Categories
Health and Disease

The 30 Minute Malaria Test

By Kyle Phong

Published 7:55 EST, September 17th, 2021

What is Malaria?

Malaria is a disease transmitted by mosquitoes that affects around 230 million people worldwide. The common symptoms of malaria consist of fever, chills, body aches, nausea, vomiting, and headaches. Without treatment, the infection can significantly worsen, causing seizures, comas, and death. This illness is particularly detrimental towards rural and underdeveloped countries where there are low funds and a lack of infrastructure to take the proper measures.  

Vecteezy, “Malaria Infographic”

Testing for Malaria

Currently, there are rapid diagnostic tests (RDTs) for malaria, but it comes with several drawbacks. It cannot detect malaria in its early stages, determine its severity, and occasionally give false positive and negative results. In Nanyang Technological University, Singapore, a team led by Dr. Quan wanted to create a test for malaria that was both accurate and inexpensive to produce.   

For RDTs, malaria-infected blood is examined under a microscope by an expert. Both factors are uncommon in rural locations, significantly delaying the diagnosis. The image below displays the only available RDT for malaria in the US.  

CDC, “BinaxNOW Malaria Test”

The new test kit from Nanyang Technological University does not rely as heavily on laboratory equipment as it only needs water and a blood sample. Requiring a mere ten microliters of blood or less than one drop, the kit mixes this with water which releases the malaria parasites. Malaria parasites digest blood to grow and proliferate, creating hemozoin as a by-product. The kit proceeds to pump blood through an area of chemical patches that light up hemozoin. A light detector called the Raman spectrometer records the frequency and strength of these flashes of light to determine the presence of malaria as well as its severity.  

Nanyang Technological University, “Malaria Test Kit”

In order to confirm the accuracy of this new test, the research team added early-stage malaria-infected blood into the kit. They found that the test detected these early-stage parasites, making them more sensitive than RDTs available in the United States. Due to the test’s sensitivity, it can quantify the number of parasites in the blood sample. Physicians can utilize this test to track how well the patient is fighting against malaria.  

Conclusion

Dr. Quan and his team hope to cooperate with an industry partner in order to continue conducting more trials and further improve this testing kit. It is estimated that the test would cost about $1 for the US to manufacture, meaning it could be utilized in the field on a large scale. In the future, these test kits will pave way for underserved populations to gain easier access to important public health resources.

Kyle Phong, Youth Medical Journal 2021

References

Center for Disease Control and Prevention, “Malaria”, 30 June 2021

https://www.cdc.gov/parasites/malaria/index.html

Center for Disease Control and Prevention, “Malaria Diagnostic Tests”, 19 February 2020

https://www.cdc.gov/malaria/diagnosis_treatment/diagnostic_tools.html

Nanyang Technological University, “Rapid malaria test kit could aid diagnosis in developing countries”, 29 June 2021

https://www.ntu.edu.sg/news/detail/rapid-malaria-test-kit-could-aid-diagnosis-in-developing-countries

News Medical Life Sciences, “Rapid test kit for malaria delivers results in 30 minutes”, 29 June 2021

https://www.news-medical.net/news/20210629/Rapid-test-kit-for-malaria-delivers-results-in-30-minutes.aspx

ScienceDirect, “Towards malaria field diagnosis based on surface-enhanced Raman scattering with on-chip sample preparation and near-analyte nanoparticle synthesis”, 15 September 2021

https://www.sciencedirect.com/science/article/abs/pii/S0925400521007310?via%3Dihub

Vecteezy, “Malaria Infographic”

https://www.vecteezy.com/vector-art/1778112-malaria-symptom-information-infographic

Categories
Biomedical Research

Treating Diabetes with a Smartwatch

By Kyle Phong

Published 1:22 PM EST, Sunday Aug. 8th, 2021

Introduction

It has been estimated that over 34 million Americans have been diagnosed with diabetes.  An ambitious research team in ETH Zurich, Switzerland, noted the rise in fitness trackers’ popularity and created a new treatment of diabetes by utilizing the green light from an everyday smartwatch.

Methods

Fitness trackers like the Apple Watch shown below emit a non-invasive green light-emitting diodes (LED) light that goes through our skin to measure our heart rate, sleep cycle, and blood pressure.  

Exist, “How do fitness trackers measure your heart rate?”

Dr. Fussenegger, the leader of the research team, developed a molecular system named “Glow Control” within human cells that can be activated by the green light from a smartwatch. They experimented with HEK293 (Human Embryonic Kidney) cells, which are commonly used in laboratories around the world. In order to test their hypothesis, the researchers implanted HEK293 cells into pork rinds and mice as shown in Figures A and C below.  Then, they used the green LED light from Apple Watches to activate these cells and produce human Glucagon-Like Peptide 1 (hGLP-1), which is responsible for the production of insulin.  Many medications today mimic the effects of this peptide to control glucose levels in patients with Type-2 diabetes.  

Nature Communications, “Fig. 5: Smart-watch-mediated transgene expression in vitro and in vivo”

The Type-2 diabetic mice displayed increased levels of hGLP-1 and lower levels of glucose compared to the mice that weren’t exposed to green LED light in the control group. Over a 12-day treatment period, the mice in the experimental group showed reduced body weight gain and insulin resistance.  

Conclusion

The Glow Control system can easily be implemented in our everyday lives. Its reliance on green LED lights from commercially available smartwatches such as the Fitbit or Apple Watch makes it accessible and eliminates the need for patients to purchase a special medical device. Artificial pancreas, one form of treatment for diabetes, is invasive and requires constant glucose monitoring.  In comparison, the Glow Control system is non-invasive and compatible with various smartwatches that can download medical software for monitoring and treatment. Dr. Fussenegger states that the smartwatch still has at least ten more years before it can be used in clinical practice. Multiple clinical phases for this smartwatch ensure that it is a safe, effective, and ethical product for patients to use.  

References

ScienceDaily, “Controlling insulin production with a smartwatch”, 7 June 2021

https://www.sciencedaily.com/releases/2021/06/210607084616.htm

Nature, “Smart-watch-programmed green-light-operated percutaneous control of therapeutic transgenes”, 7 June 2021

https://www.nature.com/articles/s41467-021-23572-4

Exist, “How do fitness trackers measure your heart rate?”, 21 February 2016

https://exist.io/blog/fitness-trackers-heart-rate/

Center for Disease Control and Prevention, “National Diabetes Statistics Report, 2020”, 11 February 2016

https://www.cdc.gov/diabetes/library/features/diabetes-stat-report.html

Hormone Health Network, “Glucagon Like Peptide 1”, May 2019
https://www.hormone.org/your-health-and-hormones/glands-and-hormones-a-to-z/hormones/glucagon-like-peptide-1

Kyle Phong, Youth Medical Journal 2021

Categories
Health and Disease

Predicting Heart Attacks

By Kyle Phong

Published 1:55 PM EST, Sat June 12, 2021

Introduction

According to the CDC, someone has a heart attack every 40 seconds in the United States.  With heart disease being the leading cause of death in the US, one wonders how can heart attacks be prevented. Doctors recommend lifestyle changes such as a balanced diet and avoiding smoking. Recently, a research team at the University Hospital of the RWTH Aachen, Germany led by Dr. Milzi developed a method of predicting heart attacks using an advanced imaging system.

What is a heart attack?

A heart attack, medically known as a myocardial infarction, is blockage of blood flow to the heart, resulting in a section of the heart’s muscle beginning to die.  The arteries are typically blocked by a buildup of plaque, a combination of fats, calcium, and other substances in the blood.  Then, a layer of tissue called the fibrous cap surrounds the plaque.  Rupturing of the fibrous cap will cause a blood clot to form, completely blocking blood from reaching the heart through that artery.

NHLBI, “Heart with Muscle Damage and a Blocked Artery”

Methods

There have been prior studies of plaque and what puts them at high risk of rupturing, yet the exact reasoning behind them are still unknown.  Dr. Milzi and her team utilized optical coherence tomography (OCT) to take high resolution photos of coronary plaques in 20 patients with type 2 diabetes as well as chronic coronary syndrome or acute coronary syndrome.  Next, they analyzed stress concentrations using kilopascals as a possible predictor of plaque rupture.  

eLife, “Figure 5: Exemplary reconstruction of a coronary plaque”

The images above display an OCT image (left) and a sample reconstruction (right) of a coronary artery containing plaque.  The reconstruction shows the fibrous cap in red, lipid core plaque in yellow, rest of the vessel in gray.  The research team utilized this sample reconstruction in simulations to test the close association between stress and plaque rupture.  They noticed that ruptured plaques showed greater stress concentrations compared to plaques that have not ruptured.  Using this new information, they found locations with high stress concentrations and predicted that ruptures were likely to occur there.

Conclusion  

Studying the stress distribution in arteries is an additional way to predict future heart attacks, especially among patients at high risk.  With the use of OCT imaging, we can improve the treatment of coronary heart disease and continue to fight against the leading cause of death in the United States.  Before applying this newfound knowledge in a clinical setting, this study must be automated and further analyzed with a greater number of patients.

Kyle Phong, Youth Medical Journal 2021

References

eLife, “Coronary plaque composition influences biomechanical stress and predicts plaque rupture in a morpho-mechanic OCT analysis”, 11 May 2021 https://elifesciences.org/articles/64020

News Medical Life Sciences, “New approach could allow cardiologists to predict future heart attacks in high-risk patients”, 19 May 2021 https://www.news-medical.net/news/20210519/New-approach-could-allow-cardiologists-to-predict-future-heart-attacks-inhigh-risk-patients.aspx

Centers for Disease Control and Prevention, “Heart Disease Facts” https://www.cdc.gov/heartdisease/facts.htm

National Heart, Lung, and Blood Institute, “Heart Attack” https://www.nhlbi.nih.gov/health-topics/heart-attack

Categories
Biomedical Research

Preventing Nerve Cell Deterioration After Traumatic Brain Injury

By Kyle Phong

Published 1:46 PM EST, Sat May 15, 2021

Introduction

Traumatic brain injury (TBI) is often caused by a blow to the head and currently affects around five million people across the US. It is known to cause several neuropsychiatric conditions such as psychosis, mania, and Alzheimer’s disease, and can also lead to nerve cell deterioration. At the Harrington Discovery Institute in Cleveland, Ohio, Dr. Pieper and his team have discovered a way to prevent TBI-induced nerve cell deterioration in the brain.  They also found a possible explanation for the relationship between TBI and Alzheimer’s disease.

Osmosis, “Traumatic Brain Injury (TBI)” 

Methods

To explore the connection between Alzheimer’s and TBI, Dr. Pieper used previous knowledge of tau and acetylation in patients.  Tau is a protein in nerve cells that help guide nutrients throughout the neuron.  However, tau tangles with other tau molecules in patients with Alzheimer’s disease, resulting in weak synaptic communication between neurons and becoming acetylated-tau.  While experimenting with mice, Dr. Pieper found high levels of acetylated-tau (ac-tau) in different forms of TBI.  The elevated ac-tau persisted chronically if left without treatment.  Furthermore, patients with Alzheimer’s disease had even higher levels of ac-tau if they had a history of TBI.

Labiotech, “Healthy Neuron vs Alzheimer’s Disease Neuron”

Dr. Pieper’s team found two anti-inflammatory drugs (salsalate and diflunisal) that helped to protect the mice’s neurons from deteriorating after TBI.  These two medications inhibit the enzyme that causes tau acetylation, therefore preventing the transformation into ac-tau.  Upon this discovery, the researchers analyzed over seven million patient records regarding the usage of salsalate and diflunisal and realized that these medications were associated with a decrease in Alzheimer’s disease and TBI cases.  Additionally, they compared these two drugs with aspirin, a common anti-inflammatory drug, that does not prevent acetylation.  Dr. Pieper did not find any evidence of aspirin showing the same neuroprotective activity as salsalate and diflunisal.

Knowing that tau is a protein that diffuses from the brain into the bloodstream, the researchers wondered about ac-tau levels existing in the blood of TBI patients.  For both mice and humans, there was a significant increase of ac-tau in the blood.  However, these elevated levels returned to normal when treated with medications such as salsalate and diflunisal, showing again that they effectively protect nerve cells from deterioration. 

Conclusion

Dr. Rosa, the co-author of this study, explains that this newfound knowledge can have a variety of uses in the clinical setting.  The research team is continuing to examine ac-tau and its relationship with neurodegenerative diseases.  Additionally, they will study salsalate and diflunisal to see whether these drugs can be used as an established neuroprotective medication for humans. 

Kyle Phong, Youth Medical Journal 2021

References

News Medical Life Sciences, “Researchers discover a new way to prevent brain nerve cells from deteriorating after injury”, 13 April 2021

https://www.news-medical.net/news/20210413/Researchers-discover-a-new-way-to-prevent-brain-nerve-cells-from-deteriorating-after-injury.aspx

Cell, “Reducing acetylated tau is neuroprotective in brain injury”, 13 April 2021

https://www.cell.com/cell/fulltext/S0092-8674(21)00363-9

Osmosis, “Traumatic brain injury: Clinical practice” Image

https://www.osmosis.org/learn/Traumatic_brain_injury:_Clinical_practice

Labiotech, “How AC Immune CEO Andrea Pfiefer is Tackling Alzheimer’s Disease” Image, 1 August 2018

https://www.labiotech.eu/interview/alzheimers-disease-acimmune-andrea-pfeifer/

Categories
Health and Disease

A Multidimensional View on Sickle Cell Disease

By Kyle Phong

Published 7:14 PM EST, Sat April 17, 2021

Introduction

Sickle cell disease (SCD), or sickle cell anemia, is a common health condition that affects about 20 million people worldwide.  Although this disease originates from mutations within our genes, there are several influences, such as psychological, environmental, and biological, that affect each person’s life expectancy and overall experience.  Recent research emphasizes the significance of understanding these influences in order to better treat SCD and all other hereditary diseases.

What is Sickle Cell Disease?

SCD is when red blood cells form a curved, crescent shape.  As shown in the diagram below, a healthy red blood cell is shaped like a disc.  Due to their deformed shape, these fragile sickle cells die quickly.  Red blood cells die faster than new ones can be created, resulting in a low red blood cell count.  Additionally, sickle cells often clog blood vessels because of their irregular shape.  This may completely block or slow the flow of blood and oxygen to various parts of the body.

Causes: SCD is a hereditary disease that is passed down from parents that both must have the sickle cell trait. Typically, having this trait is not harmful, but it can be passed onto children.  As shown in the graphic below, there is a 25% chance of having sickle cell disease if both parents have the sickle cell trait.

Symptoms: SCD can cause a variety of problems ranging from chronic pain to stroke.  Due to the fact that red blood cells play an important role throughout our body, symptoms of SCD can be seen anywhere.  Some early signs of SCD include jaundice, when our skin and eyes become yellow, as well as swelling in the hands and feet.

Treatments: Currently, a blood and bone marrow transfusion is the only known cure for SCD.  However, only specific individuals are able to receive this treatment.  These transplants are mainly done for children since they have the highest chance for success.  Additionally, a relative is needed to be a donor in order to be a good genetic match.

However, there are several medicines used today to treat SCD without curing it.  For example, Voxelotor is a newly approved medicine for ages 12 and up.  It improves blood flow by preventing red blood cells from forming a sickle shape.  

Methods

It was unsurprising for researchers to see that industrial countries with access to greater healthcare were able to extend the typical lifespan of someone with SCD.  There are seven domains of influence that all play large roles in our experience with SCD.  These domains include environmental, biological, sociocultural, structural, psychological, clinical, and behavioral.    

This Identity Networks, Genome, and Affect as Modulators of Health (INGAM) model displays a variety of SCD outcomes and factors ranging from drug addiction to anxiety.  There is often an emphasis on the biological and clinical domains of influence when dealing with SCD, but this disregards SCD’s multidimensional nature.  In order to properly treat SCD complications, one must take all factors into consideration.

Conclusion

International health organizations, such as the WHO, should encourage countries to implement more appropriate policies for SCD.  Some scientists believe that we are on the brink of discovering a molecular cure for SCD through the use of CRISPR.  However, it is unlikely for all countries to have immediate access to a newfound cure for SCD.  Therefore, it is crucial to develop new methods to reduce complications in the millions of people with SCD around the world.  Additionally, multifactorial diseases such as cystic fibrosis are greatly impacted both by genetic and environmental factors.  Rather than using a linear approach, we must consider that there are often many factors working in conjunction that result in SCD.  Using this multifaceted model, we can revolutionize the next steps in treating SCD as well as other complex diseases and ultimately improve the quality of life worldwide.

Kyle Phong, Youth Medical Journal 2021

References

Wiley Online Library, “Sickle cell disease is a global prototype for integrative research and healthcare,” 25 February 2021

https://onlinelibrary.wiley.com/doi/10.1002/ggn2.10037

News Medical Life Sciences, “A single letter difference in a single gene spells a lifetime of anemia, pain worldwide,” 2 March 2021

https://www.news-medical.net/news/20210302/A-single-letter-difference-in-a-single-gene-spells-a-lifetime-of-anemia-pain-worldwide.aspx

Center for Disease Control and Prevention, “What is Sickle Cell Disease?”

https://www.cdc.gov/ncbddd/sicklecell/facts.html

Medline, “Sickle cell disease”

https://medlineplus.gov/genetics/condition/sickle-cell-disease/

National Heart, Lung, and Blood Institute, “Sickle Cell Disease”

https://www.nhlbi.nih.gov/health-topics/sickle-cell-disease

Categories
Biomedical Research

Changing Our Understanding of Medulloblastoma

By Kyle Phong

Published 11:16 PM EST, Mon March 1, 2021

Introduction

At St. Jude Children’s Research Hospital, scientists conducted the largest analysis of primary and relapsed medulloblastoma tumors to date. The research team divided medulloblastoma into four molecular groups: WNT, SHH, (both named after their genetic mutation), Group 3, and Group 4.  Upon discovering that about one-third of these patients relapsed and displayed a five-year survival rate of 10%, the researchers sought to find out why this was occurring.

What is Medulloblastoma?

Currently, medulloblastoma is the most commonly found brain tumor in children younger than 16 years old.  If it is not detected early and treated, it tends to spread to other areas of the brain as well as the spinal cord. The specific cause of medulloblastoma is not known, but cancer is formed due to the uncontrolled, rapid division of a mutated cell. A small percentage of childhood medulloblastomas are hereditary.  

Symptoms: Typical symptoms for a child with medulloblastoma are worsening nausea and vomiting, clumsiness, headaches, and seizures.  If cancer has metastasized to the spinal cord, the child might also experience problems walking, back pain, and difficulties with controlling their excretory functions.  

Survival Rate: Assuming the tumor has not spread, the survival rate is 70-80%, which is fairly high compared to several other cancers. If it has spread to the spinal cord, the rate lowers to about 60%.  

Treatment: The three main treatments of medulloblastoma are surgery, radiation, and chemotherapy. During surgery, as much of the tumor is removed as possible without jeopardizing the patient’s health.  Depending on how much of the tumor is left, the patient then undergoes radiation therapy and chemotherapy. Radiation therapy is when high radiation such as X-rays kills cancer cells. Chemotherapy is a medicine that is injected or orally consumed to kill cancer cells. 

Research and Data Analysis 

In the study, each of the four groups of medulloblastoma was then organized by their five-year survival rate. WNT tumors have a 95% five-year survival rate, SHH and Group 4 have about a 75% five-year survival rate, and Group 3 has a 60% five-year survival rate. Next, the research team analyzed data from two trials, SJMB03 and SJYC07. SJMB03 includes international children with newly diagnosed medulloblastoma from 2003-2012.  SJYC07 includes children younger than 3 years old with newly diagnosed medulloblastoma. They found that approximately one-third of patients either experience treatment failure or relapse, which is when cancer returns, and only 10% survive past five years post relapse.  

Further analysis of results revealed that about 10% of these relapsed medulloblastomas were wrongly classified. These were actually secondary malignancy which is cancer caused by radiation or chemotherapy. These secondary cancers manifest as high-grade gliomas, which are aggressive and incurable. High-grade gliomas and relapsed medulloblastoma have different treatments, therefore patients who were misclassified received incorrect medicine.  

Researchers found that medulloblastomas typically stay in the same molecular group when relapsed, but there has been evidence of some switching from Group 3 tumors to Group 4.  Despite this evidence, the research team learned that most of the time, tumors are genetically stable. Using whole-exome sequencing, they found patterns of relapse in childhood medulloblastoma.

Conclusion

Dr. Robinson, an oncologist at St. Jude, states that this research provided a better understanding of medulloblastoma and its risks. Depending on the type of medulloblastoma, we are able to determine a more precise amount of, along with the specific type of therapy needed for the patient. Now able to better understand these tumors, treatment of relapsed medulloblastoma may significantly improve. 

Kyle Phong, Youth Medical Journal 2021

References

Journal of Clinical Oncology, “Clinical Outcomes and Patient-Matched Molecular Composition of Relapse Medulloblastoma”, 27 January 2021

https://ascopubs.org/doi/10.1200/JCO.20.01359

News Medical Life Sciences, “New results challenge the current understanding of medulloblastoma”, 28 January 2021

https://www.news-medical.net/news/20210128/New-results-challenge-the-current-understanding-of-medulloblastoma.aspx

St. Jude Children’s Research Hospital, “Medulloblastoma”

https://www.stjude.org/disease/medulloblastoma.html

Together Powered by St. Jude Children’s Research Hospital, “Medulloblastoma in Children and Teens”

https://together.stjude.org/en-us/about-pediatric-cancer/types/brain-spinal-tumors/medulloblastoma.html

National Cancer Institute Center for Cancer Research, “Medulloblastoma Diagnosis and Treatment”

https://www.cancer.gov/rare-brain-spine-tumor/tumors/medulloblastoma

Categories
Biomedical Research

A New Stroke Risk Factor for Elders

Introduction

Geisinger is a health organization that offers healthcare services in Pennsylvania and New Jersey.  A team of Geisinger researchers discovered a new risk factor for stroke that was more common in people ages 65 and up.  Dr. Abedi, a co-author of the study and genomics scientist at Geisinger, states, “Stroke is a complex multifactorial condition.”  Out of the main causes for stroke, cerebral small vessel disease is among the most common reasons.

Cerebral Small Vessel Disease

Cerebral Small Vessel Disease, abbreviated as SVD, is a general term for problems related to small blood vessels in the brain.  It is a common disease that is known to cause vascular dementia and around a quarter of ischemic strokes.  About 87% of all strokes are ischemic, meaning that the blood supply to the brain is blocked off, causing brain cells to die.  While we typically notice SVD with old age and hypertension, some of the cases are due to variants in the NOTCH3 gene.  This gene variant is quite common, about 1 in 300 people worldwide.  Additionally, CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a rare hereditary condition, is associated with a higher risk of stroke and SVD.  CADASIL is known to cause a variety of health issues, ranging from seizures to cognitive deterioration. 

Methods

The Geisinger team studied the health records of over 300 of their patients.  Out of these patients, 118 of them were found to have the NOTCH3 gene variant.  The researchers sought to find out if those with the NOTCH3 variant had more severe SVD as well as a higher risk of stroke and brain damage.  They created a control group, consisting of patients without the NOTCH3 variant, and an experimental group, consisting of patients carrying the NOTCH3 gene variant.  4.9% of the control group had a history of stroke compared to 12.6% of the experimental group.  The significant increase in the risk of stroke is likely due to the NOTCH3 gene variant.  Meanwhile, the specific NOTCH3 variant that causes CADASIL was rarely found.  In addition, patients over the age of 65 were noted as more prone to stroke and exhibited more damage to the brain.  

This diagram displays the risk of getting a stroke as we become older through the red experimental group and green control group.  From ages 0 to around 70, we notice that both groups are relatively the same percent free of stroke.  However, there is a sharp decline in percentage free of stroke after the age of 70 for those carrying the NOTCH3 gene variant.  The table below shows the N at risk, meaning the number of individuals at risk of stroke, and N stroke, which is the number of people with their first stroke in 10-year intervals.  This shorter stroke-free survival compared to the control group reinforces the idea that the NOTCH3 gene is a significant contributor to stroke risk.  

Conclusion

Due to the high number of individuals carrying the NOTCH3 variant, there is a significant risk of SVD and stroke.  Additionally, the Geisinger research team has claimed that most people with the NOTCH3 variant will have SVD after the age of 65.  With this new knowledge, we can continue to advance the field of medicine and prevent the strokes of individuals carrying the NOTCH3 gene variant, saving the lives of many.

Kyle Phong, Youth Medical Journal 2021

Referereces

Stroke Association, “Types of Stroke”

https://www.stroke.org.uk/what-is-stroke/types-of-stroke

Stroke: Journal of the American Heart Association, “Top-NOTCH3 Variants in the Population at Large”, 9 November 2020

https://www.ahajournals.org/doi/10.1161/STROKEAHA.120.031609

Stroke: PubMed, “Cysteine-Altering NOTCH3 Variants Are a Risk Factor for Stroke in the Elderly Population”, 9 November 2020

https://pubmed.ncbi.nlm.nih.gov/33161844/

News Medical Life Sciences, “A common genetic variant identified as risk factor for stroke”, 19 January 2021

https://www.news-medical.net/news/20210119/A-common-genetic-variant-identified-as-risk-factor-for-stroke.aspx

National Institute of Neurological Disorders and Stroke, “CADASIL Information Page”, 27 March 2019

https://www.ninds.nih.gov/Disorders/All-Disorders/CADASIL-Information Page#:~:text=CADASIL%20is%20characterized%20by%20migraine,higher%20risk%20of%20heart%20attack.

Categories
Biomedical Research

The Key Gene in Destroying Viruses

Introduction

The University of Texas Southwestern Medical Center has found a crucial gene that is involved in our body’s natural process of destroying viruses. Manipulating this gene can lead to the creation of many treatments for a wide range of viral infections, even COVID-19. Ph.D., Xiaonan Dong, and his team began with observing human cells infected by a variety of viruses and examining over 18,000 genes in order to find the effect they may have on autophagy. 

What is Autophagy?

Autophagy is our cells’ process of recycling damaged parts by breaking them down and using them as “building blocks” to create new components. However, it degrades more than just defective cells. Autophagy is also known to destroy bacteria and viruses that can cause infection.    

In this diagram, the unwanted material, such as dysfunctional organelles, is isolated into the autophagosome. Then, the autophagosome is fused with single-layered vesicles called lysosomes which degrade and recycle the cellular garbage.

Methods

First, the team began with herpes simplex virus type 1 or HSV-1 and Sindbis virus.  HSV-1 is a common and contagious virus known for causing sexually transmitted diseases as well as cold sores. Meanwhile, the mosquito-transmitted Sindbis virus causes rash, headache, and joint pain. From these two viruses, researchers found 216 genes that played a role in viral autophagy. In order to reveal the genes that had the most influence on autophagy, they analyzed the processes that these genes regulated through a method of bioinformatics. Bioinformatics is a method of studying biological data such as DNA and amino acid sequences with the assistance of computer science.  

Soon after, Dong and his colleagues discovered a gene named sorting nexin 5 or SNX5 which performed a recycling action similar to autophagy. Viruses typically enter cells through this specific pathway, so researchers made the hypothesis that SNX5 is a key player in autophagy. In order to confirm this, they deactivated SNX5 in their experiment with the human cells. Consequently, the cells were much more inefficient when performing autophagy on HSV-1 and Sindbis viruses. Meanwhile, autophagy to recycle dysfunctional cells and remove bacteria was activated, showing the same results as the control group. This suggested that SNX5 was a gene that specifically aided viral autophagy.

Conclusion

The research team experimented with many other viruses such as influenza A, West Nile, and poliovirus. In all of these trials, the results had suggested that SNX5 was a crucial component in our body’s defense mechanism against viruses.  Furthermore, canceling SNX5 showed an increase in susceptibility to viral infection for both human cells and animal cells.

With Dong’s identification of SNX5 is a crucial gene in viral autophagy, scientists can potentially manipulate SNX5 and find new methods of fighting off viruses. Today, we treat viruses by studying their individual weaknesses, meaning that every virus requires a different approach. Dr. Dong explains that by better understanding the way our body naturally degrades viruses, we can create a “more general strategy for developing broad-spectrum antiviral therapeutics that combat an array of different viral infections.”  With our newfound knowledge of SNX5 in viral autophagy, we can take the next step in medicine by improving our immune systems. 

Kyle Phong, Youth Medical Journal 2021

References

Nature, “Sorting nexin 5 mediates virus-induced autophagy and immunity, 16 December 2020, 

https://www.nature.com/articles/s41586-020-03056-z

News Medical Life Sciences, “Researchers identify key gene necessary for cells to consume and destroy viruses”, 17 December 2020, 

https://www.news-medical.net/news/20201217/Researchers-identify-key-gene-necessary-for-cells-to-consume-and-destroy-viruses.aspx

UT Southwestern Medical Center, “Giving cells an appetite for viruses”, 16 December 2020

https://www.utsouthwestern.edu/newsroom/articles/year-2020/giving-cells-an-appetite-for-viruses.html

National Cancer Institute, “Autophagy”

https://www.cancer.gov/publications/dictionaries/cancer-terms/def/autophagy

National Human Genome Research Institute, “Bioinformatics”

https://www.genome.gov/genetics-glossary/Bioinformatics#:~:text=Bioinformatics%20is%20a%20subdiscipline%20of,DNA%20and%20amino%20acid%20sequences.

Categories
Biomedical Research

Tai Chi: The Martial Art of Healing

Introduction

As we enter our later stages of life, it becomes even more crucial that we take good care of our bodies, whether it is maintaining a healthy diet or getting enough exercise every day.  However, there are many additional activities that can be done such as tai chi, which have a multitude of benefits, ranging from reducing the risk of falling to alleviating pain.  Tai chi is a Chinese martial art that emphasizes slow, flowing movements, meaning almost anyone is capable of doing it.

While growing older, we may notice that our muscles and bones become weaker, our reaction time is slower, and our focus is not as sharp as it used to be.  Tai chi is a simple and non-invasive method that has been shown to counter all of these issues.  Ph.D. Peter Wayne, an associate professor at Harvard Medical School and director of the Osher Center for Integrative Medicine, explains that adults over the age of 65 can see a 20% – 40% reduction in the risk of falls, even after a short six months of practicing tai chi.

Methods

A 2012 research paper by Cochrane, a British organization dedicated to cover medical research findings, found that about 30% of people over 65 years fall each year.  They pooled data from about 160 trials and over 79,000 participants, looking for methods that were the most effective in preventing seniors from falling.  One example of a method consisted of several groups and home-based programs working on strength and balance exercises.  In general, they found that any seniors that actively did exercises were less prone to falls and sustaining severe injuries.  

In addition, there is strong evidence that tai chi assists in strengthening our bones.  As we age, it is common for us to have osteopenia which is when our bones become brittle due to a lack of calcium.  Our body becomes unable to make new bone cells as fast as it reabsorbs old bone cells.  However, tai chi has been shown to stimulate bone growth which combats the effects of osteopenia.  

One research paper from the National Center for Biotechnology Information (NCBI) studied the health effects of tai chi on people with certain bone conditions such as knee osteoarthritis and bone mineral density loss.  This study recognized prior research that contained strong evidence for the beneficial effects of tai chi and sought to make a definitive claim.  

Like the paper from Cochrane, NCBI noted that tai chi does mitigate the effects of bone mineral density loss.  This research was a 24 week long program consisting of a diverse population from breast cancer survivors to diabetic older adults.  The constant use of the waist and slow full body movements were the two main features that attributed to slowing bone mineral density loss.  In addition, NCBI found that tai chi also helped with flexibility, increasing muscular strength, controlled breathing, regulating blood pressure, and balance.  This is especially beneficial to older adults with hypertension or high blood pressure and Parkinson’s disease which is known to cause loss of balance, stiffness, tremors and slow movement.  There was an in-depth look into specific forms of tai chi such as the Sun-style, composed of quick movements, and Yang-style which is the most common form associated with slow, stretching movements.  However, among the three tai chi forms, they all shared benefits, specifically relating to bone health.

Conclusion

Tai chi involves a variety of movements and emphasizes control over the body from breathing to balance.  It contains several exercises that require shifting weight and maintaining balance which is vital for many seniors.  Regardless of what style of tai chi is practiced, it has proven to be very beneficial.  From personal experience, some of my relatives have been practicing tai chi for decades and it has helped their physical and mental health tremendously.  Tai chi is a low impact form of exercise that people of any age are capable of performing.  From reducing the risk of falls to alleviating chronic pain such as knee osteoarthritis, tai chi has a variety of positive impacts on our health.

Kyle Phong, Youth Medical Journal 2020

References

Harvard Health Publishing, “Protect your bones with tai chi”, October 2020,

https://www.health.harvard.edu/womens-health/protect-your-bones-with-tai-chi

Cochrane Library, “Interventions for preventing falls in older people living in the community”, 12 September 2020,

https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007146.pub3/full

Harvard Magazine, “Easing Ills through Tai Chi”, February 2010,

https://harvardmagazine.com/2010/01/researchers-study-tai-chi-benefits

Medical News Today, “What are the health benefits of tai chi?”, 30 August 2018,

https://www.medicalnewstoday.com/articles/265507#types

NCBI, “The Effect of Taichi Practice on Attenuating Bone Mineral Density Loss: A Systematic Review and Meta-Analusis of Randomized Controlled Trials”, 1 September 2017, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615537/ 

Tai Chi Image https://www.google.com/url?sa=i&url=https%3A%2F%2Ftaichihealth.com%2Fembedded-pages%2Ftai-chi-for-seniors%2F&psig=AOvVaw037QBfOoEF8yPIBqIPJOP1&ust=1603757650441000&source=images&cd=vfe&ved=0CA0QjhxqFwoTCOj80vv80OwCFQAAAAAdAAAAABAg 

Categories
Health and Disease

Defeating Breast Cancer While Leaving Healthy Cells Unaffected

Introduction

Cancer treatment today often includes a painful experience for the patient.  Chemotherapy is known to contain powerful substances that kill rapidly dividing cells, even healthy ones.  Scientists at Johns Hopkins Medicine and the University of Oxford recently published their results with a new technique they’ve been working on that is capable of killing breast cancer cells while keeping healthy cells safe.  One common cause of cancer is a mutation within the genetic coding of a cell that causes it to multiply without anything to suppress it.  This unrestricted division of the cell can lead to them becoming cancerous. 

How does cancer start? Damaged cells multiply.

Methods

While studying lab-grown breast cancer cells, one of the lead researchers, Dr. Holland, noticed a trend amongst them.  The cancer cells were dependent on centrioles, which played a crucial role in their survival and multiplication.  Centrioles are cylindrical organelles that form necessary spindles in mitosis, a process in which cells divide.  They are the core of centrosomes that provide structure for cells and assist in separating DNA during cell division.  Although other cells were able to divide without centrioles, these breast cancer cells were not able to.  With deeper research, they found that there was a section of the cancer cells that had multiplied a strange amount of times.  One specific protein, TRIM37, was being produced excessively by genes in that area.  This protein controls centrosomes and when there are high levels of the protein, it results in defective centrosomes instead.  These flaws lead to consequences later during cell division and this instability in cell division typically contributes to the development of cancer.

In order to impede the division of cells with an excessive amount of TRIM37, researchers utilized a drug that targeted PLK4 genes.  The PLK4 inhibitor specifically hinders the proteins that form centrioles.  Unfortunately, they found that adding this drug to their lab-grown breast cancer cells with normal levels of TRIM37 does not impact their cell division even without centrioles.  However, for the cells with overexpressed TRIM37, they were unable to divide and died or did not grow anymore.  Holland devised a plan to identify cells that contained high levels of TRIM37 and allow the PLK4 inhibitor to kill the breast cancer cells without harming the healthy cells.

They came across precisely why the cancer cells with regular levels of TRIM37 were unaffected by the PLK4 drug.  Diagram D shows the effects of the PLK4 inhibitor on a cancer cell with regular levels of TRIM37 compared to a cancer cell with an excessive amount of it.  There is a substance called the pericentriolar material (PCM) around the centrioles that performs the same function as centrosomes.  In the first path, it states that the “PCM foci promote MT nucleation” which means that the pericentriolar material substitutes for the depleted centrosomes in order for cell division.  On the other hand, the cells overexpressing TRIM37 eventually died.  The high levels of TRIM37 deteriorates the pericentriolar material and the PLK4 drug stops the production of centrosomes.  Without these two, there is no way for the cell division to occur.  

Conclusion

 This research from Johns Hopkins Medicine and the University of Oxford is a breakthrough in the world of cancer.  9% of breast cancers are caused by the over-expression of TRIM37 and being able to kill these cancer cells while leaving the healthy ones unaffected is a huge step towards finding the best way to treat cancer.  Holland and the team are now working on using similar drugs to the PLK4 inhibitor because it is not stable and safe enough to use for patients.  In addition, they are testing this inhibitor on other cancer cells to see if they are sensitive as well.  Dr. Chapman, another researcher on the team, stated, “We’ve found a previously unknown genetic vulnerability in breast cancer, and discovered a means to exploit this vulnerability and selectively kill cancer cells.  We hope that in the future, other researchers and pharmaceutical companies can generate new drugs that can target this process, to produce more effective and safer cancer treatments.”

References

Nature, “Targeting TRIM37-driven centrosome dysfunction in 17q23-amplified breast cancer”, 9 September 2020, https://www.nature.com/articles/s41586-020-2690-1

Johns Hopkins Medicine. “New way to target some rapidly dividing cancer cells, leaving healthy cells unharmed.” ScienceDaily. ScienceDaily, 9 September 2020. www.sciencedaily.com/releases/2020/09/200909114901.htm

University of Oxford, “Previously unknown ‘genetic vulnerability’ in breast cancer cells target of research.” 10 September 2020 https://www.ox.ac.uk/news/2020-09-10-previously-unknown-genetic-vulnerability-breast-cancer-cells-target-research#

Johns Hopkins Medicine, “Scientists Identify New Way to Target Some Rapidly Dividing Cancer Cells, Leaving Healthy Cells Unharmed”, 9 September 2020 https://www.hopkinsmedicine.org/news/newsroom/news-releases/scientists-identify-new-way-to-target-some-rapidly-dividing-cancer-cells-leaving-healthy-cells-unharmed

Fierce Biotech, “Blocking tumor cell division to stop breast cancer.” 9 September 2020, https://www.fiercebiotech.com/research/blocking-tumor-cell-division-to-stop-breast-cancer

National Human Genome Research Institute, “Centriole”, https://www.genome.gov/genetics-glossary/Centriole

Sciencing, “What Would Happen If a Cell Didn’t Have Ribosomes?”, 16 April 2018, https://sciencing.com/would-happen-cell-didnt-ribosomes-19003.html

Patient Navigator Training Collaborative, https://www.patientnavigatortraining.org/chronic_disease/module3/1_index.htm