitive to insulin – which helps it regulate blood sugar better. It can also help cellular metabolism. Exercise is associated with a reduction in the markers of liver inflammation and may help liver cells stay healthy. Aerobic exercise, also called “cardio,” is highly recommended. Resistance training, called strength training, is also helpful, especially if aerobics are not possible. NASH patients start seeing benefits when doing exercise for 150-300 minutes (2 ½ – 5 hours) per week of moderate intensity exercise or 75-150 minutes (1 ¼ – 2 ½ hours) per week of high intensity exercise. Always ease into a new exercise routine to avoid injury. Talking to a medical professional is also a good idea before starting new exercises (there is a theme to this article).

Exercise burns calories, but to lose weight we also want to manage what calories we take in. Consult with your doctor or dietitian, but reducing caloric intake to around 500 fewer than the daily recommended value may help. Further, the number of calories is not directly correlated to the quality of the calories. NASH patients find improvements when reducing items that can damage the liver, including fructose and saturated fats. Fructose is a form of sugar that is often added to sugary beverages (usually in the form of high fructose corn syrup) and contributes to insulin resistance. Saturated fats are found in meats, including red meats and processed meats. As for specific diets, research is ongoing. The Mediterranean diet has the most research backing its success in NASH patients. It is rich in fruits, vegetables, whole grains, seafood, nuts, legumes, and olive oil. Other diets may be suitable as well, including intermittent fasting, ketogenic diet, and others. One recommendation is to take the Mediterranean diet and adjust it to fit you. Regardless of the diet choice, alcohol should be limited. For smokers and former smokers, alcohol should be eliminated entirely. It should go without saying that making major adjustments to your diet should be consulted with your doctor.

Other than diet and exercise, treatments for NASH are all achieved by treating other conditions that contribute, and will vary depending on the individual. Conditions that contribute are obesity, diabetes, high blood pressure, high cholesterol, cardiovascular disease, and obstructive sleep apnea. Cardiovascular disease and obstructive sleep apnea are major contributors of mortality for NASH patients and should be taken seriously. Obviously these conditions are best treated by going to your doctor.

NASH is a progressive disease that gets worse over time and leads to serious, occasionally deadly complications. Clinical trials may give us a medical NASH treatment in the future. Until then, give yourself a leg up (or liver) by consulting your doctor about treatments through diet, exercise, and underlying condition management.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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American Liver Foundation. (March 16, 2023). What are the treatments for NAFLD and NASH?  NASH Treatment,

Van der Windt, D. J., Sud, V., Zhang, H., Tsung, A., & Huang, H. (2018). The effects of physical exercise on fatty liver disease. Gene Expression The Journal of Liver Research, 18(2), 89-101.

Younossi, Z. M., Corey, K. E., & Lim, J. K. (2021). AGA clinical practice update on lifestyle modification using diet and exercise to achieve weight loss in the management of nonalcoholic fatty liver disease: expert review. Gastroenterology, 160(3), 912-918.


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Is the liver the most amazing organ? Yes. It turns food into usable molecules. It makes proteins, bile, and hormones. It filters dangerous drugs and toxins. Without it, you would die within minutes. Also, the liver can regenerate (like a lizard’s tail!), which is basically magic. The liver is estimated to have over 500 individual functions and interacts with most body systems. In this article we’ll look at the liver, zooming in from basic facts to its cellular units. Then we’ll explore the functions of the liver.

If you were to guess the largest organ in the body, would you guess the liver? I hope not, because it’s the skin. But the liver is in second place! It makes up around 2% of your body weight and usually contains about 10% of your blood. It’s located under the ribs, right below the diaphragm that inflates the lungs. It’s smooth and reddish brown when healthy (note: if you can see your liver’s color you are probably having a bad day). The liver can be divided into four parts called lobes and thousands of sub-parts called lobules. These are hexagonal columns of cells arranged so that blood can travel through carrying nutrients in and toxins and waste out. 

Four types of cells make up the liver: hepatocytes, epithelial cells, Kupffer cells, and stellate cells. Most of the liver is composed of hepatocytes. These are the workhorses of the liver. Hepatocytes convert fats (called lipids), sugars (called carbohydrates), and proteins (called proteins) into usable forms. They detoxify dangerous things and excrete bile and cholesterol. The barrier epithelial cells line the walls (including blood vessel walls) inside the liver and do some filtering of small particles. It is thought that these may also do some clearance of viruses. Kupffer cells are the resident immune cells. These large cells eat bacteria and debris that enter lobules. They are always touching these dangerous particles and exhibit a constant, low-level inflammation. Disruption of these cells can result in widespread, damaging liver inflammation. Finally, stellate cells store vitamin A, a critical vitamin. They are critical for promoting the liver’s amazing ability to regenerate. They form temporary scars that allow for healing. When they are damaged, however, they lose vitamin A. Damaged stellate cells can “activate” and run amok, secreting a lot of collagen that causes fibrosis and permanent scarring called cirrhosis.

To understand the liver’s major functions, let’s first look at our body cells. Cells need to have a balance of chemicals to function properly. Normally cells control what goes in and out of them using special proteins. To keep unwanted things out, cells are separated from the environment around them. This separation is done by a membrane made of phospholipids. The –lipid at the end is another word for fat. Since the borders of our cells are made of fats, things that can pass through fats (called fat-soluble) can easily pass through the cell membranes. Cells can’t control this very well, so we use the liver instead.

 Let’s run through the liver’s major functions of storage, conversion, and creation. Storage is fairly simple. The liver stores fat-soluble vitamins and converts some of them into usable forms. It stores a quick supply of energy in the form of glycogen. Blood is stored in large quantities in the liver. This makes sense, because the liver is filtering the blood. Usually it holds a little more than 10% of the body’s blood, but the liver can expand to hold much more if needed. It can also squeeze blood out if the body is bleeding profusely. This probably isn’t great for the liver, but then again neither is bleeding out and dying.

The liver converts a huge amount of material from one form into another. It acts as a gatekeeper for nearly all the blood in the body, including blood directly from the digestive tract. This includes tasty nutrients like fat and sugar, and dangerous toxins, like alcohol and methamphetamine. Blood is carried across the lobules and filtered through the hepatocytes and Kupffer cells. The liver doesn’t just remove dangerous particles, however, it metabolizes them! Metabolism is the conversion of chemicals from one form to another. One of the most important metabolic functions is detoxification. To make drugs and toxins less dangerous, the liver converts them from being fat-soluble (able to pass through cell membranes) to being water-soluble (able to be released through urine but much harder to enter cells). Carbohydrates are converted to glycogen for storage. The liver changes fats into energy for use. Proteins are broken into building blocks and waste products are removed. Remnants of dead blood cells called bilirubin are turned into bile and used for digestion. 

The conversion of materials into component parts helps the liver’s third broad function, creation. The liver creates, or synthesizes, many molecules that are used all around the body. It creates important hormones like angiotensin and thyroxine. It makes chemicals for the blood like prothrombin, fibrinogen, and clotting factors. It also makes the aforementioned bile, which is critical for digesting fats.

The liver is the ultimate hero. Through all of these functions, the liver acts in the best interest of the body. It takes the hit from dangerous chemicals and sacrifices its own blood when we need it most. The liver is a team player of the highest degree. When it goes wrong we suffer throughout our whole body. Take care of that liver!

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Lautt, W. W. Hepatic Circulation: Physiology and Pathophysiology. San Rafael (CA): Morgan & Claypool Life Sciences; 2009. Chapter 2, Overview.

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Yin, C., Evason, K. J., Asahina, K., & Stainier, D. Y. (2013). Hepatic stellate cells in liver development, regeneration, and cancer. The Journal of clinical investigation, 123(5), 1902-1910.


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The liver is an amazing and complex organ. It can regenerate from damage, helps us digest and function, filters some toxins, and in return gets thoroughly abused by us humans. Alcohol can damage the liver, but most livers are mistreated through other means, like diabetes and obesity. This is visible in the form of accumulated fat in the liver and can lead to serious problems. Nearly 1 in 4 adults in America have non-alcoholic fatty liver disease (NAFLD). When a fatty liver becomes inflamed and damaged it is called nonalcoholic steatohepatitis, or NASH. NASH is dangerous, and is an indication of decreased liver health. If untreated, NASH will degrade the liver, potentially leading to scarring known as fibrosis and permanent cirrhosis. Cirrhosis is cirrhiously bad.

At this time, there are no approved therapies for the treatment of NASH. The current standard of care is exercise and weight loss to alleviate problems that damage the liver. Unfortunately, much like trying to lick your elbow, this is easier said than done. The consequences of an impaired liver include liver failure, cirrhosis, cancer, cardiovascular disease, and more. To alleviate this burden, scientists have identified several medical approaches to combating fatty liver.  These approaches generally target the underlying mechanisms that lead to a fatty liver, aiming for a long-term solution. The broadest categories for investigative NASH medication are managing fat, sugar, and inflammation in the liver.

One of the liver’s major jobs is to balance the body’s energy storage needs by managing fat. One method of dealing with excess fats is to dump extra fats out of the body through the digestive system. Thyroid hormone receptor beta (THR-β) can help us do just that. Receptors are parts of a cell that detect what’s happening outside its borders. They interact with hormones, sugars, fats, or other things. Each receptor only reacts to specific molecules.  When activated, THR-β may help reduce the accumulation of fats in the liver by telling the body to move fats from the liver to the gut. Medications that activate THR-β are being investigated to see if they can also do this. 

Another method of helping the liver manage fat is to stop fats from being created in the first place. Unfortunately, some people create an unhealthy amount of fat. They may have a mutated gene called PNPLA3. PNPLA3 genetic disorder affects how the fat cells in the body deal with triglycerides. This mutation can increase liver fat and possibly lead to NASH. Scientists are working on ways of suppressing this gene.

Other research targets being studied for limiting fat production include peroxisome proliferator-activated receptor alpha (PPARα). This is a chemical receptor on liver cells that regulates how fats are processed. When activated, this receptor can lower fat creation and lead to lower blood triglycerides (the most common type of fat). Rampant activation can be dangerous, however, so very specialized Selective PPARα Modulator (SPPARMα) medications are being developed to target the system with specificity and finesse. These medications also target and activate a very interesting hormone called fibroblast growth factor 21 (FGF21), which we will cover in the next section.

Fats can’t take all the spotlight, though, because one of the biggest culprits of liver damage is actually sugar. As a cookie lover, this makes me very sad. Sugars, also called glucose, are converted into fats (stored in the liver) and can damage the liver, metabolic system, heart, etc. The body detects high levels of sugar in the pancreas. High blood sugar signals the release of insulin and amylin from the pancreas to the liver. The liver then starts breaking down, converting, and storing sugars. A couple of medications look to target this system to lower the burden on the liver and help with NASH. Fibroblast growth factor 21 (FGF21), mentioned above, has broad effects, including in the pancreas. It helps manage the body’s metabolism and homeostasis and makes the pancreas more sensitive to insulin. This may be particularly helpful for people with insulin resistance. Insulin resistance leads to type 2 diabetes. FGF21’s other effects appear to include increasing energy use, potentially leading to weight loss. Glucagon-like peptide-1 (GLP-1) agonists, like Semaglutide, Trulicity, and Mounjaro, act on the same system. These directly attach to pancreatic cells, preparing them for a large insulin release when they detect high glucose levels. It is hoped that this can help the liver deal with high blood sugar without taking damage. Another potential pathway to managing blood sugar is to send it down the yellow-brick road. Sodium-glucose cotransporter-2 (SGLT2) inhibitors deal with blood sugar by expelling it out of the body with urine.

The final target of potential NASH treatments is inflammation. NASH stands for nonalcoholic steatohepatitis, which literally means “non-alcoholic inflammation of the liver (due to) fat.” Inflammation is like a visit with the inlaws: good when it doesn’t last too long.  Researchers hope that reducing chronic inflammation may help limit the damage of NASH and prevent a worsening of the disease. Luckily, two avenues of treatment above also target inflammation. One complication of the PNPLA3 genetic mutation is an increase in cyclophilin, a protein that can increase inflammation. By reducing excess cyclophilin through PNPLA3 management – or by targeting it directly, inflammation may be relieved. Interestingly, FGF21, which may be used to lower blood sugar, appears to lower inflammation in the pancreas. The hope is that these medical interventions may also help the liver downstream.

Overall, the liver is complex, and trying to keep it from being damaged is difficult. The only real treatment available today is weight loss through diet and exercise. With luck and help from the clinical trial process, there may be new avenues available in the future.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Fisher, F. M., & Maratos-Flier, E. (2016). Understanding the physiology of FGF21. Annual review of physiology, 78, 223-241.

Geng, L., Lam, K. S., & Xu, A. (2020). The therapeutic potential of FGF21 in metabolic diseases: from bench to clinic. Nature Reviews Endocrinology, 16(11), 654-667.

Prasad, A. S. V. (2019). Biochemistry and molecular biology of mechanisms of action of fibrates–an overview. International Journal of Biochemistry Research & Review, 26(2), 1-12.

Shen, J. H., Li, Y. L., Li, D., Wang, N. N., Jing, L., & Huang, Y. H. (2015). The rs738409 (I148M) variant of the PNPLA3 gene and cirrhosis: a meta-analysis. Journal of lipid research, 56(1), 167-175.

Sinha, R. A., Bruinstroop, E., Singh, B. K., & Yen, P. M. (2019). Nonalcoholic fatty liver disease and hypercholesterolemia: roles of thyroid hormones, metabolites, and agonists. Thyroid, 29(9), 1173-1191.

Ure, D. R., Trepanier, D. J., Mayo, P. R., & Foster, R. T. (2020). Cyclophilin inhibition as a potential treatment for nonalcoholic steatohepatitis (NASH). Expert opinion on investigational drugs, 29(2), 163-178.

US Department of Health and Human Services, National Institute of Health, National Institute of Diabetes and Digestive and Kidney Diseases. (April, 2021). Definition & facts of NAFLD & NASH.

Wang, P., & Heitman, J. (2005). The cyclophilins. Genome biology, 6(7), 1-6.


June 30, 2023 ArthritisBlog

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Old houses have creaky doors, and old bodies have creaky joints. Both are caused by the degradation of the joints. With doors, the lubrication from the hinges may have degraded, or the hinge may be out of alignment, causing the grinding of metal on metal. Our joints, including knees, are similar. The joints degrade, often from misalignment, causing pain and deformation. Unfortunately, we can’t pick up a replacement knee at the local hardware store. The most common condition causing joint degradation is osteoarthritis (OA). It affects around 20% of the global population, 500 million people. 

At its most basic, osteoarthritis is when joints start breaking down. It can affect different joints, but the knees are the most likely to be affected. Cartilage, the strong and flexible tissue that protects your joints and bones, breaks down in osteoarthritis. This causes joint pain, swelling, and loss of function (including range of motion) for the affected joint and may exacerbate comorbidities like diabetes and heart trouble. Women are more likely than men to have osteoarthritis and tend to have more severe symptoms. One major risk factor is obesity, which puts extra stress on joints like the knees and hips. They say age is just a number, but it is also a significant risk factor for OA. The risk of osteoarthritis peaks in a person’s ’60s. The incidence of osteoarthritis has more than doubled in the last 30 years, largely due to the aging global population. A big danger of OA is physical damage caused to the joint affected. This is called a biomechanical abnormality and could be due to a joint that is misaligned or has suffered prolonged abuse. Other risk factors for developing OA include metabolic syndrome, genetics, and trauma, such as torn ligaments.

So what causes osteoarthritis? A lot of things! Cartilage is broken down, but many things may cause this. Outside of the joint, changes in bone, ligament, and muscle can cause stress or degradation. Inside the joint, inflammation, and cell death can lead to failure of the support structures. Inside joints are chondrocytes, the only type of cell in healthy cartilage. They normally spend their whole lives building and maintaining cartilage. They are so dedicated to their job that they become embedded in the structure of cartilage and die in place. With osteoarthritis, stressors (including the risk factors above) can cause chondrocytes to lament the poor work/life balance and start acting irrationally. Some chondrocytes degrade and stop supporting the cartilage (often by dying), and some go into overdrive, becoming larger and further destabilizing our cartilage structure. This causes the cartilage to shrink, and bones can start grinding against each other resulting in joint degradation. This is very painful and can reduce the quality of life dramatically.

What can be done? One of the most important steps is to stop biomechanical abnormalities. Physiotherapy may help fix misalignments. Weight loss, lifestyle changes, and assistive walking devices can help reduce stress on joints. Surgery may be needed to replace or rebuild joints. Unfortunately, there are no approved medications that can cure osteoarthritis. Some anti-inflammatory medications may provide some relief, and are often prescribed. Luckily, the future is looking bright. Researchers are looking at new ways to target osteoarthritis, including next-generation anti-inflammatory medications, metabolic therapies, and even therapies that may rebuild cartilage through medication! In the future, we might not need to pick up a new knee at the hardware store, we might be able to build a new one on-site!

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Goldring, M. B., & Otero, M. (2011). Inflammation in osteoarthritis. Current opinion in rheumatology, 23(5), 471.

Gu, Y. T., Chen, J., Meng, Z. L., Ge, W. Y., Bian, Y. Y., Cheng, S. W., … & Peng, L. (2017). Research progress on osteoarthritis treatment mechanisms. Biomedicine & Pharmacotherapy, 93, 1246-1252.

He, Y., Li, Z., Alexander, P. G., Ocasio-Nieves, B. D., Yocum, L., Lin, H., & Tuan, R. S. (2020). Pathogenesis of osteoarthritis: risk factors, regulatory pathways in chondrocytes, and experimental models. Biology, 9(8), 194.

Poole, A. R., Guilak, F., & Abramson, S. B. (2007). Etiopathogenesis of osteoarthritis. Osteoarthritis: diagnosis and medical/surgical management, 4, 27-49.

Long, H., Liu, Q., Yin, H., Wang, K., Diao, N., Zhang, Y., … & Guo, A. (2022). Prevalence trends of site‐specific osteoarthritis from 1990 to 2019: findings from the Global Burden of Disease Study 2019. Arthritis & Rheumatology, 74(7), 1172-1183.


June 23, 2023 BlogCOVID 19

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I remember a joyous time when the world was young, and we had nothing to fear or worry about except climate change, an artificial intelligence cascade, political strife, and nuclear war. But we didn’t have to worry about COVID, so it was pretty idyllic. Now, over three years later, the biggest worries of COVID are winding down. The WHO declared COVID-19 to no longer be a global health emergency on May 5, 2023, and most places have lifted or lessened restrictions put in place to stem the spread. People have stopped wearing masks, and life seems to be back to normal. But not for everyone. Long COVID has been described as COVID symptoms that last longer than 5 weeks and may last months or longer. It affects around ⅓ of COVID patients, including over 85% of those that had to go to the hospital with severe symptoms. So what is long COVID, who gets it, how does it work, and is there anything to be done about it?

Long COVID, also called long haul COVID, post-COVID syndrome (PCS), or Post-acute sequelae of SARS-CoV-2 infection (PASC), is different from person to person but can be debilitating. During acute (normal) COVID infections, people experience trouble with breathing, joint pain, headache, fatigue, stomach problems, and loss of smell and taste. When I had COVID, my sense of taste was so poor that I started liking Limp Bizkit again. Long COVID symptoms are similar to those of acute COVID. Long-lasting and often crushing fatigue is the most common symptom. I’ve heard anecdotal stories of people who run out of energy just deciding what to eat during the day; it can be very intense. Other symptoms include muscle pain, cognitive impairment such as brain fog, headaches, anxiety, and more.

Around 140 million Americans have had COVID at some point.  A recent study found that long COVID was more common and severe in people infected before the 2021 Omicron variant. Several other risk factors have also been identified. The severity of an acute COVID infection plays a role, as does having 5 or more separate symptoms. These can be mediated by being up to date on COVID vaccines. Long COVID is almost twice as common in women, and the risk is also increased if you are over 50 years old. Other health issues can also affect your chances. Being overweight, having psychiatric disorders, having asthma, and being in “poor general health” are risk factors. Interestingly, having latent Epstein-Barr virus might also increase your chances of developing long COVID.

So how does all of this work? In the acute stage of COVID, the virus spreads rapidly and tries to reproduce. It gains entry into cells using its spike protein to fool a receptor on our cells called ACE2. It then hijacks cell machinery to make copies fast. This may kill the infected cells but also brings in the immune system, which kills the invaders (if we’re lucky) and tends to cause some damage through inflammation. It is thought that long COVID occurs through many mechanisms. The immune system can be disrupted, other infections can take hold, we can experience chronic inflammation, and some body systems can be messed up. Even worse, sometimes organs can be damaged from the infection, and the virus might stick around for a while!

The major organs affected in long COVID can be deduced by looking at the symptoms. Trouble breathing, lung impairment, and low breath capacity may result from chronic inflammation and clotting in the lining of the lungs. Chest pain, irregular heartbeats, heart palpitations, and postural orthostatic tachycardia syndrome (POTS, low blood volume when standing up) are caused by chronic inflammation and cell death in the cardiovascular system. The cardiovascular system has an abundance of ACE2 receptors, meaning it is targeted for direct infection by the COVID virus. Fatigue, trouble sleeping, loss of taste and smell, and cognitive impairment are due to problems with our central nervous system. COVID can cross into the brain and cause inflammation of support cells and clotting (possibly leading to stroke!), and may also affect the brain stem. Nervous system problems affect around ⅓ of people by six months after COVID. There can also be problems with the kidney and pancreas.

So what can we do? Our best bet is to reduce the effects of COVID in the first place – or avoid it altogether. Staying up to date on COVID vaccines and boosters lowers both the severity of acute COVID and the risks of developing long COVID. Continuing to wear masks, washing hands frequently, and being careful around sick people can also help, and staying healthy with diet and exercise can give a leg up. Unfortunately, if you already have long COVID, there are no meds proven to cure it. Treating symptoms is our current best practice. Supplements may help, including B vitamins, iron, magnesium, zinc, and selenium. Multivitamins, mineral supplements, and probiotics have shown preliminary promise, as has the antiviral paxlovid. ANY alteration of medication, including supplements, should be run by your doctor first to ensure they are safe and don’t interact with other conditions or medications you may be on. Non-pharmaceutical solutions may also help. Physical rehabilitation – including pulmonary rehabilitation – as well as mental health and social assistance are vital to making it down the long road of long COVID.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Conti, V., Corbi, G., Sabbatino, F., De Pascale, D., Sellitto, C., Stefanelli, B., … & Filippelli, A. (2023). Long COVID: clinical framing, biomarkers, and therapeutic approaches. Journal of Personalized Medicine, 13(2), 334.

Koc, H. C., Xiao, J., Liu, W., Li, Y., & Chen, G. (2022). Long COVID and its Management. International Journal of Biological Sciences, 18(12), 4768.

Raveendran, A. V., Jayadevan, R., & Sashidharan, S. (2021). Long COVID: an overview. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 15(3), 869-875.

Su, Y., Yuan, D., Chen, D. G., Ng, R. H., Wang, K., Choi, J., … & Heath, J. R. (2022). Multiple early factors anticipate post-acute COVID-19 sequelae. Cell, 185(5), 881-895.

Thaweethai, T., Jolley, S. E., Karlson, E. W., Levitan, E. B., Levy, B., McComsey, G. A., … & Donohue, S. E. (2023). Development of a definition of postacute sequelae of SARS-CoV-2 infection. Jama.


June 16, 2023 BlogCancerPulmonary

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Lung cancer is distressingly common. Worldwide, over 2 million people per year are diagnosed with lung cancer, including over 200,000 in the USA. It is more common in men than women. Lung cancer has many debilitating symptoms, including chest pain, voice changes, weight loss, discomfort, coughing blood, and death. Lung cancer is the highest cause of cancer death in men and the second highest in women, and the outlook gets worse the later in the disease you are diagnosed. So what causes lung cancer, how does it work, and is there anything we can do about it?

Lung cancer has several different risk factors, including low socioeconomic status, HIV, and some lung diseases. According to the National Institute of Health, radiation from atomic bombs can also increase your risk, so avoid atomic bombs. None of these come even close to the explosive risk from smoking, however. Smoking causes lung cancer and increases your risk of developing lung cancer by 20 times versus people who have never smoked. Smoke contains a lot of chemicals. Some of these enter the cells that line the throat and lungs and damage the DNA. Unfortunately, the advent of filtered cigarettes encouraged people to inhale smoke more deeply and increased cancer rates. There are at least 15 genes implicated in the conversion of cells from normal to cancerous. Cigarette smoke, along with air pollution, other carcinogens, and random mutation, can change some of the DNA in these genes and make cells cancerous.

Let’s take a quick second to review what cancer is. Cancer cells are cells that have mutated and act more like independent, single-celled organisms than part of your body. They grow and divide even when they aren’t supposed to, they don’t kill themselves when they outlive their usefulness, and they move around invading other parts of the body. Unlike most single-celled organisms, they are extremely difficult to kill. They are made out of our cells, so most medicines can’t distinguish them, they hide from the immune system, and they convince parts of the body to aid their unrestricted growth. Each of these is an individually unlikely mutation. Still, the damaging effects of carcinogens like cigarette smoke cause many rapid changes in the genes of the cell, increasing the possibility that cells will acquire the necessary mutations. As cells reproduce out of control, they are more likely to mutate and acquire the other necessary mutations to become cancerous. They act independently and take resources, space, and blood from healthy cells, crowding them out and destroying large body systems.

Lung cancer is differentiated from other cancers in an obvious way; the cancerous cells originate in the lungs. Epithelial cells line the lungs and create a protective barrier against environmental hazards. When they are exposed to smoke and other carcinogens this can cause mutations. Medical professionals and researchers have long-differentiated subtypes of lung cancer based on the type of cell that has become cancerous. These are broadly defined as small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). SCLC is very aggressive. It makes up 15% of all cases and has a 5-year survival rate under 10%. This type of lung cancer responds well to chemotherapy but spreads rapidly and is difficult to treat when it has moved extensively. NSCLC makes up the rest of the cases, 85%. There are several subtypes, including squamous cell and large cell carcinoma and adenocarcinoma, the most common type. NSCLC has a multi-step process and can be caught early when cells are replicating or grouping together but are not yet cancerous. This type of lung cancer does not respond as well to chemotherapy. Surgery or surgery combined with chemotherapy is usually recommended.

So what can we do about lung cancer? First and foremost, if you don’t already have lung cancer, make sure you STOP SMOKING. There are programs, medications, and support groups that may help. Non-smokers should also be aware of the risks and symptoms. Beyond that, early detection is critical. Cancer can be localized in only one organ, spread to the lymph nodes, and eventually spread throughout the body. When lung cancer is localized, 5-year survival rates are over 50%. When it has metastasized and spread to other locations, that survival rate drops below 5%. If you are at risk, inquire with your doctor about lung cancer screenings and be vigilant. If you currently have lung cancer, your doctor has the best information available for your specific case. Treatments include surgery and chemotherapy, along with radiation therapy, immunotherapy, laser therapy, stents, and experimental treatments. Though ENCORE Research Group sites do not currently have any lung cancer trials enrolling, we know this is a critical matter for many people. Follow this link for lung cancer clinical trials that may be in your area:

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Schabath, M. B., & Cote, M. L. (2019). Cancer progress and priorities: lung cancer. Cancer epidemiology, biomarkers & prevention, 28(10), 1563-1579. 

NIH National Cancer Institute Non-Small Cell Lung Cancer Treatment (February 17, 2023)

NIH National Cancer Institute Small Cell Lung Cancer Treatment (March 2, 2023)

NIH National Cancer Institute What is Cancer? (October 11, 2021)


June 16, 2023 BlogUncategorized

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It’s hurricane season, which means time to break out the big wave surfboard, your best surf leash, and maybe your evacuation kit. Hurricanes are unusual as natural disasters go because, thanks to modern technology, you can actually prepare for them. The advanced notice and frequent shifts in hurricane paths can lead to some strange behaviors, where we tire of preparing and ignore the warnings. For your safety, we recommend you adhere to all warnings and directives from federal and state agencies regarding a hurricane. We also recommend you plan for what may happen before, during, and after a storm passes. Knowing what to expect may not save all of your things, but it should help keep the important things (including your health!) safe.

Before a storm hits, there is a lot of work to do. Knowing where you will go in the event of an evacuation is very important. It becomes essential if you have pets or special circumstances, as you may be limited in available options. Florida Emergency Management reminds us that the best place to shelter is with friends or family in a safe building outside of the evacuation area. Know where all of your medical information and medicines are located. Plan on what you need to take (don’t forget legal documents!) and what might get left behind (your tote bag collection). Get ready to make preparations for your home, including getting boards for windows if you need them. On the health front, make sure you’re up to date on vaccines, especially flu and tetanus!  A mobile health unit reported that 44% of all visits were requests for vaccines after Hurricane Sandy in 2012.

While a hurricane hits, you should shelter and stay safe. The middle of the storm is when you hope your preparations have paid off, not a time to check on them. Remember that wind is deadly, floods are deadly, and bridges can be deadly too. If you are planning to surf, don’t. Make sure you stay current with weather updates; a storm radio is very helpful here.

You aren’t out of the water just because a storm has passed, literally! Floods can be ongoing, including fresh-water floods from rainfall. Your residence may be damaged, unsafe, or destroyed. Food and healthcare can be difficult to access. Researchers have found that after major hurricanes, healthy foods tend to disappear quickly, while unhealthy alternatives are easily found. They discovered that fruits and vegetables were only found in 50-60% of stores, but sugary sodas were available 90-100% of the time. In addition, healthy options tend to become more expensive. Beyond food, healthcare can become stressful. Many clinics and pharmacies may be closed or restricted. After Hurricane Harvey in Texas, a major hospital had almost 3⁄4 of its beds destroyed, leading to people sleeping on cots. In addition, hospital staff may be exhausted, stressed, and get poor sleep. Remember that they also see their homes destroyed! To top everything off, mental health can be a huge concern. The lead-up to a natural disaster is stressful and anxiety-inducing. The reality of one can be traumatic. Be aware of changes to your mood and attitude; Post-Traumatic Stress Disorder (PTSD) and depression may increase due to trauma or stress. Whatever happens this hurricane season, good preparation and knowledge can help make the unpredictability of storms more manageable.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Chambers, K. A., Husain, I., Chathampally, Y., Vierling, A., Cardenas-Turanzas, M., Cardenas, F., … & Rogg, J. (2020). Impact of Hurricane Harvey on healthcare utilization and emergency department operations. Western journal of emergency medicine, 21(3), 586.

Clay, L. A., Slotter, R., Heath, B., Lange, V., & Colón-Ramos, U. (2023). Capturing disruptions to food availability after disasters: assessing the food environment following Hurricanes Florence and María. Disaster Medicine and Public Health Preparedness, 17, e17.

Florida Division of Emergency Management (n.d.) Important shelter information

Lien, C., Raimo, J., Abramowitz, J., Khanijo, S., Kritharis, A., Mason, C., … & Carney, M. T. (2014). Community healthcare delivery post-Hurricane Sandy: lessons from a mobile health unit. Journal of community health, 39, 599-605.


June 9, 2023 BlogGout

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Gout has been called the “disease of kings.” This is in part because of its ancient association with lavish, relaxed lifestyles. It is also in part because the disease is old enough that kings were common. Gout was first identified around 4,600 years ago in Egypt as an affliction of the joints. Since then, it has moved from the disease of kings to that of the common man. Gout affects over nine million Americans. Its underlying partner in crime, elevated uric acid in the blood (hyperuricemia), affects over 32 million. The disease is most common in middle-aged men. There is a genetic component:   Mexican Americans have a lower risk than White or Black Americans. In this article, we’ll dig into the nitty gritty of what gout is, how it works, and what we can do about it.

On its surface, gout is straightforward. Uric acid forms crystals in the joints, causing arthritic inflammation. Uric acid is commonly and unfairly dismissed as a waste product. It is formed when the body breaks down purines – one of the building blocks of DNA. Purines are found in high levels in the meat and seafood we eat and are also normally produced in the body. Uric acid circulates in our bloodstream, acting as a powerful antioxidant. It cleans things up and is expelled in the urine. Unsurprisingly, urine is where uric acid gets its name. It is protective when it’s in the right places in the body – and at the proper concentrations. When we have too much uric acid, problems begin. At high concentrations, it condenses into sharp, needle-like crystals. These build up in our joints.

Let’s pivot for a moment. Why would uric acid concentrations be high? There are two major mechanisms: either we make too much uric acid, or we don’t get rid of it well enough. Creating too much uric acid is actually relatively rare, making up only 10% of cases. It may be influenced by consuming meat, seafood, and beer. Low exercise, high weight, and metabolic syndrome may contribute, as do some cancers and tumors. The vast majority of cases are from an underexcretion of uric acid. This could be from other medicines, kidney issues, alcohol consumption, or genetics. We can have high concentrations of uric acid in the blood and crystals in the joints without other symptoms. This is called asymptomatic hyperuricemia. A- at the front means “not,” so asymptomatic indicates that there are no symptoms. Hyper- indicates “too much,” uric refers to the uric acid, and -emia means “presence in blood.” Asymptomatic hyperuricemia means there is too much uric acid in the blood, but there are no symptoms.

The first stage of symptoms takes the form of acute gout attacks. This is where we can see intermittent periods of often very painful symptoms. Uric acid crystals accumulate in the joints, and the body needs to get rid of them. Unfortunately, the body can’t just delete things it doesn’t like and make them disappear forever. Instead, the body uses the immune system. Three major types of cells intervene. Macrophages, also called monocytes, are gigantic immune cells that eat things. Genetic and acquired differences between people can result in different skill levels of macrophages. For many people, the problems stop here; macrophages eat the uric acid crystals, and no problems emerge. Likely these people would have asymptomatic hyperuricemia. For an unlucky subset of people, their macrophages can’t deal with the crystals by themselves, so they call for help using powerful chemicals. These calls bring in mast cells, which sound an alert and release other potent chemicals. These chemicals include histamines, cytokines, and hormones which cause inflammation and sometimes destroy the crystals. With an acute gout attack, however, neutrophils are brought in. Neutrophils are big bad destructobots that follow the chemical trails released by macrophages and mast cells. They come in and smash everything rapidly. This leads to an acute or rapid onset gout attack. It hurts a lot, and they clear out some of the uric acid crystals.

After acute gout attacks, it may take a bit for crystals to form again or for an immune response to trigger. This is called the intercritical period and usually has few or no symptoms. Unfortunately, this intercritical period tends to shorten over time, meaning attacks become more frequent.

The fourth and final stage of gout is chronic gout. This is a very painful, destructive stage. Crystals form into big, visible deposits called tophi (plural for tophus). A tophus is a swollen area filled with white and chalky uric acid deposits—these form in cartilage, around joints and tendons, and occasionally in the kidneys. The kidneys are in charge of filtering uric acid from the blood, so this creates an accelerating feedback loop. Tophi formation is accompanied by constant joint inflammation. Inflammation chemicals and tophi formation together erode bone and degrade cartilage. This is very painful and gets worse over time.

So what can be done? The first and most important is diagnosis. Gout is common but can look like other types of arthritis, so getting accurate labs and imaging is vital. If gout is positively identified, a flare-up might be helped using medication. NSAIDs like aspirin or ibuprofen are widely used but may be dangerous if you have kidney failure, which may be a cause of gout. Colchicine is also contraindicated by kidney failure, as well as many other medications. Steroids work well but come with several side effects. Each of these, as well as off-label choices, can also seriously interact with other medications and should be discussed with your doctor before use.

Chronic gout must be treated at a systemic level. Education, such as this exact article you are currently reading, is a significant first step. Consider discussing uricosuric medications in detail with your doctor. Early treatment can be successful, so be vigilant! Lifestyle changes may also help. This includes limiting meat and seafood intake, cutting back on sugary soda and beer, and increasing exercise, vegetables, and possibly vitamin C. Urate-lowering drugs, such as allopurinol, are effective but may come with side effects. These reduce the formation of uric acid or reduce the absorption of it into the bloodstream. By lowering the amount of uric acid in the bloodstream, deposits in joints will start to break down, resulting in painful flare-ups as the uric acid is cleared away. This is painful enough that it is difficult for many patients to stay on their medicine. Hopefully, new medicines will help people break up this painful condition. Though the age of kings is mostly gone, gout can still be a royal pain.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Nuki, G., & Simkin, P. A. (2006). A concise history of gout and hyperuricemia and their treatment. Arthritis research & therapy, 8(1), 1-5.

Ragab, G., Elshahaly, M., & Bardin, T. (2017). Gout: An old disease in new perspective–A review. Journal of advanced research, 8(5), 495-511.

Singh, G., Lingala, B., & Mithal, A. (2019). Gout and hyperuricemia in the USA: prevalence and trends. Rheumatology, 58(12), 2177-2180.


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Have you ever been told not to share a drink with someone? A spoon? A toothbrush? I remember being told if I shared a drink, I might get mono. But what is mono, is it really so bad, what causes it, and what can we do about it?

To start, mono is not the real name. The disease is properly termed infectious mononucleosis. The term mononucleosis was first used in the 1920s to describe how some white blood cells, called lymphocytes, grow and have a central nucleus that resembles a different type of cell, a monocyte. Infectious mononucleosis has a few different causes, but 90% of cases are from a single virus; the Epstein-Barr virus (EBV). EBV is part of the herpes family of viruses. This category includes those that cause chickenpox/shingles and genital herpes, but each are their own separate type and can’t change into another.

EBV and infectious mononucleosis are very common. Per the NIH, 90% of people can expect to get EBV at some point in their lives. Most of the time we are infected as children and have few or no symptoms. It turns out those cootie shots weren’t working after all. The most common symptoms are very generic: fatigue, fever, sore throat, and swollen lymph nodes. These usually resolve within a few weeks. For some people, however, infectious mononucleosis will persist or lead to complications. These include a rash, liver enlargement, and spleen enlargement. Further issues may develop. The liver and spleen may have problems, including a ruptured spleen if the patient engages in intense physical activities. Additionally, EBV is one of the few viruses that can lead to the development of cancer. Even without severe complications, some cases of mono can last for several weeks.

So what is Epstein-Barr virus, and how does it cause problems? EBV is, as the name implies, a virus. These are “organisms at the edge of life” and need to infect host cells to replicate. EBV infects two types of cells, the epithelial cells that line the throat and B lymphocytes, a type of defensive white blood cell. When you are first infected, EBV is in a lytic phase. Lytic is from the Greek for “loosen,” and this stage is where EBV replicates rapidly and causes most of its symptoms. DNA inside the virus is open to being replicated and does so by the thousands and millions. EBV is sneaky, though, because not all of the virus particles do this. Instead, some of these particles bend their DNA into a circle inside of B cells. These B cells don’t “know” they’re infected and go about their business as usual. This is the latent stage. Latent EBV doesn’t reproduce on its own instead, it is copied when a cell splits. Latent EBV presents no symptoms and may even be integrated into our own DNA. Some will die with B cells during normal activity, but we can never be rid of EBV once we catch it. EBV occasionally reactivates and becomes lytic again. Scientists aren’t certain exactly why this happens but think it may be in response to a different infection, where the B cells are called into action. This can increase a person’s risk of developing nasopharyngeal cancer, certain lymphomas, or stomach cancers. Non-cancerous symptoms are caused by swollen, poorly performing B cells and infected cells that line the throat called epithelial cells. 

So what can we do about infectious mononucleosis and EBV in general? Most of the time, we don’t need to do much. Most cases resolve on their own between 2-6 weeks as the body fights and EBV converts into the latent phase. During this time, treating symptoms at home can help: drink fluids, rest, and take over-the-counter medicine for pain and fever – acetaminophen is commonly used. Rest is very important, even if you don’t feel too fatigued. B cells are produced in the spleen, which can get swollen during infection. High-intensity activity, like sports, can cause it to rupture (not good). For more rare or difficult symptoms, your doctor may prescribe corticosteroids or antivirals. Antibiotics do not work, as EBV is not a bacteria. With potentially serious symptoms and EBV staying in your systems lifelong, prevention would be ideal, but is currently impractical due to the lack of a vaccine. There are also no medicines available to rid your body of EBV.  

EBV is spread through saliva and other body fluids, so you can get it from sharing a straw, kissing, or getting an organ transplant. There is no approved vaccine against EBV yet, but we are hoping one may be available in the future. Look out for a clinical trial for EBV vaccines to help quench the kissing disease.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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U.S. Department of Health & Human Services/Centers for Disease Control and Prevention (September 28, 2020). About Epstein-Barr Virus

Luzuriaga K, Sullivan JL. Infectious mononucleosis [published correction appears in N Engl J Med. 2010;363(15):1486]. N Engl J Med. 2010;362(21):1993-2000

Odumade, O. A., Hogquist, K. A., & Balfour Jr, H. H. (2011). Progress and problems in understanding and managing primary Epstein-Barr virus infections. Clinical microbiology reviews, 24(1), 193-209. 

Rybicki, E. (1990). The classification of organisms at the edge of life or problems with virus systematics. South African Journal of Science, 86(4), 182. 


May 26, 2023 BlogLyme Disease

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With warm weather upon us many of us are spending time enjoying nature and sunshine. Out in the wilderness we can enjoy blue skies, green trees, and a pain progressing from skin rash to persistent arthritis. Of course we’re talking about Lyme Disease, a growing concern in the United States. Lyme disease cases top 300,000 per year in the US, mostly in the Northeast, and affects mostly children and middle-aged Americans. Lyme disease is spread by one of nature’s grossest bugs, the tick. In case you are lucky enough to be unfamiliar with ticks, they are little arachnids (like spiders) except instead of skittering around and eating flies they hang out in long grasses and grab onto you as you walk by. Then they burrow into your skin and eat your blood while transmitting painful bacteria to your bloodstream.

In Blacklegged ticks, one of those bacteria may be Borrelia. This is a little fusilli-looking bacteria with a long, twisted body and some pretty neat tricks. It has little paddles on the outside called flagella that let it swim around inside your body, aiming for nutrients and avoiding alcohol and other things. Borrelia bacteria live in both ticks and mammals, and change their gene expression and what the surface of their body looks like depending on where they are. They wouldn’t be effective invaders, however, if it weren’t for the ticks. Ticks stab a hole through the skin, which lets Borrelia invade. Tick saliva stops clotting and suppresses our immune system. Borrelia bacteria attach bits of tick saliva to their bodies to help evade detection. This makes it extra difficult for the immune system to fight.

The bacteria themselves don’t produce toxins or dangerous proteins. When Borrelia bacteria successfully take hold, the immune system uses its major immune weapon: inflammation. Borrelia is difficult to fight, probably because of the tick saliva on the outside. This can make the fight long and painful for us. We call the disease Lyme, after the small coastal town in Connecticut where it was first documented in the 1970s. 

Lyme disease has three main stages. The early stage is characterized by skin problems around the bite location accompanied with flu-like symptoms. If we are lucky, our immune system wins here and the side effects end. However, many people experience a middle stage of headaches, stiffness, and other problems as the bacteria gets into the nerves and heart. If the bacteria has still evaded the immune system after this, it may hide in the joints, causing arthritis and long-term problems for months or years. 

So what can we do about Lyme disease? First and foremost, don’t get bitten by ticks! Avoid long grasses and wear long pants, tucking them into your sock or shoes helps to avoid these miniature monsters. Tick repellant also helps. Remove any ticks you find early! It takes around 36 hours for a tick to transmit Lyme disease to you, so being vigilant and removing ticks is critical. You need to remove the entire tick, including the head which is buried in your skin. After you remove a tick, you can kill it by drowning it in rubbing alcohol.  It’s not recommended to squash the tick as it could further expose you to disease. 

If you are unfortunate enough to be bitten by an infected tick, medical help might be needed. The symptoms are caused by our immune system failing to win the fight against Lyme disease. Antibiotics boost our immune response and are highly effective against Lyme if administered fast enough. In later stages antibiotics are still effective but may not clear all symptoms. We believe prevention is the best medicine. An effective Lyme disease vaccine would boost our immune response and prevent Borrelia bacteria from gaining the upper hand. There actually was an effective vaccine in the 1990s, but misconceptions on how Lyme was diagnosed and how the disease worked – along with poor sales – caused the vaccine to be pulled from the market. Related vaccines have been available for dogs for decades but, frustratingly, not people. Perhaps with better education and a new generation of vaccines we can keep Lyme disease from souring our walks in the woods.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Aronowitz, R. A. (2012). The rise and fall of the lyme disease vaccines: a cautionary tale for risk interventions in American medicine and public health. The Milbank Quarterly, 90(2), 250-277. 

Steere, A. C., Strle, F., Wormser, G. P., Hu, L. T., Branda, J. A., Hovius, J. W., … & Mead, P. S. (2016). Lyme borreliosis. Nature reviews Disease primers, 2(1), 1-19.


May 19, 2023 BlogClinical Trials

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May 20th is Clinical Trials Day. Of course, we are biased and think it should become a national holiday, but until that day arrives, let’s celebrate the day by studying a clinical trial designed by our founder and CEO, Dr. Michael J. Koren. The trial we will study, published in 2006, was called the Aggressive Lipid-Lowering Initiation Abates New Cardiac Events, or ALLIANCE. In case you are unaware, the sponsors of clinical trials are all very clever and enjoy coming up with neat acronyms.

ALLIANCE was a large, 16-center study conducted around the turn of the millennium and enrolled 2,442 patients. All patients had coronary heart disease – blockage of a major blood vessel to the heart. The study was designed to determine the difference in outcomes for patients with coronary heart disease when taking atorvastatin, marketed as Lipitor, at a full dose of 80 mg versus usual treatment with statins or other cholesterol drugs. Patients treated with high dose atorvastatin were monitored to keep their LDL less than 80 mg/dL.

Outcomes in a clinical trial are the variables measured: what researchers are monitoring for change. Typical outcomes will include things like changes in symptoms, cure, or death. The ALLIANCE patients had coronary heart disease, so the main outcomes being monitored were: 

  • low-density lipoprotein (LDL – the “bad” cholesterol)
  • heart-related hospitalization
  • heart attack
  • death due to heart attack

This study was significant because it looked at the difference between medications given in a clinical trial setting and “usual care” for people enrolled in managed care health plans (they all had insurance).

The study results were, frankly, amazing. In the “usual care” group, patients saw their average LDL levels drop by over 23 mg/dL, a significant decrease. These are nice results, but the “more aggressively treated” group did even better. They saw LDL levels drop by more than 34 mg/dL, a 50% greater reduction! Furthermore, the aggressive treatment led to 17% fewer events, including a whopping 47% fewer heart attacks! Needless to say, the aggressive atorvastatin treatment was a resounding success.

The stated goal of the study was to discover the effectiveness of the investigational medication, but the ALLIANCE study also measured the difference between clinical trials and standard care. The aggressive treatment group received clinical-trial-level care with specialist medical professionals and frequent check-ins. Patients had a lot of contact, and researchers were interested in any and all health changes. The study showed great success for the sponsor. It helped make Lipitor the best-selling medication of all time (recently broken by Humira). It gave us solid evidence that the clinical trial process doesn’t just lead to new potential medications but also potentially better health outcomes for patients.

Thanks, Dr. Koren, for taking leadership of this trial and the ENCORE Research Group.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Koren, M. J., Hunninghake, D. B., & Alliance Investigators. (2004). Clinical outcomes in managed-care patients with coronary heart disease treated aggressively in lipid-lowering disease management clinics: the alliance study. Journal of the American College of Cardiology, 44(9), 1772-1779.


May 15, 2023 BlogBlood Pressure

Sometimes when I’m desperately trying to fall asleep I instead think of all the things that might kill me. Alligators, drunk drivers, hurricanes, and running out of cookies usually top the list. Do you know what doesn’t top the list? High blood pressure. It really should though. High blood pressure is a leading preventable cause of premature death, affecting well over a billion people worldwide and causing upwards of 9 million deaths a year. Maybe the alligators can chew on those facts for a while. So what is high blood pressure, why is it such a big deal, why do we get it, and what can we do?

High blood pressure is exactly what it sounds like; when the blood in your arteries is being forced through more strongly than normal. The medical name for high blood pressure is hypertension. Hyper– means over or above, and -tension, in this case, indicates the stress of your arteries. Hypertension is excessive stress on your arteries.  Blood pressure can be split into two numbers, systolic and diastolic. These refer to the action of the heart, where systolic is the contracted, pumping blood pressure, and diastolic is the relaxed blood pressure. When you get your blood pressure checked, these are reported as two numbers “over” each other. A reading of 140/90 mmHg or higher is high blood pressure, but there is an increased risk of complications with blood pressure above 120/80 mmHg.

High blood pressure is particularly dangerous. It is easy to see why: the bloodstream is how we deliver oxygen to the cells, and it touches every cell in the entire body. Two of the biggest dangers with elevated blood pressure are ischemic heart disease and stroke, conditions where the blood supply doesn’t reach the heart or brain. High blood pressure can also cause brain bleeds, chronic kidney damage, and other types of heart damage. All of these organs are vital to our survival, so a condition that potentially damages all of them is life-threatening. 

What are the causes of high blood pressure? High blood pressure is calculated the same as in any pipe at its most basic level. The amount of blood coming out of the heart is counteracted by the resistance from the arteries. More output or more resistance makes blood pressure rise. High blood pressure on its own isn’t bad, it’s adaptive for critical situations. When we see a lion and it charges us, we become stressed and initiate the sympathetic nervous system, also known as fight, flight, and freeze. Part of this system’s job is to constrict blood vessels and raise the heart rate to deliver large amounts of oxygen to cells. We see damage when we have high blood pressure for long amounts of time. Some body systems that cause prolonged elevations in blood pressure are:

  • Kidneys regulate the volume of blood in veins, using urine to get rid of extra fluid
  • Blood vessels can constrict and dilate to regulate resistance. They can also stiffen, lose muscle, and become inflamed or damaged
  • The brain activates the kidneys and blood vessels. Constant stress or disorders can keep them active for too long and keep blood pressure high
  • Inflammation is caused by inflammatory cells and hormones, including angiotensin, which can accumulate (sometimes due to salt) in blood vessels and the kidney
  • Several other systems and mechanisms are at play, including genetics, the microbiome, and reactive oxidative stress

These are the major players in primary or essential hypertension. Secondary hypertension is caused by another identifiable disease, like kidney disease.

So what can we do? Some outcomes depend on things we can’t easily change, like access to quality healthcare and blood pressure medication. Many lifestyle options can be changed to improve our blood pressure:

  • Relax! Lowering stress has many positive effects, including lowering blood pressure as well as the feelings of not being stressed (being not stressed is recommended).
  • Alcohol has mixed results. Consuming a small amount corresponds to lower blood pressure, but there isn’t great evidence of it causing lower blood pressure. Avoid excessive drinking.
  • Physical activity can have big effects. Even a daily light walk can reduce hypertension.
  • Obesity has a direct, linear relationship with blood pressure. For each kilogram (~2.2 pounds) you lose, blood pressure decreases by around 1 mmHg.
  • Diet can be hard to change, but can also affect blood pressure.
    • Avoid: red and processed meats, sweetened foods, saturated and trans fats
    • Consider eating: fruits and veggies, nuts and seeds, lean dairy, vegetarian and mediterranean diets
  • Sodium (salt) intake matters:  salt directly affects how much fluid is in the bloodstream. The average person consumes almost 4000 mg of sodium per day, the recommended amount is under 2300 mg. Though lowering sodium decreases blood pressure, studies are mixed with regard to heart disease outcomes
  • Potassium acts in direct opposition to sodium. Increasing the amount of potassium can lower blood pressure – don’t go too crazy, though! Extreme amounts can slow or stop the heart (stopping your heart is not recommended).

Even though we have good evidence for lifestyle changes lowering blood pressure, the biggest difference between countries in terms of controlling blood pressure is access to medicine. Blood pressure medicines have saved countless lives and helped stem the blood tide of hypertension. There are several types of blood pressure medicines on the market. Diuretics get rid of sodium and water in the blood. Angiotensin-converting-enzyme (ACE) inhibitors and Angiotensin-receptor blockers (ARB) help ease inflammation, relax the blood vessels, and keep them from constricting. Calcium channel blockers reduce heart rate. These all have side effects, but the biggest challenge with them is that they are daily oral medications, which can be forgotten, missed, or hard to adhere to. Longer-term solutions are in clinical trials and may be available to you if you qualify. So don’t sleep on your high blood pressure. Check with your local ENCORE Research office to see what studies are enrolling. See ya’ later, alligators!

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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Harrison, D. G., Coffman, T. M., & Wilcox, C. S. (2021). Pathophysiology of hypertension: the mosaic theory and beyond. Circulation research, 128(7), 847-863. 

Lifton, R. P., Gharavi, A. G., & Geller, D. S. (2001). Molecular mechanisms of human hypertension. Cell, 104(4), 545-556.

Mills, K. T., Stefanescu, A., & He, J. (2020). The global epidemiology of hypertension. Nature Reviews Nephrology, 16(4), 223-237.


Clinical research is vital in developing knowledge geared toward improving future health practices. It is often the only feasible solution to medical conditions where standard treatment has failed. Research can be groundbreaking and progressive but study populations lack diversity, especially regarding demographics such as race, ethnicity, age, and sex. Which begs the question: “Why is diversity important to research?” Simply put, various subsets of people can process the same medication differently. Through the clinical research process (guided by strict safety protocols), researchers gather data on how participants experience the same investigational product (IP). Suppose a clinical trial includes people from many different age, gender, and racial/ethnic groups. In that case, researchers will then have data on how several groups of people respond to the same product based on those differences. When these new products reach the market, doctors will know what works best, what doesn’t, and for whom based on those findings. Through research, doctors learned that it is best to prescribe particular medications based on patients’ ethnicity/racial background when treating hypertension. As we move forward, the clinical research community thrives on increasing the participation of all minority age, gender, and  racial/ethnic groups to improve the safety profile of medical products. The US government must lead this effort through legislation.

At ENCORE, we recognize that to benefit the communities we serve, we must take the steps necessary to best represent ALL in the trials we conduct. However, this requires overcoming numerous challenges, including long-standing mistrust and economic barriers which prevent minority groups from accessing and participating in research.

Even though clinical trials have evolved from historically unethical practices involving minority racial groups to a transparent process where participant safety and protection are paramount, there is still a significant lack of trust on the part of potential study subjects. Especially for those who are dubious, establishing credibility and integrity within clinical research practice is crucial to growing minority group participation. We believe that physicians, especially those who serve ethnically/racially variant communities, play a significant role in achieving Diversity in clinical trials by bridging trust between researchers and minority participants. ENCORE physicians have dedicated their efforts to working alongside primary care physicians and specialists who serve these communities; to provide them with research material relevant to their practice. Doctors then have the information to make informed recommendations on whether a particular clinical trial is appropriate for their patients. Not only are people more likely to be confident in the recommendations coming from their doctors, but doctors find themselves better prepared to help patients who have failed on current therapeutic approaches.

Unlike when seeking intervention via traditional means, economic hindrance isn’t a preventative factor when one chooses to participate in clinical research. Healthcare costs are a significant burden to many; however, all of the investigational medical products available here at ENCORE cost our patients nothing. All study-related materials, evaluations, blood tests, and imaging are done for free. Study participants will never be billed.  Sponsors such as pharmaceutical companies, governments, and foundations fund medical research through study grants. Grants provide the funding to conduct studies at local research sites, so the cost is not transferred to the volunteers. This allows people experiencing financial constraints or without health insurance the opportunity to receive potentially groundbreaking medical treatment at no cost to them. A small monetary compensation is often provided for participants’ time and inconvenience associated with participating in a clinical study. Payment is kept within a reasonable amount to prevent enticement and undue influence on participants.

Despite these steps, we recognize that much more needs to be done to garner diverse research participants in all our trials. Appropriately representing Diversity in clinical trials is an ethical and medical obligation that bounds all stakeholders. Critical players like research sponsors, investigators, referring physicians, coordinators, recruiters, and patients must work collaboratively to achieve this goal. A multi-level stakeholder approach can be more successful than one which addresses a single barrier or involves individual stakeholders. As a research facility, our responsibility in achieving increased Diversity amongst trial participants will build on our investments towards nurturing long-standing relationships. These relationships are between sponsors, community members, our diverse pool of staff and physicians, and our commitment to engagement and learning from diverse patient groups. With this approach, we are confident that trial enrollment will continue to become more diverse and result in a more accurate representation of the people that products are intended to treat.

Albertha V. Lalljie, MBBS, MPH


Alzheimer’s Disease is a devastating brain disorder that gets worse over time. Early onset Alzheimer’s occurs before age 65. Most early Alzheimer patients develop symptoms in their 40s and 50s with some particularly aggressive forms starting as early as the late 20s. Any form of Alzheimer’s is a tragedy, but early onset Alzheimer’s can be particularly cruel.

We do not know exactly what causes Alzheimer’s Disease. We do know that there are genetic and environmental causes that seem to mix with a high amount of randomness. We also know that some diseases exist alongside Alzheimer’s and may be risk factors. These include diabetes, hypertension, cholesterol issues, and metabolic syndrome.

Alzheimer’s produces a number of terrible symptoms:

  • Memory Loss
    • The most iconic symptom, the brain appears unable to form new memories.
  • Executive function changes
    • High level processing like judgment, mood and personality, and completing tasks
  • Language difficulties
  • Visual and spatial troubles

Together, these symptoms combine into cognitive decline, loss of independence, and death. Early onset Alzheimer’s can have these symptoms, but is also more aggressive with shorter lifespan and larger changes in the brain. Interestingly, up to a quarter of patients with early Alzheimer’s may develop cognitive decline without memory loss. This can present as trouble with:

  • Movement
  • The Visual system
  • Speaking
  • Numbers

We are still uncertain how genetic and environmental conditions translate into Alzheimer’s but the leading theory involves an accumulation of protein in the brain called amyloid plaques and tau tangles. Amyloid plaques are a buildup of a protein between neurons. It is thought that this buildup somehow causes the accumulation of tau inside of neurons. Tau is another protein that folds incorrectly and tangles up inside of neurons, leading to their eventual death.

It has been very difficult to study the root causes of Alzheimer’s. This is in large part because of the inconsistency of who gets it. This also means that creating medications for Alzheimer’s has been difficult. One of the most promising avenues for study has been targeting amyloid plaques for disposal by the immune system. With luck, research can pin down a treatment to help slow or even stop the march of early Alzheimer’s.

If you would like to be screened for Alzheimer’s, a free Memory Assessment is available at the Jacksonville Center for Clinical Research at 4085 University Boulevard, South, Suite 1, Jacksonville, FL 32216.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA


Ayodele, T., Rogaeva, E., Kurup, J. T., Beecham, G., & Reitz, C. (2021). Early-onset Alzheimer’s disease: what is missing in research?. Current neurology and neuroscience reports, 21, 1-10.

Mintun, M. A., Lo, A. C., Duggan Evans, C., Wessels, A. M., Ardayfio, P. A., Andersen, S. W., … & Skovronsky, D. M. (2021). Donanemab in early Alzheimer’s disease. New England Journal of Medicine, 384(18), 1691-1704.

Reitz, C., Brayne, C., & Mayeux, R. (2011). Epidemiology of Alzheimer disease. Nature Reviews Neurology, 7(3), 137-152.


May 3, 2023 BlogDiabetes

Sugars are sweet, tasty, and disastrous for your health in large quantities. They are also ubiquitous in modern society. We find them added to everything from salad dressings, drinks, bread, even peanut butter! Sugars and other carbohydrates make up over half of the calories consumed by Americans. Carbohydrates are broken down into a simple sugar called glucose and delivered around the body after eating. This can be surprisingly tricky. Too little glucose and cells can’t function. Too much and it gets converted to fat and damages the metabolic system, heart, and bloodstream. Type 1 Diabetes is a condition where the body doesn’t produce enough insulin. Type 2 Diabetes is more complicated; the body doesn’t respond to raised glucose in the bloodstream properly. A big culprit for failure is when insulin isn’t released well. To remedy this a class of drugs called glucagon-like peptide-1 (GLP-1) agonists have been developed.  Agonist in this case means the medication has a similar function to the natural hormone. The opposite is an antagonist, which acts in opposition to them. GLP-1 medicines include Trulicity, Mounjaro, and semaglutide / Ozempic. In this article, we will review how insulin works, how GLP-1 works on the cellular level, and what GLP-1 medicines do to the body.

Insulin is the main hormone that tells your body how to process sugar. Before we can understand how GLP-1 works, we need to understand the healthy release of insulin. This starts in the pancreas, an organ near our gut. The pancreas is filled with many types of cells called islet cells. These are responsible for regulating the balance of glucose in our bloodstream. Two major types are alpha and beta islet cells. Alpha islet cells produce glucagon and GLP-1. Glucagon tells the liver to increase blood sugar when you need energy. Beta cells make insulin and amylin, which help lower blood sugar. Alpha and beta islet cells work in opposition. They keep each other in check and our blood sugar levels just right. In Type 1 Diabetes, alpha cells may be dysfunctional and beta cells don’t exist or get destroyed. WIth Type 2 Diabetes, problems can occur when beta cells don’t function properly. Beta cells make insulin and release it in two stages. When these cells detect high blood glucose, they “trigger” and release insulin right away. This short response lasts 10-20 minutes, but is still several steps long. After triggering, a complicated “amplifying” pathway turns on to produce and release more insulin. Together this is powerful, slow, complex and has many potential points of failure. Beta cells are vital, and when they fail it often signals the transition from obesity to Type 2 Diabetes.

GLP-1 is like a shortcut for beta cells. When it is detected the triggering response is primed and the cells are ready to release insulin as soon as glucose is detected. This pathway bypasses a lot of the complicated cellular machinery that is damaged in diabetic patients. The upshot is that GLP-1 stimulates insulin release from islet cells. An added benefit is that the insulin is only released in the presence of elevated glucose. This is good because you don’t release too much insulin, which can be dangerous. GLP-1 medications also last much longer in the body than natural GLP-1, giving longer-term effects which can last for up to a day!

Now we know a little of how GLP-1 acts inside our cells, but what effects does this have on the body? Many, and widespread, it turns out! GLP-1 affects cells all over the body. The three biggest effects are decreased blood glucose, appetite suppression, and weight loss.

Insulin decreases blood glucose, and GLP-1 increases the response to glucose. But GLP-1 medications have a secret extra benefit. Remember that alpha and beta cells work opposite each other. Normally when blood sugar is low, we release GLP-1 from our pancreas along with glucagon. Glucagon is very useful, and one of its uses is to stimulate the liver into producing more blood sugar. GLP-1 medications suppress glucagon production and the liver stays quiet. The pancreas still releases insulin, but the liver produces 45% less glucose!

GLP-1 affects two of the biggest portions our appetite: our stomach and our brain. It slows the absorption of nutrients from the stomach, a process called gastroparesis. Food – and the glucose inside – is retained in the stomach and gut instead of the bloodstream. GLP-1 can also affect the brain. It can cross from the bloodstream into the brain, but also affect the vagus nerve – the major nerve connecting the brain and gut. Here it acts on the hypothalamus, suppressing the appetite and giving you feelings of being full. With the stomach slowing down and the brain signaling that it’s full, we tend to eat less.

Combined, lower blood sugar and appetite can have serious effects on weight. This can be a big benefit of GLP-1 medications. Weight loss is linked with better outcomes for Type 2 Diabetes patients. Getting to a healthy weight is also good for the heart, joints, liver, and so on. Significant weight loss has been seen with GLP-1. Let’s not sugar-coat this though; not all weight loss is created equal. Ideally we’d cut our body fat while maintaining – or building – our muscle. This is especially true with diabetes, as skeletal muscle uses up extra glucose. Unfortunately, when we lose weight through diet restriction we lose more than just fat. This is true of gastric surgery, diet-induced weight loss, and GLP-1 medications. In GLP-1 medication studies, 20-50% of the weight lost is things other than fat – including muscle. Studies vary widely. The type of GLP-1 medication and other medications patients are taking may affect this. The best way to offset this is through building muscle with exercise!

GLP-1 medications are truly amazing. They increase insulin response, lower blood glucose, suppress appetite, and lead to weight loss. It’s not all sugar and spice, however. Side effects can be rough, including vomiting and diarrhea. Additionally, meds can’t do it alone. When taking GLP-1 medications, the goal should still be to create an environment conducive to healthy living. Limiting carbohydrate intake is one critical step. Exercising is another. When fighting weight loss, victory is very sweet, but our diets shouldn’t be!

Written By Benton Lowey-Ball, BS Behavioral Neuroscience


Campbell, J. E., & Newgard, C. B. (2021). Mechanisms controlling pancreatic islet cell function in insulin secretion. Nature reviews Molecular cell biology, 22(2), 142-158.

Cervera, A., Wajcberg, E., Sriwijitkamol, A., Fernandez, M., Zuo, P., Triplitt, C., … & Cersosimo, E. (2008). Mechanism of action of exenatide to reduce postprandial hyperglycemia in type 2 diabetes. American Journal of Physiology-Endocrinology and Metabolism, 294(5), E846-E852.

Cohen, E., Cragg, M., deFonseka, J., Hite, A., Rosenberg, M., & Zhou, B. (2015). Statistical review of US macronutrient consumption data, 1965–2011: Americans have been following dietary guidelines, coincident with the rise in obesity. Nutrition, 31(5), 727-732.

Drucker, D. J. (2018). Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell metabolism, 27(4), 740-756.

Dungan, K., & DeSantis, A. (2013). Glucagon-like peptide-1-based therapies for the treatment of type 2 diabetes mellitus.

Baggio, L. L., & Drucker, D. J. (2014). Glucagon-like peptide-1 receptors in the brain: controlling food intake and body weight. The Journal of clinical investigation, 124(10), 4223-4226.

Sargeant, J. A., Henson, J., King, J. A., Yates, T., Khunti, K., & Davies, M. J. (2019). A review of the effects of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors on lean body mass in humans. Endocrinology and Metabolism, 34(3), 247-262.


April 24, 2023 AsthmaBlog

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They say in stressful situations you should take a breath and calm down, but what if you literally can’t? Asthma is a common disease that affects around 25 million Americans. It results in several million ER visits and hundreds of thousands of hospitalizations yearly. It can also get worse over time. So what is asthma, how does it cause trouble, and what can we do about it? Take a deep breath as we dive in.

To start, asthma is a medley of several related conditions that can be divided in many ways. Into allergic and non-allergic, eosinophilic and neutrophilic, adult onset, asthma with persistent airflow, asthma with obesity, and severe asthma. Several of these categories overlap and make a big mess of everything. The common threads between all types of asthma are the symptoms. Asthma is defined by its symptoms:

  • Wheezing
  • Shortness of breath
  • Chest tightness
  • Cough

A collection of symptoms are needed to diagnose asthma; a single symptom isn’t enough. Symptoms are also variable, getting worse at night, in the morning, or in response to a stimulus. Stimuli include irritants, allergens, exercise, infection, and weather. A pattern of symptoms in response to irritants may lead to an asthma diagnosis.

Our need to breathe makes this a dangerous disease. Asthma symptoms are variable, but they all involve the airway. The airway is affected in three ways: inflammation, bronchial hyperresponsiveness, and structural remodeling.

Inflammation is complicated. In allergic asthma, immune cells respond to dust, pollen, and other airborne items. These are detected by defense cells in our windpipe which mistake them as dangerous. Immune cells act quickly to try and kill the “invaders”. In asthma, the big guns are brought in. Eosinophils and neutrophils are like a bazooka: highly effective at killing invaders, but can cause area-of-effect damage when used improperly. Eosinophils cause bronchial hyperresponsiveness, impaired throat function, inflammation, phlegm, and long-term allergen sensitivity. Eosinophils can also occur in non-allergic asthma. They might get involved because of genetic predisposition, polyps, viruses, and fungi. Neutrophils are similar to eosinophils in causing inflammation, but cause more severe symptoms. They generally need more irritants to activate and can be triggered by tobacco smoke, pollutants, microbes, and obesity. You can have eosinophilic or neutrophilic asthma, or both at the same time. Whatever the flavor, inflammation is the result.

One of the effects of inflammation from eosinophils and neutrophils in the throat is bronchial hyperresponsiveness. Bronchial refers to the windpipe, hyper- means abnormally high, and responsiveness in this case refers to how narrow the throat gets. Bronchial hyperresponsiveness is an abnormally high constriction of the throat in response to stimuli, such as irritants. The responsiveness is temporary, leading to the characteristic variability in symptoms. Long term inflammation can cause persistent damage, called airway structural remodeling. This is when the cells of the airway grow in different ways. The walls of the airway are thickened, there is more muscle mass in the throat, the throat contracts harder, and the airway is reduced in size. This is a more permanent change in our throat, making this a long-term effect.

The symptoms are very constricting, is there relief? Yes! Eosinophils respond well to anti-inflammatory medicines known as corticosteroids, like cortisone. These are used for both long-term control and for asthma attacks. Unfortunately, these don’t work on neutrophils, and can actually prolong their lifespan, exacerbating symptoms. Bronchodilators open airways and reduce swelling. Allergy-induced asthma may also be alleviated using allergy shots, tablets, or medications. Newer medicines include monoclonal antibodies that target allergens or specific cells for destruction. Medicines that directly target eosinophils or neutrophils might provide a deeper relief from asthma. Don’t hold your breath, but keep an eye out for new research opportunities!

Written By Benton Lowey-Ball, BS Behavioral Neuroscience


Cockcroft, D. W., & Davis, B. E. (2006). Mechanisms of airway hyperresponsiveness. Journal of allergy and clinical immunology, 118(3), 551-559.

Global Initiative for Asthma. (2000). Global Strategy for Asthma Management and Prevention updated 2022.

Pate, C. A., Zahran, H. S., Qin, X., Johnson, C., Hummelman, E., & Malilay, J. (2021). Asthma surveillance—United States, 2006–2018. MMWR Surveillance Summaries, 70(5), 1. 

Pelaia, G., Vatrella, A., Busceti, M. T., Gallelli, L., Calabrese, C., Terracciano, R., & Maselli, R. (2015). Cellular mechanisms underlying eosinophilic and neutrophilic airway inflammation in asthma. Mediators of inflammation, 2015.


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All diseases are different. Some are immediately apparent, like a heart attack. Some have the gall to hide undetected for years. This might sound nice, but the damage that can be done while undetected gets worse over time. Primary Biliary [billy-ur-ee] Cholangitis [kow-luhn-jai-tuhs] (PBC) destroys our bile ducts, often without our knowledge until other parts of the body are damaged.

PBC is a somewhat rare disease, affecting 1 in every 3-4 thousand people, so around 100,000 Americans. Of these, around 90% of cases are in women. Most patients with PBC are diagnosed in their 50’s and 60’s, though the disease may start as young as 30. On its own, PBC may not have many symptoms, but leads to debilitating conditions of the liver such as cirrhosis, failure, and cancer. It also causes downstream damage across the body such as metabolic bone disease and malabsorption of nutrients.

So what is Primary Biliary Cholangitis? There are clues in the name. The biliary system carries bile, a digestive fluid produced in the liver and sent to the gallbladder and intestines. Chol- also means bile, ang- means vessel, and -itis means inflamed. Cholangitis means the tubes that carry bile from the liver (called bile ducts) are inflamed. This disease is termed “primary” because it is the direct cause of inflammation and damage. A “secondary” disease is one caused by previous infection or disease; bile ducts can also be damaged by chemotherapy or surgical trauma to the lower bile system, for example. Altogether, primary biliary cholangitis is a disease that directly causes inflammation and damage to bile ducts.

There are many bile ducts and many kinds of bile ducts, with the smallest being ultra-fine and located throughout the liver. These collect digestive fluid and transport them to ever bigger ducts to be stored in the gallbladder and sent to the digestive tract. In PBC, these small ducts are destroyed. A good rule of thumb is that when digestive fluid isn’t going to the digestive tract there may be problems. The buildup of bile damages the liver over time. Bile is critical for digesting fats and many vitamins. When bile fails to be de-livered to the digestive tract we may suffer malnutrition and fatigue.

Most PBC patients are symptom-free but several experience debilitating symptoms, especially at later stages. Major symptoms are fatigue and itching (called pruritus). Jaundice, skin pigmentation, and fat buildup under the skin are other potential problems. Since so many people have no symptoms, or vague ones that can be attributed to other things, PBC is detected by looking at the blood.  The primary evidence is the presence of antimitochondrial antibodies. These are immune system proteins that target mitochondria, the powerhouse of the cell.

Increased antimitochondrial antibodies give us a good clue as to the true nature of primary biliary cholangitis. PBC is an autoimmune disorder – our immune system attacking healthy cells in the body. The cells at hand are the ones that make up the bile ducts. How this happens is complicated, and not fully known. We do know that there is a strong genetic component. X marks the spot in this case; since it affects mostly women, the X chromosome is a good candidate for where the trouble lies. The genetics aren’t enough, however.

PBC requires an environmental component. Environmental in this case means anything that started outside of our own bodies and got in. Environmental risks include things that aren’t alive, like nail polish, hair dye, cigarettes, and toxic waste. Here at ENCORE Research Group we recommend avoiding toxic waste sites whenever possible. Living environmental factors include bacteria that degrade the immune system. This is a slow process. The bile duct cells become affected and some die. As they die they present parts of their mitochondria to the immune system, which learns to attack them. Eventually, the immune system starts attacking bile duct cells directly, causing scarring and cell death. This causes the eventual collapse of the small bile ducts.

So what can be done? We can’t fight the underlying autoimmune disease yet. Current treatments are aimed at restoring the function of bile. The major medication is ursodeoxycholic [er-sudi-oxy-cholic] acid (UDCA), as synthetic bile acid. This only helps 60% of the time, and may be supplemented with obeticholic [oh-bet-i-colic] acid (OCA) to aid in the process. Neither of these help with symptoms. Itching may be treated with creams and cold water, and fatigue is treated with exercise, occupational, and physical therapy. Sicca, meaning dry eyes and mouth, is also a symptom, and is treated with artificial tears and saliva, or medications that increase these. Future treatments would target the underlying immune response or the associated inflammation. Either way, a treatment that stops damage is needed to help sufferers of PBC – and to keep those that aren’t suffering feeling well!

Written By Benton Lowey-Ball, BS Behavioral Neuroscience


Dauphinee, J. A., & Sinclair, J. C. (1949). Primary biliary cirrhosis. Canadian Medical Association Journal, 61(1), 1.

Lleo, A., Invernizzi, P., Mackay, I. R., Prince, H., Zhong, R. Q., & Gershwin, M. E. (2008). Etiopathogenesis of primary biliary cirrhosis. World journal of gastroenterology: WJG, 14(21), 3328.

Onofrio, F. Q., Hirschfield, G. M., & Gulamhusein, A. F. (2019). A practical review of primary biliary cholangitis for the gastroenterologist. Gastroenterology & hepatology, 15(3), 145.

Ruemmele, P., Hofstaedter, F., & Gelbmann, C. M. (2009). Secondary sclerosing cholangitis. Nature Reviews Gastroenterology & Hepatology, 6(5), 287-295.

Strazzabosco, M., & Fabris, L. (2008). Functional anatomy of normal bile ducts. The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology: Advances in Integrative Anatomy and Evolutionary Biology, 291(6), 653-660.


April 11, 2023 BlogClinical Trials

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Sticks and stones may break my bones, but words can never hurt me. But what if words could hurt you? Meet the nocebo effect, the evil twin of placebo. The nocebo effect is an increase in negative symptoms in response to patient expectations. This occurs in both clinical trials and normal clinical care. In clinical trials, this frequently presents as adverse events occurring during a placebo administration (such as a sugar pill instead of a blood pressure med), but it’s important to note that nothing needs to be administered for an increase in symptoms. Nocebo effects may sound like no big deal, but symptoms can be significant. In clinical trials, 4-26% of patients who discontinue medication do so because of nocebo reactions.  Unfortunately this burden isn’t evenly spread. Women experience an outsized effect, as do those suffering from certain psychiatric illnesses, such as anxiety and depression. Furthermore, both pessimistic and type A individuals experience higher rates of nocebo effect.

So how does it work, and are the effects real? Nocebo effects are due to our own expectations. When a doctor, nurse, or researcher states the potential side effects for a medication or procedure, patients are more likely to experience those effects. This has been shown in several anecdotal settings, but also in multiple research studies. During the COVID clinical trials, patients were reporting serious side effects that tracked popular media descriptions – even when they were given saline instead of the real vaccine!

These effects show the power of negative expectations, one of the three psychological mechanisms underpinning the nocebo effect. Negative results are a direct result of expectations. Researchers in one study tested the effect of word phrasing on pain outcomes. When pregnant women were preparing to get an anesthesia injection the researchers talked them through what might happen. Half the patients were given the standard spiel, “You are going to feel a big sting and burn in your back now”. The other half were given the same information in much more neutral language: “We are going to inject the local anesthetic that will numb the area.“ The neutral language group experienced significantly less pain during the injection – just from phrasing! Scientists think the negative expectations might increase focus on symptoms. The expectations don’t have to come just from doctors or nurses, however. Seeing someone else suffer a side effect or hearing stories can produce the same effect!

Two other psychological underpinnings for the nocebo effect are less direct. Misattribution is the blaming of normal aches and pains to a new medicine. Progressive disease effects can also be misattributed to a placebo medication. Finally, conditioning has a large effect. Conditioning is the long-term associations we make between seemingly related things. Some patients feel nauseous at the smell of a hospital, for instance. This can also be very specific; the color of a pill can induce distinct side effects. Patients taking blue sugar pills are more likely to experience and report drowsiness than those taking pink sugar pills. Psychology shows us the framework for understanding what’s happening, but what’s going on under the hoodie?

Our brains experience changes at suggestions. Scientists think these changes may be due in large part to anticipatory anxiety. Anticipatory anxiety activates at least two pathways in the brain: pain and stress. Part of the pain pathway is called the CCKergic pronociceptive [pro-no-si-cep-tive] system. It is activated by a peptide called cholecystokinin [kow·luh·si·stuh·kai·nuhn] (CCK), and increases our perception of pain at the spinal level. This undermines anesthesia and increases our feelings of pain. The stress pathway moves through a few brain regions along the hypothalamus–pituitary–adrenal (HPA) axis and produces cortisol. Cortisol is a hormone that causes all of the classic signs of stress – increased heart rate and blood pressure, sweating and breathing, among others. The activation of these two major pathways primes our brain and bodies to experience worse symptoms – especially those we are expecting.

So what can be done? Well, reading this article is a great start! Around 75% of patients haven’t heard of or don’t believe in the nocebo effect, even though they experience it. Thinking about risks in terms of percentages instead of raw numbers can help. Four in a thousand may increase anxiety more than 0.4%.Other methods may be in the hands of medical professionals. Positive framing, such as with the injection example above, can make a lot of difference. In addition, identifying risky patients may help with how information is presented. Fortunately, understanding the mechanistic nature behind the nocebo effect can help lessen your anxiety – and symptoms!

Written By Benton Lowey-Ball, BS Behavioral Neuroscience


Kong, J., Gollub, R. L., Polich, G., Kirsch, I., LaViolette, P., Vangel, M., … & Kaptchuk, T. J. (2008). A functional magnetic resonance imaging study on the neural mechanisms of hyperalgesic nocebo effect. Journal of Neuroscience, 28(49), 13354-13362.

Planès, S., Villier, C., & Mallaret, M. (2016). The nocebo effect of drugs. Pharmacology research & perspectives, 4(2), e00208.

Varelmann, D., Pancaro, C., Cappiello, E. C., & Camann, W. R. (2010). Nocebo-induced hyperalgesia during local anesthetic injection. Anesthesia & Analgesia, 110(3), 868-870.


April 3, 2023 BlogObesity

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Obesity is a big medical concern. It is when there is an excessive amount of fat that causes medical problems. It is usually defined using the Body Mass Index, or BMI. BMI is a very crude calculation determined only by height and weight. In the USA, “overweight” is defined as a BMI over 25 kg/m2, and “obese” is over 30. This measurement is simplistic and does not take into account any nuance. For example, the CDC has found that the average American male is 5’9” and just under 200 lbs. This gives a BMI of 29.4, which is overweight. Arnold Scwartzenneger is 6’2”. At his peak performance, he weighed around 235 lbs, giving him a BMI of 30.2, which is classified as obese. Independent tests, however, have found that the average male has 28% body fat, whereas Arnold was at 8%. Nuances aside, BMI is an important calculation.

If the main measurement for obesity can give silly results, does that mean obesity is a made-up condition? Absolutely not. Obesity causes and makes several medical conditions worse. Four major mechanisms cause damage: inflammation, stress, fat, and weight. Inflammation can lead to diabetes, cancer, infertility, polycystic ovary syndrome (PCOS), and more. Stress is bad for many body systems, including mental health. Increased fat (also called lipids) can lead to liver damage. Stress and increased fat together can increase the chances of blood vessel damage, high blood pressure, heart attack, and stroke. Finally, the pressure of weight itself can degrade joints, squeeze organs, damage the kidneys, and constrict blood vessels.

So what causes obesity? At its simplest level, weight gain is caused by consuming more calories than you need. The reasons why some people can’t burn all of the calories can be vastly more complex. They can be broadly lumped into four categories: environmental, genetic, inflammatory, and brain-based mechanisms.

Environmental causes happen outside of the body. These include low exercise, a sedentary lifestyle, poor diet, and some medications. Eating disorders can be inherited, though the mechanism is unknown. The genetic factors of obesity are very complicated. There are over 200 genes that may affect obesity. To make matters worse, your body alters parts of the genetic code in response to environmental factors. This process, called epigenetics, complicates things a lot. On top of these two, inflammation is a big risk. Inflammation can lead to conditions such as metabolic syndrome and insulin resistance which affects how the body processes energy. Energy mismanagement on a systemic or cellular level is very hard to fight.

Brain-based mechanisms are complicated, but very powerful. We must first remember that some brain functions are specialized for a bygone time. Our brains are biased to ensure we are safe in times of scarcity, not times of plenty. This can lead to trouble in our modern era of readily available food. The brain can change on a physical level. When we routinely engage in dangerous behavior it is usually because parts of the brain have changed in an unhelpful way.

An example of brain changes can be found in systems around a hormone called Leptin. Leptin is secreted by fat cells and helps regulate our appetite. When fat stores run low, the brain detects low levels of leptin and kicks on your appetite – you get hungry. When you are full and fats are plentiful, there are abundant leptin molecules; your brain interprets this as full. When there is a change in this system – if the brain becomes resistant to leptin, for instance – trouble emerges. You might experience the feeling of hunger far after your body has eaten enough because your brain is misinterpreting the signals. The reward system can change dramatically in response to energy-dense foods. Rats exposed to tasty, fatty foods like cheesecake and bacon have reward system reductions similar to those seen with cocaine and heroin.

Obesity can spiral out of control, making it harder to reverse over time. Those four methods of creating damage: inflammation, stress, fat, and weight are all risk factors for obesity. Inflammation, for instance, can increase metabolic syndrome, a big driver of obesity. Obesity causes inflammation and might make metabolic syndrome worse. They can also disrupt the brain pathways that affect reward, inhibition, appetite, etc. Stress and changes to the reward pathway can lead to mental health trouble and worsen everything.

So what can be done? The best place to start is by targeting causes. It is necessary to keep a healthy environment where you are encouraged to exercise and limit calories. Other changes may need more assistance. Medications may be available or in trials to correct changes in gene expression, inflammatory responses, and specific hormones that affect the brain. Equally important is support from friends, family, and medical professionals. The struggle against obesity can quickly spiral out of control. Don’t be afraid to look for help with this condition.

Written By Benton Lowey-Ball, BS Behavioral Neuroscience


Chooi, Y. C., Ding, C., & Magkos, F. (2019). The epidemiology of obesity. Metabolism, 92, 6-10.

Kenny, P. J. (2011). Reward mechanisms in obesity: new insights and future directions. Neuron, 69(4), 664-679.

Obradovic, M., Sudar-Milovanovic, E., Soskic, S., Essack, M., Arya, S., Stewart, A. J., … & Isenovic, E. R. (2021). Leptin and obesity: role and clinical implication. Frontiers in Endocrinology, 12, 585887.

St‐Onge, M. P. (2010). Are normal‐weight Americans over‐fat?. Obesity, 18(11), 2067-2068.

Upadhyay, J., Farr, O., Perakakis, N., Ghaly, W., & Mantzoros, C. (2018). Obesity as a disease. Medical Clinics, 102(1), 13-33 .


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Diabetic Neuropathy is a nerve damage complication of Type 1 and Type 2 Diabetes. It is a result of high blood sugar (glucose) which harms nerves typically in feet and legs. Diabetic Neuropathy affects everyone differently, symptoms can range from mild to impairing as it can lead to problems in the digestive system, heart, urinary tract, and blood vessels. Diabetic Neuropathy is a serious health condition that affects about 50% of people who have diabetes. 

There are four main types of diabetic neuropathy which have a variety of symptoms depending on the type and how a persons’ nerves are affected. Due to slow development of symptoms, a person is typically unaware that they have diabetic neuropathy until the nerve has suffered significant damage. 

The four types of diabetic neuropathy:

Peripheral Neuropathy

This is the most common type and it first affects the legs and feet.  It can progress to affect the hands and arms. Symptoms of peripheral neuropathy normally increase at night and include:

  • Numbness to pain or temperature changes
  • Tingling or burning sensation
  • Cramps or sharp pains
  • Muscle fatigue
  • Overly sensitive to touch
  • Foot problems inducing joint damage and infections

Autonomic Neuropathy

This type can affect nerves in the internal organs such as the heart, digestive system, sexual organs, sweat glands, and urinary tract. Signs and symptoms include:

  • Unawareness of hypoglycemia
  • Decrease in blood pressure that causes dizziness or fainting when standing up or sitting down
  • Bladder or bowel issues
  • Gastroparesis which causes nausea, vomiting, or loss of appetite
  • Change in amount of sweating
  • Problems in sexual response (differs in men and women)

Proximal Neuropathy (diabetic polyradiculopathy)

This is the most uncommon type and is seen in about 1% of people with type 2 diabetes. It results in problems with the nerves in legs, buttocks, thighs, or hips. Symptoms typically are on one side of the body but can spread to the other side. Symptoms include:

  • Sharp pains in hip, thigh, or buttocks
  • Weakness in thigh muscles
  • Difficulty sitting upright after sitting
  • Chest or abdominal pain

Mononeuropathy (focal neuropathy)

This type only affects one nerve at a time typically in the face, torso, arm, or leg. Symptoms can differ depending on the nerve being affected however they typically include:

  • Difficulty focusing vision
  • Paralysis on one side of face
  • Tingling sensation or numbness in hands
  • Weakness in hand and inability to hold objects
  • Sharp pain in foot or shin
  • Inability to lift front part of foot
  • Pain in front of thigh

When diabetic neuropathy is diagnosed in early stages there is a higher chance that the medicine will be more effective. In order to diagnose diabetic neuropathy doctors often run tests and examinations such as:

  • Checking muscle strength and reflexes
  • Check muscle response to vibrations, temperature, and touch
  • Ultrasound of urinary tract
  • Electromyography to test muscles response to electrical currents
  • Nerve conduction studies to evaluate flow of electrical current through a nerve
  • Skin biopsy to determine cutaneous nerve innervation
  • Muscle and nerve biopsies for histopathological evaluation

In addition to these tests and examinations, a doctor often tests blood glucose, blood pressure, and cholesterol in order to narrow down the root of the problem.

Treatment for diabetic neuropathy can sometimes be as simple as changes in lifestyle, however more serious stages of neuropathy require medications in order to manage symptoms and pain.

  • In order to prevent further nerve damage a doctor will give you personalized blood sugar goals to decrease blood glucose levels. A few ways to manage glucose levels include developing healthier eating habits which include high amounts of protein and low amounts of carbs. Exercising regularly also manages blood sugar levels and increases insulin sensitivity. 
  • Controlling risk factors such as high blood pressure, high triglycerides, or cholesterol are a must when trying to relieve symptoms. Some ways to control these risk factors are by doing aerobic exercises daily, quitting smoking, and losing weight (if obese or overweight).
  • Managing pain is achieved through different treatments such as medications.

Written by: Sofia H. Davila, Clinical Researcher.


Mayo Foundation for Medical Education and Research. (2022, April 29). Diabetic neuropathy. Mayo Clinic. Retrieved February 23, 2023, from,in%20the%20legs%20and%20feet. 

“Diabetic Neuropathy.” Diabetic Neuropathy | Johns Hopkins Medicine, 18 Aug. 2020, 


Fats are tasty in food, but not particularly good in the bloodstream. They can also be toxic to the liver and cells in general. We have special cells called adipose cells that store fat in our body. These cells have defenses against dangerous fat components called free fatty acids. Free fatty acids are the high-energy parts of fats, the part that gives you energy. Fatty acids are a great way to store energy and can be turned into power for your body, but the high energy content can also be dangerous in the wrong places. 

The liver transforms free fatty acids into usable energy. From here, the energy is delivered to cells all over the body. The liver is part of the system that makes sure the body’s energy demands match the available energy. Unfortunately, when too many free fatty acids are delivered to the liver, they can start to build up in the liver tissue and cause damage.

Fatty liver is one of the most common ailments in Western countries. One in every three to four people in the US havw a fatty liver. Excessive alcohol consumption can cause a fatty liver, but most sufferers develop non-alcoholic fatty liver disease (NAFLD). Either way, people have steatosis. Steato- means fat, and -osis indicates a condition, especially an abnormal one. Steatosis of 5-10% is problematic and is the earliest indication that the liver is starting to suffer damage. Many people with fatty liver and no other abnormalities can make a full recovery, usually by stopping whatever is causing the steatosis.

We know that alcohol can directly damage the liver, but how does NAFLD start? The causes are complicated, but some similarities exist. Excess fat released from fat cells, excess fat created by the liver, and excess fats from the diet all find their way into the liver. These are normally not an issue, but all are affected when the body isn’t regulating insulin properly. Insulin lets body parts know when you have food or are starving. When insulin isn’t processed correctly the body thinks it’s starving and tries to compensate – even when there is plenty of food present. In the middle of this the liver suffers.

After a prolonged period of fat accumulation, a patient with NAFLD may develop non-alcoholic steatohepatitis, or NASH. Steato- for fat, hepat- indicating the liver, and -itis which means inflammation. This second leg on the terrible journey develops when fat causes inflammation in the liver. The gut changes and gives the wrong signals to the liver. Cells develop insulin resistance and can’t convert sugars into energy or fats correctly. Free fatty acids cause cell problems and elicit an immune response. Stresses on the liver cause a feedback loop, where inflammation disrupts cell function. The body tries to fix the liver but can’t overcome the massive amount of dangerous fats. Cells in the liver die, and the living cells can be damaged trying to compensate. With NASH, the inflammation is long-lasting, also called chronic.

The liver can regenerate from NAFLD and NASH. It can’t sustain forever, however. When the liver is permanently damaged, the tissue can scar and die. This is a permanent reduction in liver function. We call this scarring Cirrhosis. Cirros- is the Greek word for yellow-brown (the color of a dying liver), and -osis refers to a condition, especially an abnormal one. Cirrhosis has multiple stages and can be asymptomatic but cannot be recovered from without intervention. The current treatment for cirrhosis is a liver transplant.

Though we’ve been talking about the dangers of fats in the bloodstream and liver, it should be noted that the body makes a lot of these fats out of carbohydrates – sugars. A healthy diet without too many sugars and with lots of exercise are the best preventative measures for these conditions. Conditions related to insulin resistance, such as type 2 diabetes and metabolic syndrome can both cause and be caused by these conditions. Also, even though we have presented these as a pathway, note that you can progress from NASH to NAFLD or become symptom-free; it’s not a one-way journey! If you have any of these conditions, talk to your primary care physician to look for solutions. Also, keep an eye out for clinical research trials that may alleviate symptoms or the underlying fat buildup.


Pierantonelli, I., & Svegliati-Baroni, G. (2019). Nonalcoholic fatty liver disease: basic pathogenetic mechanisms in the progression from NAFLD to NASH. Transplantation, 103(1), e1-e13. .

Sanyal, A. J. (2019). Past, present and future perspectives in nonalcoholic fatty liver disease. Nature reviews Gastroenterology & hepatology, 16(6), 377-386.


March 8, 2023 BlogCirrhosisNASH

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The liver is an amazing and necessary organ. It can regenerate from a minor injury, break down dangerous chemicals and drugs, and help maintain the proper balance of nutrients, fats, and sugars in the body. It has hundreds of other important roles as well. With all this responsibility, we are in trouble when the liver stops working.

One way the liver stops working is through non-alcoholic steatohepatitis (NASH). Steato- means fat, hepato- indicates the liver, and -itis means inflammation. Steatohepatitis is inflammation of the liver caused by fat accumulation. This is a progressive form of non-alcoholic fatty liver disease – the most common liver disorder in western countries. Progressive means that this disease gets more severe over time. 

NASH is a large problem in America, affecting 3-12% of adults. Furthermore, NASH can lead to cirrhosis, where the liver is permanently damaged, and lead to possible liver transplantation. Over a million adults in America have NASH-related cirrhosis.

How do we get NASH? As the name indicates, this is not caused by alcohol. There are many pathways to developing NASH, but the underlying cause may be excess carbs and fatty acids. This can be due to diet or behavior, underlying genetics, or associated syndromes. Some of the syndromes associated with NASH are:

  • Metabolic syndrome
  • Obesity
  • Type 2 diabetes
  • High blood pressure
  • Dyslipidemia
  • Hypothyroidism
  • Cardiovascular risk
  • Advanced liver problems

The underlying mechanism of NASH can be very complex. A leading precursor to NASH is insulin resistance, where cells fail to respond to insulin. Conditions that cause or are caused by insulin resistance, such as type II diabetes and metabolic syndrome,  may increase your chances of developing NASH. They also may develop or worsen as NASH symptoms get worse. 

Insulin resistance causes different types of fats to accumulate in the liver. This makes it very difficult for the liver to process the fats and they ultimately build up in liver cells. These fats, especially ones called nonesterified fatty acids (NFEAs), are very dangerous. They cause damage to liver cells and can also activate cytokines that start the inflammation process.

Eventually, we get NASH, an inflammation cascade in the liver caused by fats. Cytokines start inflammation in the liver. Cell death attracts the immune system, which enters and causes inflammation while trying to help. Liver cells die and are less able to process fats, which leads to a compounding effect. Eventually, we may transition to cirrhosis, where permanent liver scarring and damage occur.

There are few treatments on the market for NASH. As usual, the primary therapy for NASH is a good diet and regular exercise. Medicinal remedies are all in the experimental phases. Potential targets include increasing insulin sensitivity, decreasing fat creation, decreasing circulating fats, breaking fats down, and anti-inflammation treatments. 

One way to decrease circulating fats is by expelling them through the digestive system. In the liver, moving fats to the gut is regulated by thyroid hormones. Thyroid hormones activate receptors, which exist all over the body and cause many different effects. Thyroid hormone receptor Beta (THR-β) exists almost exclusively in the liver. Scientists are working to create medicines that activate THR-β and help clear fats from the liver in NASH patients. If you are interested in participating in a research study, contact your local ENCORE Research Group site today! 


Noureddin, M., & Sanyal, A. J. (2018). Pathogenesis of NASH: the impact of multiple pathways. Current Hepatology Reports, 17, 350-360.

Parthasarathy, G., Revelo, X., & Malhi, H. (2020). Pathogenesis of nonalcoholic steatohepatitis: an overview. Hepatology communications, 4(4), 478-492.

Pierantonelli, I., & Svegliati-Baroni, G. (2019). Nonalcoholic fatty liver disease: basic pathogenetic mechanisms in the progression from NAFLD to NASH. Transplantation, 103(1), e1-e13. .

Pramfalk, C., Pedrelli, M., & Parini, P. (2011). Role of thyroid receptor β in lipid metabolism. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1812(8), 929-937.


March 8, 2023 AsthmaBlogPulmonary

Eosinophilic asthma is a type of asthma that is characterized by high levels of eosinophils in the airways. Eosinophils are a type of white blood cell that are involved in the body’s immune response to allergens and other triggers. When eosinophils are activated, they release inflammatory chemicals that can cause damage to the airways, leading to asthma symptoms.

Symptoms of eosinophilic asthma include wheezing, coughing, shortness of breath, and chest tightness. These symptoms may be more severe than those of other types of asthma and may not respond as well to traditional asthma treatments like inhaled corticosteroids.

Diagnosis of eosinophilic asthma involves a blood test to measure eosinophil levels and a sputum test to look for eosinophils in mucus from the lungs. Treatment may involve targeted biologic medications that specifically target eosinophils, such as mepolizumab, reslizumab, and benralizumab. These medications work by reducing the number of eosinophils in the airways, which can help to reduce asthma symptoms and improve lung function.

If you or someone you know has severe asthma, clinical trials may be an option for you. Clinical trials are an important way to test new medications and treatments for asthma and other conditions. They allow researchers to gather important data on the safety and effectiveness of new treatments, and they provide patients with access to cutting-edge therapies that may not be available through traditional channels. By participating in a clinical trial, you can play an important role in advancing medical research and helping to improve the lives of people with eosinophilic asthma and other conditions.

Clinical trials for this condition are currently available at ENCORE Research Group’s Jacksonville Center for Clinical Research, University Blvd. location.  To learn more, you can contact us by phone, or sign up on our website. Our knowledgeable staff can guide you through the process and help you determine if a clinical trial is a good option for you.


February 27, 2023 BlogCeliac Disease

Celiac disease is a genetic autoimmune disease that affects the digestive system. It is triggered when a person consumes gluten, which is a protein found in rye, wheat, and barley. When a person with celiac disease eats gluten, their immune system reacts to the protein by attacking the small intestine. The role of the small intestine is to digest food and allow the body to use the nutrients. When the body attacks the small intestine, it damages the lining of the small intestine, resulting in symptoms that include bloating, abdominal pain, and weight loss. Eventually, after the small intestine has suffered damage, it can result in the body’s inability to absorb nutrients, therefore leading to a deficiency of nutrients and health problems. 

It is often difficult to tell if children have celiac disease, as the symptoms in children and adults differ. 

Symptoms in adults include:

  • Fatigue
  • Weight loss
  • Bloating and gas
  • Abdominal cramps/pain
  • Nausea and vomiting
  • Constipation

Adults can also experience a variety of symptoms unrelated to the digestive system, such as: 

  • Anemia
  • Loss of bone density
  • Headaches
  • Cognitive impairment
  • Joint pain

Digestive problems are commonly seen in children with celiac disease, rather than in adults with celiac.

Symptoms in children include:

  • Nausea and vomiting
  • Diarrhea
  • Bloating
  • Constipation
  • Gas
  • Weight loss
  • Anemia
  • Irritability

Symptoms are often not enough to tell if someone has celiac disease. People are more susceptible to celiac disease if they have some of the risk factors listed below:

  • Family history of celiac disease and/or dermatitis herpetiformis (itchy skin rash)
  • Type 1 diabetes 
  • Turner Syndrome or Down Syndrome
  • Autoimmune thyroid disease
  • Microscopic colitis 
  • Addison’s disease

Diagnosis of celiac disease is through blood tests that check for certain antibodies and biomarkers. 

  • A serology test detects elevated antibodies which indicate the body is reacting to the gluten protein. 
  • A genetic test detects human leukocyte antigens in order to eliminate the possibility of celiac disease. 

Often following these blood tests is an endoscopy/biopsy of the small intestine to evaluate the damage caused by the body’s response to the gluten protein.  

Although there is no cure for celiac disease, a change in diet helps to regulate the symptoms of celiac disease. A gluten-free diet often consists of gluten-free foods and vitamin and mineral supplements to regulate the body’s nutrients. Following a gluten-free diet allows the small intestine to heal. Doctors and dietitians can help guide people on their diet and inform them of gluten-free alternatives. This diet is normally life-long in order to prevent symptoms or a flare-up of the small intestine again. Doctors sometimes prescribe steroids as well to help regulate the inflammation of the small intestine. 

It is often difficult for people with celiac disease to eat out at restaurants or buy pre-made food from stores as it is tricky to be one hundred percent certain that a food is truly gluten-free. Stickers on foods say “may contain gluten” as a way to protect the manufacturing companies from lawsuits. However, most of the time the food does not contain gluten itself but has a small chance that it could have been cross-contaminated during the production process. This limits food that people with celiac disease feel safe consuming and buying. The FDA has standards that must be met in order for a food to be labeled as “gluten-free”. The final product must contain, at most, 20 mg/kg (20 parts per million) gluten or less. However, this rule does not apply to alcohol which can contain gluten. This amount of gluten (20 ppm) will not result in any side effects in a person with celiac disease, since it is too small of an amount. Another way people can be sure that they are consuming gluten-free foods is to call a restaurant ahead of time and ask if they have a gluten-free menu or serve alternatives for people with gluten intolerance. 

Written by: Sofia H. Davila, Clinical Researcher


Mayo Foundation for Medical Education and Research. (2021, August 10). Celiac disease. Mayo Clinic. Retrieved February 17, 2023, from 

NCI Dictionary of Cancer terms. National Cancer Institute. (n.d.). Retrieved February 17, 2023, from

U.S. Department of Health and Human Services. (n.d.). Eating, diet, & Nutrition for Celiac Disease. National Institute of Diabetes and Digestive and Kidney Diseases. Retrieved February 20, 2023, from 


Atrial fibrillation (AFib) is a heart rhythm disorder characterized by irregular heartbeats in the heart’s upper chambers, called the atria. In AFib, the electrical signals that regulate the heartbeat become abnormal, causing the heart to beat too fast or slow instead of contracting normally. Atrial fibrillation can have detrimental effects such as stroke, heart failure, and blood clots. 

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As a result of the irregular heart beatings, a variety of symptoms can be present such as:

  • Palpitations (fluttering, pounding, or rapid sensation)
  • Shortness of breath
  • Fatigue
  • Weakness
  • Dizziness / lightheaded
  • Chest pain

In some cases, people with AFib may not experience any symptoms, making it difficult for some people to tell whether or not they may have AFib.  

Some broader symptoms can include:

  • Abrupt weight gain
  • Coughing or wheezing
  • Fainting
  • Nausea and appetite loss
  • Depression

Sometimes even these broader symptoms can not help people determine if they have AFib. The only way for people to know if they have AFib without experiencing any symptoms is to get tested and diagnosed by a doctor. It is strongly recommended that if a person has any of the risk factors below, they get checked, just to be safe, by a doctor. 

AFib is often seen in older adults, with risk factors that include:

  • History of heart disease
  • High blood pressure
  • Advancing age
  • Obesity
  • Diabetes
  • Heart failure
  • Hyperthyroidism
  • Chronic kidney disease
  • Smoking or excessive alcohol use

Some treatments are more effective when delivered in the early stages of AFib, which means that a person should not postpone getting checked by a doctor for AFib. However, symptoms and causes of AFib can often differ between men and women. In women, AFib usually is caused by problems with the heart valves. Compared to men, where AFib usually stems from coronary artery disease (CAD). As a result, women with AFib have a greater chance of having a stroke than men with AFib. Women with AFib also are more likely to have heart attacks and congestive heart failure than men with AFib. As a result, treatments for men and women often differ slightly. 

Treatment for AFib is typically a medication to control heart rhythm and prevent blood clots. However, in some cases, procedures such as electrical cardioversion, ablation, or implantation of a pacemaker or defibrillator may be necessary. Men with AFib are often placed on non-drug therapies such as pacemakers and catheter ablation. Women with AFib are more likely to have a cardioversion and be prescribed antiarrhythmic medications such as dofetilide. However, typical treatments for both men and women include blood-thinning medications, surgery, and lifestyle changes to manage AFib risk factors. 

Written by: Sofia H. Davila, Clinical Researcher


Miller, K. (2022, December 27). Atrial fibrillation: The difference between men and women. Healthgrades. Retrieved February 17, 2023, from 

Centers for Disease Control and Prevention. (2022, October 14). Atrial fibrillation. Centers for Disease Control and Prevention. Retrieved February 17, 2023, from


February 13, 2023 BlogClinical Trials

Our patients are enthusiastic and excited to take part in clinical research.  There are a variety of reasons a patient would want to participate in a clinical trial: they join to benefit future generations, to advance medicine, to get medical help and compensation, and to increase diversity. The most frequent reason for joining a clinical study, however, is to help others. Clinical research is the best framework for ensuring the safety and effectiveness of new medications, devices, and procedures. This includes everyone from participants of phase 1 clinical trials to final consumers after FDA approval. But what does the process actually look like for patients?

People hear about us from a wide variety of sources: advertisements, community outreach programs, the internet, and personal referrals from family and friends. Thousands of our patients are referred to us by friends, family, and their own physicians. People’s great experiences with us make them very likely to recommend us to others. Most of our patients are repeat offenders. In fact, over 99% of our patients return for another study. 

When you are interested in an ENCORE Research Group study, our experienced and compassionate recruiters will talk with you. These experts care about your time more than anything else. They will run through a quick checklist to see if you prequalify for a study. If you prequalify, they will schedule an evaluation. They will find a time that works best for you to come in or receive a call with a research coordinator.

Here the compassionate and attentive nature of ENCORE Research Group excels. You will receive forms to fill out your medical history, medications, and contact information. During your appointment, our attentive and detail-oriented staff will review your documents. They will confirm and expand on any medical conditions that may affect your participation. This step makes sure you are always safe and gives our staff personal knowledge to help you during your study. Patient safety is always our number one priority.

After an evaluation, if you choose to participate, you will start the informed consent process. Here you will review the clinical trial process and the plan for your specific study. Research coordinators will explain and review a highly detailed and regulated consent form. This document informs you about the study, potential side effects, the goals and endpoints of the study, your rights, and what to expect. This is a vital step. We will also remind you that you can end participation in the study at any time for any reason. Your voluntary participation does not oblige you to continue at any point.

What happens from here depends on your specific study, but some things will remain constant. Our doctors and medical staff will talk with you. Other patients describe them as professional, friendly, and compassionate. You may receive medication, a placebo, device, or undergo a procedure. This will have been explained in detail during the informed consent process. One big difference between ENCORE Research Group and a normal doctor’s office is the comprehensiveness and amount of follow-up. Our doctors give you their full, undivided attention when you are in their office. They have plenty of time and want to know the intricacies of your medical history. For most studies, our staff will periodically check up on you after you leave. We are also keenly interested in knowing if you experience any new or changing symptoms. This will continue until your study has concluded. Then, if you wish, we will contact you if you qualify for more studies.

This process results in a streamlined, professional, and personal system. You get to help medicine and society, but also experience top-quality, attentive care for a variety of conditions. Join the clinical trial process with ENCORE Research Group and see why nearly all of our patients come back!

By Benton Lowey-Ball, BS Behavioral Neuroscience


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There are many ways to think of the human body. One of my favorites is that the body is like a donut. The inside of the donut is our entire body and everything that makes us what we are. The outside is our skin. The hole in the middle is made of our mouth, throat (esophagus), stomach, and intestines. The body treats the entirety of the digestive tract as the outside world. The intestines act like the skin; keeping most things out of the body and only letting specific molecules through.

This has some important implications. The whole outside of the donut – including the throat and intestines – is covered in epithelial cells. These are tight cells that interact with the outside world. When these cells determine that they are touching something dangerous they signal to get rid of it immediately. This might feel like burning or itching on the skin, and may be something like diarrhea or vomiting in the digestive tract. These may feel crummy to us, but they are very useful in keeping us safe.

The immune system is in charge of identifying and reacting to chemical and biological dangers. These can be harmful bacteria, worms, and things like splinters or some drugs. The immune system kicks into action, trying to kill or remove the dangerous particles without damaging body cells. This is a tricky dance. Antibodies will identify the dangerous particles or creatures and special B or T cells will widely sprinkle alarm particles, calling for reinforcements.

What the body does next is determined by where the danger is found. In the gut – which the body treats as the dangerous outside world – the defenses are strong. One of the biggest guns we have is a cell called an eosinophil. These are very dangerous cells. They contain highly toxic particles and proteins that aggressively dunk in on invaders. They also signal to the intestines to  contract and eject the contents. They only exist in specific parts of the body and are normally difficult to activate.

Unfortunately, sometimes our body identifies otherwise safe items as dangerous. This is called allergies, and can be very annoying. Many of us suffer from seasonal allergies, but that doesn’t mean we should glaze over the dangers of allergic reactions. One difficult condition is eosinophilic esophagitis. Eosinophilic means it is caused by the dangerous eosinophil cells. Esophagitis refers to the fact that this happens in the esophagus, the throat. Eosinophils do not normally reside in the throat at all. The throat’s main job is to move food into the stomach, so it doesn’t need to detect danger. When eosinophils mistakenly reside in the throat, however, they can misidentify otherwise safe foods before the stomach gets a chance to digest them. This can result in the eosinophils damaging the throat.

Eosinophilic esophagitis affects four in every thousand people, and can affect people of all ages. Most sufferers were diagnosed as children. In fact, it is one of the most common diagnoses for children who have trouble eating. It is chronic, or long lasting,  and symptoms are debilitating. Sufferers experience inflammation of the throat, poor food intake, vomiting, and a poor appetite. Unfortunately there are few treatments available to fix this condition. The most effective has been reducing the diet of patients. This may consist of starting with a very strict diet and reincorporating food slowly to discover triggers. Scientists are actively looking at the underlying causes of why eosinophils are in the throat to begin with. Possible future treatments would likely stop eosinophils in the throat at a cellular or genetic level.  The body may be a donut, but that doesn’t mean everything is tasty and fresh. If you are suffering from eosinophilic esophagitis or other conditions, call ENCORE Research Group and ask about studies you may qualify for.

By Benton Lowey-Ball, BS Behavioral Neuroscience

Furuta, G. T., & Katzka, D. A. (2015). Eosinophilic esophagitis. New England Journal of Medicine, 373(17), 1640-1648.

Janeway Jr, C. A., Travers, P., Walport, M., & Shlomchik, M. J. (2001). Effector mechanisms in allergic reactions. In Immunobiology: The Immune System in Health and Disease. 5th edition. Garland Science.

Rothenberg, M. E. (2004). Eosinophilic gastrointestinal disorders (EGID). Journal of Allergy and Clinical Immunology, 113(1), 11-28.

Zuo, L., & Rothenberg, M. E. (2007). Gastrointestinal eosinophilia. Immunology and allergy clinics of North America, 27(3), 443-455.


January 30, 2023 BlogCardiovascular

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In the 1990’s the philosopher Haddaway posed a critical question: What is love? This Valentine’s Day, many of us will experience love and companionship. We like to think of love as an amorphous, idealistic quality, but there are serious biological underpinnings. What is the biology behind love, and is the heart really where love lies (spoiler: maybe?)

We know that the brain directs our physical actions, but for the brain to come up with an idea, it needs input from the outside world. Interestingly, the brain can’t sense anything directly. If someone were to open up your skull and have a poke around, you would undoubtedly have a weird bit of sensation, but you wouldn’t experience the feeling of touch on the brain. We need special sensors (usually located on the skin) to feel things like touch. Indeed, our brain relies on signals coming in from all over the body to tell us about the outside world. Interestingly, we also rely on signals to tell us about the inside world – what we are experiencing. The brain interprets signals from the body, and we can experience that interpretation as an emotion.

As an example: your heart beats automatically all day, every day, at a hopefully regular interval of around once a second. When you see a scary event, such as a wild lion charging you, your brain and body respond in sync. The heart rhythm changes, beating much faster to provide your muscles, sensory organs, brain, etc., extra oxygen in order to move fast. But this effect isn’t strictly rational. After we escape from the lion, we still feel “amped up.” This effect can last for thirty minutes or so, and the reason for the long-lasting effect is complicated. Our autonomic nervous system – the one in charge of things we don’t consciously control – has kicked into action. This pathway acts like cupid, shooting cortisol through our body and activating special nervous system pathways that take a while to cool down. But our brain also looks at the state of our body to interpret our emotional state. If our palms are sweaty, we’re breathing heavily, and our heart is racing, the brain interprets that as being amped up and decides we’re still pretty excited or scared. The brain is in charge of deciphering which emotion we’re feeling, but the body lets us know how strongly we’re feeling that emotion.

This is why we sometimes still feel the need to continue an argument after the other party has conceded. It’s why telling someone to “calm down” doesn’t work – but taking some deep breaths does. Meditation, stretching, exercise, and sleep all affect our emotional state because the brain looks at the condition of the body and tries to figure out how it’s feeling. In addition, a healthy heart that can respond well to changes may increase a person’s emotional regulation. Does it do this with love as well?

According to neuroendocrinology researcher Robert Sapolsky, it does! The science may not be entirely clear, but the easiest way to be certain of this is by looking at the irrationality of love. Love doesn’t make sense, and it’s so strong that we base enormous portions of our life just on this single emotion. Love is the basis of countless pieces of art, works of literature, grand buildings, and justifications for war. When we experience love – that fluttering of the heart, the excitement and elation, the involuntary smile on our face, and the giddiness so high that our mouths stop working and we say embarrassing, cheesy things – it’s the body to blame. Our heart races when we’re in love and the brain sees this as a huge exciting event – because it is. Just seeing the person we love can change our heart rate. Physical touch from a loving partner can help lower our heart rate in response to stressful situations. And the long-term effects of companionship sometimes include a partial synchronization of our heart rhythms.

We can thank our hearts for at least some of what we call love. This Valentine’s day, get your heart racing with a partner or loved one, and keep that heart beating strong!

By Benton Lowey-Ball, BS Behavioral Neuroscience

Ditzen, B., Neumann, I. D., Bodenmann, G., von Dawans, B., Turner, R. A., Ehlert, U., & Heinrichs, M. (2007). Effects of different kinds of couple interaction on cortisol and heart rate responses to stress in women. Psychoneuroendocrinology, 32(5), 565-574.

Kandel, E. R., Schwartz, J. H., Jessell, T. M., Siegelbaum, S., Hudspeth, A. J., & Mack, S. (Eds.). (2000). Principles of neural science (Vol. 4, p. 980). New York: McGraw-hill.

Mather, M., & Thayer, J. F. (2018). How heart rate variability affects emotion regulation brain networks. Current opinion in behavioral sciences, 19, 98-104.

Sapolsky, RM. (various works)


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Cardiovascular disease has remained the number one cause of death worldwide.  Multiple clinical trials have revealed that a common and modifiable risk factor for cardiovascular disease is high cholesterol, and if a person lowers their cholesterol, they can lower their risk for heart-related diseases.

Most of us have heard of cholesterol, but what is it? Why is having too much cholesterol a bad thing? How do we get cholesterol in our bodies? What can you do to lower your cholesterol to healthy levels? 

Cholesterols are a broad and useful type of fat found in the body. The body needs them to create hormones, essential vitamins (like vitamin D), and other molecules. They float on the surface of our cells, helping to maintain the structure and function of cell barriers. Cholesterols regulate cell activity and act outside of cells. They insulate the neurons in our brain, allowing us to think.  In fact, cholesterol is so important to daily function, that every cell in the body can make cholesterol from basic materials, except your eyelashes!

There are times when cholesterol is downright bad. LDL cholesterol and Lipoprotein a [Lp(a)] have some particularly sticky portions that can get stuck to the inside of our bloodstream. We call one of these portions ApoB. Sticky cholesterol obstructs blood flow in the form of plaques. Without help, this leads to atherosclerosis, scarring, and hardening of the arteries. Atherosclerosis further cascades into cardiovascular disease, clots, heart attacks, and stroke. This is very bad. Unfortunately, it is also very common; atherosclerosis in the neck is found in ¼ of people worldwide. Lowering excess cholesterol is a global health concern.

Our liver creates enough cholesterol to supply our bodies. We are also able to absorb cholesterol from our diets and make some in other cells. The most effective methods of reducing cholesterol are lifestyle and diet changes. However, for some people, diet and exercise don’t seem to budge their cholesterol numbers at all. For others, the ability to exercise and dietary restrictions may be limited. This is where medications can step in.

To understand how a medication may reduce LDL and/or Lp(a), we need to learn a bit about how the body makes things from DNA. Genes are bits of DNA that contain the blueprint for a protein. Genes provide the blueprint to messenger RNA (mRNA). The mRNA translates genetic code into proteins. The cells then fold proteins into complicated, machine-like shapes. Proteins interact with molecules and other proteins to create all sorts of things for the body – including cholesterol. Clinical research has been expanding which of these steps we can target for medications.

Statins are the first line treatment for reducing cholesterol. They target hydroxymethylglutaryl coenzyme A (HMG-CoA). HMG-CoA is a protein used to construct cholesterol molecules. Reducing HMG-CoA slows the body’s ability to create cholesterol, lowering cholesterol levels. Statins block the production of the “bad” LDL-C cholesterol and lower levels by as much as 60%. The benefits for statins to reduce cardiovascular events have been proven in multiple clinical trials over a diverse patient population.

Other oral medications, including ezetimibe and bempedoic acid, can be taken with statins. Ezetimibe can lower LDL-C levels by approximately 20% by inhibiting cholesterol absorption in the intestines, making it a useful add-on medication when statins alone are insufficient. Bempedoic acid can lower LDL-C by 15-25% by decreasing cholesterol synthesis in the liver.  Because bempedoic acid is converted to an enzyme found only in the liver and not the muscles (like statins), it is often an alternative for patients who have statin-associated muscle myalgias.    

Monoclonal antibodies (MoAbs) are a newer class of medication. MoAbs like alirocumab and evolocumab act like signaling molecules. These two stay outside of cells and tell the liver to produce less of the protein PCSK9. Controlling PCSK9 is a newer method of changing a person’s cholesterol profile. PCSK9 controls how much extra LDL cholesterol is absorbed and recycled by cells. MoAb medications affect this by targeting signaling receptors on the outside of the liver.

Even newer medications target the process by which genes get turned on inside the cells.  They are called gene silencing therapies because they aim to “silence” the gene’s effects.  Antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) stop the liver from producing functional LDL or Lp(a) mRNA molecules. These act at different, very early stages of the cholesterol process. In addition, specialized packaging on the medications deliver them to the liver and not other cells. This can make for very targeted medications that (hopefully) have fewer side effects.

Inclisiran is the first FDA-approved siRNA therapy to lower LDL cholesterol.  It is a subcutaneous injection taken twice a year.  Imagine going to your physician’s office just twice a year to get your “cholesterol vaccine”!

Even more amazing, gene editing tools such as CRISPR could reduce overexpression of PCSK9 or other genes on a long-term basis. These are still in early phase trials, but the future is looking bright.

Lipoprotein a,or “L-P-little-a”,  or Lp(a), is a new target for decreasing the risk of cardiovascular disease. Lp(a) is genetically inherited and increases the risk for both heart disease and stroke because it can promote plaque buildup, blood clots, and inflammation.  New gene silencing therapies are in clinical trials right now using both ASO and siRNA technology.

Diet, lifestyle changes, and statins remain the front-line defense against high cholesterol. New medicines may work with or replace these classical defenses. As technologies move through the clinical research apparatus, we may be able to tailor custom combinations of medications for individual patients. ENCORE Research Group has been involved in every step along this path, helping to study medications in every category. Join our team and help pave the way for new medications to help combat high cholesterol! 


Craig, M., Yarrarapu, S. N. S., & Dimri, M. (2018). Biochemistry, cholesterol.

Fernandez-Prado, R., Perez-Gomez, M. V., & Ortiz, A. (2020). Pelacarsen for lowering lipoprotein (a): implications for patients with chronic kidney disease. Clinical Kidney Journal, 13(5), 753-757.

Prati, P., Vanuzzo, D., Casaroli, M., Di Chiara, A., De Biasi, F., Feruglio, G. A., & Touboul, P. J. (1992). Prevalence and determinants of carotid atherosclerosis in a general population. Stroke, 23(12), 1705-1711.

Tokgözoğlu, L., & Libby, P. (2022). The dawn of a new era of targeted lipid-lowering therapies. European Heart Journal.


The Role of Apolipoprotein C-III (apoC-III) in Atherosclerosis and Cardiovascular Disease

After we eat a meal, all that energy has to go somewhere. Body cells can use freely floating glucose sugar in the bloodstream, but fats are a bit trickier. Just like oil and water don’t mix, fats have trouble moving through the blood in our veins and arteries. They must be packaged inside special containers called lipoproteins in order to travel where they need to go. For fats that we eat, the fats (called triglycerides) are packaged into ultra-low-density chylomicrons by the digestive system. Our liver also processes and repackages fats. The liver makes very low-density lipoproteins (VLDL) out of triglycerides and ejects them into the bloodstream. VLDLs can then use the bloodstream to travel to fat cells or be converted into other forms of energy storage. The number of triglycerides in the bloodstream at once needs to be well regulated.

For adults, fasting triglyceride levels should be under 150 mg/dL. This number decreases to below 90 mg/dL for people under 19 years of age. Unfortunately, one in ten adults have high levels, called hypertriglyceridemia. When there are too many triglycerides, they can stick to the inside of the bloodstream. They can create and contribute to hard plaques, a condition called atherosclerosis. These put stress on the cardiovascular system and can lead to atherosclerotic cardiovascular disease (ASCVD). Very high triglycerides above 500 mg/dL is called severe hypertriglyceridemia. This can lead to even more problems, including chylomicronemia, pancreatitis, and death.

What contributes to high triglyceride levels? A lot, actually! A diet that is high in sugars and fats, excessive alcohol consumption, being overweight, and a sedentary lifestyle can contribute. Some conditions, such as diabetes, kidney and liver disease, and thyroid problems increase your chances. Anything that affects liver function is likely to change how the body processes fats and may increase triglycerides. This means some life-saving medications, including several cancer, hypertension, and HIV treatments may increase triglycerides. Some people have high or very high triglycerides – usually in the form of chylomicrons – even without these risk factors. This may be because of our genes.

One of the major genetic culprits for increased triglycerides is a gene called APOC-3. This gene codes for a protein of the same name: Apolipoprotein C-III (apoC-III). You can tell these apart because the gene is uppercase, italicized, and uses a (3), while the protein is mostly lowercase and uses roman numerals (III). The protein apoC-III can lead to some detrimental effects. Normal triglycerides bind to a different protein, apoC-II. This helps them get broken down in the bloodstream. ApoC-III binds to triglycerides in the same place as apoC-II but makes them less able to be processed. These triglycerides build up in the bloodstream and can cause atherosclerosis and ASCVD. Scientists also have evidence that apoC-III makes triglyceride-rich molecules stickier to the arteries. ApoC-III binds to chylomicrons very well, making these fats especially resistant to breaking down.

So why do we have apoC-III anyway? It turns out, not all of us do! Different people have different variations of the APOC-3 gene. Some people have a gene that produces excessive apoC-III protein, and a few have genes that produce none! People with defective APOC-3 genes seem to be just as healthy as everyone else. Maybe healthier, as their levels of triglycerides are very low, even after a fatty meal! Researchers consider a defective APOC-3 gene to be cardioprotective, meaning that it lowers the chances of heart disease.

Are there methods for us to lower the production of apoC-III and our triglyceride-rich chylomicrons? It looks possible. The liver produces more apoC-III in response to high levels of blood sugar and most fats, so lowering these may help. It decreases production of apoC-III when it encounters high levels of insulin or polyunsaturated fats (such as Omega-3 fatty acids). This may be helpful, but is bad news for those with type 2 diabetes. In these patients the bloodstream has extra glucose and lacks insulin.

Treating high triglycerides can be complicated. A diet low in alcohol, carbs, and fats but high in omega-3 fatty acids can help. Exercise and weight loss are often helpful. Doctors may also prescribe fibrates, nicotinic acid (niacin), or statins. Unfortunately, these medications may not work if you have excessive levels of apoC-III and high chylomicrons. A diet that is very low in fats – under 20 grams a day – has been the only option for some patients. New classes of medication may be helpful as well. Antisense oligonucleotides, gene therapy, and custom antibodies can be used to target the production of specific proteins. Antisense oligonucleotides, for instance, bind to APOC-3 mRNA in the cell, preventing it from creating apoC-III proteins. They do this with extreme specificity, targeting only the gene in question. They can also do this only in liver cells by being packaged in a special way. Drugs that target apoC-III production may be able to bring down otherwise stubbornly high triglycerides without too many side effects. A side effect of reading the ENCORE Research Group website is learning about these new medicines and when they may be available for you in a trial!


Alves-Bezerra, M., & Cohen, D. E. (2017). Triglyceride metabolism in the liver. Comprehensive Physiology, 8(1), 1.

Goldberg, R. B., & Chait, A. (2020). A comprehensive update on the chylomicronemia syndrome. Frontiers in endocrinology, 11, 593931.

National Institute of Health, National Heart, Lung, and Blood Institute. (April 7, 2022). High blood triglycerides. U.S. Department of Health and Human Services.

Rahmany, S., & Jialal, I. (July 18, 2022). Biochemistry, Chylomicron.

Taskinen, M. R., Packard, C. J., & Borén, J. (2019). Emerging evidence that ApoC-III inhibitors provide novel options to reduce the residual CVD. Current atherosclerosis reports, 21(8), 1-10.


January 11, 2023 BlogDiabetes

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In fifth grade, I learned that mitochondria are the powerhouses of the cell. But what’s the fuel? The answer is carbohydrates. Big carbohydrates are broken down by digestion and converted into a couple of simple sugars. The most abundant of these simple sugars in our bodies is glucose. 

Glucose is small, simple, and packed with energy. We transport it through our bloodstream to cells in our body. Glucose levels are regulated by the liver and pancreas. Unfortunately, conditions like diabetes can result in the dysregulation of blood glucose levels. Having too much sugar in the blood is very bad over time. It can result in damage to the eyes, kidneys, nerves, and heart. On the flip side, having low blood sugar can get dangerous right away. Glucose is the fuel that powers our cells, without it the brain and other organs can’t function.

We know that glucose is critical to body function. We also know that glucose levels can get out of control. What can we do to make sure glucose levels stay safe? The most important piece of the puzzle is information. Good information on what our blood glucose levels are is critical to know what to do. We get this information by testing our blood glucose levels. There are three major ways of testing blood glucose; chemical redox reactions, color change, and enzyme-based reactions.

  • Chemical redox reaction testing works because glucose reacts with metals. By measuring how the metals react to blood, we can indirectly measure the amount of glucose. Unfortunately, other chemicals in the blood react to metal as well and can complicate the results. This method is rarely used these days.
  • The second method is through color change. This method combines blood and a special chemical called o-Toluidine. The o-Toluidine reacts to a specific part of the glucose molecule and changes it to be bright green (normally it is white or colorless). We can measure the color change visually, using test strips or with a digital glucose meter. Color change is cheap and effective, but the o-Toluidine can react to other sugars and give distorted results.
  • The industry standard for the last few decades has been enzyme-based reactions. A special enzyme, usually glucose oxidase or glucose dehydrogenase reacts with blood. This enzyme is very specific and only reacts to glucose. A result of this reaction is the production of H2O2, hydrogen peroxide. This is easily measured by digital devices. This method is inexpensive and specific, giving good results.

Now we know the chemical methods of measuring glucose, but how do we actually test our glucose level? Three broad testing types exist: oral, self-test, and continuous glucose monitors. These are differentiated mainly by the frequency and invasiveness of the test. 

  • Oral tests are a lengthy and (frankly) pretty gross affair. You fast for several hours, then drink an offensively sweet beverage and wait another hour. Blood is drawn and tested to determine how well your body can break down and clear the glucose from the bloodstream.
  • Self-tests involve drawing blood and putting it on a strip or in a digital detector. This is quick and can be done many times a day if needed. Unfortunately, repeated pricks can be annoying and you can’t test overnight unless you wake up. 
  • Continuous glucose monitors (CGMs) are worn like a patch and have a tiny sensor that goes just under the skin into the interstitial space and sends results to an external monitor. This tests blood glucose constantly, typically reporting every 1-5 minutes. CGMs can let people know their glucose via a phone app or external device. 

As the old saying goes, knowledge is power! With the help of the latest CGM technology, we are able to see information in real-time such as how food, exercise, and stress impact glucose levels. This helps us take immediate action to manage our glucose levels. So, take action to keep your blood glucose in the healthy range with your new knowledge, a good diet, and consistent exercise. Make sure it stays there by monitoring your blood glucose levels regularly. Keep your eyes open to look for new studies looking at ways to monitor your blood glucose and keep your cells powered up!


American Diabetes Association (n.d.). Understanding A1C diagnosis. American Diabetes Association.

McMILLIN, J. M. (1990). Blood glucose. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Chapter 141.

Wang, H. C., & Lee, A. R. (2015). Recent developments in blood glucose sensors. Journal of food and drug analysis, 23(2), 191-200.


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Cardiovascular disease (CVD) is the leading cause of death in the United States. There are several risk factors for cardiovascular disease. This can include things you can’t change, such as sex, age, and genetics. They can also include things you can change. The WHO identifies four big behaviors that can change your risk of developing CVD:

  • Poor diet
  • Low exercise
  • Excessive alcohol consumption
  • Smoking

These behaviors generally lead to other undesirable indicators of health, including obesity, hypertension, high blood sugar, and increased cholesterol. Clearly, ceasing the behavioral risks is a high priority. Unfortunately, this is often easier said than done.

One of the most difficult habits to quit is smoking. Studies show that those attempting to quit without assistance have an over 90% relapse rate. Several medications exist to help quit smoking, including Bupropion SR (aka Wellbutrin) and Varenicline (aka Chantix). There are also nicotine-based alternatives, including gum, inhalers, lozenges, nasal sprays, and patches.  Nicotine rewires the brain as it’s consumed. It releases dopamine, the brain’s reward drug, and rewards us for smoking. Researchers think the frequency of smoking may be partially to blame for the intensity of the addiction. The amount of dopamine released is not particularly high compared with other drugs, but nicotine also causes changes to the striatum. The striatum is part of the reward circuit in the brain. Through a complicated mechanism, nicotine increases the amount of a protein called FosB, which changes the striatum’s sensitivity to dopamine. This is a change at the genetic level which makes the brain more susceptible to further reward signals. Nicotine seems to make normal activities more pleasurable. Unfortunately, as nicotine adjusts the brain’s mechanisms, the brain relies on it to get to a baseline of reward. Upon quitting smoking, the brain finds normal activities less enjoyable.

On its own, nicotine may have negative effects, and in heavy doses it has been shown to be dangerous. The biggest dangers of smoking, however, are likely in the myriad of other chemicals in tobacco and cigarettes. Though nicotine causes changes in the brain, cigarettes cause changes to the fats in your body, further increasing CVD risk. Along with this, cigarettes cause cancer, COPD, diabetes, erectile dysfunction, and immune system changes. Clearly, quitting smoking is critical to health. With the addictive nature of nicotine and the low success rate of quitting cold turkey, assistance may be needed. 

The brain gets addicted to nicotine, but we can fight back using behavior. You can actually help yourself “break the cycle” of nicotine addiction by changing your daily routines. For example if the first thing you do in the morning is reach for a cigarette, change your routine to going to the bathroom and brushing your teeth first instead. Behavioral interventions can make a significant difference. Combining behavior changes and counseling with a nicotine replacement or medication can help quit rates approach 30%. Indeed, nicotine replacements are most effective when used with behavioral interventions. 

Changing your behavior or routine can have positive impacts on your health. So next time you want to reach for a cigarette, grab your phone instead! Give us a call and discover what clinical trials you can take part in!


Bancej, C., O’Loughlin, J., Platt, R. W., Paradis, G., & Gervais, A. (2007). Smoking cessation attempts among adolescent smokers: a systematic review of prevalence studies. Tobacco control, 16(6), e8-e8.

Fiore, M. (2008). Treating tobacco use and dependence; 2008 guideline.

Garbin, U., Fratta Pasini, A., Stranieri, C., Cominacini, M., Pasini, A., Manfro, S., … & Cominacini, L. (2009). Cigarette smoking blocks the protective expression of Nrf2/ARE pathway in peripheral mononuclear cells of young heavy smokers favouring inflammation. PloS one, 4(12), e8225.

Koren, M. (Host). (2022, May 22). Nicotine replacement therapies to help stop smoking  [Audio podcast episode]. In Medevidence! Truth behind the data. ENCORE Research Group.

Messner, B., & Bernhard, D. (2014). Smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis. Arteriosclerosis, thrombosis, and vascular biology, 34(3), 509-515.

NIDA. (2018, September 28). Recent Research Sheds New Light on Why Nicotine is So Addictive.

US Department of Health and Human Services. (2014). The health consequences of smoking—50 years of progress: a report of the Surgeon General.


December 26, 2022 BlogResearch in General

We humans seem to like making a fresh start. Whether it’s the beginning of a semester, a month, or a week, we like having a “clean slate” to make changes. The most widely used of these fresh start times are at the beginning of the year, with a New Year’s Resolution. Over 40% of all Americans make New Year’s resolutions, but much like a firework, we make a bright claim with a loud noise, only for it to burn out quickly as the year goes on. How can we make good resolutions that we are likely to follow, and are there strategies we can use to help us follow through?

Probably the most important piece of a New Year’s Resolution is coming up with a good resolution in the first place! Surveys show that around two-thirds of all resolutions are health-oriented, including eating healthier, exercising, getting in shape, etc. Psychological studies have shown that the wording of your resolution matters. Most resolutions can be broadly lumped into either activation or avoidance goals. Activation goals are those that encourage you to do something: exercise more, eat more greens, etc. Avoidance goals are those that encourage you to not do something: watch less TV, eat less pizza, etc. Several studies have shown that activation goals are significantly more likely to be successful than avoidance goals

Sometimes our end goal is to decrease something: to lose weight, stop smoking, or eat slightly fewer cookies. In order to increase chances of success, it can be helpful to reimagine these goals as activation goals. Instead of losing weight, we can aim to exercise four days a week. Instead of stopping smoking, we can try to chew gum daily. Instead of eating fewer cookies, we can try to do some push-ups instead. When trying to avoid negative things, it can be hard to find rewards and easy to identify failures. By trying to do positive things, we can enjoy the reward of achieving our goal incrementally. Even small changes can help. Instead of “I resolve to eat no cookies this year” we can set the goal as “I resolve to do a push-up instead of eating a cookie every day.” Eventually, we will focus more on the positive action, the push-up, than the negative one, the cookie. This way our brain will spend more time focusing on the things we resolve to do!

When we follow through on a resolution, we are making a behavioral change. These changes are governed by our brain, and mimic changes within it. Some of our most popular resolutions correspond to changes in our reward pathway, called the mesocorticolimbic circuit. This contains several brain structures and is a part of the brain that is hijacked by addictive drugs. Two structures in particular, the nucleus accumbens and striatum, seem to be affected by things like resolutions. Addictive things including sugar decrease these areas’ sensitivity to naturally occurring dopamine. This makes the brain need more and more of those items to find the same level of reward. Lowering sugar, drugs, and alcohol can help restore the dopamine receptors and give your brain a fighting chance. Studies have also shown that exercise increases dopamine sensitivity of the mesocorticolimbic circuit, giving some protection against addictive undesirable behaviors. Other behaviors that we do frequently and repetitively will also make changes to the brain’s pathways, reinforcing the behaviors.

So now we know how to structure our resolutions, and how our brain responds to changes, but what can we do to make sure we don’t give up on our resolutions? The most important change is a lifestyle change. This is true with resolutions, but also with weight loss medications, smoking cessation, etc. Changing the triggers for what you want to avoid makes it easier to do the activities you desire. Even small changes – like sitting in a different chair than your preferred cookie-binge recliner – can make the process easier. Along with this, we want to make sure we have strategies to deal with tempting situations. If work has cookies on Fridays, drinking a lot of water can fill your stomach and help alleviate the temptation. Unexpected situations can also arise. If your mother invites you for afternoon tea and biscuits – only for you to learn that “biscuit” is British for “cookie”- having a plan to politely decline can be very handy. Finally, realize that resolutions aren’t all-or-nothing. If I succumb to chocolatey chip temptation and eat a cookie today, it doesn’t mean I’ve failed at my resolution and should give up. Instead of looking at hiccups as failures, look at them as learning opportunities. These are great opportunities to learn what triggered your lapse and practice a strategy to act positively and avoid this trigger in the future.

Taken together we have solid starting points for our resolutions. Resolve to do positive actions that you want to accomplish. Structure resolutions to be activation based and give yourself opportunities to celebrate success instead of regretting failure. Give yourself the advantage of changing your lifestyle to accommodate and incentivize your resolution. Give yourself a break when you miss a day and learn how to move forward better tomorrow. When we resolve to do things we want to do, we only have to countdown the days until we celebrate another New Year and a successful resolution!

Written by Benton Lowey-Ball, BS Behavioral Neuroscience


Larimer, M. E., Palmer, R. S., & Marlatt, G. A. (1999). Relapse prevention. An overview of Marlatt’s cognitive-behavioral model. Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism, 23(2), 151–160.

Oscarsson, M., Carlbring, P., Andersson, G., & Rozental, A. (2020). A large-scale experiment on New Year’s resolutions: Approach-oriented goals are more successful than avoidance-oriented goals. PLoS One, 15(12), e0234097.

Trifilieff, P., & Martinez, D. (2014). Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity. Neuropharmacology, 76 Pt B(0 0), 498–509.

Wimmer, S., Lackner, H. K., Papousek, I., & Paechter, M. (2018). Goal orientations and activation of approach versus avoidance motivation while awaiting an achievement situation in the laboratory. Frontiers in psychology, 9, 1552.


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Most of us have heard by now that chocolate is healthy, or that a small amount is healthy, or that you can eat an infinite amount of chocolate and it will be healthy forever. Where do these claims come from, and do they add up? 

There is evidence of people consuming chocolate up to 1600 years ago. It is native to the Americas and was said to be the “food of the gods” in mesoamerica. Today we think of chocolate as sweet and delicious and the perfect food, but this was not always the case. Chocolate is thought to have originally been mixed with water and drunk as a bitter, spiced beverage. During the 1500’s chocolate was brought to Europe, where it was considered as exotic as Mars. Healers claimed chocolate healed diseases of the liver and stomach, and that it could help with fever.

By 1631, chocolate had changed. Adding sugar was now typical, and the prescriptions for chocolate had changed as well. Chocolate in this era was used to help gain weight (likely due to sugar), stimulate the brain (likely due to caffeine), and aid in digestion.

Ironically, the same benefits chocolate seemingly presented to chronically underweight pre-industrial people has become a bit of a problem for us. By the mid to late 1800’s there were investigations into the health problems associated with chocolate’s additives – milk and sugar. They found that regularly eating fatty, sugary foods might not be healthy. By the 1900’s chocolate began to be associated with obesity, tooth decay, gum disease, etc. The “dark” chocolate age had begun.

By the early 2000’s, the opinion pendulum on chocolate had begun to swing back. Individual components of chocolate, such as flavanols, methylxanthines (Methyl-zan-theens) and polyphenols were shown to be beneficial to heart function in a lab. Since then there have been claims that chocolate helps everything from cardiovascular problems to metabolic ones and even cancer. It looked like chocolate was on a holiday high in medical opinion.

Unfortunately, these results may have been candy-coated. Research trials haven’t shown as much benefit as in the lab. One sweet spot picked up by newspapers was an observational meta-study which looked at over 300,000 participants. This study looked for an association between chocolate consumption and coronary artery disease (CAD). They found that people who ate chocolate more than once a week (or more than 3½ times a month) had a significantly lower incidence of CAD, heart attack, heart failure, and acute coronary syndrome. It is important to note that this was not an interventional study, and only looked at associations. Additionally, this didn’t take into account the type of chocolate eaten. Finally, this study found that some negative indicators actually rose, likely due to the extra calories from fats and sugars added to chocolates.

The best way to look for health benefits or drawbacks of any medicine is to do an interventional experiment – a clinical trial. This is where you compare groups randomly assigned to take chocolate or a placebo. An examination of 15 such studies where chocolate was the medicine sadly found few benefits. These studies looked for changes in:

  • Skin condition
  • Weight / BMI
  • Blood glucose
  • Blood pressure
  • Cholesterol
  • Cognitive function

When looking at all 15 studies, there was no significant change in any of these indicators. The only significant change across studies was a decrease in triglycerides. This can be helpful, as high triglycerides can be a risk factor for CAD, stroke, and pancreatitis. Overall, however, chocolate doesn’t appear to be the miracle drug it’s been touted as for the last millennium and a half. As we have learned countless times, using randomized clinical (interventional) trials is the best and often only way to discover if medicines have the effects people claim!

Interventional trials are conducted at clinical research organizations such as ours, ENCORE Research Group. We are a premier clinical research organization that has conducted more than 2,500 clinical trials over 25 years and has worldwide recognition for providing patients access to cutting edge medical research.

Written by Benton Lowey-Ball, BS Behavioral Neuroscience


Krittanawong, C., Narasimhan, B., Wang, Z., Hahn, J., Virk, H. U. H., Farrell, A. M., … & Tang, W. W. (2021). Association between chocolate consumption and risk of coronary artery disease: a systematic review and meta-analysis. European journal of preventive cardiology, 28(12), e33-e35.

Lippi, D. (2015). Sin and pleasure: the history of chocolate in medicine. Journal of agricultural and food chemistry, 63(45), 9936-9941.

Montagna, M. T., Diella, G., Triggiano, F., Caponio, G. R., Giglio, O. D., Caggiano, G., … & Portincasa, P. (2019). Chocolate,“food of the gods”: History, science, and human health. International Journal of Environmental Research and Public Health, 16(24), 4960.

Tan, T. Y. C., Lim, X. Y., Yeo, J. H. H., Lee, S. W. H., & Lai, N. M. (2021). The health effects of chocolate and cocoa: A systematic review. Nutrients, 13(9), 2909.


December 12, 2022 BlogUncategorized

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With the onset of frosty weather and short days, we can all use a boost. Luckily, giving gifts can produce a “warm glow” to help out. This isn’t just decorative talk, giving gifts has been shown to increase well-being in people across the globe. In study after study, psychologists have found that acts of kindness, such as giving gifts, have positive results on both the receiver and the giver.

In one study, scientists gave children treats while measuring happiness. The children were then asked to give treats to a puppet. These could be their own treats or ones from a researcher’s supply. The data showed the children were happier to give a treat to the puppet than to receive one for themselves and were happiest when they gave their own treat to the puppet. Overall, the cheer of giving seemed maximized when giving away more important gifts.

Why could this be, though? Why would gift giving be beneficial for the person losing something? Could it be that giving a gift clears your already extremely crowded gingerbread house and increases your Feng shui? The real answer is that gift giving is a prosocial behavior. This means that it promotes social acceptance and friendship. This is a positive behavior in social contexts. Prosocial behaviors are seen in several social animals, including apes and dogs.

Scientists have shown that giving gifts can increase synchronization between friends. In two studies, scientists hooked pairs of friends up to brain scanning devices. The friends performed cognitive tasks, then one would give the other a gift (at a random time), and they would perform the task again. The scientists found that accuracy on the tasks increased. In addition, activity increased in the dorsolateral prefrontal cortex (DLPFC). This is part of the brain located beneath the hairline (assuming you have hair). It is associated with decision making and memory, and is also implicated in suppressing selfishness and building relationships. This helps with cognitive tasks, but also with forming and maintaining friendships. Even more interesting, they found that the brain waves of friends were synchronizing! The brainwaves measured in the DLPFC would “sync up” and produce similar patterns after gift giving! Giving a gift doesn’t just increase friendship, it helps you think like your friends too!

The DLPFC isn’t the only section of the brain that’s active when giving. When giving to charity, people’s mesolimbic reward system and subgenual areas activate. The mesolimbic reward system is a general reinforcement pathway in the brain, and also rewards for things like food, sex, and drugs.  The subgenual area releases important hormones such as oxytocin (the love hormone) and vasopressin. These make us feel good and increase our social happiness.

So this winter, give gifts to keep yourself warm inside and out. By giving gifts you can increase your own happiness, strengthen bonds with friends, and release dessert-like chemicals in the brain. Also, consider giving the gift of health to others by volunteering for a clinical trial at one of our ENCORE Research Group locations. 

By Benton Lowey-Ball, BS Behavioral Neuroscience


Aknin, L. B., Barrington-Leigh, C. P., Dunn, E. W., Helliwell, J. F., Burns, J., Biswas-Diener, R., … & Norton, M. I. Prosocial Spending and Well-Being: Cross-Cultural Evidence for a Psychological Universal.

Aknin, L. B., Hamlin, J. K., & Dunn, E. W. (2012). Giving leads to happiness in young children. PLoS one, 7(6), e39211.

Balconi, M., Fronda, G., & Vanutelli, M. E. (2019). A gift for gratitude and cooperative behavior: brain and cognitive effects. Social cognitive and affective neuroscience, 14(12), 1317-1327.

Balconi, M., Fronda, G., & Vanutelli, M. E. (2020). When gratitude and cooperation between friends affect inter-brain connectivity for EEG. BMC neuroscience, 21(1), 1-12.

Curry, O. S., Rowland, L. A., Van Lissa, C. J., Zlotowitz, S., McAlaney, J., & Whitehouse, H. (2018). Happy to help? A systematic review and meta-analysis of the effects of performing acts of kindness on the well-being of the actor. Journal of Experimental Social Psychology, 76, 320-329.

Moll, J., Krueger, F., Zahn, R., Pardini, M., de Oliveira-Souza, R., & Grafman, J. (2006). Human fronto–mesolimbic networks guide decisions about charitable donation. Proceedings of the National Academy of Sciences, 103(42), 15623-15628.


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The familiar wub-dub of the heart accompanies us throughout our lives, providing a gentle beat that keeps us alive. But for some of us, the beat might not be so steady. For 33 million people worldwide, the heartbeat lacks a rhythm at all. It sounds like shoes in a clothes dryer and gets progressively worse. This is called Atrial Fibrillation, or AFib for short. The risks of AFib increase with age, and there is a genetic component as well. Other risk factors include:

  • Heart failure
  • Ischemic (low blood flow) heart disease
  • High blood pressure
  • Diabetes
  • Obesity
  • Sleep Apnea

In order for AFib to occur, doctors believe there needs to be a trigger and a substrate. A trigger, or driver, is the electric signal that travels to the heart and initiates an arrhythmic event. This can be from several areas, but is frequently from one of the big pulmonary veins that carry oxygen to the heart. A substrate is the underlying condition that makes a sustained event possible and could be structural or electrical. Common substrates include the electrical system of the heart, dilation (or stretching) of the atrium, cellular-molecular changes, and/or an increase in disruptive cells called fibroblasts. In general, many or all of these changes would occur, leading to constant AFib.

AFib is very dangerous. Other than a wonky pulse, there are three major complications: heart failure, stroke, and myocardial infarction (a heart attack). Heart failure is when the heart can’t pump enough blood, while stroke and myocardial infarction can be caused by stray blood clots. Heart failure is both a risk and a symptom, which illustrates one way in which AFib is a progressive disease. Through complicated electric and biocellular mechanisms, long term AFib seems to cause more AFib.

Treating AFib has proven difficult. It is effective to treat the underlying risk factors, such as obesity and diabetes, but this is difficult and the actual cause of AFib isn’t always clear. Controlling the rhythm of the heart is also tough and risky, as messing with heart rhythm can easily lead to big problems. Atrial fibrillation ablation is an effective treatment. It is an intensive surgical procedure where doctors scar problem areas to reduce electrical activity. Even with this method, the risk of resurgence is over 30% after 5 years.

Two of the biggest complications of AFib are related to blood clots. Because of this – and the difficulty of other treatments – major pharmaceuticals often target thromboembolisms, or clots. The clotting system itself is very complicated. A simple version is that platelets activate and produce several enzymes. These enzymes make thrombin, which makes a big mesh-like protein called fibrin. This would be a slow process, except that thrombin also activates amplifier enzymes, which makes this process very fast. The fibrin then catches red blood cells and blocks wounds – or blood vessels. When these clots travel to the brain they can cause a stroke. When they restrict blood flow to the heart they can cause a myocardial infarction – a heart attack.

Classic anticoagulants, such as Warfarin (also called Jantoven and Coumadin) work by stopping the clots before they start. These are Vitamin K dependent anticoagulants and can be effective at reducing clots. Unfortunately, they are occasionally too effective. The biggest side effect of Vitamin K dependent anticoagulants is increased bleeding. This can be a serious problem for several patients, including high-risk older patients. 

Doctors are investigating new classes of medications which do not depend on vitamin K. These are called Non-vitamin K oral anticoagulants (NOACs) and some target the amplification pathway of clotting instead. There are  currently four FDA-approved NOAC drugs on the market; dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa). Thrombin and fibrin still get produced and some clotting can occur, but the rapid amplification is shut down. The hope is that this can allow the body to repair trauma and stop external bleeds without building internal clots from AFib. With your help and participation in clinical trials, we can push science without pushing clots.

By Benton Lowey-Ball, BS Behavioral Neuroscience


Iwasaki, Y. K., Nishida, K., Kato, T., & Nattel, S. (2011). Atrial fibrillation pathophysiology: implications for management. Circulation, 124(20), 2264-2274.

Wijesurendra, R. S., & Casadei, B. (2019). Mechanisms of atrial fibrillation. Heart, 105(24), 1860-1867.

Vann, M. R. (May 10, 2013) The Sound of an Afib Heartbeat. Everyday Health.


November 28, 2022 BlogC. DiffGastrointestinal

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Clostridioides difficile, C. difficile, or just C. diff is a particularly nasty bacteria that can make us very sick. The bacteria itself has the name difficile because it was difficult to isolate and study when it was first discovered. Forms of the problem bacteria are found all over the environment, but most can’t make us sick. The organism itself doesn’t kill cells like a virus; instead, it can produce toxins that can kill cells in the gut. C. diff has over 800 different strains, but only a few produce dangerous toxins. Overall, C. diff causes dangerous infections in hundreds of thousands of patients each year.

Several people have C. diff inside their gut already, but it doesn’t cause them problems. Other bacteria in our gut can outcompete C. diff and keep it from causing damage. Unfortunately, one of the biggest medical breakthroughs, antibiotics, can destroy these helpful bacteria and allow C. diff to start running amok. In fact, any kind of immunosuppression can increase your risk of developing C. diff, including HIV/AIDS medications and those used after organ transplants. Being above 65 years old is another large risk factor. Close contact with some animals, like pigs, can also pose a risk. The most dangerous forms of C. diff are spread from person to person. This occurs with our most vulnerable populations: those in hospitals and those in elderly care. Due to the innate nature of care, people in hospitals and care homes can be exposed to C. diff unknowingly.

How does C. diff survive in the notoriously clean hospital environment? The bacteria has a special trick up its sleeve; it can become dormant – and almost invincible. C. diff has two life cycle stages, the spore and vegetative stage. While in the spore stage, C. diff is inactive. It doesn’t need to eat or breathe. While in this stage it can survive in the environment, the stomach, through most antibiotics, and through alcohol washes. When a C. diff spore makes it into our gut, however, trouble can begin. It germinates in the duodenum – the part of the intestine connected to the stomach. Here it transforms into the vegetative stage. In the vegetative stage, C. diff is active. It can’t survive the stomach or in oxygen, but thrives in the intestines. Here it grows and reproduces. This is also where some strains produce dangerous toxins.

The toxins of C. diff can produce a host of issues. The toxins can degrade and kill intestinal cells and cause inflammation of the intestines. Major symptoms are diarrhea, inflammation of the gut, and tissue necrosis (cell death). Other symptoms can include:

  • Fever
  • Tenderness and pain in the stomach
  • Loss of appetite and nausea
  • A severely dilated colon (toxic megacolon)
  • Sepsis (severe infection response)
  • Death

So what can be done to fight C. diff? The first line of defense is the simplest: wash your hands! Prevention is the strongest barrier: avoid close contact with people who have an active infection and wash clothes and linens regularly. A medical professional (who should be wearing gloves!) can monitor any antibiotics an infected person is currently taking and might suggest probiotics. Some specific antibiotics target C. diff, including Metronidazole, Vancomycin, and Fidaxomicin. These may have unpleasant side effects, but can be effective. Treatments available include fecal microbiota transplantation (FMT), antitoxins, new antibiotics, and injectable antibodies. Additionally, prophylactics that can help protect the gut and vaccines against the dangerous toxins are in development. Keep an eye out, and with your participation in clinical trials, we can help protect those at the highest risk from  C. diff!

By Benton Lowey-Ball, BS Behavioral Neuroscience


Dayananda, P., & Wilcox, M. H. (2019). A review of mixed strain Clostridium difficile colonization and infection. Frontiers in microbiology, 10, 692.

Smits, W. K., Lyras, D., Lacy, D. B., Wilcox, M. H., & Kuijper, E. J. (2016). Clostridium difficile infection. Nature reviews Disease primers, 2(1), 1-20.

U.S. Department of Health & Human Services/Centers for Disease Control and Prevention (September 7, 2022). What is C. diff


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When EMTs arrive on the scene of an emergency, they have to remember their ABCs. These are Airway, Breathing, and Circulation. The absolute top priority for any patient is to ensure they have an open airway to breathe, that air is entering the lungs, and that the heart is pumping blood to the brain and other organs. This is also the most important thing our body does in daily life as well. We can go weeks without food, days without water, hours without ice cream, and minutes without oxygen.

In order to get oxygen from the lungs to our brain and organs, we rely on one of the most remarkable organs in our body: the heart. The heart pumps automatically, nonstop, 24/7, from womb to grave. It consists of four chambers, two on top, and two on the bottom. Each heartbeat pulls blood into the top two chambers and pumps it out of the bottom two. The bottom two are more muscular and do the heavy lifting. Unfortunately, the heart can deteriorate and lead to heart failure. 

Heart failure is a condition where the heart can’t pump well enough to deliver oxygen to the organs effectively. The heart is still pumping, but organs are not receiving enough oxygen to function. This is not good. Heart failure affects over six million Americans and ten times as many people worldwide. Risk factors for heart failure include:

  • Heart disease, including Coronary Artery Disease
  • High Blood pressure
  • Tobacco
  • Excessive alcohol
  • Poor diet
  • Lack of exercise
  • Obesity
  • Diabetes

Heart failure has several signs and symptoms. Some of the most consistent are edema and shortness of breath. Edema is fluid trapped in the body’s tissues and most often pools in the lower extremities and the abdomen. Shortness of breath is due to the heart failing to deliver enough oxygen. This is particularly prevalent when trying to do activities or when lying down. Shortness of breath can keep patients from exercising or sleeping, which only exacerbates problems. Patients who have limited exercise in their routine may not be aware of progressive difficulty, masking this important symptom.

Other symptoms can be broad and nonspecific. They include:

  • Sudden weight gain
  • Persistent coughing or wheezing
  • Lightheadedness and fainting
  • Depression
  • Nausea and loss of appetite
  • Irregular heartbeat, high pulse, and palpitations
  • Fatigue

If you have heart failure and find yourself experiencing several of these conditions simultaneously, especially with edema and shortness of breath, we urge you to contact your physician immediately. Additionally, you may want to keep track of your level of fatigue because this symptom increases as the heart failure progresses. The excellent news is that new and exciting monitoring devices are currently being developed to help patients manage their heart failure and determine if their condition is deteriorating.

Check out clinical research options available to you with ENCORE Research Group on our enrolling studies page. 

By Benton Lowey-Ball, BS Behavioral Neuroscience


Albert, N., Trochelman, K., Li, J., & Lin, S. (2010). Signs and symptoms of heart failure: are you asking the right questions?. American Journal of Critical Care, 19(5), 443-452.

Groenewegen, A., Rutten, F. H., Mosterd, A., & Hoes, A. W. (2020). Epidemiology of heart failure. European journal of heart failure, 22(8), 1342-1356.

U.S. Department of Health & Human Services/Centers for Disease Control and Prevention (October 14, 2022). Heart failure


November 16, 2022 Blog

We all know how Thanksgiving works. A giant meal with a giant turkey followed by tasty desserts. Then, after the meal, sleepiness sets in. But why? We usually blame the turkey and the tryptophan in the protein. But I’m a vegetarian, and I still get the post-thanksgiving snoozies. So, what is tryptophan, and does it make us tired, or is there something else to blame? This article contains a cornucopia of information to help answer these questions.

Tryptophan is an essential amino acid. Amino acids are the building blocks of proteins and are baked into many of the body’s needs. Being an “essential” amino acid means that we can’t create our own tryptophan and must instead gather it from the foods we gobble up. We need some tryptophan in our diet because it is used to create some critical molecules our body uses.

Two of these important molecules are the neurotransmitter serotonin and the hormone melatonin. These are critical little molecules derived from tryptophan and – interestingly, both interact with our sleep cycle. Serotonin acts on parts of the brain involved with learning, pain, social behavior, and sleep, among many others. Melatonin is like turkey dressing; it’s harvested further from serotonin and can increase sleepiness. Neither of these gets produced in large quantities after eating turkey, however. The large amount of other amino acids found in turkey protein keep tryptophan from making a pilgrimage to the brain after a meal because the amino acids compete for rides on the path to our brain.

So then, why do we feel tired after a big Thanksgiving meal? Well, one reason might be linking carbs (sugars) to tryptophan. Some carbohydrates can increase the ability of tryptophan to cross into the brain and get serotonin and melatonin cooking. Additionally, heavy carbohydrate intake has been associated with higher levels of tiredness and lower levels of alertness. This can be attributed to the rise in blood sugar from the heavy carbohydrates which is followed by release of insulin to lower the blood sugar.  The lower blood sugar causes you to feel tired.  So too much dessert might be resulting in a blood sugar crash after the meal.

In fact, too much of everything may be making you tired. When we eat large meals, the body activates the parasympathetic nervous system. This is also known as the “rest and digest” pathway, and does exactly what it sounds like. After a large meal, the body focuses on relaxation and digestion. This can cause extra blood flow into the stomach and can make you less alert and awake.

Turkey may get too much blame for our tiredness. As my sweet tooth will attest, the desserts may be a bigger culprit. So, this Thanksgiving, feel free to gather the family to feast (and nap) as you please, but squash the blame on the turkey!

Written by: Benton Lowey-Ball, BS Behavioral Neuroscience


Ballantyne, C. (2007). Does Turkey Make You Sleepy? Scientific American.

Høst, U., Kelbaek, H., Rasmusen, H., Court-Payen, M., Christensen, N. J., Pedersen-Bjergaard, U., & Lorenzen, T. (1996). Haemodynamic effects of eating: the role of meal composition. Clinical Science, 90(4), 269-276.

Mantantzis, K., Schlaghecken, F., Sünram-Lea, S. I., & Maylor, E. A. (2019). Sugar rush or sugar crash? A meta-analysis of carbohydrate effects on mood. Neuroscience & Biobehavioral Reviews, 101, 45-67.

Vreeman, R. C., & Carroll, A. E. (2007). Medical myths. Bmj, 335(7633), 1288-1289.


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Several of my friends hate flossing their teeth. They go months without flossing, which I think is pretty gross. But then an odd thing happens. About a week before their dental appointment, these same friends will start flossing. By the time they reach their appointment, they have unusually clean gums (though dentists can see through this fairly well, I’m told). On a different tone, some family members have a condition called White Coat Syndrome. When they go to the doctor’s office, their nervousness causes a spike in blood pressure or heart rate, giving deceptively high readings. What’s going on? Can psychological effects like these be used to our advantage?

The Hawthorne Effect is a term used to describe a very beneficial effect seen in clinical trials. This is named after a productivity study in Hawthorne Works, a Western Electric factory in the 1920s and 30s. The study was attempting to discover a link between the amount of light and productivity of workers. When increasing the amount of light, productivity increased. Strangely, when lowering the amount of light, productivity also increased! Researchers attributed the increase in productivity to the workers simply being observed. In research, we tend to see increased positive results for patients simply because we are observing them in a study.

Hawthorne Works

Let’s analyze a 2014 sleep study. Researchers measured 195 patients’ amount and quality of sleep at night. 81 days later, before any medical intervention, researchers measured the patients again. They found that patients slept an average of 30 minutes longer per night and had an increased quality of sleep. This was before any medication or intervention! The change was attributed to the Hawthorne Effect.

Patients at ENCORE Research Group comment on the excellent quality of care they receive during clinical trials. Instead of seeing a doctor for a few minutes once a year, patients see doctors and medical staff for much longer and are encouraged or required to call and report changes in health. Quality of care is increased and makes for a pleasant and healthful patient experience. Patients in clinical trials may also experience more observation time from medical professionals due to the attention to detail that clinical trials require for data integrity in studies.

Finally, patients are found to have better adherence to medication requirements while undergoing clinical trials. The increased emphasis on accuracy and adherence results in better patient outcomes, even when they are part of a placebo or standard-of-care group.

In clinical trials, we see these benefits and must account for them. Randomization of patients helps spread the effect. Everyone sees increased baseline results on average; we are interested to find out if those receiving investigational treatment do even better. Join a clinical trial today and experience the Hawthorne Effect for yourself… and floss your teeth!

Written by Benton Lowey-Ball, BS Behavioral Neuroscience


Benedetti, F., Carlino, E., & Piedimonte, A. (2016). Increasing uncertainty in CNS clinical trials: the role of placebo, nocebo, and Hawthorne effects. Lancet Neurol, 15, 736-47.

Cizza, G., Piaggi, P., Rother, K. I., Csako, G., & Sleep Extension Study Group. (2014). Hawthorne effect with transient behavioral and biochemical changes in a randomized controlled sleep extension trial of chronically short-sleeping obese adults: implications for the design and interpretation of clinical studies. PLoS One, 9(8), e104176.

ENCORE Research Group. (2020, October 14). Hawthorne effect.[Video]. Youtube.

Mayo, E. (1993). The human problems of an industrial civilization. The Macmillan Company. 

McCarney, R., Warner, J., Iliffe, S., Van Haselen, R., Griffin, M., & Fisher, P. (2007). The Hawthorne Effect: a randomised, controlled trial. BMC medical research methodology, 7(1), 1-8.


October 24, 2022 BlogCirrhosisLiverNASH

The liver is critical to maintain body function. Unfortunately, millions of Americans suffer from liver disease. When the liver suffers prolonged damage, scarring can form. This scarring, called cirrhosis, is debilitating and reduces liver function. Cirrhosis is sometimes called end stage liver disease, and is irreversible. On its own, cirrhosis can be painful and cause suffering, but is frequently made worse through complications. One of these is encephalopathy.

Encephalopathy is a broad term used to describe several diseases and disorders. The unifying concept is that these diseases change the brain’s structure or function. When the cause of this change is through cirrhosis, the condition is called hepatic encephalopathy. This is the condition caused by cirrhosis of the liver, and can be horrible. It comes with a high mortality rate, over 25%, and affects over 30% of people with cirrhosis.

The full mechanism of how hepatic encephalopathy works isn’t fully known. The most likely candidate for hepatic encephalopathy is a buildup of ammonia in the bloodstream. Ammonia is a common waste product for many cells. A damaged liver has trouble filtering ammonia from the blood. The ammonia accumulates in the blood where it can travel to the brain and cause confusion and disorientation at first. Additionally, liver damage can result in reduced muscle mass and immunosuppression. Muscles can remove excess ammonia from the blood, but may become damaged without a functional liver and be unable to help. A reduced immune system can lead to a buildup of harmful bacteria that produce excess ammonia. These combine to create excess toxic levels of ammonia in the bloodstream that make their way to the brain.

The brain is normally protected from toxins in the blood through the blood brain barrier. Astrocytes are special cells in the brain that surround blood vessels and help filter the blood, letting only specific nutrients and particles through. Excess ammonia in the blood appears to damage astrocytes, with wide ranging effects on the brain. When the blood-brain barrier is reduced, toxins can enter the brain. This can lead to damage in neurotransmission, meaning the brain cannot function effectively. There is also an increased chance of infection in the brain and alterations to brain metabolism.

This is a devastating compilation which can drastically reduce quality of life. In the early stages of hepatic encephalopathy, people may experience a general slowing of the brain. This is noticeable in attention, some motor response, and other vague areas. As the encephalopathy progresses, people experience more severe symptoms. Changes in personality have been reported, such as irritability and impulsivity. They may angrily buy m&ms in the checkout line. It also slows the brain and reduces its ability to function. People may become disoriented, experience distortions of time and space, become excessively sleepy, and descend into a coma. Clearly this condition needs medical attention!

Luckily, hepatic encephalopathy can be reversible in many patients! The most important short-term treatment is to get rid of excess blood ammonia. The current standard of care is lactulose, a chemical that binds to ammonia and expels it rectally. This helps in the short term, and can also be recommended to help reduce recurrence. Though effective, lactulose is a laxative and can cause bloating, cramping, and other undesirable side effects. Because of this, many patients don’t like using this drug long term. Since the immune system is suppressed with cirrhosis, antibiotics may help as well. In fact, antibiotics may be helpful in preventing hepatic encephalopathy in the first place by eliminating harmful, ammonia producing bacteria before they can produce too much ammonia. Used with or without probiotics and drugs that help restore normal brain chemistry, we may be able to lower the burden of hepatic encephalopathy for those who suffer.

Written by Benton Lowey-Ball, BS Behavioral Neuroscience


Bustamante, J., Rimola, A., Ventura, P. J., Navasa, M., Cirera, I., Reggiardo, V., & Rodés, J. (1999). Prognostic significance of hepatic encephalopathy in patients with cirrhosis. Journal of hepatology, 30(5), 890-895.

Ferenci, P. (2017). Hepatic encephalopathy. Gastroenterology report, 5(2), 138-147.


In science and medicine we measure if and how well things work using measurements. This idea may sound simple, but it’s often a challenge to find out exactly what to measure – and how. We typically measure things that can change – things that can vary. We call these things variables. Variables can be broadly split into two major categories: dependent and independent. Either type of variable can change, the difference is what changes them.

Independent variables are changed by researchers, particularly in clinical (patient) research. This variable in a medical research study is what we are testing. The changes to an independent variable may include dose, length, and method of drug delivery. We evaluate independent variables that may change outcomes of the people in a study – but sometimes they do not. In order to understand the effect of medicines, researchers test the medicine against a control. The control could be a placebo (something that has no effect) or a standard of care (the current normal medicine).

Dependent variables are what we expect to change during a trial. In a clinical research, we may expect changes in blood pressure, cholesterol levels, disease symptoms, mortality, and other categories. In a well designed study, we assess changes in the dependent variables related to changes in the independent variables. There is always the chance that the dependent variables are changed by other things, however. A patient might take a new blood pressure medicine but retire from their job. The reduced stress could decrease their blood pressure even if the medicine did not. 

Because of individual changes in people’s circumstances, researchers use statistics to find trends. If your blood pressure medicine was only studied on the one person above, you might have erroneous results. Instead clinical trials have dozens, hundreds, or even thousands of participants. With large populations these little differences get figured out. One person might retire, but another might get fired, having an opposite effect. Altogether, statistical analysis can help discover if any changes in the dependent variable are due to the effects of the independent ones.

Chart 1. Each amount of Rosuvastatin on the left corresponds to an amount of LDL on the right. The dependent variable (LDL levels) change in proportion to the amount of independent variable (rosuvastatin) taken by the patient.

Other variables exist in a study. The most concerning of these variables is known as a confounding variable. This is a variable that can undermine the study at a fundamental level. A confounding variable can be introduced by researchers and might include things like placing all overweight patients in the 10 mg group and all underweight people in the placebo group. ENCORE Research Group (and any legitimate clinical research group) avoids confounding variables and bias by randomizing patients. Patients are randomized through an impartial method (usually a computer program) which will randomly place patients into any of the test groups. By randomizing patients, we can avoid the most concerning confounding variables and make sure we are studying what we intend to!

To learn more about the clinical trial process, call our Recruitment Team at (904) 730-0166.

Written by Benton Lowey-Ball, BS Behavioral Neuroscience


Schweiger, C. (2003). Clinical trials with rosuvastatin: efficacy and safety of its use. Italian Heart Journal: Official Journal of the Italian Federation of Cardiology, 4, 33S-46S.

Stewart, P. A. (1978). Independent and dependent variables of acid-base control. Respiration physiology, 33(1), 9-26.


October 10, 2022 BlogInfluenzaVirus

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A pandemic spread around the planet in the first quarter of the century. Not this century, however, but the last. The 1918 Flu Pandemic was the largest and deadliest outbreak of disease since the bubonic plague in the 1300s. The first official reported case was in Kansas in 1918. This gives the disease its proper name, the 1918 Influenza Pandemic. A much more common name, however, is the Spanish Flu.           

The name Spanish Flu is an unfair name. Spain lost around a quarter million people to the 1918 Influenza. This is less than half as many as the USA, and fewer than Afghanistan, Mexico, Russia, Italy, and Japan. On top of that, India lost somewhere above 18 million people, and China between four and nine million. The big difference in losses was due to Spain being neutral during World War I. Because of this, they weren’t shy about publishing accurate data. Spain was the first country to publicly disclose that the pandemic was real, and other countries underreported or lied about numbers for years. This may strike some as familiar; during the COVID-19 pandemic, several national and local governments around the world tried to downplay the severity of COVID for political gain.           

But what is influenza? Influenza, known as the flu, is very similar to COVID-19 in many ways. It is a viral infection, and its primary symptoms are cough, fever, joint pain, headache, body aches, and others. However, more serious complications such as pneumonia, liver damage, or brain problems can be triggered by influenza. It spreads through the air and can survive in water. Soap, changes in pH, and heat can destroy the influenza virus. The most dangerous part of influenza is how variable it is.  

The influenza virus has several subtypes, and each of these mutates constantly.  This makes it hard for the immune system to detect and fight new forms of the virus. It also means the specific symptoms of infections can change. In the 1918 influenza pandemic, the strain of influenza was particularly deadly for young, healthy people. This resulted in a lot of excess deaths compared to other strains. 

The 1918 Influenza Pandemic was made much worse because of World War I. The war resulted in overcrowded barracks, troops stuffed in ships, and people crowding in shelters. Additionally, it spread wide and far as governments deployed troops around the world. A lack of accurate reporting and proactive measures certainly didn’t help. The biggest difference between then and now was medicine. 

1918 was over a hundred years ago, but in the realm of medicine, it may as well have been much longer. Viruses were only discovered around 20 years prior, and there were no effective ways to fight them. There were no antiviral medications. For patients that developed pneumonia, there were no ventilators and no antibiotics. On top of this, there was no influenza vaccine. 

The “Spanish flu” of 1918 helped refocus medical attention around pandemics – particularly influenza. In the early 1930s new vaccines were being developed from chicken eggs, and less than ten years later, the first experimental influenza vaccines were developed. Today, our yearly flu shots come from a direct line of response from the 1918 influenza pandemic. A century later, we have come a long way with medical advances, and since we know the influenza virus mutates regularly, the best way to help continue the fight against it is to participate in a clinical trial for the latest flu vaccines.

Written by Benton Lowey-Ball, BS Behavioral Neuroscience


Hayden, F. G., & Palese, P. (2009). Influenza virus. Clinical virology, 943-976.

Jester, B., Uyeki, T. M., Jernigan, D. B., & Tumpey, T. M. (2019). Historical and clinical aspects of the 1918 H1N1 pandemic in the United States. Virology, 527, 32-37.

Johnson, N. P., & Mueller, J. (2002). Updating the accounts: global mortality of the 1918-1920″ Spanish” influenza pandemic. Bulletin of the History of Medicine, 105-115.

Knobler, S. L., Mack, A., Mahmoud, A., & Lemon, S. M. (2005). The threat of pandemic influenza: are we ready? workshop summary.

Mayer, J. (29 January 2019). “The Origin Of The Name ‘Spanish Flu’”. Science Friday. Retrieved 30 July 2021.

CDC, National Center for Immunization and Respiratory Diseases. (September 28, 2022). Similarities and Differences between Flu and COVID-19​.


September 27, 2022 BlogDiabetes

How does the body use energy? After we eat, most food is broken down into parts that cells can use for energy. The bloodstream carries these pieces through the bloodstream to our cells, which let them in and convert food to energy. In some cases, the cells don’t let food particles in. In these cases, the problem may be diabetes.

Cells need to separate their insides from the environment around them. Cells only let in specific molecules at specific times. Insulin is the molecule that tells cells to let in sugars in the form of glucose. It is produced by the pancreas and is released when the pancreas detects high levels of sugars in the blood. In some cases, such as with obesity, fatty acids can disrupt how cells absorb and use sugar in the blood. When this happens, cells are less sensitive to insulin and absorb less blood sugar per unit of insulin in the blood. Since blood sugar stays high, the pancreas produces more and more insulin, which has less and less effect. Cells can’t respond to all the excess insulin and are increasingly resistant to its effects.

Insulin is also the hormone the pancreas uses to communicate with the liver about blood sugar. When the liver detects insulin it converts blood glucose into glycogen, a short term storage molecule. When high levels of insulin persist, the liver sends extra energy to fat cells.

After long periods of insulin resistance, the pancreas itself stops working properly. Pancreatic cells become damaged and unable to produce insulin. This is called Type 2 Diabetes (T2D). With T2Ds, blood sugar stays high, insulin stops being produced, any produced insulin is less effective, and cells stop metabolizing properly. On top of this, the body gains excess weight which can stress the pancreas further. Other symptoms include cardiovascular disease, nerve dysfunction in the extremities (called neuropathy), and increased chance of death.

Diabetes is very common in the United States. Tens of millions of Americans have T2D. Type 1 diabetes is an autoimmune disorder which results in pancreatic damage. Type 2 diabetes is an insulin resistance disorder and can have a slow onset.  Major risk factors are obesity and lack of exercise. These should be the first steps to managing T2D as well.

When a healthy diet and exercise aren’t enough to manage healthy blood sugars, or aren’t an option, several key medications exist to help with type 2 diabetes:

  • Insulin: By injecting insulin with meals, the effects of a compromised pancreas can be reduced. Synthetic insulin, such as glargine, is in wide use.
  • Glucagon-like peptide-1 receptor agonists (GLP-1 RA): These stimulate the pancreas and coerce it into properly releasing the correct amounts of insulin. It slows some pancreatic cells and helps restore the pancreas-liver communication lines. One generic name for GLP-1 RA drugs is semaglutide, often branded as Ozempic and Rybelsus. A benefit of these drugs is that a common side effect is weight loss, one of the drivers of type 2 diabetes.
  • Metformin: Originally inspired by the French Lilac plant, metformin lowers blood sugar levels by acting on the liver, bloodstream, intestinal tract, and even the gut microbiome! The complex action on different areas of the body results in overall lower blood sugar levels.
  • SGLT2 Inhibitors: These act on the kidneys, changing the threshold of reabsorption of sugar so they excrete more than usual removing blood sugar through the urine. 

Altogether, there are several medications which may be helpful for controlling type 2 diabetes. Discovering how these medications interact, lowering side effects,  and finding treatments that are easy and straightforward is key. If you have type 2 diabetes, look for enrolling studies soon and improve your diet and exercise if possible!

Written by Benton Lowey-Ball, BS Behavioral Neuroscience


Berg, J. M., Tymoczko, J. L., & Stryer, L. (2012). Biochemistry (7th Ed., pp 798-803). New York: W. H. Freeman and Company

DeFronzo, R. A., Ferrannini, E., Groop, L., Henry, R. R., Herman, W. H., Holst, J. J., … & Weiss, R. (2015). Type 2 diabetes mellitus. Nature reviews Disease primers, 1(1), 1-22.

Olokoba, A. B., Obateru, O. A., & Olokoba, L. B. (2012). Type 2 diabetes mellitus: a review of current trends. Oman medical journal, 27(4), 269.

Rena, G., Hardie, D. G., & Pearson, E. R. (2017). The mechanisms of action of metformin. Diabetologia, 60(9), 1577-1585.

U.S. Department of Health & Human Services/Centers for Disease Control and Prevention (August 10, 2021). Insulin Resistance and Diabetes

U.S. Department of Health & Human Services/Centers for Disease Control and Prevention (December 16, 2021). Type 2 Diabetes

Witters, L. A. (2001). The blooming of the French lilac. The Journal of clinical investigation, 108(8), 1105-1107.


September 19, 2022 Alzheimer's DiseaseBlog

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Methods used to diagnose Alzheimer’s disease are changing. In the past, the only definitive way to diagnose Alzheimer’s disease was after death, by an autopsy, which is not exactly helpful for treatment. The autopsy would reveal both amyloid plaques and tau tangles in the brain; these are hallmarks that characterize Alzheimer’s disease. Thankfully, science has drastically improved over the years. We currently have spinal fluid tests that look for these two key biomarkers and imaging tests that show changes in the brain.

A recent example of other evolving diagnosis methods is COVID-19. Early in the pandemic, when there were no COVID-19 tests, the only way to know if someone might have the virus was to check for a fever. Nowadays, we look for biomarkers – such as with a rapid antigen test – which can detect antigens to the virus even in asymptomatic people. 

We now understand that a person can be suffering from the progressive nature of Alzheimer’s even if they do not yet show signs of cognitive impairment. Without biomarker testing, most patients’ first symptoms are memory loss, including long and short-term. Alzheimer’s is usually associated with increased age because the biological underpinnings of the disease accumulate over time. Diagnosis can be made by using something called the ATN framework. This framework describes the two major proteins involved, amyloid plaques and tau tangles, and the associated neurodegeneration – changes in the brain structure.

Let’s discuss the AT part of ATN: the two protein accumulations called amyloid plaques and tau tangles. It is no coincidence that these are also the biomarkers sought by scientists and doctors when diagnosing Alzheimer’s. Amyloid plaques are bundles of protein that build up outside of cells in the brain. They disrupt how cells connect and communicate with each other. Tau tangles are proteins found inside the neurons. In a healthy neuron, tau proteins help stabilize the microtubule that transfers nutrients. In Alzheimer’s patients, the tau proteins become corrupted and tangled, blocking the neuron’s transport system. This leads to cell death. As more cells die and neural network connections break down, areas in the brain begin to shrink.  In the late stages of Alzheimer’s disease, there is widespread loss of brain volume.

The N of ATN is neurodegeneration which is the deterioration of neurons causing specific structural changes to the brain. A structural MRI and a radioactive PET scan are two classic methods of determining neurodegeneration. These are effective as staging tools, discovering how far along the disease has progressed. They are effective but can be expensive and time-consuming.

The good news is that researchers are currently working on blood tests that will hopefully be able to detect tau biomarkers quickly and easily. A blood test should be easy, cheap, and relatively simple. With luck, these early biomarker findings will also help drive the effectiveness of clinical therapies, paving the way for better Alzheimer’s treatments in the years to come.

By Benton Lowey-Ball, BS Behavioral Neuroscience


Kandel, E. R., Schwartz, J. H., Jessell, T. M., Siegelbaum, S., Hudspeth, A. J., & Mack, S. (Eds.). (2000). Principles of neural science (Vol. 4, pp. 1149-1159). New York: McGraw-hill.

Largent, E. A., Wexler, A., & Karlawish, J. (2021). The Future Is P-Tau—Anticipating Direct-to-Consumer Alzheimer Disease Blood Tests. JAMA neurology, 78(4), 379-380.