Coeliac Disease

 For my first physiology blog I decided to research Coeliac disease. My brother was diagnosed with coeliac in elementary school, so I have always been curious about the condition. Coeliac occurs when ingestion of gluten triggers a heightened autoimmune response. Recent studies suggest coeliac occurs in roughly 1% of individuals, which is higher than previously thought. Unfortunately, it can be difficult to diagnose. This is partially due to lack of reliable tests which diagnose the disease. Testing anti-reticulum bodies and anti-gliadin antibodies lack specificity for diagnosing the Coeliac. Other metrics revealed high false-positive results in patients with other mucosal damage in the gastrointestinal tract. The most accurate method for testing coeliac has been revealed to be Endomysial antibodies (EMA) and anti-tissue transglutaminase antibodies (tTG). Pairing these tests with a duodenal biopsy increases accuracy of diagnosis further. To show further prove the difficulty of diagnosis, the average delay of prognosis is an average of 13 years. Coeliac has a range of symptoms including steatorrhea, diarrhoea, weight loss and anemia. Other symptoms for less severe cases include iron deficiency, and osteoporosis. Despite this, it isn't even necessary to experience these symptoms to be diagnosed with the disease. If the biopsy reveals villous atrophy (damage to the small intestine) along with a positive result from the previously mentioned tests, a diagnosis is possible. The only treatment for Coeliac is a lifelong diet free of gluten. In most cases, negative side effects and long term consequences are removed after adherence to the diet. Doctors should follow up with patients annually to track diet compliance and make up for nutrient deficiencies. A concern of ethics with coeliac is the availability of faulty tests to the public. There are testing kits which draw a small amount of blood to measure tTG positivity, which isn't accurate enough to diagnose on it's own. However, this has led to patients self-diagnosing the disease, without a biopsy or any other diagnosable metrics. Coeliac requires multiple tests in order to confidently diagnose patients, and other autoimmune diseases might be at fault for results in that single test. This is a beneficence violation for patients who may need to go to the doctor to get a more advanced diagnosis for a disease which might not even be Coeliac. 

Citation: Burden S, Langley-Evans S, Talley N. Coeliac disease: pathogenesis, prognosis and management. J Hum Nutr Diet. 2014 Jun;27(3):203-4. doi: 10.1111/jhn.12233. PMID: 24826997.

Semaglutide for Weight Loss

 As Americans we are stereotyped as the obese or overweight country. Which is not all off when 15 million Americans have life-threatening obesity and 70% of adults over 20 years are affected by some kind of overweight  or obesity. Around 25% of the U.S children are also overweight. Being overweight is considered by the body mass index’s (BMI) of 25-19.9 kg/m^2 and obesity as over 30 kg/m^2. Although there is other physiological reasons for being overweight, our country sells big amounts of fast foods for a very small amount of money. Leading our diets to be high in carbohydrates and high in calorie intake. The average meal of a crispy chicken sandwich with bacon, fires, and a coke from McDonalds is around 1,290 calories when according to WebMD women should be consuming about 1,600 to 2,400 calories a day and men should consume form 2,200 to 3,000 calories a day. For our fast past life the average American ends up eating more than 3,000 calories worth of fast food a day. It’s cheap, easy, and not very time consuming which lead the American Medical Association (AMA) to recognize obesity as a disease requiring treatment.

To fight the health concerns pharmacological treatments like glucagon-like-peptide-1 receptor agonist (GLP-1 RAs) which stands out as the most effective options among all the others. GLP-1 RAs have shown great improvements in glycemic controls and weight loss. Among all the GLP-1 RAs Semaglutide have been shown to be superior in achieving weight loss. There is a verity of mechanisms that show the benifits of Semaglutide. It activates the GLP-1 receptors in the gut and pancreas, slowing gastric emptying and inhibiting glucagon release and showing a slow appetite. It also activated them in the brains hypothalamus which decreases the feeling of hunger and decreasing food cravings. Overall when Semaglutide when taken once-weekly subcutaneously can result in significant weight loss without many risks of serious adverse events and can lead into future studies of weight loss and cardiovascular health / diabetes type 2.

Sources:

Barro, J., Griggs, T., Leonhardt, D., & Miller, C. C. (2014, December 22). What 2,000 calories looks like. The New York Times. https://www.nytimes.com/interactive/2014/12/22/upshot/what-2000-calories-looks-like.html 

Kommu, S., & Berg, R. L. (2024). Efficacy and safety of once‐weekly subcutaneous semaglutide on weight loss in patients with overweight or obesity without diabetes mellitus—a systematic review and meta‐analysis of Randomized Controlled Trials. Obesity Reviews, 25(9). https://doi.org/10.1111/obr.13792 

No White Flags: From Football Star to Living with ALS

It was September 25th, 2006; the New Orleans Saints played their first game back after Hurricane Katrina devastated the city. The Atlanta Falcons lined up to punt the ball. As the play started, safety Steve Gleason tore through the Falcons’ line and blocked the punt. The Saints recovered and scored a touchdown. The crowd roared, and Steve Gleason’s name spread throughout the city as the figurehead of the rebirth of the Saints’ spirit. 

However, in January 2011, my cousin Steve Gleason received devastating news. He was diagnosed with Amyotrophic Lateral Sclerosis (ALS). ALS is a progressive neurodegenerative disease that causes muscle weakness and paralysis, eventually affecting the ability to speak, eat, and breathe by impacting motor neurons in the brain and spinal cord. On a molecular level, ALS pathology involves a combination of genetic and environmental factors that lead to protein aggregation (e.g., SOD1) within neurons, disrupting normal cell function and proteostasis. Additionally, neuroinflammation driven by microglia and astrocytes accelerates motor neuron death.

Steve was given 2-5 years to live but is still alive today, 13 years later. He uses a motorized wheelchair to move around and needs assistance with breathing, eating, and talking, which he does through a computer that allows him to type with his eyes. Steve challenged Microsoft to create this eye-tracking technology, which was completed in 2019 and is now used worldwide by those living with ALS.

Although the disease is debilitating, it typically does not affect cognitive function. If you talk to Steve or listen to a minute of his interviews (linked below), that is apparent. He has not lost an ounce of his wit, drive, determination, and love for life. Steve has a family consisting of his wife, Michelle, and his children, Rivers and Gray. Both were conceived via in vitro fertilization, with Rivers born in 2011 shortly after Steve's diagnosis, and Gray in 2018. Being a parent is Steve’s greatest commitment and motivation to continue.

He is an inspiration to many, and he won’t surrender until there is a cure. “No white flags.”

Interesting videos/links about Steve Gleason: 

Blocked punt footage: https://www.youtube.com/watch?v=MYwPmzRs-nc

Recent interview with CBS Mornings: https://www.youtube.com/watch?v=aflvYUOMgic

Amazon Gleason documentary: https://www.amazon.com/Gleason-Steve/dp/B08CS4L48W

Team Gleason website: https://teamgleason.org/

Steve’s book: A Life Impossible: https://www.penguinrandomhouse.com/books/721744/a-life-impossible-by-steve-gleason-with-jeff-duncan/

Resources: 

Brown, R. H., & Al-Chalabi, A. (2017). Amyotrophic Lateral Sclerosis. New England Journal of Medicine, 377(2), 162–172. https://doi.org/10.1056/NEJMra1603471

Mejzini, R., Flynn, L. L., Pitout, I. L., Fletcher, S., Wilton, S. D., & Akkari, P. A. (n.d.). ALS Genetics, Mechanisms, and Therapeutics: Where Are We Now? - PMC. Retrieved September 9, 2024, from https://www-ncbi-nlm-nih-gov.dml.regis.edu/pmc/articles/PMC6909825/

Hydroxychloroquine and the Importance of Science Communication

In recent years Hydroxychloroquine has garnered controversy for its potential use as a treatment for Covid-19, with opposing sides of the political aisle adopting a pro or anti stance on the drug. It is important, however, to strip hydroxychloroquine of its new political connotations, examine the empirical evidence of its potential as a Covid-19 treatment, and recognize the failure of science communicators to properly characterize this drug.

            Hydroxychloroquine has been used since the 1940s as an anti-malaria drug and as an rheumatoid arthritis drug since 1955, with its most common side effects being gastrointestinal disruption and skin irritation. Its potential to treat Covid-19 comes from its ability to reduce the immune system’s inflammatory response without downregulating the immune response needed to combat a virus. It also has been shown to inhibit the uptake of viral materials by host cells and inhibit a virus’ ability to function properly, by disrupting its ability to add carbohydrates to proteins and by inhibiting viral enzymes.

            When testing the effects of the medication on patients with Covid-19 the results reflected its known anti-viral properties. In a study with over 100 patients infected with Covid-19, it was found that patients had better lung imaging, less severe pneumonia symptoms, and a shortened infection period when given hydroxychloroquine. It was also found in another study that patients had a 70% decrease in Covid-19 viral load after 6 days of hydroxychloroquine administration, compared to patients that were not given hydroxychloroquine. The study also found a 100% decrease in viral load when both hydroxychloroquine and azithromycin was administered in conjunction for 6 days.

These results show that hydroxychloroquine is neither an ineffective medicine nor is it a coronavirus cure-all. In reality, it is a medication that has been shown to aid patients’ recovery from Covid-19, when managed by healthcare professionals. As scientists, we must not only ensure the rigor of our research but also make a deliberate effort to properly communicate our findings to the public. The politicization of hydroxychloroquine and political pundits either dismissing its uses or exaggerating its effectiveness, is evidence that pollical actors are not the best science communicators. In a time of increasing political polarization, scientists must make a new effort to directly communicate to the public. Scientists must also separate their credibility from science communicators who are both unknowledgeable about the scientific literature and communicate scientific information with a bias.

Source

Sinha, N., & Balayla, G. (2020). Hydroxychloroquine and COVID-19. Postgraduate medical journal, 96(1139), 550–555. https://doi.org/10.1136/postgradmedj-2020-137785

Maybe I Won't Have an Another Energy Drink..

    Imagine working in an Emergency Department and a male patient in their early 20's comes in complaining of lightheadedness. You see him get registered and call him over to check some vitals. He slowly walks to you and seems calm. As you put the pulse oximeter over his finger and walk back to your computer, you hear the beeps of the machine wailing with an alarm. As you turn, you see his pulse is in the 170 bpm range. You rush over to get an EKG and call the charge nurse to secure a room for him. The patient isn't complaining of anything other than the lightheadedness. As you do the EKG it shows signs of supraventricular tachycardia (SVT). You bring the patient back to a room, to where the physician tells the nurse to get 6mg of Adenosine. While waiting for the medication, the physician tells the patient to bare down as if he was going to have a bowel movement and is changed from a sitting position to a Trendelenburg position. The monitor's sporadic movement and noise slowly diminish, and just like nothing the patient's heart rate went into normal range without the use of medication. 

    This is a common occurrence when dealing with an arrhythmia such as supraventricular tachycardia. SVT is a type of arrhythmia that is caused by an issue with electrical conduction, making the heart not fill up correctly with blood, making the heart speed up to compensate for its lack of perfusion. Patients under SVT will usually have heart rates over 150bpm without doing any physical activity. Most are symptomatic with lower blood pressure, lightheadedness, diaphoretic, and palpitations. Some do present asymptomatically, but can be caught quickly when triaging the patient. For many young adults, causes usually come from excessive caffeine or drug use. 

    To help combat this arrhythmia physicians will use Valsalva maneuver, Adenosine, and or cardioverting the patient. Valsalva maneuver is usually used first during SVT as a noninvasive alternative. It requires the patient to bare down as they would be when trying to have a bowel movement. This technique increases vagal parasympathetic tone which in turn causes the baroreceptors in your brain to increases parasympathetic output (an example is added below) (Neihues & Klovenski, 2024). Adenosine is used to block the conduction of the AV node allowing the heart to reset. If nothing has been successful, cardioverting is used to shock the heart to reset its electrical activity. 

    Next time you're cramming for your next midterm, maybe don't reach for another Celsius and grab a tea instead. 

Valsalva Maneuver:

https://www.youtube.com/watch?v=NVFAr9-THKo

References:

Niehues, L. J., & Klovenski, V. (2024). Vagal Maneuver. In StatPearls. StatPearls Publishing.

Physiological Effects of Gender-Affirming Hormone Therapy

    Gender-affirming hormonal treatment (GAHT) causes significant increases in the physiological and psychological well-being of transgender individuals. Transgender people are faced with gender dysphoria (GD), which increases anxiety, stress, and depression due to their physical appearance not matching their gender identity. GAHT is used to inhibit or reduce androgen synthesis of either testosterone or estrogen, and there are three types of antiandrogen. There are the antiandrogens that impede on androgen-receptor signaling, the ones that limit conversion of testosterone to dihydrotestosterone (DHT), and those that lessen the androgen production. To decide which one to take, it ultimately depends on how the medications will be administered.

    Testosterone therapy in transmen will start to show signs in around three months, which includes the lack of menstruation, an increase in body hair, acne, changes in skin, alterations in fat distribution and muscle mass, and voice deepening. Estrogen therapy in transwomen will show signs gradually throughout 18 to 24 months, which includes breast growth, increased body fat, and reduced body and facial hair growth. GAHT increases the quality of life and causes positive effects on mood. It has been found that the serotonin reuptake transport binding (SERT) in transwomen that take estrogen and antiandrogen medications is lowered, while SERT in transmen is increased in different brain regions. This provides reasonable data that hormone treatment alleviates physiological stress, especially due to the significantly lower cortisol levels and stress in transgender individuals within 12 months of treatment. Transgender people have had reduced anxiety, perceived stress, and social distress after GAHT, as well as improvements in mental health, quality of life, self-esteem, and mood. 

    GAHT has also been found to increase certain health issues in transwomen, due to the increase of estrogen in the body. Specifically, estrogen therapy has caused an increase in venous thromboembolic events (VTE), which includes heart attacks, strokes, pulmonary embolisms, and cardiovascular mortality. This mostly occurs when taking estradiol orally, due to the “first-pass” effect in the liver, which increases prothrombotic factors. Transwomen may also experience bone loss due to the introduction of more estrogen in the body, which impedes on the body’s natural distribution of testosterone to help bone health and muscle mass. Transmen receiving exogenous testosterone in physiological amounts creates an anabolic effect on cortical bone and can be sufficient in preventing bone demineralization in transgender patients. Transmen may also experience more executive dysfunction due to the importance of estrogen in the prefrontal cortex. 

Reference: Moustakli, Efthalia, and Orestis Tsonis. “Exploring Hormone Therapy Effects on Reproduction and Health in Transgender Individuals.” MDPI, Multidisciplinary Digital Publishing Institute, 29 Nov. 2023, www.mdpi.com/1648-9144/59/12/2094.

Does less glucose lead to neurogenesis?

We all know that the brain's favorite source of energy is glucose. We also know the body will do anything to make sure the brain has adequate glucose, which serves a myriad of functions in the central nervous system. Can too much of a good thing become a bad thing? A recent Stanford Medicine study published in Nature a few days ago delves into the role of elevated glucose levels in neural stem cell inactivation. 

Although it was initially believed that adult brains cannot undergo neurogenesis, the growth of new neurons, neural stem cells continue to produce neurons well into old age. This process, however, declines as we age, proving to be detrimental to preserving memory and recovering from neurological injuries such as strokes. Further, it seems likely that inactive neural stem cell populations contribute to neurodegenerative diseases like Alzheimer’s Disease or Parkinson’s Disease. Elevated glucose levels have been found around inactive neural stem cell populations, leading researchers to examine the link between elevated glucose and decreased neurogenesis. 

Anne Brunet, PhD and her team used CRISPR to knock out a GLUT4 gene and observe its effects on living mice. What they found is nothing short of ground-breaking. By reducing glucose intake, they observed neurogenesis in relevant areas of the brain via activation and proliferation of neural stem cells. Their results even showed over a 2-fold increase in “newborn” neurons in old mice. Why is it significant that they used old mice and not young mice? It’s significant because it has a more direct clinical application in age-related neurodegenerative diseases. This is rightfully classified as a massive win for patients suffering from the detrimental and life-altering effects of these diseases. We can use this finding to inform development of genetic therapy drugs that can turn off glucose transporters in patients with neurodegenerative disease and thus promote neurogenesis, exemplifying the principle of beneficence. With the knowledge and resources, we have at our disposal, we are using them for the good of patients. We teeter on the cutting edge of scientific advancement that will hopefully create avenues for better clinical outcomes. 

Ruetz, T.J., Pogson, A.N., Kashiwagi, C.M. et al. CRISPR–Cas9 screens reveal regulators of ageing in neural stem cells. Nature (2024). https://doi.org/10.1038/s41586-024-07972-2