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On June 25th, 2024, Flourish Research, a portfolio company of NMS Capital, announced its partnership with ENCORE™ Research Group. Dr. Michael Koren, founder and CEO of ENCORE™, has scaled the organization significantly since its inception in 1997.  ENCORE™ is comprised of an extensive physician network in Northern and Western Florida that provides an effective and differentiated approach to clinical research. ENCORE™ has conducted 3,200+ clinical trials across 50+ therapeutic areas. 

Excerpt from NMS/Flourish press release:

Dr. Koren said, “We have been very impressed during our interactions with the Flourish team and feel confident that we’ve found the right partner for our next phase of growth. Our staff and extensive network of physician investigators have expressed enthusiasm about our future with Flourish, working together to provide the best clinical trial services as part of a national company.”

CEO of Flourish Research, Reinhold Schulz, added, “We are excited to welcome ENCORE™ to the Flourish family. I’ve gotten to know Dr. Koren and his key lieutenants very well and the cultural fit was evident from our initial meetings. ENCORE™ brings expertise that will be additive to Flourish and has a robust backlog and pipeline of studies that will bring immediate value to the combined organization.”

Senior Partner at NMS Capital, Luis Gonzalez, stated “The partnership with ENCORE™ further enhances Flourish’s geographic footprint and capabilities in its core therapeutic areas while bringing a deep bench of scientific thought leaders. The transformative partnership will provide ENCORE™ the opportunity to leverage the significant infrastructure investment Flourish has made in its differentiated patient recruitment, commercial, and diversity strategy. This approach will result in a win-win for our patients, employees, and biopharma customers”

NMS Capital, formed in 2010, is a private equity firm with $1.5+ billion in assets under management. NMS Capital focuses on driving sustainable growth for healthcare and business service companies.


Please visit the company websites for more details:


On May 31, 2024, The US FDA approved Moderna’s mRESVIA(R) respiratory syncytial virus (RSV) vaccine for adults over 60 years of age. RSV is a highly contagious virus that infects the lower lungs and can cause pneumonia. It causes thousands of deaths per year among older patients in the United States. One of the major structures needed for RSV to infect a host cell is the fusion, or F glycoprotein. This structure enables the virus to merge with human cells and deliver its contents. mRESVIA(R) is an mRNA vaccine, the first mRNA vaccine to be approved other than for COVID-19. This vaccine instructs our cells to recognize and destroy the F glycoprotein present on RSV, providing significant protection of the lower airway from infection. Jacksonville Center for Clinical Research and Fleming Island Center for Clinical Research participated in the Phase II ConquerRSV Trials. Moderna expects mRESVIA(R) to be available for the 2024-2025 RSV season.



June 7, 2024 BlogCOPDPulmonary

When a looming deadline stresses me out, I often remember the classic advice to take a deep breath – but what if you can’t? This may be the case for people with chronic obstructive pulmonary disease, also called COPD. COPD is a progressive lung disease that may feel like you are trying to breathe through a tiny cocktail straw. This difficulty in breathing is caused by the deterioration of the structure of the lungs. It affects around 10% of the global population and nearly 15% of Americans, resulting in approximately 150 thousand deaths per year in the US. COPD rates increase as socioeconomic status drops, meaning it is more prevalent among poorer individuals.

COPD symptoms can range from mild to severe. Shortness of breath, cough, and excess phlegm are common. More severe COPD can result in hospitalization and death. Cardiovascular disease, diabetes, obesity, and chronic bronchitis both affect and are affected by COPD.  Lifelong accumulation of damage to the lungs characterizes COPD, with risk factors including most things that affect lung health. Some risk factors can’t be helped, like genetics or lung development from childhood. Others are environmental, including air pollution and infections like tuberculosis or HIV. Several risks can be mitigated through lifestyle choices, the most important being smoking. Smoking directly puts destructive particles into your lungs, greatly increasing your chances of developing COPD. This includes cigarettes, but also vaping, and marijuana. Inactivity, a poor diet, and jobs that expose you to particulate matter, like stone dust and pesticides, also contribute. The final risk factor is time. Lung capacity peaks in your early 20s and damage to the lungs from the above causes accumulates over time. So how do these things cause damage, and what can we do about it?

To understand COPD, let’s first inhale a little crash course on the lungs. I always see lungs drawn like they’re giant balloons, but they’re really more like sponges. The airway moves from the big throat to smaller and smaller fractal channels called bronchi and bronchioles until they reach the alveoli. These are teeny-tiny little balloons, and there are hundreds of millions of them in the lungs. These tiny sacs have thin walls and are the interface between air and blood, allowing for carbon dioxide to be exchanged for fresh oxygen. The tiny sacs provide a lot of surface area for this exchange to take place. Altogether, the inner surface of all the alveoli is called the lung parenchymal, and its surface area is close to the size of a tennis court! The lungs can’t expand on their own, so the smooth muscle of the lungs keeps bronchi and bronchioles from collapsing. When the lung is damaged over time, COPD may occur. This damage manifests in the airway, the alveoli, or both.

The airway, made up of bronchi and bronchioles, can become inflamed, resulting in bronchitis (bronchi + itis, meaning inflammation of). The lungs have their own immune system, including a slimy mucus layer, but chronic insults to the lungs (like smoking for years and years) can degrade this system. With bronchitis, big and dangerous immune cells like macrophages, neutrophils, and lymphocytes may enter the lungs. These cells are good at removing invaders but can cause damage to surrounding tissue through inflammation. When the damage lasts for years, this chronic inflammation can narrow the airways, degrade tissue, and cause a thickening or scarring of lung tissue called fibrosis. The end result of all of this is increased resistance from the airway: it’s harder for the lungs to draw in air. Emphysema occurs when the lung parenchymal is damaged. Alveoli are destroyed, some of them combine into larger holes, and functional surface area is reduced. This reduces the lungs’ capacity and elasticity, making them less able to deflate. The combined effects of bronchitis and emphysema lower lung function – you can’t exchange as much carbon dioxide for oxygen.

So what can we do to fix COPD? The first step is to stop the damage. Smokers with COPD should stop immediately. Quitting smoking can be extremely hard, especially as many smokers started in their teens when the brain was still cementing lifelong habits. You should also improve other modifiable lifestyle risks; increase exercise, make sure your diet is healthy, and try to reduce exposure to air pollution. Doctors recommend lowering the risks of exacerbating infections by getting vaccines for flu, RSV, COVID, pneumonia, and Tdap. Beyond these measures, pharmacology can provide relief. Medical treatments are generally added in a stepwise, increasing fashion to control symptoms and to reduce exacerbations with a minimum of side effects.

The major available medications are usually lumped into bronchodilators and antimuscarinic drugs. Bronchodilators do just what it sounds like they do, they dilate (expand) the bronchi and bronchioles. Beta2 agonists are the archetypal bronchodilators, they change the function of lung muscle and widen airways. They can be short-acting beta-agonists (SABA) or long-acting (LABA). Antimuscarinic drugs are similar. They act on muscarinic receptors in smooth muscle. These receptors regulate bronchodilation, mucus secretion, and inflammation. There are short and long-acting muscarinic receptor antagonists (SAMA and LAMAs). On top of these, an inhaled corticosteroid (ICS) may help reduce inflammation. LABA medications may increase the effectiveness of ICS inflammation reduction. When a single medication fails to control symptoms or stop complications, a dual medication of LABA + ICS or LABA + LAMA may be prescribed. Mounting evidence is also showing that a triple medication of LABA + LAMA + ICS may provide advanced relief when a dual medication isn’t sufficient. If these combination medications pan out, those with COPD may be able to finally breathe a sigh of relief.

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

Listen to the article here:


Adeloye, D., Chua, S., Lee, C., Basquill, C., Papana, A., Theodoratou, E., … & Global Health Epidemiology Reference Group (GHERG. (2015). Global and regional estimates of COPD prevalence: 

Systematic review and meta–analysis. Journal of global health, 5(2).

Alagha, K., Palot, A., Sofalvi, T., Pahus, L., Gouitaa, M., Tummino, C., … & Chanez, P. Íp(2014). Long-acting muscarinic receptor antagonists for the treatment of chronic airway diseases. Therapeutic advances in chronic disease, 5(2), 85-98.

GOLD, 2023 Global Initiative for Chronic Obstructive Lung Disease (GOLD). (2023). 2023 Report: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease.

Rabe, K. F., Martinez, F. J., Ferguson, G. T., Wang, C., Singh, D., Wedzicha, J. A., … & Dorinsky, P. (2020). Triple inhaled therapy at two glucocorticoid doses in moderate-to-very-severe COPD. New England Journal of Medicine, 383(1), 35-48.

Suki, B., Stamenovic, D., & Hubmayr, R. (2011). Lung parenchymal mechanics. Comprehensive Physiology, 1(3), 1317.

CDC & National Center for Health Statistics. (May 2, 2024). Leading causes of death.


As an avid surfer, I occasionally hear concerns about shark attacks at the beach. Diving into the statistics of unprovoked shark attacks, I learned that they are astronomically unlikely. Deaths are even rarer, with only around one fatal shark attack per year in the U.S. So then what is the deadliest animal? Worldwide, scorpions kill a few thousand people annually, dogs around ten thousand annually, and snakes kill some 75,000 people a year! That’s a drop in the bucket compared to other humans, who kill around half a million people per year. But then there are mosquitoes. Mosquitoes kill more people than every other animal combined – including humans; something like 750,000 to 1 million people per year. Let’s get the buzz on why.

Mosquitoes don’t kill us directly. At least not normally. Sometimes blood loss from mosquito bites can kill animals as big as cows, but this is an exception rather than the rule. Normally, mosquitoes kill people by acting as vectors, which transmit disease. The deadliest known disease in the history of the planet is malaria, and it is responsible for at least several billion deaths throughout history (the exact number is quite controversial, with estimates ranging from 5% – 50% of all people ever to live). Mosquitos also transmit dengue, yellow fever, chikungunya, zika, and more. The question then is… why? Why us in particular?

Actually, only some mosquitoes like humans in particular. There are around 3,600 types of mosquito. Some species, like Aedes aegypti (a-ee-dees a-gyp-thai), hunt humans specifically for blood. Others target snakes, frogs, or birds. Many are generalists and hunt anything with blood. However, consuming blood is actually a rare occurrence in the life of a mosquito. For most of their lives mosquitoes are vegetarians. They eat plant nectar, fruits, and the sugary waste of aphids called honeydew. Mosquitoes pollinate flowers, like to eat apples and bananas, and wanna hang out for a nice long walk on the beach. Some mosquito species actually stay vegetarian their whole lives. In fact, male mosquitoes don’t consume our blood, it’s only females when they need to lay eggs. Fruit juice is nice, but – as every good vegan knows – you need to get your protein somehow. For mosquitoes, some species need the extra protein found in blood to help their young thrive. How mosquitoes actually locate a host is pretty complex.

It’s easy to guess how a mosquito might find us by looking at what signals we give off. We breathe, we smell, we’re warm, we look like people, and we taste like humans. Each of these features attract mosquitoes from progressively shorter distances. Let’s move through how.

  • Breath
    • When we exhale, CO2 comes out. These puffs of carbon dioxide travel through the air, dispersing into relatively big clouds. Mosquitoes have a special nerve cell called a cpA neuron that can detect CO2. Mosquitoes follow the trail of CO2 upwind until they smell us.
  • Odor
    • Mosquitoes can detect the specific scent profile animals emit using those same cpA neurons. They then determine if the smell matches the creatures they prefer to hunt using their antennae and other nose-like organs. Humans emit a lot of scents. Key among these are acetoin, made by skin bacteria, and volatile carboxylic acids, like lactic acid. The amount and composition of these chemicals change based on genetics and environmental changes. Having malaria, for instance, makes you smell more attractive to mosquitoes.
  • Temperature
    • When a mosquito gets close enough, it can start detecting body heat, which draws them in.
  • Shape and Color
    • Mosquitoes use vision to detect us from a few inches away. Their eyes are specialized to detect redder wavelengths of light, similar to many skin tones, and they preferentially fly towards high contrast objects: think a dark arm against a bright blue sky.
  • Taste
    • The last step before ruining our outdoor fun is to make sure we taste good. Rubbing disgusting-tasting bug spray all over our bodies helps keep mosquitoes from wanting to eat us, but normally they’re way into the taste of old skin and sweat.

People exhibit variations on all these areas (except for breathing). Our smells change, some of us wear insulating clothes, skin tones vary, and according to Dr. Hannibal Lecter, we taste different. Scientists have studied the variation between people and how many mosquitoes bite them in an effort to seek relief from mosquito bites. Mosquitoes tend to bite pregnant individuals more frequently and genetics play a role, but these factors are difficult to alter in many people. Instead, researchers tend to target our most modifiable attractant, smell. Our skin microbiome and genes affect our scent, but diet seems to as well – though not as much as many people claim. Randomized clinical trials have found no evidence that vitamin B, garlic, and green grapes affect mosquito bites. There is some preliminary evidence pointing to caffeine as a possible attractant. Studies have found evidence that eating bananas and drinking beer both increase mosquito interest. As stated before, having malaria makes you more attractive to mosquitoes. Unfortunately, you may have noticed that none of these reduce our attractiveness to mosquitoes. 

Bug spray containing DEET makes it more difficult for bugs to smell you and is recommended, but can be sticky, stinky, and unpleasant to use. Next-generation bug repellents may block multiple scents or even inhibit the cpA neurons directly! Physical barriers like long sleeves can help as long as they don’t overheat you. Really, the problem is best summarized in a paper by Van Breygel et al. (2015):

For a human hoping to avoid being bitten by a mosquito, our results underscore a number of unfortunate realities. Even if it were possible to hold one’s breath indefinitely, another human breathing nearby, or several meters upwind, would create a CO2 plume that could lead mosquitoes close enough to you that they may lock on to your visual signature. The strongest defense is therefore to become invisible, or at least visually camouflaged. Even in this case, however, mosquitoes could still locate you by tracking the heat signature of your body provided they get close enough. The independent and iterative nature of the sensory-motor reflexes renders mosquitoes’ host seeking strategy annoyingly robust.

The obvious reaction to this is to think “kill ‘em all!” Unfortunately, even this method fails. Insecticides have a nasty habit of prompting natural selection to favor bugs immune to them – and they manage to kill many innocent bugs in the process. Traps have limited effectiveness, can be expensive, and also manage to murder countless other ecologically important bugs. With this in mind, perhaps the solution to saving lives from the world’s deadliest animal isn’t in reducing our attractiveness (my mom tells me I’m very attractive), but in reducing our susceptibility to the diseases they carry. Across the globe, scientists are in various stages of research seeking vaccines for malaria, dengue, and other mosquito-borne diseases. If these manage to be successfully tested and distributed, maybe we won’t have anything to fear from mosquitoes after all! Except for the itching. And the annoyance. And the constant ankle biting. And that they like to fly at our eyeballs. And that they might literally take more blood out of us than those sharks everyone tells me to watch out for.

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

Listen to the article here:


Associated Press. (September 9, 2020).  Thick clouds of mosquitoes kill livestock after hurricane.

CDC Global Health Center. (April 8, 2024). Fighting the world’s deadliest animal. Centers for Disease and Control.

Brown, J. E., Evans, B. R., Zheng, W., Obas, V., Barrera-Martinez, L., Egizi, A., … & Powell, J. R. (2014). Human impacts have shaped historical and recent evolution in Aedes aegypti, the dengue and yellow fever mosquito. Evolution, 68(2), 514-525.

Ellwanger, J. H., da Cruz Cardoso, J., & Chies, J. A. B. (2021). Variability in human attractiveness to mosquitoes. Current Research in Parasitology & Vector-borne Diseases, 1, 100058.

U.S. Environmental Protection Agency. (September 25, 2023). Insect repellents: DEET.

Giraldo, D., Rankin-Turner, S., Corver, A., Tauxe, G. M., Gao, A. L., Jackson, D. M., … & McMeniman, C. J. (2023). Human scent guides mosquito thermotaxis and host selection under naturalistic conditions. Current Biology, 33(12), 2367-2382.

Peach, D. A., & Gries, G. (2020). Mosquito phytophagy–sources exploited, ecological function, and evolutionary transition to haematophagy. Entomologia Experimentalis et Applicata, 168(2), 120-136.

Potter, C. J. (2014). Stop the biting: targeting a mosquito’s sense of smell. Cell, 156(5), 878-881.

Raji, J. I., & DeGennaro, M. (2017). Genetic analysis of mosquito detection of humans. Current opinion in insect science, 20, 34-38.

Shen, H. H. (2017). How do mosquitoes smell us? The answers could help eradicate disease. Proceedings of the National Academy of Sciences, 114(9), 2096-2098 .

Tauxe, G. M., MacWilliam, D., Boyle, S. M., Guda, T., & Ray, A. (2013). Targeting a dual detector of skin and CO2 to modify mosquito host seeking. Cell, 155(6), 1365-1379.

Van Breugel, F., Riffell, J., Fairhall, A., & Dickinson, M. H. (2015). Mosquitoes use vision to associate odor plumes with thermal targets. Current Biology, 25(16), 2123-2129.


May 24, 2024 BlogClinical Trials

Last week we talked about the actions of the Nazis, which resulted in the World Medical Association’s Declaration of Helsinki. The declaration provides an ethical guideline for physicians engaging in research involving humans. It has since become a requirement in most medical research. Unfortunately, in America, a study that began seven years prior to World War II undermined this ideal. It wouldn’t be until the 1970s that this study was exposed, and America was faced with its own dark practice of human research.

In 1932, doctors at the Tuskegee Institute (Now called Tuskegee University) started a fundamentally unethical experiment. The road to this study winds from good intentions to simple, terrible means. The historical context behind the study involves the Julius Rosenwald Fund, a wholly honorable philanthropic endeavor. This fund built schools in the South, funded Booker T. Washington to attend the Tuskegee Institute, and worked with the U.S. Public Health Service to provide medical services to the poorest Black Americans in the South. One of these medical service endeavors was providing syphilis treatment. Part of this effort involved cataloging the rate of syphilis in several areas. The great depression and Julius Rosenwald’s death brought much of this to a halt, and the syphilis project ended in 1932.

Other scientists wanted to pick up where the Julius Rosenwald Fund left off. These scientists believed that different races experienced diseases differently. The new study would observe the ravages of untreated syphilis in Black populations. They already had the groundwork built. They had a large number of men with untreated syphilis, a nearby hospital at Tuskegee Institute, a bank of goodwill built by Rosenwald, and a store of trust in medical professionals and the U.S. Public Health Service. The scientists successfully exploited all of these. They intentionally coerced and deceived 400 Black Americans into their study. The study had no protocol, patients had no informed consent, and one of the major endpoints was to wait until patients died and then deceive their loved ones into allowing an autopsy. This alone is terrible, but it was – unfortunately – much worse. After the end of World War II, an effective treatment for syphilis became widely available: penicillin. The researchers didn’t provide this to their patients and, in fact, actively thwarted its use in this population. They convinced hospitals, government agencies, and even the U.S. military that the torturous observation of sick and dying people was more important than their health and well-being. This continued for 40 years and only ended in 1972 after the experiment started getting public attention and press.

The Tuskegee study ended almost a decade after the Declaration of Helsinki and prompted the passage of the National Research Act and the creation of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. A group of 11 people spent four years developing the Belmont Report.  Whereas the Declaration of Helsinki outlines ethical standards to follow, the Belmont Report gives specific guidelines and actionable procedures for determining the legitimacy of research involving human participants. It was initially incorporated into federal law in 1981 as the Protection of Human Subjects.

The Belmont Report first outlines the difference between medical practice and research. The goal of practice is normal therapy with a reasonable chance of success, while the goal of research is to test a hypothesis and answer a question. Whereas practice follows the needs of the patient, research follows well-defined, written protocols. The Belmont Report maintains the same three ethical principles in the Declaration of Helsinki – Respect for Persons, Beneficence, and Justice. It then outlines the practical, actionable processes: Informed Consent, Risk/Benefit Assessment, and Subject Selection.

Respect for Persons is the idea that most people can make their own choices, and those that can’t must be afforded special protection. These protections must be assessed by third parties, protect participants from harm, and be periodically reevaluated. The Belmont Report applies respect for persons as Informed Consent. Informed consent requires that before a study begins, all information, including the procedure, risks, etc. be clearly written and organized. It requires comprehension by all potential human participants of the above information. Patients cannot be enrolled if they do not understand the informed consent, and the information can’t be written in tiny print and put off to the side like a used car ad. This also means that vulnerable populations (those with limited comprehension, like children) must have extra protection, and third parties (like parents) must help determine comprehension. Finally, informed consent is only given if it is voluntary. This means no large sums of money, threats, or exaggerated promises can be used to coerce people into studies. This can make it more difficult to enroll patients but is critical to avoiding disasters like the Tuskegee syphilis study.

Beneficence is the obligation to secure the well-being of patients and to do no harm. Researchers may not injure some people to help others. This is applied as Risk/Benefit Analysis. Under this concept, all benefits must be weighed against potential risks. Risks are a possibility of harm, and include the chance harm will occur and the severity of the harm. This may include things like pain from the site of an injection and must be clearly laid out in the informed consent. Risk/Benefit Analysis is done by researchers, but is overseen and double-checked by Institutional Review Boards (IRBs) – third party boards that oversee studies involving human participants. The Belmont Report lays out specific ways these IRBs assess the risks of a study. These are then weighed against benefits. Benefits are a positive change in health or welfare and are usually much clearer – the alleviation of symptoms from being in a medical study, for instance.

Justice is an equal distribution of burdens and benefits across society. Further, justice demands that the groups that participate in research should be the ones that receive the benefits. The racially biased attitudes that formed the basis of the Tuskegee study are the prime example of a failure of justice. These groups were denied benefits, and researchers demanded they take the burdens. The Belmont Report applies justice by way of Selection of Subjects. On the individual level this means that all subjects get fair treatment: you can’t give UF fans all of the investigational medication and FSU fans all placebo, for instance. Societally, the selection of subjects should be done in ways that minimize risks, like choosing adults before children. Selection should be done as fairly as possible and should target the populations that will benefit from research.

Unfortunately, the Tuskegee study has undermined trust in government and research in some communities for the past 80 years. From this historical tragedy have arisen solid, unambiguous rules for conducting human research. These ensure safety, oversight, and mitigation of risk so participating in clinical research is beneficial for the community. With the Belmont Report, communities can get access to new medications, find relief from symptoms, and help define their legacy to find possible cures for future generations.

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

Listen to the article here:


National Commission for the Protection of Human Subject of Biomedical and Behavior Research. (1977). U.S. Department of Health and Human Services.

Baker, S. M., Brawley, O. W., & Marks, L. S. (2005). Effects of untreated syphilis in the negro male, 1932 to 1972: a closure comes to the Tuskegee study, 2004. Urology, 65(6), 1259-1262.

Brandt, A. M. (1978). Racism and research: the case of the Tuskegee Syphilis Study. Hastings center report, 21-29.

Gray, F. D. (1998). The Tuskegee syphilis study: The real story and beyond. NewSouth Books.


May 17, 2024 BlogClinical Trials

In 1945-1946, after the conclusion of the Second World War, several Nazi German leaders and doctors stood trial for crimes against humanity, war crimes, and other atrocious crimes.  One of the trials, the so-called Doctor’s Trial (U.S.A. v. Karl Brandt et al.), helped shape how we view and perform clinical research today. One of the major defenses in the Doctor’s Trial was a lack of international law or agreement against the horrible activities the Nazis were doing. To remedy this, the trial ruling (in which seven defendants were sentenced to death) gave an outline of “Permissible Medical Experiments.” This was called the Nuremberg Code and was later expanded by the World Medical Association into the Declaration of Helsinki.

The Declaration of Helsinki, originally released in 1964, is the cornerstone of modern clinical research. The medical atrocities during the Holocaust showed that the unsaid rules of medicine needed to be said, printed, and widely distributed. The World Medical Association’s original Declaration of Helsinki has been revised seven times and has since grown by 300%. It concerns the ethical treatment of human participants in medical research.

The foundational notions of the Declaration of Helsinki rest on the following two ideas: “The health of my patient will be my first consideration” and “A physician shall act in the patient’s best interest when providing medical care.” The fact that these were up for debate is wild to me, but thanks to the Declaration of Helsinki these are now universal statements. The rest of the Declaration of Helsinki has similar “this should be obvious” content but has been critical for ensuring the safe and ethical treatment of people in research.

The document first states that human medicine must be tried in humans at some point. There are also stipulations about what must happen before a study can begin. A protocol must be written that outlines the entire study. An independent review board (IRB) must approve the protocol and any changes. Funding and results should be transparent and public. The document also outlines in broad terms how to do this with respect, beneficence, and justice.

Respect comes from the assertion that individual people matter more than new knowledge. This is how we get concepts like informed consent – that all trial participants must have full knowledge of what they are getting into before signing up. Respect also states that patients must voluntarily sign up and be able to discontinue at any time. Further, special protections must be in place for vulnerable populations – like children, prisoners, and people with mentally disabilities.

Beneficence is the concept of weighing benefits against risks. In medical research, the benefits must always outweigh the risks. Benefits must help the individual person, a population, or society. Risks must be minimized wherever possible. This is one reason you often see a long list of things that can exclude a person (like being pregnant) from a study: to minimize risks. Beneficence also mandates that studies must be stopped if the risks become too high – if an unintended side effect emerges, for instance.

Justice is the concept that research should be for the benefit of everyone. Medications that would target a specific population should be researched in that population. If left-handed people made up 90% of smokers, for instance, then smoking cessation studies should aim to enroll mostly left-handed people. Justice also means groups should be fairly selected and that studies should help people who live where the studies take place. You shouldn’t test a pants-lengthening drug on people in Bermuda (for their Bermuda shorts) and refuse to sell it to them.

Altogether, these seem like common-sense rules to have in place, but they need to be written. The Nazis claimed the ends justify the means – even though their end goals were abhorrent. In this world, however, there are no ends – only means.

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

Listen to the article here:


Bošnjak, S. (2001). The declaration of Helsinki: The cornerstone of research ethics. Archive of Oncology, 9(3), 179-184.

Nuremberg Trials Project (n.d.). NMT case 1. Harvard Law School.

Shrestha, B., & Dunn, L. (2019). The Declaration of Helsinki on medical research involving human subjects: a review of seventh revision. 

Taylor, T. (1955). Nuremberg Trials, The. Colum. L. Rev., 55, 488.

United States Holocaust Memorial Museum, Washington, DC. (n.d.). The Nuremberg code. Holocaust Encyclopedia. Accessed 5/13/2024. 

World Medical Association. (2013). World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. Jama, 310(20), 2191-2194.


Diabetes is a widespread disease where the body cannot process sugars effectively. It has myriad effects on the body, including in the gut. Diabetes affects nearly every part of the gastrointestinal tract, from the throat to the anus. Diabetes is one of the most common causes of a condition called gastroparesis. Gastroparesis is from the Greek language. Gastro- means “stomach,” –paresis indicates a partial paralysis, so gastroparesis means a partial paralysis of the stomach; it empties food slowly. This condition is more likely to affect women than men, but there aren’t good numbers on how many people it affects in total. Symptoms of diabetes and gastroparesis may overlap but include feeling full, weight changes, nausea, vomiting, bloating, and diarrhea. Gastroparesis can lead to serious complications like malnutrition, decreased quality of life – including anxiety and depression, and significantly higher mortality. The effects of diabetes further exacerbate these complications. How diabetes actually affects stomach muscles is complex and fascinating.

The digestive tract is lined with smooth muscle. Smooth muscle isn’t connected to bone and contracts in long, slow, low-energy waves. This is great for contracting blood vessels or moving food through the stomach and intestines. These are involuntary muscles, meaning we can’t consciously control them. In fact, the brain modulates the activity of gastrointestinal muscle, but it’s controlled by our “little brain” in the intestines! This little brain is made of around 500 million neurons and is called the enteric nervous system. The enteric nervous system is a distributed brain-like bunch of neurons and other cells spread throughout our abdomen that may be able to act independently of our big brain. It is responsible for getting the smooth muscle to contract rhythmically and in response to food. The enteric nervous system also includes cells that aren’t neurons. An important type is interstitial cells of Cajal (kuh-jaal). These are pacemaker cells that regularly generate electrical signals to coordinate muscle.

The prominent players in the enteric nervous system, however, are neurons. Though neurons are electric, they communicate with other neurons by releasing neurotransmitters and receiving them in specialized receptors. These are often the same neurotransmitters we find in the brain, though they may have different functions. Dopamine is a great example. In the brain, dopamine receptors are part of the reward pathway, giving you feelings of pleasure and motivation. In the enteric nervous system, dopamine receptors act to suppress muscle movement. More dopamine in the brain makes you feel happy, but more dopamine in the gut restricts the movement of food.

In diabetes, this can get all messed up. A key aspect of uncontrolled diabetes is the inability of the body to regulate blood sugar. This causes a few significant disturbances. Primary among these is neuron damage. Since the affected neurons are involuntary, we call this autonomic neuropathy. Autonomic neuropathy in the gastrointestinal tract can take the form of fewer neurons and ones that can’t communicate well because of damage. Diabetes can also lead to changes in the signaling pathways of smooth muscle and may destroy some of the pacemaking interstitial cells of Cajal. Together, these changes result in fewer smooth muscle contractions and a slower flow of food through the stomach and intestinal tract. The slow flow of food in gastroparesis can cause a feedback loop. Slow food is more likely to be mistaken for invaders, potentially causing inflammation. Even worse, the extra time in the digestive tract means there is more time for glucose, a major sugar, to get absorbed – increasing blood sugar and making the symptoms of diabetes worse. 

So, what can be done with diabetic gastroparesis? The first step is lifestyle alteration. Smaller and more frequent meals may help alleviate symptoms. Increasing noncarbonated liquids and decreasing fat and fiber may also help. Monitoring nutrient levels and electrolytes is critical. Beyond this, few medications are currently available. The most prominent are dopamine D2 receptor antagonists; meaning they inhibit the effect of dopamine. Metoclopramide (meh-tow-klow-pruh-mide) inhibits dopamine and mimics serotonin. It is effective at increasing the speed of emptying. It can cross the blood-brain barrier, however, causing unintended side effects in the brain. Domperidone (daam-peh-ruh-down) is another dopamine receptor antagonist. It doesn’t cross into the brain but can affect the heart, slowing the time it takes to recharge between beats. This medication is not approved in the United States, though it’s been approved in several other countries for decades. Clinical research is currently looking into new medications that may provide the same dopamine receptor inhibition as metoclopramide and domperidone but without the ability to affect the brain or heart! With the help of clinical volunteers, diabetic gastroparesis may pass quicker than we expected!

At the time of writing this article, clinical research for diabetic gastroparesis is enrolling at our Nature Coast Clinical Research – Inverness office. 

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

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Aswath, G. S., Foris, L. A., Ashwath, A. K., & Patel, K. (2017). Diabetic Gastroparesis.

Bharucha, A. E., Kudva, Y. C., & Prichard, D. O. (2019). Diabetic gastroparesis. Endocrine reviews, 40(5), 1318-1352. 

Isola, S., Hussain, A., Dua, A., Singh, K., & Adams, N. (2018). Metoclopramide.

Puoti, M. G., Assa, A., Benninga, M., Broekaert, I. J., Carpi, F. J. M., Saccomani, M. D., … & Borrelli, O. (2023). Drugs in focus: Domperidone. Journal of pediatric gastroenterology and nutrition, 77(2), e13-e22. DOI: 10.1097/MPG.0000000000003822

Sanders, K. M., Koh, S. D., Ro, S., & Ward, S. M. (2012). Regulation of gastrointestinal motility—insights from smooth muscle biology. Nature reviews Gastroenterology & hepatology, 9(11), 633-645.

Sugumar, A., Singh, A., & Pasricha, P. J. (2008). A systematic review of the efficacy of domperidone for the treatment of diabetic gastroparesis. Clinical gastroenterology and hepatology, 6(7), 726-733.

Tonini, M., Cipollina, L., Poluzzi, E., Crema, F., Corazza, G. R., & De Ponti, F. (2004). Clinical implications of enteric and central D2 receptor blockade by antidopaminergic gastrointestinal prokinetics. Alimentary pharmacology & therapeutics, 19(4), 379-390. doi: 10.1111/j.1365-2036.2004.01867.x

Uranga-Ocio, J. A., Bastús-Díez, S., Delkáder-Palacios, D., García-Cristóbal, N., Leal-García, M. Á., & Abalo, R. (2015). Enteric neuropathy associated to diabetes mellitus.

Yarandi, S. S., & Srinivasan, S. (2014). Diabetic gastrointestinal motility disorders and the role of enteric nervous system: current status and future directions. Neurogastroenterology & Motility, 26(5), 611-624.


Breathing has been described by top scientists as “important” for some reason. Unfortunately, some of us have trouble breathing at night, which is… less than ideal. Obstructive sleep apnea (OSA) is a condition where the airway is periodically blocked while sleeping, leading to sleep disruptions. The word apnea comes from the Greek language. The prefix  a– means “not” and –pnea comes from the word for breath, the same root as the word “pneumatic.” OSA is very common, with around one billion people suffering from the condition worldwide. Most people are unaware they have OSA because the breathing interruptions occur when sleeping. Regardless, OSA can cause people to snore, wake up at night, and have sleep that isn’t restful. This can lead to complications with cardiovascular and mental health, quality of life, and excessive sleepiness – which makes driving more dangerous. So how does breathing work, why does the airway get blocked with obstructive sleep apnea, and is there anything we can do about it?

Breathing is actually a pretty complex operation. Normally, breathing out is mostly an act of relaxing, but breathing in is a highly coordinated effort. Muscles in the diaphragm and chest contract to open the lungs and create a vacuum. The upper airway consists of the respiratory tract from the nose to above the vocal cords. This unique part of the body processes both food and air, requiring elasticity and flexibility to accomplish these competing tasks. It also produces speech sounds, chewing, sneezing, etc. The muscles that coordinate these tasks need to be contracted when breathing in for the airway to remain open. In OSA, the upper airway gets blocked.

When we lie down the fluid that pools in our legs flows up to the rest of the body, causing it to swell. When we sleep, the brain may not keep the throat muscles firm, causing a partial collapse of the throat. This is exacerbated when lying on the back, as the tongue and jaw fall into the airway. Alone, none of these would cause OSA. A partial blocking of the airway frequently results in snoring as bits of the throat flap in the breeze. OSA occurs when the changes we experience during sleep accompany structural damage to the upper airway. This damage can take many forms: a jaw that is small or set back in the throat, enlarged adenoid glands, and shifting bone structure. Additionally, increased adipose (fat) tissue in the neck can narrow the airway. Other risks include being male, obese, older, pregnant, and sleeping on the back. Some substances can increase the risk of OSA, including alcohol, cigarettes, sedatives, and hypnotics like benzodiazepines. These risk factors cause the throat to narrow or the brain to relax the jaw (or both) which causes the airway to temporarily collapse. Instead of pulling air into the lungs, the vacuum pulls the throat together. The body doesn’t get enough oxygen, and trouble increases from there.

So what can be done? A lot, actually! The first step is a diagnostic test. A nighttime in-laboratory sleep test called polysomnography is the go-to test, but home and portable sleep tests exist as well. Guidelines and directions must be carefully followed on portable kits to ensure accurate findings. If you do have OSA, the remedies vary widely. First, it’s a good idea to abstain from things that exacerbate OSA; like drinking and smoking. Second, sleeping on the side may provide some relief in mild cases. Beyond this, medical professionals may look into treating related disorders like asthma and heart failure. A sleep specialist may recommend or prescribe a Continuous Positive Airway Pressure (CPAP) machine, which pushes air into the throat instead of relying on the lungs to pull it in. These are highly effective but have low adherence, with around 50% of patients using the machines for less than 3 hours a night after the first month. In more severe cases, a specialist may recommend an oral appliance and/or surgery to physically change the structure of the airway. For many people, the solution to OSA may be to expand the airway by losing weight. This can be easier said than done, and clinical trials are looking into the effects of medications that induce weight loss for their ability to also tackle OSA. With luck, these new routes of treatment will let those with OSA breathe a little easier at night. 

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

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Choudhury, N., & Deshmukh, P. (2023). Obstructive Sleep Apnea in Adults and Ear, Nose, and Throat (ENT) Health: A Narrative Review. Cureus, 15(10). 

Del Negro, C. A., Funk, G. D., & Feldman, J. L. (2018). Breathing matters. Nature Reviews Neuroscience, 19(6), 351-367.

Eckert, D. J., & Malhotra, A. (2008). Pathophysiology of adult obstructive sleep apnea. Proceedings of the American thoracic society, 5(2), 144-153.

Otis, A. B., Fenn, W. O., & Rahn, H. (1950). Mechanics of breathing in man. Journal of applied physiology, 2(11), 592-607. Downloaded from ( on April 30, 2024

Sankri-Tarbichi, A. G. (2012). Obstructive sleep apnea-hypopnea syndrome: Etiology and diagnosis. Avicenna Journal of Medicine, 2(01), 3-8. 

Slowik, J. M., Sankari, A., & Collen, J. F. (2022). Obstructive sleep apnea. In StatPearls [Internet]. StatPearls Publishing.


When we think of an animal, we generally think of a single creature with a unique DNA code. A human starts as a single fertilized egg cell with the combined genetic code from our parents. By the time we’re walking and talking, however, we’ve already transformed into a superorganism. If you were to count the number of cells that make you up, only half would be human. Mature red blood cells lack a nucleus, so if we count only cells with nuclei, we’re only about 10% human. Going further, if we count all the genetic material in our body, only about 1% of it is human. Genetically, we’re 99% nonhuman. So then, what are we?

Bacteria. We’re primarily bacteria. These bacteria live with us our whole lives. They live on our skin, in our hair, on our eyelashes, and in our gut. The bacteria that live in the digestive tract, along with the relatively minuscule amounts of viruses, archaea, and yeasts, make up the gut microbiome. The gut microbiome is incredible. It establishes itself until around age two. It changes in response to the food we eat, diseases we get, medications we take (especially antibiotics), and our hygiene. We eat around 60 tons of food in our lives, and the gut microbiome has a hand in all of it. We usually think of bacteria (and viruses, etc) as parasitic (doing damage). The reality is the gut microbiome is truly symbiotic, we need it as much as it needs us.

The gut microbiome performs many tasks for us. It shapes the human cells and the mucus that lines our gut, strengthening it. It protects us from infections, keeps our cells together in a tight barrier, and communicates with the immune system. Microbiome cells outcompete other, destructive bacteria. They can also release bacteriocins (bacteria-targeting toxins) that destroy dangerous bacteria. The microbiome is so stellar it helps us even when it’s just eating.

The gut microbiome breaks down foods we can’t process, like dietary fiber. Through the process of fermentation, it uses this food to make vitamins, minerals, etc. As an example: we can’t make vitamin B12 at all in our cells; we rely on microorganisms to make it for us! Finally, the gut microbiome makes short-chain fatty acids. Short-chain fatty acids are the primary energy source for the human cells that line the intestine. They also increase insulin sensitivity and mediate immune regulation, inflammation, and other body processes.

Unfortunately, the gut microbiome can get out of whack, and issues like ulcerative colitis – an inflammatory bowel disease – can occur. To understand what can go wrong, let’s first investigate a healthy gut microbiome. The colony of colon bacteria is unique in everyone. A healthy microbiome has three qualities: high diversity, high richness, and high stability. Diversity is just what it sounds like: the total number of different species present. Richness is the balance between species; having roughly equivalent numbers of bacteria from each. Stability is the consistency of finding the same types and numbers of organisms over time. So what does a disruption in the balance of the gut microbiome look like? Loss of diversity, overgrowth of some types of organisms, and changes to the composition of the gut microbiome over time. The degradation of diversity, richness, or stability is called dysbiosis.

One cause of dysbiosis is antibiotics. They are designed to kill bacteria, which is bad news for the gut bacteria. Antibiotics frequently lead to a redistribution of gut microbiota. Other things that can cause dysbiosis include hygiene, infection, and smoking. The most important, however, is diet. All of the food we eat travels through the gut. In the western world, our diets aren’t always built to cultivate a healthy gut microbiome. Much of our food is built for shelf stability and is made using enzymes or chemicals instead of bacteria. We tend to eat more animal fats and proteins and fewer plant fibers than indigenous populations. To top this off, we eat refined sugar. Like, a LOT of refined sugar. Around 50 to 100 pounds of refined sugar per year. I’m not a nutrition expert, but I am a cookie expert, and that’s way too many cookies.

When the microbiome is in a state of dysbiosis, it can’t perform its helpful functions. The mucus layer is reduced, bacteria can’t interact with the immune and inflammation systems, and the gut is more permeable to undesirable substances. On top of this, short-chain fatty acid production decreases, making it more difficult for the human cells lining the gut. This loss of function is linked to diseases like ulcerative colitis. The exact causes of ulcerative colitis are unknown, but scientists think it is related to the gut microbiome. Ulcerative colitis is a chronic inflammatory disease with periods of high and low activity. Inflammation leads to painful ulcers along the colon and rectum. 

So what can we do when the gut is out of whack? This is still a relatively new area of research, so there are many questions we have to answer. Our best solutions so far are food and feces. The importance of food to the gut microbiome should be obvious by now. Foods high in dietary fibers from plants are needed for gut bacteria to survive and thrive. The role of bacteria derived from human feces is still being developed. Fecal transplantation is a fascinating, but not-for-the-dinner-table line of study. The basic idea is that doctors would transfer some of the gut microbiome from a healthy person to a sick one, perhaps someone with ulcerative colitis. These bacteria would hopefully colonize and outcompete whatever is disrupting the sick microbiome, restoring diversity, richness, and stability. Focusing on the symbiotic relationship we share with our individual microbiome will revolutionize our approach to healthcare. Clinical trials may pave the way forward for treatments that support our human cells and our microbiome, nurturing the microbial communities vital to our survival and well-being as a superorganism. Also, don’t forget to eat your veggies.

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

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Bengmark, S. (1998). Ecological control of the gastrointestinal tract. The role of probiotic flora. Gut, 42(1), 2-7.

Fan, Y., & Pedersen, O. (2021). Gut microbiota in human metabolic health and disease. Nature Reviews Microbiology, 19(1), 55-71.

Gomaa, E. Z. (2020). Human gut microbiota/microbiome in health and diseases: a review. Antonie Van Leeuwenhoek, 113(12), 2019-2040.

LeBlanc, J. F., Segal, J. P., de Campos Braz, L. M., & Hart, A. L. (2021). The microbiome as a therapy in pouchitis and ulcerative colitis. Nutrients, 13(6), 1780.

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Świrkosz, G., Szczygieł, A., Logoń, K., Wrześniewska, M., & Gomułka, K. (2023). The Role of the Microbiome in the Pathogenesis and Treatment of Ulcerative Colitis—A Literature Review. Biomedicines, 11(12), 3144.

Tan, J., McKenzie, C., Potamitis, M., Thorburn, A. N., Mackay, C. R., & Macia, L. (2014). The role of short-chain fatty acids in health and disease. Advances in immunology, 121, 91-119.

The Human Microbiome Project Consortium. (2021). Structure, function and diversity of the healthy human microbiome. Nature 486, 207–214. 

Thursby, E., & Juge, N. (2017). Introduction to the human gut microbiota. Biochemical journal, 474(11), 1823-1836.

Xiong, R. G., Zhou, D. D., Wu, S. X., Huang, S. Y., Saimaiti, A., Yang, Z. J., … & Li, H. B. (2022). Health benefits and side effects of short-chain fatty acids. Foods, 11(18), 2863.

Young, V. B., & Schmidt, T. M. (2008). Overview of the gastrointestinal microbiota. Advances in experimental medicine and biology, 635, 29–40.


High blood pressure is amazingly prevalent, affecting nearly half of all Americans. It’s a major risk factor for heart attack, stroke, kidney failure, eye damage, and more. Unfortunately, this condition remains highly prevalent despite the numerous medications designed to treat it. For many patients, adhering to medications can be difficult, and for others, some medicines are not effective in reducing blood pressure levels. But what if there were a way to lower blood pressure at the source, the heart?

First, let’s examine how the heart relates to blood pressure. It might seem obvious, but it’s actually quite complex. The heart draws blood in and pushes it out with each beat. The amount of blood pumped is called the stroke volume. A good stroke volume helps to ensure the heart has enough blood pressure to deliver oxygen throughout the body. A healthy heart will pump out around 50-70% of the total volume of blood. This means there remains some unpumped fluid in the heart chambers after pumping is complete. When the next heartbeat comes, the heart muscle has to stretch enough to accommodate this unpumped blood. This extra blood increases our blood pressure because of the Frank-Starling law of the heart.

The Frank-Starling law of the heart is over 100 years old and states that the amount our heart muscles stretch before pumping scales with the force they deliver when pumping. Think of a rubber band. If you stretch it a little, it’ll flop back in place. If you stretch a rubber band a lot, almost to its breaking point, it’ll snap back so hard as to leave a welt on your skin. The heart is similar; extra blood in the heart before pumping increases the pressure of each beat and maintains our blood pressure. If there were a way to lower the amount of blood in the chamber after beating, it follows that blood pressure may be lowered. Note that just the pressure would be lowered. The stroke volume would (ideally) remain the same. But how could we do this?

For most people, we don’t have any way of convincing the heart to empty more effectively. For a select few, however, the hardware may already be in place. Pacemakers are amazing technology that has helped countless people whose hearts aren’t working properly. Over a million pacemakers are implanted every year worldwide and help people with arrhythmias. Arrhythmias are conditions that involve irregular heartbeat. Pacemakers are surgically implanted devices that send small amounts of electricity where they are needed in the heart. Heart muscles are triggered by this little zap and beat in response to it. Pacemaker rhythms can be customized for several types of conditions, and can even be programmed after being implanted to adapt to changing patient conditions. This is where a pacemaker’s ability to help with high blood pressure is theorized.

By customizing how a pacemaker fires, it is possible to cause the heart to release more of its contents and lower the amount of blood remaining in the heart before pumping. According to the Frank-Starling law of the heart, this should result in lower blood pressure (indeed, early clinical trials show this to be the case).

Finally, we have to make sure changes to our blood pressure bypass the sympathetic nervous system. This pathway, also called the “fight or flight” pathway, helps ensure the body is awake, alert, and alive. Integral to this system are receptors that sense our blood pressure. If the sympathetic nervous system senses a prolonged drop in blood pressure, it kicks in to correct this. This is a critical system that keeps us from constantly fainting but can be problematic when trying to lower blood pressure. A clever workaround being investigated is to have a pacemaker lower the blood pressure intermittently. It runs the chamber-emptying algorithm for short periods of time. This may help bypass our sympathetic nervous responses. If clinical trials bear out, pacemakers may be able to change not just the pace of the heart, but the pressure too!

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

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Centers for Disease Control and Prevention. (2023). Facts about hypertension. U.S. Department of Health & Human Services.

Mond, H. G., & Proclemer, A. (2011). The 11th world survey of cardiac pacing and implantable cardioverter-defibrillators: calendar year 2009–a World Society of Arrhythmia’s project. Pacing and clinical electrophysiology : PACE, 34(8), 1013–1027.

Kalarus, Z., Merkely, B., Neužil, P., Grabowski, M., Mitkowski, P., Marinskis, G., … & Kuck, K. H. (2021). Pacemaker‐Based Cardiac Neuromodulation Therapy in Patients With Hypertension: A Pilot Study. Journal of the American Heart Association, 10(16), e020492.

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Neuzil, P., Merkely, B., Erglis, A., Marinskis, G., de Groot, J. R., Schmidinger, H., … & Kuck, K. H. (2017). Pacemaker‐mediated programmable hypertension control therapy. Journal of the American Heart Association, 6(12), e006974.

Sequeira, V., & van der Velden, J. (2015). Historical perspective on heart function: the Frank–Starling Law. Biophysical reviews, 7, 421-447.


April 12, 2024 BlogClinical Trials

It’s spring, which means lots of sneezing, sweets, and sunlight! Of those three, sunlight is probably the healthiest, so let’s shine a light on what sunlight does in the body and why we need it. First, the sun is vital for keeping the planet habitable. Without the sun, we would all die very fast as oxygen would solidify on the surface, and we’d be unable to breathe. Beyond being vital to life, sunlight is used by the skin to produce Vitamin D!

Vitamin D is actually a collection of very similar molecules called calciferols. These are fat-soluble steroid hormones that are used throughout the body. Vitamin D deficiency is a worldwide problem, and affects at least ⅓ of Americans. It is linked to complications in bones, kidneys, heart, and brain, as well as to diabetes, immune system issues, obesity, and poor pregnancy outcomes. Though indications of this deficiency seem robust, the solutions are anything but. Unfortunately, the effects of supplemental vitamin D, and therefore sunlight, are grossly understudied. Trial after trial after trial (check the extensive references list) shows that supplemental vitamin D – and in some cases supplemental light – does not have a significant effect on measurable outcomes for patients. These trials consistently find that the levels of circulating vitamin D in the bloodstream are increased, but symptoms are unaffected. The only results I could find from randomized, placebo-controlled clinical trials showing actual benefits to patients were for those with sickle-cell disease and in reducing respiratory infections in elderly patients.

This is counter to “common knowledge” and to the assumed knowledge found in several research papers. Observational studies, where scientists look at populations, find a myriad of problems associated with vitamin D and sunlight deficiency. Let’s try to illuminate why clinical trials haven’t found benefits when giving supplemental vitamin D. The answer is likely that the problems that cause vitamin D deficiency aren’t solved by supplementation! Vitamin D production starts in the skin, then goes to the liver and kidneys before the body can use it. The symptoms associated with low levels of vitamin D may not improve if there are underlying liver or kidney issues, though those conditions can hinder the production of Vitamin D.

Further, observational studies look at a population and investigate the correlations between items. This can tell us things that may be associated with each other but does not indicate that one thing is causing the other. An example would be looking at the availability of toilet paper and used car prices over the last 10 years. In 2020 toilet paper was unavailable and used car prices soared! This wasn’t because we needed toilet paper to run our used cars or anything; there was a pandemic disrupting supply chains! In the case of vitamin D deficiency, the lack of vitamin D is probably the effect of not going outside! If a mental disorder like depression keeps people indoors, this would lower the vitamin D they produce, not the other way around. On top of this, it is very difficult for scientists to isolate sunlight (and therefore vitamin D) from exercise. People who stay inside and never see the sun are, on average, less active. This can lead to some of the problems we associate with vitamin D deficiency, including bone issues, obesity, diabetes, and heart problems. In these cases vitamin D deficiency is more a canary in the coal mine than the smoke of a fire.

So, what can we take away from this? First and most importantly is that in all of these clinical trials supplemental vitamin D has been found to be safe. If vitamin D helps you with an issue, there is nothing wrong with continuing your care. Always consult with your doctor before making changes to your medication. Second, clinical trials are vital to our medical system! Observational studies are no substitute for actual experimentation in a placebo-controlled, randomized trial. The common knowledge is that sunlight and vitamin D are good for us. This is true, but it’s best to start at the source, the sun (if you can), rather than supplementing after the fact. We should spend more time outside in the nice weather, but remember your sunscreen.

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

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Aranow, C., Kamen, D. L., Dall’Era, M., Massarotti, E. M., Mackay, M. C., Koumpouras, F., … & Diamond, B. (2015). Randomized, double‐blind, placebo‐controlled trial of the effect of vitamin D3 on the interferon signature in patients with systemic lupus erythematosus. Arthritis & rheumatology, 67(7), 1848-1857.

Burns, A. C., Saxena, R., Vetter, C., Phillips, A. J., Lane, J. M., & Cain, S. W. (2021). Time spent in outdoor light is associated with mood, sleep, and circadian rhythm-related outcomes: a cross-sectional and longitudinal study in over 400,000 UK Biobank participants. Journal of affective disorders, 295, 347-352.

Eckard, A. R., O’Riordan, M. A., Rosebush, J. C., Lee, S. T., Habib, J. G., Ruff, J. H., … & McComsey, G. A. (2018). Vitamin D supplementation decreases immune activation and exhaustion in HIV-1-infected youth. Antiviral therapy, 23(4), 315-324.

Guralnik, J. M., Sternberg, A. L., Mitchell, C. M., Blackford, A. L., Schrack, J., Wanigatunga, A. A., … & STURDY Collaborative Research Group. (2022). Effects of vitamin D on physical function: results from the STURDY trial. The Journals of Gerontology: Series A, 77(8), 1585-1592.

Ginde, A. A., Blatchford, P., Breese, K., Zarrabi, L., Linnebur, S. A., Wallace, J. I., & Schwartz, R. S. (2017). High‐dose monthly vitamin D for prevention of acute respiratory infection in older long‐term care residents: a randomized clinical trial. Journal of the American Geriatrics Society, 65(3), 496-503.

Hansen, K. E., Johnson, R. E., Chambers, K. R., Johnson, M. G., Lemon, C. C., Vo, T. N., & Marvdashti, S. (2015). Treatment of Vitamin D Insufficiency in Postmenopausal Women: A Randomized Clinical Trial. JAMA internal medicine, 175(10), 1612–1621.

Huiberts, L. M., & Smolders, K. C. (2021). Effects of vitamin D on mood and sleep in the healthy population: Interpretations from the serotonergic pathway. Sleep Medicine Reviews, 55, 101379.

Javed, A., Kullo, I. J., Balagopal, P. B., & Kumar, S. (2016). Effect of vitamin D3 treatment on endothelial function in obese adolescents. Pediatric obesity, 11(4), 279-284.

Juraschek, S. P., Miller III, E. R., Wanigatunga, A. A., Schrack, J. A., Michos, E. D., Mitchell, C. M., … & Appel, L. J. (2022). Effects of vitamin D supplementation on orthostatic hypotension: results from the STURDY trial. American journal of hypertension, 35(2), 192-199.

Karsy, M., Guan, J., Eli, I., Brock, A. A., Menacho, S. T., & Park, M. S. (2019). The effect of supplementation of vitamin D in neurocritical care patients: RandomizEd Clinical TrIal oF hYpovitaminosis D (RECTIFY). Journal of neurosurgery, 1–10. Advance online publication.

Michos, E. D., Kalyani, R. R., Blackford, A. L., Sternberg, A. L., Mitchell, C. M., Juraschek, S. P., … & Appel, L. J. (2022). The relationship of falls with achieved 25-Hydroxyvitamin D levels from vitamin D supplementation: the STURDY trial. Journal of the Endocrine Society, 6(6), bvac065.

Okereke, O. I., Reynolds, C. F., Mischoulon, D., Chang, G., Vyas, C. M., Cook, N. R., … & Manson, J. E. (2020). Effect of long-term vitamin D3 supplementation vs placebo on risk of depression or clinically relevant depressive symptoms and on change in mood scores: a randomized clinical trial. Jama, 324(5), 471-480.

Osunkwo, I., Ziegler, T. R., Alvarez, J., McCracken, C., Cherry, K., Osunkwo, C. E., … & Tangpricha, V. (2012). High dose vitamin D therapy for chronic pain in children and adolescents with sickle cell disease: results of a randomized double blind pilot study. British journal of haematology, 159(2), 211-215.

Øverland, S., Woicik, W., Sikora, L., Whittaker, K., Heli, H., Skjelkvåle, F. S., … & Colman, I. (2020). Seasonality and symptoms of depression: A systematic review of the literature. Epidemiology and psychiatric sciences, 29, e31.

Palacios, C., & Gonzalez, L. (2014). Is vitamin D deficiency a major global public health problem?. The Journal of steroid biochemistry and molecular biology, 144, 138-145.

Ponda, M. P., Liang, Y., Kim, J., Hutt, R., Dowd, K., Gilleaudeau, P., Sullivan-Whalen, M. M., Rodrick, T., Kim, D. J., Barash, I., Lowes, M. A., & Breslow, J. L. (2017). A randomized clinical trial in vitamin D-deficient adults comparing replenishment with oral vitamin D3 with narrow-band UV type B light: effects on cholesterol and the transcriptional profiles of skin and blood. The American journal of clinical nutrition, 105(5), 1230–1238.

Rorie, A., Goldner, W. S., Lyden, E., & Poole, J. A. (2014). Beneficial role for supplemental vitamin D3 treatment in chronic urticaria: áaárandomized study. Annals of allergy, asthma & immunology, 112(4), 376-382.

Sadock, B.J., Sadock, V.A., & Ruiz, P. (2017). Comprehensive textbook of psychiatry (Vol. 1/2). Sadock, B.J., Sadock, V.A., & Ruiz, P. (Eds.). Philadelphia: Lippincott Williams & Wilkins.

Sokol, S. I., Srinivas, V., Crandall, J. P., Kim, M., Tellides, G., Lebastchi, A., … & Alderman, M. H. (2012). The effects of vitamin D repletion on endothelial function and inflammation in patients with coronary artery disease. Vascular medicine, 17(6), 394-404.

Shaffer, J. A., Edmondson, D., Wasson, L. T., Falzon, L., Homma, K., Ezeokoli, N., … & Davidson, K. W. (2014). Vitamin D supplementation for depressive symptoms: a systematic review and meta-analysis of randomized controlled trials. Psychosomatic medicine, 76(3), 190-196.

Simha, V., Mahmood, M., Ansari, M., Spellman, C. W., & Shah, P. (2012). Effect of vitamin D replacement on insulin sensitivity in subjects with vitamin D deficiency. Journal of investigative medicine, 60(8), 1214-1218.

Sokol, S. I., Srinivas, V., Crandall, J. P., Kim, M., Tellides, G., Lebastchi, A., … & Alderman, M. H. (2012). The effects of vitamin D repletion on endothelial function and inflammation in patients with coronary artery disease. Vascular medicine, 17(6), 394-404.×12466709

Wei, W., Shary, J. R., Garrett-Mayer, E., Anderson, B., Forestieri, N. E., Hollis, B. W., & Wagner, C. L. (2017). Bone mineral density during pregnancy in women participating in a randomized controlled trial of vitamin D supplementation. The American Journal of Clinical Nutrition, 106(6), 1422-1430.

Winthorst, W. H., Bos, E. H., Roest, A. M., & de Jonge, P. (2020). Seasonality of mood and affect in a large general population sample. Plos one, 15(9), e0239033.

Wirz-Justice, A., Skene, D. J., & Münch, M. (2021). The relevance of daylight for humans. Biochemical pharmacology, 191, 114304.

Zahoor, I., & Haq, E. (2017). Vitamin D and multiple sclerosis: An update. Exon Publications, 71-84.


April 5, 2024 BlogHypothyroidism

The body is as amazing as it is complex. Consider the thyroid, this tiny gland sits in your neck, just under the Adam’s apple (larynx), and is butterfly-shaped (technically, thyroid comes from the Greek word for an oblong shield, but it’s butterfly season, and I haven’t used a Greek shield in a hot minute.) It’s unassuming, easy to miss, and affects nearly every cell in the body. The thyroid is part of the endocrine system, which is responsible for producing and releasing hormones that regulate countless bodily functions. The endocrine system is a messenger system of interwebbed feedback loops that regulate how the body metabolizes food products into energy, cellular materials, and waste. Disruptions in this system can have enormous downstream effects, as with the thyroid.

The thyroid is part of the hypothalamus-pituitary-thyroid axis. The hypothalamus is in the brain. When it senses low levels of thyroid hormones, it tells the pituitary gland (at the base of the brain) to release Thyroid-stimulating hormone (TSH). This, predictably, stimulates the thyroid to produce more hormones. Doctors monitor TSH levels when checking on thyroid function. TSH activates the thyroid, which produces Thyroxine (tetraiodothyronine, or T4) and Triiodothyronine (T3). These names are long and complicated, but the presence of “iodo” in the middle provides a clue that iodine is a key part of these chemicals. Stay tuned for more on that later. The thyroid also produces calcitonin, which can regulate calcium levels. T4 and T3 are the hormones monitored by the hypothalamus: if it detects enough in the blood, it tells the pituitary gland to lower TSH production. Together, measuring the levels of TSH, T4, and T3 can give a good idea of how the thyroid is performing.

Surprisingly, the thyroid produces only about 20% of the body’s T3, the majority is derived from T4 which has been delivered to body tissue! You can think of T4 as a long-lasting store of T3, though it also has some effect on specific cells. T3 is a big deal, it has metabolic effects on basically all cells and promotes protein production. Strangely, 99% of all T3 and T4 are bound in proteins and unable to activate cell receptors. The unbound 1% is called free T3 (and free T4) and is what’s responsible for the metabolic effects. When the thyroid is disrupted all sorts of things can go wrong.

People who have an underproduction of thyroid hormones have hypothyroidism. Hypo– means low, or under, thyroid indicates the thyroid, and –ism means a condition of. Hypothyroidism is a condition where the thyroid underproduces hormones. Hypothyroidism affects between 2-11% of the adult US population. The primary risk factor is age, with those over sixty having higher rates of hypothyroidism. It is 20 times as prevalent in women. Worldwide, the highest cause of hypothyroidism is low iodine intake, which restricts T4 and T3 production. Here in the US we get plenty of iodine in our diets, so the highest cause here is autoimmune inflammation, a condition called Hashimoto’s disease. The next highest cause of hypothyroidism is treatment for hyperthyroidism – when the thyroid is overactive. This makes intuitive sense, as getting the balance exactly perfect is nearly impossible. In rare cases, the hypothalamus or pituitary gland may malfunction.

The causes of hypothyroidism can be widespread, and so can the effects. When tissues can’t get enough T3, all sorts of problems arise. Common symptoms include fatigue, weight gain, changes to hair and skin, sensitivity to cold, and mental changes to mood and memory. Several patients experience no symptoms, and several patients have comorbidities (such as other autoimmune inflammation), making isolating symptoms and causes difficult. Untreated hypothyroidism can lead to heart problems and swelling of the thyroid, which is called a goiter. So what can be done? Is there any hope?

It should be no surprise that the solution to hypothyroidism is to take supplemental T4 and/or T3. In ye olden days (the 1950’s) the solution to hypothyroidism was to consume dried and prepared sections of animal thyroid – which would otherwise go to waste anyway. This can still be found under several names: desiccated thyroid, thyroid extract, Armour Thyroid, Thyroid USP, natural thyroid, and more. In the 1960’s, levothyroxine – synthetic T4 – was developed. A diagnosis of hypothyroidism may include low T4 and T3 levels, along with elevated TSH. Levothyroxine has been the standard treatment since the 1960’s and can bring hormone levels back in line. Unfortunately, a significant amount of patients do not find symptomatic relief from levothyroxine. It is thought that even though T4 levels are being raised, T3 may not be reaching the tissue. Perhaps the feedback loop isn’t complete. To compensate for this, some doctors have been prescribing T3 along with levothyroxine, with mixed results. Researchers have also been studying if the past solution, animal thyroid, may be the future solution. Thyroid extract generally results in lower free T4 and more free T3. With luck (and clinical trials!) we can find solutions to keep the butterfly in our throats flying high and functioning majestically.

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

Listen to the article here:


Biondi, B., & Wartofsky, L. (2014). Treatment with thyroid hormone. Endocrine reviews, 35(3), 433-512.

Boucai. L., (2024). Overview of thyroid function. Merck Manual, Professional Version.

Boucai. L., (2024). Hypothyroidism. Merck Manual, Professional Version.

Hegedüs, L., Bianco, A. C., Jonklaas, J., Pearce, S. H., Weetman, A. P., & Perros, P. (2022). Primary hypothyroidism and quality of life. Nature Reviews Endocrinology, 18(4), 230-242.

Wyne, K. L., Nair, L., Schneiderman, C. P., Pinsky, B., Antunez Flores, O., Guo, D., … & Tessnow, A. H. (2023). Hypothyroidism prevalence in the United States: a retrospective study combining national health and nutrition examination survey and claims data, 2009–2019. Journal of the Endocrine Society, 7(1), bvac172.


March 29, 2024 BlogHolidays

We’ve all been there: we finally ask out the total hottie we’ve been crushing on for months, only for them to reply with “…who are you?” Oof and ow. Hands tremble, eyes water, we turn away in shame, and our heart literally breaks in half. This is very dangerous! The heart actually works best when it’s all in one piece, pumping blood, and not when it’s in many pieces crying.

Scientists have long looked for ways to mend a broken heart. The classic adage “time heals all wounds” has been the primary standard of care, but that has been deemed “very boring” by experts. Other researchers have looked into things like “sad music,” “eating,” and “partying.” In spite of these classical treatments, over the course of someone’s life, there is a nearly 100% chance they will experience hurt feelings! Clearly, a new approach is needed.

Previous methods of dealing with heartbreak have all been focused on the mental state; our psychological health. Now research scientists have been looking into physically reassembling the heart. Initial attempts at welding and gluing failed. Researchers went back to first principles to find the proper adhesive. Then, Dr. Jimmy Scientist – who was having an HVAC system installed in his house – looked up what a duct was. The first Google result says a duct is “a bodily tube or vessel.” The heart is a pump, sure, but it still has blood flow through it, which sorta makes it a duct. Using the axiom of “well technically…” scientists recently announced a new way to fix a broken heart: duct tape!

Using duct tape to fix a broken heart is not an easy process. Taping it all back together requires open heart surgery which has been described as “ouchie” and “yucky.” On top of this, the tape doesn’t stick if the heart is all wet and bloody, so they have to drain all the blood out of you first, which can make you light-headed. Then surgeons have to find most (at least a few) of the little broken pieces and tape it all together. At the end of the procedure, a really good doctor will even remember to put the blood back in the body.

So how does this work? A healthy heart pumps blood using the power of squishy-wishy. This blood reaches your whole body, including the brain. Some scientists suspect the brain might actually be a vampire because it really likes blood. In fact, the brain drinks ~2 ½ cups of blood every minute, which has been described as “radical” and “totally metal.” The brain is happy when it drinks this blood, and that makes you happy. When the heart is all leaky and broken, however, the brain can’t get enough blood. It gets angry and starts fluttering its bat wings or whatever. This can wobble your tear ducts, causing them to leak, and also makes your feelings hurt.

Duct tape keeps the heart watertight (bloodtight?!?) and gives it a chance to squish-wish blood up to your endraculated brain. With luck, we’ll be able to bounce back from heartbreak with speed. So if you experience heartbreak before the next April Fool’s, consider the duct tape method: all it takes is some open-heart surgery, a roll of adhesive tape, and a surgeon with no scruples.

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

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We all do things for our parents. Some of us make them a card for their birthday, call them to say hello, or discover key mechanisms behind how the body metabolizes sugar in an attempt to save them from diabetes. Falling into that last category is the first American woman to win a Nobel Prize, Dr. Gerty Cori. She was born to a Jewish family in Prague in 1896. She became a doctor, got married, and worked in research at Carolinen Children’s Hospital. Gerty and her husband, Carl, collaborated and published multiple papers. Central Europe became challenging for Jewish people during the interwar period. She immigrated to the USA with her husband in the 1920s and naturalized in 1928. Her father was diagnosed with diabetes, and it’s said that’s where she got her inspiration.

America in the first part of the 20th century was a tough place to be a female researcher. Gerty Cori’s husband was offered prestigious positions that were denied to Gerty based on her gender. Carl Cori would not stop collaborating with his wife and refused positions where Gerty was not welcome. They eventually were hired at Washington University in St. Louis, though Gerty was given a token salary 1/10th of what Carl made. There, Gerty and Carl collaborated and investigated how sugar was broken down and stored in the body. It was said that Gerty had the ideas, and together the husband and wife team made breakthroughs. This culminated in their description of how the body delivers energy to muscles during intense exercise in what came to be called the Cori Cycle.

The Cori Cycle is essential to our understanding of how the liver and muscles work together. Our muscles need energy to do anything and everything. Normally, sugar in the form of glucose is broken down using oxygen, releasing energy. During prolonged and/or intense exercise, we can’t get enough oxygen to the muscles fast enough, and they have to produce energy without oxygen. To do this they convert glucose to pyruvate to lactate. Lactate is released into the blood, where it could cause damage if not for the liver. Gerty Cori and her husband’s experiments found that the liver regenerates glucose from the extra lactate. The liver uses more energy to make the glucose than the muscles can generate from it without oxygen, so the Cori Cycle is the shifting of the energy production from the muscles to the liver.

Because of this and other critical work illuminating how the body metabolizes glucose, Gerty and her husband shared the 1947 Nobel Prize in Physiology and Medicine, making Gerty the first American woman to win the prize. Earlier that year, Gerty was also finally offered a full professorship at Washington University. She continued her work on glucose metabolism and spent time investigating enzymes and hormones. Her work would later be critical to our understanding of how glucose is regulated through the body, giving targets for diabetes medications. 

This Women’s History Month, as we honor the remarkable women who have impacted our world, let’s recognize the pioneering spirit of the first American woman to win a Nobel Prize in Physiology or Medicine. Her groundbreaking work laid the foundation for our understanding and treatment of diabetes.

We can draw on her inspiration to make our parents proud and continue the legacy of progress and compassion.

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

Listen to the article here:


National Center for Biotechnology Information (2024). PubChem Pathway Summary for Pathway WP1946, Cori cycle, Source: WikiPathways. Retrieved March 19, 2024 from

Washington University School of Medicine. (2004). Gerty Theresa Cori. Bernard Becker Medical Library.

Ginsberg, J. (2010). Carl and Gerty Cori and Carbohydrate Metabolism. National Historic Chemical Landmark.

Gerty Cori – Biographical. (1964). Nobel Lectures, Physiology or Medicine 1942-1962. Elsevier Publishing Company.


On March 14, 2024, the US FDA granted accelerated approval for Madrigal Pharmaceuticals’ Rezdiffra (resmetirom) with diet and exercise for the treatment of Nonalcoholic Steatohepatitis (NASH), also known as Metabolic Dysfunction-Associated Steatohepatitis (MASH). NASH, a form of fatty liver, affects around 5% of adults in the United States and can lead to debilitating liver failure over the long term. Rezdiffra selectively activates thyroid hormone receptor-β. When combined with diet and exercise, this significantly decreases liver fibrosis and can lead to NASH resolution. Rezdiffra has been the target medication of multiple clinical trials at ENCORE Research Group sites. Jacksonville Center for Clinical Research, Nature Coast Clinical Research – Inverness, and St. Johns Center for Clinical Research have all participated in trials involving Rezdiffra. Madrigal expects Rezdiffra to be available to limited pharmacies in April 2024.



I’ve been watching horror films lately, so before we get into the main topic of lipoproteins let’s talk about blood. Blood is watery and kind of gross but very useful. I like to think of the bloodstream as a highway we use to transport nutrients, cells, molecules, water, and waste to and from all the cells in the body. One problem with blood is that it can’t transport things that don’t dissolve in it very well. Fats, also called lipids, don’t dissolve in water, a lesson I think we all learned with the old oil and water demonstration from elementary school.  Because of this, the body bundles lipids into little packages that can dissolve in watery blood. These packages combine water-repelling lipids with special proteins that organize them so they can flow through the blood. These lipid-protein packages are called lipoproteins. They have more functions than just transport, but that’s the one we’re focusing on today.

Lipoproteins are very neat. The outside is a membrane very similar to a human cell. The inside is a mix of lipids, including triglycerides and cholesterol, and the proteins hold everything together. Lipoproteins travel through the bloodstream, carrying important lipids to cells all over the body. They can be sorted by size and “density,” but density is defined differently here, more like buoyancy. Imagine a pot of water. Olive oil is almost entirely made of lipids, and if you pour it into the pot of water it floats on the surface; it’s low-density. A steak contains a lot of fatty lipids, but there’s also a ton of protein in steak. Toss it in a pot of water and it sinks (and becomes gross); it’s high-density. Lipoprotein density is more about the ratio of lipid to protein. Even more fascinating is that the ratio of lipid to protein can change over time! A very low-density lipoprotein (VLDL) will deliver triglycerides (a type of lipid) from the liver to cells, lose some density, and may become an intermediate-density lipoprotein (IDL). These are proportionally higher in cholesterol. An IDL may deliver more lipids to become a low-density lipoprotein (LDL). LDL is the primary transporter of cholesterol through the body and delivers it to cells, which use cholesterol for some essential purposes, including maintaining the membrane that surrounds cells. High-density lipoproteins (HDL) work in reverse. They transport cholesterol from the cells back to the liver, getting larger (and lower in density) as they pick up more material.

Lipoproteins aren’t just determined by their size, however. Connected to the lipoproteins are other special proteins called apolipoproteins (apo– meaning “next to” or “away”). These determine how lipoproteins form, act, are recognized, and are broken down. One dangerous lipoprotein variant is apolipoprotein (a), usually shortened to apo(a). When this attaches to an LDL-like particle, it is called Lp(a). Since the names are important and the letter “a” is common in this space, it is usually pronounced “Lp little a.” Lp(a) is bad news.

When apo(a) attaches to an LDL, everything changes. The density of Lp(a) changes and it is more likely to clog the bloodstream. High amounts of low-density lipoproteins (including Lp(a)) can cause a lot of damage to the cardiovascular system, increasing the chances of serious cardiovascular events like cardiovascular disease, heart attack, and stroke. Even worse, the body can’t break down Lp(a) the same way it does LDL, so the problems of high “bad” cholesterol are compounded. Because of this, classic methods of controlling cholesterol – lifestyle changes like diet and exercise, statins, and other medication typically have no effect on Lp(a) levels!

High Lp(a) is a serious health problem, affecting around 20% of people. Levels of Lp(a) in the bloodstream can vary up to 1000x from person to person! The highest levels are seen in Black and South Asian populations. As stated earlier, Lp(a) levels are unaffected by normal risk factors. Instead, Lp(a) is genetically controlled. If your parents have elevated Lp(a), it is likely you will too. The problem is one of several genetic mutations that affect the amount of Lp(a) created. As we discovered earlier, Lp(a) doesn’t break down like normal LDL, so levels are primarily determined by how much is produced.

So what can we do if we have high Lp(a)? As unintuitive as it sounds, diet and exercise are still good options! This isn’t because they affect Lp(a) levels, but because a healthy lifestyle can help protect your heart. Medications that protect the cardiovascular system may also be protective against high Lp(a) levels. Currently, in extreme cases, some patients may undergo a process called lipoprotein apheresis. This is where the blood is removed from the body and lipoproteins are physically separated from the blood before it is returned to the body, just like a good horror movie! Clinical trials are investigating methods of enhancing the body’s ability to break down Lp(a) or disrupt the production of Lp(a). Production may be targeted by disrupting the body’s ability to produce apo(a)! Consider joining a research study to help find new treatment options for high Lp(a). Also, with Lp(a) day approaching on March 24th, impress all your friends with your new pedantic vocabulary.

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

Listen to the article here:


Biggerstaff, K. D., & Wooten, J. S. (2004). Understanding lipoproteins as transporters of cholesterol and other lipids. Advances in physiology education, 28(3), 105-106.

Devaraj, S., Semaan, J. R., & Jialal, I. (2019). Biochemistry, apolipoprotein B.

Feingold, K. R. (2024). Introduction to lipids and lipoproteins. Endotext [Internet].

Kamstrup, P. R., Neely, R. D. G., Nissen, S., Landmesser, U., Haghikia, A., Costa-Scharplatz, M., … & Nordestgaard, B. G. (2024). Lipoprotein (a) and cardiovascular disease: sifting the evidence to guide future research. European Journal of Preventive Cardiology, zwae032.

Koschinsky, M. L., Stroes, E. S., & Kronenberg, F. (2023). Daring to dream: Targeting lipoprotein (a) as a causal and risk-enhancing factor. Pharmacological Research, 106843.

Lampsas, S., Xenou, M., Oikonomou, E., Pantelidis, P., Lysandrou, A., Sarantos, S., … & Siasos, G. (2023). Lipoprotein (a) in Atherosclerotic Diseases: From Pathophysiology to Diagnosis and Treatment. Molecules, 28(3), 969.

Schmidt, K., Noureen, A., Kronenberg, F., & Utermann, G. (2016). Structure, function, and genetics of lipoprotein (a). Journal of lipid research, 57(8), 1339-1359.


March 8, 2024 AcneBlogDermatology

I remember my introduction to puberty, my real introduction. It wasn’t a growth spurt, a voice change, or new body hair. It was a big. fat. zit. Right on the face. I was lucky, only getting a few zits here and there, but they still managed to kill my confidence. Unfortunately, it can be much, much worse for many people. Acne affects hundreds of millions of people worldwide and millions in the United States alone. Though most (85%) people experience acne in adolescence, nearly half of adults in their twenties have the condition. Beyond a simple zit here or there, acne can cause grease, lesions, and permanent scarring to the face and upper body. Acne can be graded based on the severity as mild, moderate, or severe. This can have serious negative impacts on mental health and quality of life. To really get under the skin of what’s going on with acne and what to do about it we first have to understand where and how it happens.

Acne arises in the sebaceous gland. Sebaceous comes from Latin and shares its root word with soap. These glands produce an oily fat called sebum that coats our hair and skin and helps keep them from drying out. Instead of being gross, they are super helpful. The gland itself is embedded in the skin with a hair follicle, where hair is made. Together, these make up a pilosebaceous unit (Latin for hair-grease). Along with producing oils, the sebaceous gland also has the ability to sense its surroundings. It detects and responds to changes on the skin and hormonal changes in the body. Unfortunately, they can be confused and cause acne.

There are many causes of acne, but they can be roughly divided into four main factors: increased sebum, obstruction of the pilosebaceous unit, colonization by a bacterium, and an inflammatory response.

Increased sebum is when too much of the oily, waxy fat is produced. This is usually called androgen-mediated sebogenesis, which gives a clue. The issue is an imbalance of hormones known as androgens. These are a type of steroid that can cause the sebaceous gland to produce too much sebum, which can clog the pilosebaceous unit.

This brings us to obstruction of the pilosebaceous unit. Most of the machinery of the pilosebaceous unit is located in the middle layer of skin, and it squeezes out of a small pore at the top. This pore can get clogged by sebum and hair components. A small clog is called a microcomedo. The micro– is there because the skin still looks and feels normal. If the buildup continues, there is swelling and we get a full comedo (plural comedones). This is the zit, a clogged pilosebaceous unit. Side note: the comedo can be fully covered (closed) or exposed to air (open). When covered, skin pigments are preserved and we get a whitehead. When open, oxygen causes discoloration and darkening of the sebum, leading to a blackhead.

But why does the buildup start? What’s causing this excess production? Surprisingly, the culprit has to do with the skin microbiome! This includes large amounts of (mostly helpful) bacteria that live on and in the top few layers of the skin. With acne, the little guy in question is named cutibacterium acnes, formerly called propionibacterium acnes. This bacteria is everywhere and lives happily without oxygen inside your pilosebaceous unit your whole life. It usually regulates the stability of the sebaceous gland. There are multiple strains of cutibacterium acnes (c. acnes), and some are worse than others. On the surfaces of the bacteria are proteins that vary by strain and conditions around the sebaceous gland. These can help it survive and can fight other bacteria. In some instances, these proteins can attach to the parts of the pilosebaceous unit that sense its environment. In acne-causing strains of c. acnes, the proteins activate receptors that regulate inflammatory responses. These strains are more likely to be dominant when the skin microbiome is out of whack and/or the pilosebaceous unit is producing too much sebum. The problem with c. acnes, then, isn’t the bacteria itself, but destructive strains and a skewed skin microbiome.

This brings us to the last factor contributing to acne: inflammation. Inflammation is the body’s response to dangerous invaders. It is responsive and quick but can have trouble learning from its mistakes. With acne, the inflammation system is activated by rogue c. acnes strains and attacks enemies that aren’t there. This results in the reddening and swelling typical of a zit.

So, what can be done about acne? With the enormous number of people who get acne and the very public nature, there are a lot of treatments with varying results. Skin cleansers have inconsistent data showing efficacy.

The first medical lines of defense are topical agents. Retinoids, derived from vitamin A, bind to skin cells and promote extra skin cell production, which helps clear sebaceous ducts and microcomedones. Benzoyl peroxide is cheap and effective, generating killer free radicals that enter the pilosebaceous unit and kill c. acnes indiscriminately. Topical antibiotics can be effective at combating rogue c. acnes, but improper or excessive use can create antibiotic resistance, an increasing problem with acne.

The second lines of defense are systemic agents that affect the whole body. These include medications that suppress androgens, oral antibiotics, and systemic retinoids. Since they are systemic, side effects are typically more severe than with topical treatments, but they can be used to treat moderate-to-severe acne. But what if there were another way? On the very verge of research is a c. acnes vaccine! An effective vaccine would target just the dangerous strains of the bacteria and would hopefully provide lasting protection. With luck, future generations can be introduced to puberty with parental embarrassment instead of acne!

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

Listen to the article here:


Barbieri, J. S., Wanat, K., & Seykora, J. (2014). Skin: basic structure and function.

Das, S., & Reynolds, R. V. (2014). Recent advances in acne pathogenesis: implications for therapy. American journal of clinical dermatology, 15, 479-488.

Del Rosso, J. Q., & Kircik, L. (2024). The cutaneous effects of androgens and androgen-mediated sebum production and their pathophysiologic and therapeutic importance in acne vulgaris. Journal of Dermatological Treatment, 35(1), 2298878.

Dréno, B., Pécastaings, S., Corvec, S., Veraldi, S., Khammari, A., & Roques, C. (2018). Cutibacterium acnes (Propionibacterium acnes) and acne vulgaris: a brief look at the latest updates. Journal of the European Academy of Dermatology and Venereology, 32, 5-14.

Mayslich, C., Grange, P. A., Castela, M., Marcelin, A. G., Calvez, V., & Dupin, N. (2022). Characterization of a Cutibacterium acnes Camp Factor 1-Related Peptide as a New TLR-2 Modulator in In Vitro and Ex Vivo Models of Inflammation. International Journal of Molecular Sciences, 23(9), 5065. 

Mayslich, C., Grange, P. A., & Dupin, N. (2021). Cutibacterium acnes as an opportunistic pathogen: An update of its virulence-associated factors. Microorganisms, 9(2), 303.


Most of us have two kidneys. They are fist-sized and shaped like, um, kidney beans. The kidneys filter blood, but it’s more complicated than it sounds. They filter all the blood in the body several times a day. Kidneys differentiate between proteins, cells, minerals, acids, salts, and water. They regulate the amount of small particles to filter out or retain, and they release hormones to regulate blood pressure, red blood cell count, and some aspects of bone growth. To do this, each kidney is packed with tiny filtering units called nephrons (from the Greek word for kidney). Blood goes into these units, where it is separated and filtered by a structure called a glomerulus (from the Latin word for “ball of thread”). The filter has three layers which allow progressively smaller items through. The endothelium blocks cells and other large items. The glomerular basement membrane blocks proteins. The narrowest filter is called the epithelium and is made of special cells called podocytes (from the Greek word for foot). These look like octopi and use their many “legs” to form slits which regulate what gets through. Water, sodium, minerals, and acids are all separated from the blood. The nephrons sense the levels of these items and excrete excess amounts (along with waste products) into the urine. The pressure across the filter heavily influences filtering, so the kidneys have a system to regulate the blood pressure in the nephrons. Unfortunately, when kidneys are deformed, damaged, or otherwise can’t filter for a prolonged period we are subject to chronic kidney disease.

Chronic kidney disease (CKD) is an enormous problem around the world. At least 13% of the global population (including 37 million Americans) live with chronic kidney disease. It is defined as an abnormality in structure or function for at least three months and is a big driver of cardiovascular disease. In the early stages, people may not have any symptoms; in fact, only around 5% of people with early CKD are aware they have the disease. Advanced CKD presents with myriad debilitating symptoms, including pain in the chest, changes in appetite and urination, headaches and fatigue, shortness of breath, skin issues, concentration issues, and more. Unfiltered blood can increase the amount of inflammation throughout the body. On top of all this is the most dangerous effect: damage to the cardiovascular system. When the kidneys fail to filter effectively, blood clots become more common, blood pressure may change, and the heart and vascular systems suffer. So what causes this to happen?

Since chronic kidney disease is diagnosed based on kidney function and not cause, there are many potential culprits, and each patient will have different circumstances. Most risks can be divided into modifiable and non-modifiable. Modifiable risks may be managed through lifestyle or medication. One-third of people with diabetes have CKD. Diabetes may come with excessive glucose in the blood, which damages the blood vessels in the kidneys. High blood pressure, high cholesterol, obesity, and metabolic syndrome are other significant modifiable risk factors. On top of these, heart disease can lead to renal failure (which unfortunately then leads back to more heart disease). Non-modifiable risks include age, family history, and ethnicity. Let’s go a little deeper.

When CKD is diagnosed or staged for severity, doctors look at the kidneys’ output. They may measure the amount of albumin, a component of blood, in the urine. High levels (over 30 milligrams in 24 hours) indicate issues. They may also try to measure or estimate the glomerular filtration rate (GFR). The average American starts with a healthy GFR of around 118 milliliters of blood each minute (mL/min), but someone with CKD filters fewer than 60 mL/min. This is the total amount of blood that is filtered per minute. It can be conceptualized as the filtration rate of a single nephron times the total number of nephrons. GFR gives a good indication of what goes wrong in CKD: the number of nephrons decreases significantly. Before we’re born, we have all the nephrons we’ll ever get – around one million per kidney. This is more than we need, and a person with healthy renal (Latin for kidney) function could donate literally half of them without suffering ill effects. We tend to lose nephrons over our lives, but the rest take up the slack. As nephrons are destroyed, the amount that each one filters has to increase. They try to grow and compensate, and they are often successful. With CKD, the compensation fails, and nephrons suffer compounding damage. High blood pressure in the kidneys can cause the filter to let in improper substances. It can also cause the podocytes to detach and clog the nephron.

So what can we do? Despite a lot of effort, we have no way to clean the filters or regenerate nephrons (though scientists are trying!). Current best practice is to mitigate the risks posed to other parts of the body, especially the cardiovascular system. Anticoagulants are used to stop clotting in the bloodstream. These come with the unintended side effect of making bleeds worse, so new anticoagulants that target things like FXI are being investigated to make the blood vessels less prone to clots. Other solutions include mitigating inflammation, reducing the effects of excess albumin, and managing medications and complications that may cause a feedback loop with renal distress, like blood pressure and cardiovascular risks. Clinical trials targeting CKD are currently enrolling, so let’s give unfiltered thanks to our kidneys!

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

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Evans, M., Lewis, R. D., Morgan, A. R., Whyte, M. B., Hanif, W., Bain, S. C., … & Strain, W. D. (2022). A narrative review of chronic kidney disease in clinical practice: current challenges and future perspectives. Advances in therapy, 39(1), 33-43.

Chen, T. K., Knicely, D. H., & Grams, M. E. (2019). Chronic kidney disease diagnosis and management: a review. Jama, 322(13), 1294-1304.

Lin, L., Tan, W., Pan, X., Tian, E., Wu, Z., & Yang, J. (2022). Metabolic syndrome-related kidney injury: A review and update. Frontiers in Endocrinology, 13, 904001.

National institute of Diabetes and Digestive and Kidney Diseases. National Institutes of Health. (October, 2016). Chronic Kidney Disease. U.S. Department of Health and Human Services

Puy, C., Rigg, R. A., & McCarty, O. J. (2016). The hemostatic role of factor XI. Thrombosis research, 141, S8-S11.

Romagnani, P., Remuzzi, G., Glassock, R., Levin, A., Jager, K. J., Tonelli, M., … & Anders, H. J. (2017). Chronic kidney disease. Nature reviews Disease primers, 3(1), 1-24.


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

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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

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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 15, 2024 ENCORE News

Clinical researchers (including our very own Dr. Michael J. Koren) have recently confirmed the success of an oral PCSK9 inhibitor in lowering cholesterol in patients who are taking the maximum amount of currently approved cholesterol medications. PCSK9 is short for proprotein convertase subtilisin/kexin type 9. This protein lowers the liver’s ability to break down LDL cholesterol, so by inhibiting (decreasing) PCSK9, the liver is more effective. All PCSK9 inhibitors that are currently approved must be injected, so an oral medication that successfully inhibits PCSK9 is a big step forward. In the current study, patients on the oral PCSK9 inhibitor saw similar drops in LDL cholesterol to the injectable medication! Remember that this is in patients who were already on the maximum dose of approved oral cholesterol medications!

To find out more, the study is available at:


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

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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.


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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.


November 15, 2023 ENCORE News

On November 10, 2023, the US FDA approved Valneva’s IXCHIQ chikungunya vaccine for adults 18 and older who are at an increased risk. Chikungunya is a mosquito-borne disease caused by the chikungunya virus. Outbreaks are unpredictable and rapid. Though it is not endemic to the United States, it has still infected millions of Americans over the past 10 years. Overall mortality is low, but morbidity is high with symptoms including fever, joint pain which may become chronic, and rash. IXCHIQ is a live-attenuated vaccine and is the world’s first to be approved. It targets all viral strains. St. Johns Center for Clinical Research participated in two phase three clinical trials testing safety, efficacy, and consistency of the vaccine. Valneva expects IXCHIQ to be available commercially by early 2024.



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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 8, 2023 ENCORE News

On November 1st, 2023, the US FDA approved Phathom Pharmaceuticals’ VOQUEZNA for healing treatment of erosive Gastroesophageal Reflux Disease (GERD). Around 20% of people suffer from GERD, where stomach acid moves up into the esophagus. With erosive GERD, this acid reflux causes damage to throat tissue. This is painful, but can also lead to complications and a worsening condition. Though current medications exist, over half of patients with erosive GERD continue to have symptoms. Potassium-competitive acid blockers (PCABs) are a new class of acid-fighting medications that block acid production in the stomach. These have been called the “next generation” of proton-pump inhibitors. VOQUEZNA is a PCAB medication and has shown superior activity in clinical trials. ENCORE Research Group is proud to have participated at two sites, ENCORE Borland Groover Clinical Research in Jacksonville, FL and Nature Coast Clinical Research in Inverness, FL. Phathom Pharmaceuticals expects the VOQUEZNA to be commercially available in December, 2023.



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

Listen to the article here:


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

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

Listen to the article here:


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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Eng, F. J., & Friedman, S. L. (2000). Fibrogenesis I. New insights into hepatic stellate cell activation: the simple becomes complex. American Journal of Physiology-Gastrointestinal and Liver Physiology, 279(1), G7-G11.

Geerts, A. (2001). History, heterogeneity, developmental biology, and functions of quiescent hepatic stellate cells. In Seminars in liver disease (Vol. 21, No. 03, pp. 311-336).

Kalra, A., Yetiskul, E., Wehrle, C. J., & Tuma, F. (2018). Physiology, liver. 

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

Ozougwu, J. C. (2017). Physiology of the liver. International Journal of Research in Pharmacy and Biosciences, 4(8), 13-24.

Vaja, R., & Rana, M. (2020). Drugs and the liver. Anaesthesia & Intensive Care Medicine, 21(10), 517-523.

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 20, 2023 ENCORE News

On May 31, 2023, the US FDA approved Pfizer’s ABRYSVO Respiratory Syncytial Virus (RSV) Vaccine for adults 60 and older. RSV is a serious respiratory concern for older adults, resulting in tens of thousands of hospitalizations and thousands of deaths annually. The F protein is on the outside of Respiratory Syncytial Virus and allows it to attach (or fuse) to a target human cell. ABRYSVO targets this protein before it fuses to a cell (in its perfusion state), and is effective against both the A and B strains of RSV. Thus ABRYSVO is a bivalent (targeting 2 strains) prefusion F protein-based vaccine. The vaccine was also granted Breakthrough Therapy Designation in February and is the only vaccine intended as both a protective (before infection) and a therapeutic (to stop infection and relieve symptoms). Nature Coast Clinical Research in Crystal River, Florida participated in clinical trials researching this vaccine. ABRYSVO was found to be safe and effective in older populations. Pfizer expects ABRYSVO to be available before fall 2023 and the start of RSV season.



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 13, 2023 ENCORE News

On May 26, 2023, Lexicon Pharmaceuticals’ INPEFA (sotagliflozin) was approved by the US FDA with broad label uses for treatment of heart failure. Heart failure is a significant, debilitating condition where the heart does not deliver enough oxygen to the cells in the body. It affects over 6 million Americans and hospitalizes over a million Americans per year. INPEFA has been shown to reduce cardiovascular death, hospitalization, and urgent heart failure by 33% when compared with placebo. It is approved in patients with left ventricular ejection fraction (LVEF) and for adults with cardiovascular risk factors, including type 2 diabetes and chronic kidney disease. INPEFA is a sodium-glucose cotransporter inhibitor and affects glucose regulation. Jacksonville Center for Clinical Research participated in the SOLOIST and SCORED clinical trials which were critical in showing the effectiveness of INPEFA. Lexicon expects INPEFA to be available by the end of June, 2023.



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.


June 6, 2023 ENCORE News

On May 18, 2023, the US FDA approved AbbVie’s RINVOQ (upadacitinib) as a daily pill for adults with moderate or severe Crohn’s disease. Crohn’s disease is an autoimmune disorder causing inflammation anywhere between the mouth and anus and is frequently interspersed with healthy tissue. It can cause wide-ranging, often painful GI and oral symptoms. RINVOQ is a selective tyrosine kinase inhibitor that has been approved in six other applications from rheumatoid arthritis to ulcerative colitis. RINVOQ is now the first approved oral treatment for moderate to severe Crohn’s disease. ENCORE Borland Groover Clinical Research participated in phase III trials to determine safety and efficacy in moderate and severe Crohn’s patients who did not respond to other treatments.



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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 22, 2023 ENCORE News

On May 13, 2023, Astellas’ VEOZAH was approved by the FDA. VEOZAH, also known as fezolinetant, is the first non-hormonal treatment for moderate to severe vasomotor symptoms in women with menopause. Vasomotor symptoms are the most common symptoms of menopause, affecting between 60-80% of women.They include hot flashes and night sweats, and are thought to be due to an imbalance of estrogen and neurokinin B. Unlike estrogen supplication, VEZOAH targets neurokinin B receptors in the temperature regulation center of the brain, the hippocampus. Three ENCORE Research Group centers participated in the pivotal SKYLIGHT trials to investigate efficacy and safety of VEZOAH: the Fleming Island Center for Clinical Research, St. Johns Center for Clinical Research, and Nature Coast Clinical Research – Crystal River. These three centers also participated in the SKYLIGHT 4 trial to study long-term safety. 



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


May 9, 2023 ENCORE News

On May 3, 2023, the FDA issued approval for GlaxoSmithKline’s (GSK) Arexvy RSV vaccine for adults 60 and older. RSV is a respiratory virus that hospitalizes around 177,000 adults over 65 each year, with 14,000 resulting in death. Arexvy is an adjuvanted recombinant glycoprotein antigen and the first RSV vaccine to be approved in adults. Clinical trials have shown efficacy above 82% in older adults and over 94% in those with relevant medical conditions. The Westside Center for Clinical Research, an ENCORE Research Group clinical site, has been participating in the Phase III study to show efficacy and safety of Arexvy against placebo treatment. GSK aims to make the vaccine available for adults over 60 before the end of 2023.



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 ENCORE News

On April 26, 2023, The US FDA announced approval of VOWST, formerly known as SER-109, for preventing recurrence of C. difficile. C. difficile is a major health threat, with 200,000 cases in American hospitals and over 12,000 deaths per year. VOWST is an orally administered microbiota-based medication and is the first of its kind to be approved. Clinical trials found that VOWST reduced the recurrence of C. difficile at rates nearly 50% higher than placebo controls. Studies found this at both 8 weeks and 6 months after intervention. ENCORE Borland Groover Clinical Research participated in the clinical trials ECOSPOR III and ECOSPOR IV and helped pave the way for this exciting, safe, and effective new medication. Nestlé Health Science and Seres Therapeutics expect VOWST to be available by June of 2023.



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 exercise