Wednesday, October 18, 2023

Nutrition and Exercise Physiology in Female Athletes

    Since the passing of the Title IX act in 1972, there has been a significant increase in involvement and engagement surrounding women's athletics. However, with all this development, there has been a consequential lack of research into female-specific areas of athletics, such as nutrition and exercise physiology. As we see in most areas of medicine, this lack of research is mostly due to the assumption that the female body is much more complicated to study due to hormonal implications. A female menstrual cycle can significantly impact what is going on physiologically in the rest of the body, and hormone cycles (specifically luteinizing hormone and follicle-stimulating hormone) can require longer periods of observation, to ensure all data is being collected. Due to all of these “complications” with research into the female body, there is little to no research into what a balanced nutrition looks like for a woman as well as how women should plan out and execute their exercise methods. However, there is some hope, as a 2021 review article from Holtzman and Ackerman investigated these exact issues and aimed to provide insight for female athletes. They looked heavily into how nutrition plays a significant role into the success of female athletes, and what their diet should look like based around their hormonal cycle. From this research, they suggested a few key things for women to consider when making a dietary plan. First, they state that women should pay close attention too their menstrual cycle in order to monitor for any deficiencies that may occur, then they suggested eating a wide range of foods in order to get the micronutrients that are necessary for the body to function, and the last main point they made in regards to diet was that women, and specifically female athletes, should be taking supplemental vitamins like iron and calcium in order to replenish what can be lost during menstruation. Overall, while this paper is beneficial in providing some insight into how the female body is different regarding athletics, nutrition, and exercise physiology, there is still a lot of research that needs to be done to help aid female athletes and the growth of the women’s game, as well as just the female population.

 

 

Holtzman, B., Ackerman, K.E. Recommendations and Nutritional Considerations for Female Athletes: Health and Performance. Sports Med 51 (Suppl 1), 43–57 (2021). https://doi.org/10.1007/s40279-021-01508-8

Caffeine in Children and Adolescents: Are energy drinks and sports drinks the same?

    Sports and energy drinks are a large and growing beverage industry that aim to market to children and adolescents for a variety of uses. Sports drinks suggest optimization of athletic performance and replacement of fluid and electrolyte loss. Whereas, energy drinks suggest energy boosts, decreased fatigue levels and enhanced concentration and mental alertness. The primary objective of this report is to help improve education on the differences between sports and energy drinks and how to eliminate inappropriate uses by children and young adults. 

 

Caffeine, the primary ingredient in energy drinks, has been shown to enhance physical performance in adults by increasing aerobic endurance and strength, improving reaction time, and delaying fatigue. However, these effects are extremely variable, dose dependent, and, most importantly, have not been studied in children and adolescents. Ergogenic effects have been reported with doses of 3 to 6 mg/kg, with some adult athletes reaching daily caffeine intakes of up to 13 mg/kg. Notable effects of caffeine intake are an increase in heart rate, blood pressure, speech rate, motor activity, attentiveness, gastric secretion, diuresis, and temperature. Caffeine can increase anxiety in those with anxiety disorders, play a role in triggering dangerous heart arrhythmias, and disturb regulated sleeping patterns.

 

The study noticed a heightened awareness of the risks of caffeine use, abuse, and even toxicity in children and adolescents. For example, in 2005, the American Association of Poison Control Centers reported more than 4600 calls regarding caffeine, with 2600 of these calls involving patients younger than 19 years old and 2345 patients requiring treatment.

 

Sports drinks have an important, specific role in the diet of young athletes who are engaged in prolonged vigorous sports activity—primarily to rehydrate and replenish carbohydrate, electrolytes, and water lost during exercise. However, the confusion about energy drinks versus sports drinks in children and adolescents can lead to unintentional ingestion of energy drinks. Using energy drinks instead of sports drinks for rehydration can result in ingestion of potentially large amounts of caffeine or other stimulant substances and the adverse effects previously described.

 

COMMITTEE ON NUTRITION AND THE COUNCIL ON SPORTS MEDICINE AND FITNESS. Adolescents: Are They Appropriate? Clinical Report – Sports Drinks and Energy Drinks for Children and Adolescents: Are They Appropriate? Pediatrics, 127 (6): 1182-1189, 2011. https://publications.aap.org/pediatrics/article/127/6/1182/30098/Sports-Drinks-and-Energy-Drinks-for-Children-and?autologincheck=redirected

Tuesday, October 17, 2023

Adjunctive LAT-Activating CAR T (ALA-CART) and Implications on Cancer Treatment

 

Cancer is more common than you think. It is the second leading cause of death, after heart disease in the U.S[1], and a leading cause of death globally.[2] In developed countries, 40-50% of people will get cancer in their lifetime[3], and of the 40-50% of people who get cancer, around 50% will be cured.[4] Traditional treatments for cancer include chemotherapy, surgery, and radiation.[5] Traditional treatments have several limitations, for instance, surgery and radiation can only remove or kill cancer cells in localized tumors but cannot eliminate tumor cells that have left the primary tumor site. Chemotherapy works by killing rapidly dividing cells, including tumor cells but also healthy cells that rapidly divide. The limitations of traditional therapies lead to treatment failures and relapses which cause the majority of cancer-related deaths. Therefore, there is a need for new therapies for cancer, including immunotherapy which utilizes the body’s T-cells.

Over the summer, I did research with the Kohler Lab on a type of cancer immunotherapy treatment called Chimeric Antigen Receptor (CAR) T-cell. It is a treatment where T-cells from a patient are genetically modified so they will target cancerous cells through the recognition of an antigen expressed on the surface of cancer cells by the Chimeric Antigen Receptor. CAR T-cells have had multiple successes in patients. Currently, there are six FDA-approved CAR T-cell therapies treatment. Four of those target CD19 antigens, and two of those target BCMA.[6] However, there are limitations in CAR T-cell therapies which lead to relapses. Those are short persistence and decreased sensitivity to low levels of antigens. Those limitations are predicted to stem from a weakening of LAT signaling, which is an important molecule in T-cell’s activation mechanism.

To combat these limitations, the Kohler Lab is researching on Adjunctive LAT-activating CAR T-cell (ALA-CART). ALA-CART places a LAT CAR next to a standard CAR to force the interaction between the LAT molecule and the CAR T-cell[7], instead of relying on endogenous LAT molecules. LAT molecule is an important molecule in T-cell's activation mechanism. So far, ALA-CART has shown promising results, which enhances antigen sensitivity and persistence of CAR T-cells.[8],[9]



[1] Centers for Disease Control and Prevention. An Update on Cancer Deaths in the United States. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention, Division of Cancer Prevention and Control; 2022. https://www.cdc.gov/cancer/dcpc/research/update-on-cancer-deaths/index.htm

[2] World Health Organization. Cancer. Feb 3 2022. https://www.who.int/news-room/fact-sheets/detail/cancer

[3] American Cancer Society. Cancer Facts & Figures 2022. Atlanta: American Cancer Society; 2022.

[4] American Cancer Society. Cancer Facts & Figures 2022. Atlanta: American Cancer Society; 2022.

[5] MedlinePlus [Internet]. Gersten, Todd (MD): National Library of Medicine (US); [updated Oct 28 2021; cited 2023 Jul 16]. Available from: https://medlineplus.gov/ency/patientinstructions/000901.htm#:~:text=If%20you%20have%20cancer%2C%20your,%2C%20hormonal%20therapy%2C%20and%20others.

[6] National Cancer Institute: “CAR T Cells-Engineering Patients’ Immune Cells to Treat Their Cancers”. Updated March 10 2022 https://www.cancer.gov/about-cancer/treatment/research/car-t-cells

 

[7] University of Colorado Cancer Center: Eric Kohler, MD, PhD, Receives Award to Improve CAR T-cell Therapy”. Feb 24, 2023. https://news.cuanschutz.edu/cancer-center/eric-kohler-ash-scholar-award

 

[8] Danis, Catherine, et al. 2023. https://doi.org/10.1158/1538-7445.AM2023-3190

[9] Danis, Catherine, et al. 2022. https://doi.org/10.1158/1538-7445.AM2022-3607

 

Friday, October 13, 2023

Deadly Duo

As most know, the leading cause of death in developed and developing countries is coronary heart disease (CHD). CHD occurs when plaque is formed within the coronary arteries and therefore has a difficult time distributing blood and oxygen to the cardiac muscle tissue. Over recent years there has been seen an increased correlation between atrial fibrillation (AF) and the cause of CHD and vice versa due to their common risk factors. CHD can cause AF due to reentry formation, focal ectopic activity, and neural remodeling, all of which are common cardiac arrhythmia origins. To me, the most interesting cause here is the neural remodeling in which the autonomic nervous system change’s function due to CHD and therefore causes AF. On the other hand, AF can cause CHD via atherosclerosis, mismatched blood supply and oxygen consumption, and thrombosis by changing the heart’s ability to affectively beat. Interestingly enough, atherosclerosis from AF has been hypothesized to cause CHD because of the increased von Williebrand factor in these patients, making their blood vessels weaker and narrowing the blood supply potential. In this journal entry it was found that patients that already had AF developed CHD 34% of the time. With this comorbidity much worse outcomes occur, such as myocardial infarctions and even death.  Although there is a clear and proven correlation between CHD and AF, the exact mechanisms for their causation are still unknown. What research needs to be done to break up this “vicious cycle”? Knowing that one disease causes the other, if we can prevent either from their initial onset, then the comorbidity will never occur. 

As someone who has a family lineage of heart disease it is important for me to understand this dual relationship and watch out for the common risk factors more than the average person. Some of these risk factors include: hypertension, diabetes, obesity, and sleep apnea. I can combat these factors by maintaining a healthy lifestyle and focusing on heart healthy foods and exercise. Knowing that I am higher risk to develop heart disease and therefore AF, what further research can be done in terms of preventative care for not only me but others who suffer from similar genetic backgrounds? 

 

Source: Liang, F., & Wang, Y. (2021). Coronary Heart Disease and Atrial Fibrilation: A Vicious Cycle. In American Journal of Physiology-Heart and Circulatory Physiology (Vol, 320, Issue 1, pp. H1-H12). American Physiological Society. https://doi.org/10.1152/ajpheart.00702.2020

What is Diabetic Retinopathy?

Working as an optometric technician for the past year, I was able to familiarize myself with ocular diseases. There were patients that would come in for eye exams specifically to check on their ocular health because they were diabetic. Diabetes, a metabolic disorder that causes an imbalance in blood glucose levels, can be accompanied by diabetic retinopathy (DR), which can lead to blindness (Sapra & Bhandari, 2022; Jenkins et al., 2015). Out of the 463 million people that have diabetes, 126 million have diabetic retinopathy (Saeedi et al. 2019; Jenkins et al. 2015).
 
Diabetic retinopathy occurs when there is a problem with one’s vasoregulation, meaning blood flow in the vessels becomes dysfunctional (Chen et al., 2022). These vasoregulation problems are caused by the increase in glucose in the body, which affects the blood vessels in the retina, the inner layer of the eye where light is converted to images (Mahabadi & Khalili et al., 2023). On the retina is the macula, where an individual’s most sensitive and accurate vision occurs; thus, if an individual has improper vascular flow, fluid can build up and push on the retina (Chen et al., 2022). These physiological disruptions can lead to diminished vision or vision loss.
 
Diabetic retinopathy can be manageable if diagnosed early on. Diagnosing DR can include taking ultra wide fundus photos of the retina, allowing optometrists or ophthalmologists to easily see the majority of the retina, and using Optical Coherence Tomography, which images a cross section of the retina (Park & Roh, 2016). The early stage of DR is called non-proliferative diabetic retinopathy and is characterized by leaking of blood vessels, causing microaneurysms and possible swelling of the macula (Wang & Lo, 2018). The later stage of DR is called proliferative diabetic retinopathy and can worsen vision problems due to hemorrhaging in the eye and retinal detachment (Wang & Lo, 2018).
 
After diagnosing the diabetic retinopathy, discussing treatment methods is critical as to not further one’s vision loss. One of the most common treatments is the use of laser photocoagulation, which prevents further vision loss but does not restore it (Wang & Lo, 2018). Less frequently used are intravitreal steroids, and, in advanced cases of DR, surgery is performed (Wang & Lo, 2018). It is important for diabetics to visit their optometrist or ophthalmologist to monitor their ocular health.

References

Chen, Y., Coorey, N. J., Zhang, M., Zeng, S., Madigan, M. C., Zhang, X., Gillies, M. C., Zhu, L., & Zhang, T. (2022). Metabolism Dysregulation in Retinal Diseases and Related Therapies. Antioxidants (Basel, Switzerland), 11(5), 942. https://doi.org/10.3390/antiox11050942

Jenkins, A. J., Joglekar, M. V., Hardikar, A. A., Keech, A. C., O'Neal, D. N., & Januszewski, A. S. (2015). Biomarkers in Diabetic Retinopathy. The review of diabetic studies : RDS, 12(1-2), 159–195. https://doi.org/10.1900/RDS.2015.12.159

Mahabadi N, Al Khalili Y. Neuroanatomy, Retina. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK545310/

Park, Y. G., & Roh, Y.-J. (2016). New diagnostic and therapeutic approaches for preventing the progression of diabetic retinopathy. Journal of Diabetes Research, 2016, 1–9. https://doi.org/10.1155/2016/1753584 

Saeedi, P., Petersohn, I., Salpea, P., Malanda, B., Karuranga, S., Unwin, N., Colagiuri, S., Guariguata, L., Motala, A. A., Ogurtsova, K., Shaw, J. E., Bright, D., Williams, R., & IDF Diabetes Atlas Committee (2019). Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes research and clinical practice, 157, 107843. https://doi.org/10.1016/j.diabres.2019.107843

Sapra A, & Bhandari P. Diabetes Mellitus. [Updated 2022 Jun 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551501/ 

Wang, W., & Lo, A. C. Y. (2018). Diabetic Retinopathy: Pathophysiology and Treatments. International journal of molecular sciences, 19(6), 1816. https://doi.org/10.3390/ijms19061816


Wednesday, October 11, 2023

The Gamble of Transplant Patients

 Transplantation of stem cells or other vital organs in the body is one of the only  treatment options to increase one’s quality of life and enhance one’s survival for patients with life ending organ failure, blood diseases, or bone marrow diseases. When finding a “match” in transplantation, one of the largest aspects to ensure the acceptance of the transplant is that of the MHC molecule or the HLA molecule in humans. The HLA molecule is essential for initiating the adaptive immune response by presenting antigen peptides to the two types of T cells: Helper T cells (enhance the immune response) and Cytotoxic T cells (kill all infected cells). There are hundreds of thousands of different variant types of HLA molecules that exist all over the world. However, all hope of finding their match isn’t lost as these can be inherited to have similar HLA molecules that decreases the transplantee’s chances of rejection. The catch is that without your body’s particular HLA molecule, any others will be recognized as a foreign object and therefore the body attacks the organ with this foreign HLA molecule. This leads to the acute or chronic rejection of the transplant and therefore the death of the patient. With HLA molecules being so specific, how can physicians reduce this very high chance of rejection? Upon transplantation, the immune system has to be suppressed to basically absence of the immune response altogether through the use of a variety of immunosuppression pharmaceuticals. The immune system is therefore suppressed for the rest of the patient’s life, putting them at very high risk for infectious diseases with a potential of not being able to fight these infections off. Many of these transplant patients will die from the rejection of the transplant or from an infection. 

Because this isn’t the most efficient way in enhancing one’s quality of life or the chance of an enhanced survival rate long term, there is also an ongoing clinical treatment trial in rats where the donor rat’s MHC antigens are extracted. They then dilute these molecules into smaller values and inject them into the transplantee rat. The more injections that are given to the patient have more MHC molecules of the donor to help reduce the chances of rejection. However the optimal dosage of these MHC molecules to inject into the rats is still yet to be found. However, the question that we all have is will this be efficient in humans?



Source: Carol Clayberger, Alan M Krensky, Immunosuppressive peptides corresponding to MHC class I sequences, Current Opinion in Immunology, Volume 7, Issue 5, 1995, Pages 644-648, ISSN 0952-7915, https://doi.org/10.1016/0952-7915(95)80071-9. (https://www.sciencedirect.com/science/article/pii/0952791595800719)

Wednesday, October 4, 2023

Increasing Patient Autonomy in The Dental Field Through Stem Cells


One of the four main biomedical ethical values is autonomy, or the respect for the patient's right to self-determination. Patients should be offered options and allowed to make voluntary choices concerning medical procedures that may have life-changing consequences. One way to increase autonomy in healthcare is to increase the number of options/procedures available to a patient to solve their issues. In the dental field, the main problem plaguing patients is tooth decay or caries. Dental caries are caused by a combination of factors that include frequent consumption of sugary foods/drinks, poor dental hygiene, and bacteria in the mouth that lead to acid buildup and the decay of tooth tissues. Caries that eat through the first two layers of tooth tissue (enamel and dentin) can usually be fixed through normal fillings (decay is drilled out and replaced with a silver amalgam filling or a white composite filling). But when the decay has eaten through the third layer of tooth tissue (pulp) that contains blood vessels, nervous tissue, and other connective tissue, the patient must extract the tooth or get a root canal (drilling out of decayed pulp and sealing with a rubber like material called gutta-percha) and crown (a cap that covers the old crown of the tooth) to fix the tooth. In an article from the American Journal of Medicine, researchers have started utilizing dental mesenchymal stem cells (DMSCs) to create a scaffold capable of regenerating the dentin/pulp complex. DMSCs cannot be used clinically yet as the cells are not abundant in periodontal tissues, but as research progresses new methods may be found to obtain them. However, the idea of regenerating the pulp/dentin complex without using gutta-percha gives patients a new procedure to solve their decay issue. Instead of getting a crown after a normal root canal, patients with a regenerated dentin/pulp complex can just receive a filling to replace enamel tissue that was lost. The article shows us a glimpse of the promising near future of dental care as it gives patients more options to solve their problems! 

Reference:
Orsini, G., Pagella, P., & Mitsiadis, T. A. (2018). Modern Trends in Dental Medicine: An Update for Internists. The American journal of medicine, 131(12), 1425–1430. https://doi.org/10.1016/j.amjmed.2018.05.042