Categories
Infectious Diseases

Does the Smallpox Vaccine Provide Protection Against Monkeypox?

Andia Tofighbenam—McMaster Honours Life Sciences 2024

Despite the name, chickens do not give humans chickenpox. Wouldn’t it be nice if the same could be said about monkeypox?

Human monkeypox is a viral zoonotic disease (spread between humans and animals), first discovered in laboratory monkeys in 1958, at the State Serum Institute in Denmark (1). The monkeypox virus (MPXV) is a member of the orthopoxviral genus from the Poxviridae family and is spread by contact with body fluids, lesions, and respiratory droplets of an infected person or animal (2). This enveloped double-stranded DNA virus has two strains: the west African clade and the central African clade (Congo Basin). As opposed to the west African clade, the central African clade is more transmissible and severe (2). The incubation period of this virus can range from 5 to 21 days, starting with a fever, extreme headache, lack of energy (asthenia), and muscle aches (myalgia). Around 1 to 3 days following a fever, skin eruption begins on the face, hands, feet, genitals, and cornea. These rashes evolve from macules to papules, vesicles, pustules, and crusts, which eventually fall off (2).

The first identified human monkeypox case was discovered in Africa in 1970, two years after the elimination of smallpox. Although not new, the west African clade of monkeypox has recently become a global outbreak concern (2). In 2003, the United States experienced the first monkeypox outbreak outside Africa. By May 2022, several human monkeypox cases were discovered in multiple non-endemic countries (2).

SOURCE: The Lancet

Another virus that is a member of the orthopoxvirus family is smallpox. Smallpox is an acute contagious disease caused by the variola virus and was the cause of millions of deaths before its eradication in 1980 (4).  There are two types of the variola virus: variola major and variola minor, both of which are spread by exchanging body fluids and large respiratory droplets with an infected individual. Variola major is exceedingly severe and has a mortality rate of 30%, while variola minor had a mortality rate of 1%. Symptoms of this virus include fever, back pain, fatigue, and a characteristic rash consisting of bumps filled with clear fluid that later turns into pus and dries out (4). 

SOURCE: The Lancet

Although both smallpox and monkeypox have similar symptoms, smallpox is not a zoonotic disease and is more severe. With that being stated, they are both members of the orthopoxvirus family, have 2 strains of differing severities, are more fatal in children when compared to adults, and are spread in similar ways (6).

Due to their similarities, smallpox vaccines are effective against the monkeypox virus. There are currently two smallpox vaccines effective for monkeypox as well: IMVAMUNE and ACAM2000. IMVAMUNE is an attenuated, non-replicating orthopoxvirus vaccine (7). This live viral vaccine was licensed in September 2019 by the FDA (US Food and Drug Administration) and is 85% effective against monkeypox. ACAM2000 was FDA licensed in August 2007 and is also made of live vaccinia virus. The Centers for Disease Control and Prevention set emergency access measures allowing access to this vaccine during non-variola orthopoxvirus (monkeypox) outbreaks (7).

Although there is no current treatment specific to monkeypox, an antiviral drug that protects against smallpox can also be used against monkeypox due to their similarities (8). This drug is called Tpoxx, or Tecovirimat, and is manufactured by SIGA technologies. Although this drug may be used for monkeypox treatment, it is important to note that it is only FDA-approved for the treatment of smallpox. For this reason, a consent form must be filled out before Tecovirimat is administered to patients with monkeypox (8).

With their differences kept in mind, smallpox and monkeypox are still both members of the orthopoxvirus family. This is advantageous as certain smallpox vaccines can be used for monkeypox, given there is currently no cure for the zoonotic monkeypox virus. 

References

1. Di Giulio DB, Eckburg PB. Human monkeypox: an emerging zoonosis. The Lancet Infectious Diseases [Internet]. 2004 Jan [cited 2022 Nov 23];4(1):15–25. Available from: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(03)00856-9/fulltext

‌2. World. Monkeypox [Internet]. Who.int. World Health Organization: WHO; 2022 [cited 2022 Nov 23]. Available from: https://www.who.int/news-room/fact-sheets/detail/monkeypox?gclid=EAIaIQobChMIvtb99eLE-wIVsDizAB1K-QDnEAAYASABEgIlLPD_BwE

3. Moore, Z. S., Seward, J. F., & Lane, J. M. (2006). Smallpox. The Lancet, 367(9508), 425–435. https://doi.org/10.1016/s0140-6736(06)68143-9‌‌

4. World. Smallpox [Internet]. Who.int. World Health Organization: WHO; 2019 [cited 2022 Nov 23]. Available from: https://www.who.int/health-topics/smallpox#tab=tab_1

‌5. Geddes AM. The history of smallpox. Clinics in Dermatology [Internet]. 2006 May [cited 2022 Nov 23];24(3):152–7. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0738081X05001707

‌6. ​​Kmiec D, Kirchhoff F. Monkeypox: a new threat?. International journal of molecular sciences. 2022 Jul 17;23(14):7866. Available from: https://doi.org/10.3390/ijms23147866

7. Rizk JG, Lippi G, Henry BM, Forthal DN, Rizk Y. Prevention and Treatment of Monkeypox. Drugs [Internet]. 2022 Jun [cited 2022 Nov 23];82(9):957–63. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9244487/#CR17

‌8. ​​CDC. Patient’s Guide to Monkeypox Treatment with Tecovirimat (TPOXX) [Internet]. Centers for Disease Control and Prevention. 2022 [cited 2022 Nov 23]. Available from: https://www.cdc.gov/poxvirus/monkeypox/if-sick/treatment.html

Categories
Uncategorized

Brewing Up a Defense: The Potential of Green Tea in Fighting Alzheimer’s Disease

Tiana Castiglione—McMaster Honours Life Sciences 2026

Alzheimer’s disease (AD) is characterized by the progressive deterioration of cognitive function. This fatal disease, resulting in memory loss, is the most common cause of dementia.¹ In 2017, there were approximately 76,000 new dementia cases per year, accounting for an AD prevalence of 7.1%.¹ It is anticipated that these numbers will increase in the near future.²

The accumulation of β-amyloid peptide (Aβ) in the brain is a primary characteristic of AD.¹ Interestingly, recent studies have shown that green tea is an effective therapeutic agent in both treating and preventing AD through monitoring Aβ levels.¹ Green tea contains an ester group, operating as a bioactive polyphenol called epigallocatechin-3-gallate (EGCG).¹ Contrary to fully fermented tea, green tea preserves its original polyphenolic compositions, therefore having  important antioxidant, anti-inflammatory, antidiabetic, anticarcinogenic and antineurodegenerative properties.¹ This review focuses on the latter property of neuroprotection as a result of EGCG in green tea.¹

SOURCE: Shutterstock

In a study conducted by Youn et al., EGCG treatment was administered in amyloid precursor protein (APP) transgenic mouse models for 3 months.It was demonstrated that only 40% of the initial Aβ buildup was left in the front cortex, and 48% left in the hippocampus.¹ These results are consistent with another study conducted by Rezai-Zadeh et al., where it was found that when EGCG was injected intraperitoneally, it was able to reduce Aβ deposition in transgenic APP mouse models.³ Similar effects were perceived in these mouse models when EGCG was administered orally in drinking water.³

Moreover, EGCG has also been shown to reduce the onset of Aβ-generated mitochondrial impairment and oxidative stress.¹ This was seen in both cellular and mouse models, where EGCG decreased lipid peroxidation in hippocampal neurons, thereby inhibiting Aβ-caused impairment.¹ For instance, oral administration of green tea extract over a 26-week period depressed reactive oxygen species concentrations in the hippocampus and lipid peroxides in the plasma of rats, in addition to regenerating mitochondrial function and ATP levels in mice.¹ This reduction in Aβ accumulation results in a lower risk of AD onset.

SOURCE: Adobe Stock

EGCG especially holds promise for the prevention of AD given its permeability of the blood-brain barrier (BBB).¹ The BBB is a barrier that prevents certain compounds from entering the brain tissue from the blood.¹ In order for neuroprotective agents to be effective, they must have the ability to cross the BBB.¹ After consumption, a proportion of EGCG appeared to successfully enter the bloodstream in humans and rats.¹

In summary, the neuroprotective role that green tea provides through increased levels of EGCG occurs in the inhibition of Aβ accumulation via controlling amyloid precursor protein processing, as well as the attenuation of Aβ-induced oxidative stress and neuroinflammatory response.¹ However, although the properties of EGCG as a therapeutic agent and its BBB permeability are promising in preventing AD, additional research and human clinical trials are required to substantiate the potency of EGCG as a neuroprotectant.¹

References

  1. Youn K, Ho C, Jun M. Multifaceted neuroprotective effects of (-)-epigallocatechin-3-gallate (EGCG) in Alzheimer’s disease: an overview of pre-clinical studies focused on β-amyloid peptide. Food Sci Hum Wellness [Internet]. 2022 [cited 2022 Nov 21];11(3):483-493. Available from: https://www.sciencedirect.com/science/article/pii/S2213453021001348 doi: 10.1016/j.fshw.2021.12.006
  1. Public Health Agency of Canada. Dementia in Canada, including Alzheimer’s disease [Internet]. Government of Canada; 2017 [updated 2017 Sep 29; cited 2022 Nov 21]. Available from: https://www.canada.ca/en/public-health/services/publications/diseases-conditions/dementia-highlights-canadian-chronic-disease-surveillance.html
  1. Cascella M, Bimonte S, Muzio MR, Schiavone V, Cuomo A. The efficacy of Epigallocatechin-3-gallate (green tea) in the treatment of Alzheimer’s disease: an overview of pre-clinical studies and translational perspectives in clinical practice. Infect Agents Cancer [Internet]. 2017 [cited 2022 Nov 21];12(36). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477123/ doi: 10.1186/s13027-017-0145-6
  1. Singh NA, Mandal AKA, Khan ZA. Potential neuroprotective properties of epigallocatechin-3-gallate (EGCG). Nutr J [Internet]. 2016 [cited 2022 Nov 21];15(60). Available from: https://nutritionj.biomedcentral.com/articles/10.1186/s12937-016-0179-4 doi: https://doi.org/10.1186/s12937-016-0179-4
Categories
AI Genomics Proteins

Unlocking the Secrets of Proteins with Alphafold2: A Breakthrough in Bioinformatics

Rubani Suri—McMaster Health Sciences 2026

The word “protein” has an ever-changing definition throughout our lives. As children, we often unknowingly consume protein in the form of nuggets or hamburgers. As we reach adolescence, proteins often appear on food guides and in our biology classes through the form of polypeptides and amino acids. However, not until the recent developments of AlphaFold2 Artificial Intelligence have proteins been defined as a complex three-dimensional network of amino acid residues.

To understand the significance of AlphaFold2, we must first understand the “protein folding problem.” Three-dimensional proteins are more than amino acid chains and are known for having multiple side chains on their structure. These side chains have the capacity of interacting with one another, creating configurational changes to the structure of the protein. As a result, it becomes nearly impossible to determine the structure of a three-dimensional protein due to side chain complexities (1).

That’s where AlphaFold2 comes in.

Using the power of Artificial Intelligence (AI), AlphaFold2 has mastered the technique of homology modeling: using evolutionary history to find proteins with known structure that are genetically similar to the “target protein,” and use them to deduce structural similarities with the target protein (2). Using comprehensive databases, AlphaFold2 uses AI to predict target protein structure through the following steps (3):

  1. The input sequence (genome of target protein) is inputted
  2. Multiple Sequence Alignments (MSAs), which are amino acid sequences that share evolutionary similarities with the target protein, are inputted into Alpha Fold machinery to create predictions for the structure based on evolutionary relatedness
  3. Protein database structures, which are similar in structure to the target, are also used as templates for target protein structures
  4. The input sequence is paired with itself in a matrix to produce an array of numbers that represents all the potential pairs of amino acid sequences in the target protein.
  5. The pair representations are put into “EvoFormer” technology, which collates all this data to analyze relationships between individual amino acids, to gain an understanding of the structures that specific amino acids would form when bonded to one another
  6. These predicted relationships are then put through a Structure Module technology, which builds a geometric protein model.
  7. This protein model is then analyzed, and the rotation and angle of each amino acid is calculated, creating a three-dimensional protein model.
  8. Side chains are predicted using a technology that detects ‘chi angles’ (angles between intersecting planes) on the three-dimensional residue structure.
  9. The bond lengths and angles are finalized by running the final structure through a relaxation step, which removes any inconsistencies within the protein structure.
  10. The final accuracy is then improved by running the predicted protein chain through the network three times more.
  11. Along with the predicted structure, the Alpha Fold technology creates two confidence matrices which provides a ‘confidence score’ for each angle between the residues by analyzing the predicted error in the predicted structure.

Figure 1. SOURCE: AlphaFold Protein Structure Database

Figure 1 depicts a structural prediction for a target protein once all the steps above are complete. The protein depicted in Figure 1 is hemoglobin, a globular transport protein found in erythrocytes.

Figure II. SOURCE: AlphaFold Protein Structure Database

Figure II depicts the confidence score of Hemoglobin, as determined in step 11 of the process shown above.

Although in its developmental stages, AlphaFold2 is a technological advancement that has the capacity to revolutionize both the pharmaceutical and biochemical world. This innovation has been groundbreaking, especially for pharmaceutical companies. This has been crucial as they are interested in the structure prediction of allosteric sites where small molecules can bind to produce cell responses such as inflammation, itching, and pain. Understanding the structure of these protein binding sites will allow drug developers to create specific inhibitors for these binding sites, preventing small molecules from binding and creating a painful response (4). The understanding of binding site structure will allow for the possibility of “structure-based drug design” (4), a technique that is estimated to accelerate the research and development of drugs from “years to months” (4).

In conclusion, the publicly accessible nature of AlphaFold2 protein structure data allows drug development companies to have readily available protein information at their fingertips, accelerating drug development and efficacy. Through its continued success, AlphaFold2 has the ability to revolutionize the pharmacological world, allowing for the accessibility of effective, fast-acting medications around the world.

References

  1. Singh J. The history of the protein folding problem: A seventy year symbiotic relationship between… [Internet]. Medium. Medium; 2020 [cited 2022Nov27]. Available from: https://medium.com/@jaguarsingh/the-history-of-the-protein-folding-problem-a-seventy-year-symbiotic-relationship-between
  2. Alessia David Person Envelope Suhail Islam Evgeny Tankhi levich Michael J.E.Sternberg, Highlights AlphaFold, et al. The alphafold database of protein structures: A biologist’s guide [Internet]. Journal of Molecular Biology. Academic Press; 2021 [cited 2022Nov27]. Available from: https://www.sciencedirect.com/science/article/pii/S0022283621005738
  3. Callaway E. What’s next for alphafold and the AI protein-folding revolution [Internet]. Nature News. Nature Publishing Group; 2022 [cited 2022Nov27]. Available from: https://www.nature.com/articles/d41586-022-00997-5#:~:text=AlphaFold%20deploys%20deep%2Dlearning%20neural,the%20PDB%20and%20other%20databases.
  4. Mullard A. What does alphafold mean for drug discovery? [Internet]. Nature News. Nature Publishing Group; 2021 [cited 2022Nov27]. Available from: https://www.nature.com/articles/d41573-021-00161-0
Categories
COVID-19 Sleep

Chronic Fatigue Syndrome in the Time of COVID-19: Understanding the Connection

Bhavana Soma—McMaster Life Sciences 2024

Imagine constantly feeling tired to the point where it is difficult to perform daily activities, having no amount of rest make you feel energized, having difficulty sleeping, taking a long time to recover after physical activity, and having issues with thinking, concentrating and remembering. This miserable slew of symptoms that deeply affect the quality of one’s life is characteristic of a debilitating condition known as chronic fatigue syndrome (CFS). Presentation of these symptoms, in addition to physiological symptoms including heart palpitations, general malaise, flu-like symptoms and body pains, over an extended period of time can lead to a diagnosis of CFS if not thoroughly explained by underlying medical conditions [1]. This complicated disorder affects anywhere between 836 000 to 2.5 million Americans, and millions more worldwide [2].

SOURCE: Medical News Today

Scientists have identified a similar condition in those that have contracted COVID-19. COVID-19 starts with a respiratory infection that produces common flu-like symptoms. However, it can have extensive systemic effects on the body as the virus attacks cells and disrupts bodily functions. This means that it may eventually affect the heart, blood vessels, brain, liver, eyes, and kidneys in the long term, in addition to the respiratory system and immune system [3]. The long-term effects become apparent when the test that initially detected the virus is no longer able to, which implies that affected individuals should return to normal since the virus is no longer present in their bodies [4]. However, COVID-19 research has demonstrated that this is not always the case.

Ongoing research suggests that up to a year after having COVID-19, 20% of adults have at least one medical condition that may be a result of the viral infection. This increases to 25% for seniors above the age of 64 [5]. The development of new conditions may be attributed to damage to different organ systems throughout the body and the experience of severe COVID-19, resulting in hospitalization, could trigger mental health conditions [5]. Not only have individuals been diagnosed with new conditions after supposedly having recovered from COVID-19 within a few weeks, many have been experiencing long-term symptoms including, but not limited to, fatigue, difficulty thinking, remembering or concentrating, cognitive difficulties, sleep disturbances, shortness of breath, increased instance of mental health issues, and body pains [6]. These ongoing symptoms are collectively being referred to as a condition called “Long COVID [4].”

SOURCE: RCNi

With the significant overlap between the symptoms of Long COVID and CFS, and the fact that the onset of both Long COVID and up to 75% of CFS cases are confirmed to be linked to a viral infection, many researchers have begun to wonder if the two conditions are actually the same the condition [7].

As of present, there is no cure for either condition. The treatment of CFS is mainly concerned with searching for underlying causes and treating any that are found, as well as alleviating symptoms. Doctors attempt to address the most debilitating symptom prior to treating others that are present [8].

As for Long COVID, researchers all over the world are currently conducting studies and trials to learn more about the condition. In one recent study, people who had been infected with the virus prior to vaccination had a 9 percent lower risk of developing Long COVID after receiving two doses of an mRNA or adenoviral vector vaccine. According to many researchers, we can learn more about the disease and how to better treat it by looking at in-depth analyses of markers such as autoantibodies that are associated with the disease. Current trials that are being conducted include anti-inflammatory drugs, and future potential research could be conducted on immune-suppressing drugs [9].

Since the overlap between Long COVID and CFS has been identified and the question of Long COVID being a form of CFS has been raised, influential CFS researchers believe that the similarities between the two could help millions manage their condition. Their research has shown how CFS may develop due to an overactive immune response in the early stages of the disease that results in immune exhaustion which is also found in chronic viral infections. Future research suggestions include examining biological markers of those who successfully made a full recovery from COVID-19 to better understand the mechanisms that result in a full recovery [7].

References

  1. Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) [Internet]. NHS. NHS; 2021 [cited 2022 Nov 28]. Available from: https://www.nhs.uk/conditions/chronic-fatigue-syndrome-cfs/
  2. Institute of Medicine, Board on the Health of Select Populations, Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Beyond myalgic encephalomyelitis/chronic fatigue syndrome: Redefining an illness. Washington, District of Columbia: The National Academies Press; 2015. 
  3. How COVID-19 affects your body in pictures [Internet]. WebMD. WebMD; 2020 [cited 2022 Nov 28]. Available from: https://www.webmd.com/lung/ss/slideshow-covid-19-body-effects
  4. Komaroff AL, Bateman L. Will COVID-19 lead to myalgic encephalomyelitis/chronic fatigue syndrome? Frontiers in Medicine. 2021;7. 
  5. Mayo Clinic Staff. Covid-19: Long-term effects [Internet]. Mayo Clinic. Mayo Foundation for Medical Education and Research; 2022 [cited 2022 Nov 28]. Available from: https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/coronavirus-long-term-effects/art-20490351
  6. Public Health Agency of Canada. Government of Canada [Internet]. Post-COVID-19 condition (long COVID) – Canada.ca. / Gouvernement du Canada; 2022 [cited 2022 Nov 28]. Available from: https://www.canada.ca/en/public-health/services/diseases/2019-novel-coronavirus-infection/symptoms/post-covid-19-condition.html#s
  7. Is long covid really chronic fatigue syndrome by another name? [Internet]. Columbia University Mailman School of Public Health. Columbia University Irving Medical Center; 2021 [cited 2022 Nov 28]. Available from: https://www.publichealth.columbia.edu/public-health-now/news/long-covid-really-chronic-fatigue-syndrome-another-name
  8. Chronic fatigue syndrome [Internet]. Mayo Clinic. Mayo Foundation for Medical Education and Research; 2022 [cited 2022 Nov 28]. Available from: https://www.mayoclinic.org/diseases-conditions/chronic-fatigue-syndrome/diagnosis-treatment/drc-20360510
  9. Ledford H. Long-Covid Treatments: Why the world is still waiting [Internet]. Nature News. Nature Publishing Group; 2022 [cited 2022 Nov 28]. Available from: https://www.nature.com/articles/d41586-022-02140-w
Categories
Environment Water

Seawater Desalination: A Solution to Water Scarcity

Saad Iqbal—McMaster Molecular Biology & Genetics 2024

All living organisms on our planet require water to survive. Humans, plants, animals, and bacteria, would all perish without water. It is easy to believe that we will always have water, as water covers approximately 71% of the earth.1 However, only 3% of the world’s water is fresh water that we need to drink, bathe in, and irrigate farm fields with, alongside other necessary uses. According to the World Wildlife Fund (WWF), by 2025 two thirds of the global population will face freshwater shortages. The most evident example of water shortage is the increasing frequency of droughts due to climate change.2 Climate change is forcing us to find a solution quickly to prevent catastrophic water shortages in the near future. Some researchers suggest that the desalination of seawater into fresh water is a viable solution to our problem.

Desalination refers to the process of removing salts, minerals, and other contaminants from seawater in order to obtain fresh water. The two most common desalination techniques are thermal distillation and reverse osmosis.3 

Thermal distillation is the process of boiling seawater. While the seawater is being boiled, it produces steam. This steam does not contain any of the salts or minerals from the seawater. The steam is collected, and then condensed to produce fresh water which we can then drink and use.3

SOURCE: Craig Refugio4

Another method of desalination is reverse osmosis, which relies on a membrane filtration system.In natural osmosis, water molecules move through a semipermeable membrane from a less concentrated solution into a more concentrated solution. However, in reverse osmosis the opposite occurs. Salt water is more concentrated than fresh water, water molecules will move away from the salt water, through the semi-permeable membrane. As the water molecules move through the semi-permeable membrane, the membrane traps salt and minerals on one side, creating fresh water on the other side of the membrane.3 The fresh water is then sterilized with ultraviolet light. As this method goes against natural osmosis, it requires extremely high amounts of pressure to push the water molecules through the membrane. 

SOURCE: BYJU’S 5

Although desalination is a possible solution to prevent future water shortages, there remain some lingering concerns. Desalination is currently one of the most expensive and energy intensive methods to obtain fresh water.3 As of today, most desalination factories use large amounts of fossil fuels, which contribute to increasing levels of greenhouse gases. Additionally, desalination has negative impacts on marine life. Desalination factories create a waste product known as brine. Brine is a solution of water containing extremely high concentrations of salt and chemical residues. Globally, approximately 155 million tons of brine is released into the ocean each day.3 The hyper-salinity of brine is toxic to marine animals and has the potential to dispirit ecosystems of the ocean.

However, there is hope on the horizon. Researchers are currently finding ways to improve desalination techniques, and solve some of these problems. For example, renewable energy sources such as solar energy and wind power are currently being explored and implemented in some desalination plants, which would limit the use of fossil fuels.6 Additionally, researchers are trying to limit the impact of brine. One suggestion is that brine can be converted into useful chemicals through an electrochemical process that forms sodium hydroxide, hydrogen, and hydrochloric acid.3

As researchers are actively attempting to reduce the problems associated with desalination, the process does have the potential to be an efficient way to produce fresh water in the future.

References

  1. Water scarcity [Internet]. WWF. World Wildlife Fund; [cited 2022Nov28]. Available from: https://www.worldwildlife.org/threats/water-scarcity 
  2. Horvatin J. By 2025, the World Wildlife Fund (WWF) estimates that two thirds of the global population may be facing water shortages. [Internet]. Aclarus Ozone // H2O Solved – Superior Water Treatment With Ozone. Aclarus Ozone // H2O Solved – Superior Water Treatment With Ozone; 2021 [cited 2022Nov28]. Available from: https://www.aclarusozone.com/did-you-know/by-2025-the-world-wildlife-fund-wwf-estimates-that-two-thirds-of-the-global-population-may-be-facing-water-shortages 
  3. 26 RC|A, Cho R, Shown, Kathyhorsluvr@hotmail.com. A 1,000 year drought is hitting the west. could desalination be a solution? [Internet]. State of the Planet. 2022 [cited 2022Nov28]. Available from: https://news.climate.columbia.edu/2021/08/26/a-1000-year-drought-is-hitting-the-west-could-desalination-be-a-solution/ 
  4. Reverse osmosis conditions | download table – researchgate [Internet]. ResearchGate.net. 2018 [cited 2022Nov28]. Available from: https://www.researchgate.net/figure/Reverse-osmosis-conditions_tbl2_268514267 
  5. Raveendran B. Reverse osmosis (RO) – definition, principle, process, experiment, advantages, disadvantages with faqs on reverse osmosis. [Internet]. BYJUS. BYJU’S; 2022 [cited 2022Nov28]. Available from: https://byjus.com/chemistry/reverse-osmosis/ 
  6. Singh R. Membrane Technology and engineering for water purification: Application, systems design and Operation. 2nd ed. Amsterdam: Butterworth-Heinemann; 2016.  
Categories
Sleep

Exploring the Latest Advances in Narcolepsy Research

Zahra Alam—McMaster University Life Sciences 2024

Narcolepsy is a chronic and neurological sleep disorder, where the brain is unable to control the sleep-wake cycle. This results in excessive daytime drowsiness, sudden and recurring attacks of sleep, hallucinations, sleep paralysis, and disturbed sleep [1]. Narcolepsy is deemed to be a rare condition, as less than 2% of the worldwide population is affected [2]. However, the percentage is estimated to be higher since many cases are either undiagnosed or misdiagnosed. The unpredictability of narcolepsy consisting of uncontrollable urges to fall asleep spontaneously and chronic fatigue drastically affects an individual’s quality of life [2].  

There are two types of narcolepsy: Type 1 (NT1) and Type 2 (NT2). NT1 presents itself to be the more common form. It is characterized by the presence of a symptom called cataplexy, which is the loss of muscle tone, resulting in involuntary muscle weakness and temporary paralysis in response to strong emotions, such as fear or excitement [3]. This is caused by a lack of a brain chemical called hypocretin (or orexin) present in cerebrospinal fluid which is responsible for activating arousal and regulating sleep-wake patterns [2]. 

SOURCE: SLEEPOLIS

Low hypocretin levels are the defining feature of NT1 in narcoleptics (individuals with narcolepsy), and although the true cause of the loss of hypocretin-producing cells remains unknown, research suggests that it is due to an autoimmune reaction. It is suspected that the immune system mistakenly attacks the small group of neurons in the hypothalamus that are responsible for producing this chemical due to variations in the HLA-DQB1 gene or environmental factors such as influenza A virus [1]. There is not much research pertaining to NT2, however, it is known that NT2 differs from NT1 narcoleptics as they do not have cataplexy and have normal levels of hypocretin [1]. Both types of narcolepsy can also occur along with conditions of the central nervous system and brain injuries, specifically to the hypothalamus [1]. 

Despite copious amounts of research, the exact mechanisms of narcolepsy are unknown. As of now, there is still no cure, however, treatments and therapies are being investigated to treat the symptoms. There has been significant evolution in the treatment of narcolepsy within the last year in which mouse models have been used to mitigate the pathogenetic mechanisms of narcolepsy more accurately than ever before. Researchers were able to follow and track T-cells (immune system cells) to determine how the Pandermix influenza vaccination triggers an autoimmune response against orexinergic neurons (hypocretin-producing cells) [4]. This study provides more evidence of narcolepsy being an immune disorder, which has been the focal point of research in this field for decades [4]. Mouse models have also been the vessel through which treatments have been tested. A new breakthrough drug, Danavorexton, is an example of a drug being heavily researched. This drug reduced cataplexy-like episodes and sleep disturbance in mice [5]. This new drug was then administered intravenously in humans in a phase 1 clinical trial, proving to be well  tolerated and have an association with better sleep latency in both NT1 and NT2 patients [5].  

SOURCE: Winship Cancer Institute

This shows promising potential as a therapeutic agent and shows that more clinical trials need to be investigated. Stem cell transplantation and immunotherapy have demonstrated to be new and successful medical initiatives and treatments. For the first time, both hypothalamic stem cell transplantation and immunotherapy are being tested together to treat sleep disorders, with the goal of replacing  the damaged neurons that are unable to produce hypocretin in NT1 cases [6]. 

Overall, there has been significant growth in the field of narcolepsy research. However, in order to fully understand its implications, pathways, and causes, further research is required. Many promising studies have shown great treatment potential, and thus presents hope for success in the future towards combating narcolepsy.  

References

  1. Bassetti CLA, Adamantidis A, Burdakov D, Han F, Gay S, Kallweit U, et al. Narcolepsy — clinical spectrum, aetiopathophysiology, diagnosis and treatment. Nature Reviews Neurology [Internet]. 2019 Jul 19;15(9):519–39. Available from: https://www.nature.com/articles/s41582-019-0226-9 
  1. Rahman T, Farook O, Heyat BB, Siddiqui MM. An overview of narcolepsy. IARJSET. 2016 Mar;3:85-7. 
  1. Dauvilliers Y, Siegel JM, Lopez R, Torontali ZA, Peever JH. Cataplexy—clinical aspects, pathophysiology and management strategy. Nature Reviews Neurology. 2014 Jun 3;10(7):386–95. 
  1. Bernard-Valnet R, Frieser D, Nguyen XH, Khajavi L, Quériault C, Arthaud S, et al. Influenza vaccination induces autoimmunity against orexinergic neurons in a mouse model for narcolepsy. Brain [Internet]. 2022 May 13 [cited 2022 Nov 29];145(6):2018–30. Available from: https://academic.oup.com/brain/article-abstract/145/6/2018/6581499
  1. Evans R, Kimura H, Alexander R, Davies CH, Faessel H, Hartman DS, et al. Orexin 2 receptor–selective agonist danavorexton improves narcolepsy phenotype in a mouse model and in human patients. Proceedings of the National Academy of Sciences. 2022 Aug 22;119(35). 
  1. José Ortega-Albás J, López García R, Martínez Martínez A, Carratalá Monfort S, Antonio Royo Prats J, Albiol Varela L, et al. Narcolepsy Treatment: Present and Future. Sleep Medicine and the Evolution of Contemporary Sleep Pharmacotherapy. 2022 Jan 7 
Categories
Health Monitoring

How does Remote Patient Monitoring Facilitate Care?

Pooja Sharma—McMaster Life Sciences (Honours) 2023

Chronic diseases are the leading cause of death and disability, causing two-thirds of deaths in Ontario1. 80% of adults over the age of 45 have a chronic condition and almost 70% suffer from more than one chronic condition1. As expected, this comes with an economic cost, one that costs the Canadian healthcare system millions, but also an even larger personal cost for patients.

The traditional health care model that most of us are accustomed to excepts patients to come in for in-person visits. However, this may not be possible for many patients as they are hindered by road blocks such as work schedules, travel time, mobility issues, weather and lack of transportation2. As a result, access to care is limited and many patients are left self-managing their fluctuating symptoms until their next doctor’s appointment, if they are even able to make it to one.

However, this might not be the case moving forward, as the healthcare sector, like many others, is quickly recognizing and adopting innovative solutions that are making the delivery of healthcare more convenient, timely, and cost-efficient for all stakeholders involved. One of the tools that the healthcare sector is turning to help bridge pre-existing gaps and facilitate care remotely is remote patient monitoring.

SOURCE: FREEPIK

What is Remote Patient Monitoring?

Remote patient monitoring, a subset of telehealth, is a health care delivery model that leverages digital technology to monitor and record real-time patient health data outside of traditional healthcare settings such as the doctor’s office and/or the emergency room3. Undoubtedly, remote monitoring devices such as glucose meters, introduced decades ago, have allowed patients to monitor their blood sugar at home. However, remote patient monitoring adds new value as data is shared (through electronically connected devices) to health care providers to assess and recommend changes to treatment if any concerning results appear. As a result, data does not immediately dissipate after you are finished using your monitoring device, instead it remains in your health records and allows for patient-centered and data-driven care.

With increasing advances to technological innovations, there are many remote patient monitoring devices that providers may use to manage different health care conditions. However, the most common remote patient monitoring devices include weight monitors, blood pressures monitors, spirometers, and blood glucose meters4.

Benefits of Remote Patient Monitoring

1. Increased Convenience and Accessibility

Remote patient monitoring programs bridge the gap of accessing care as it delivers care to patients regardless of their location and/or time. This allows patients with limited mobility, chronic conditions, and seniors to receive care in the comfort of their homes. Seniors aged 85 and older are the fastest growing population in Canada today, and over 78% of them want to be able to age in place in their homes5. Remote patient monitoring programs may be one part of the solution to helping them remain healthy and independent at home5.

2. Improved Quality of Care

Through remote patient monitoring programs healthcare practitioners have access to health data between visits which enables them to have a holistic understanding of the patient’s healthcare condition. As a result, they are able to alter treatment plans immediately in real-time. This leads to fewer emergency room visits, clinic visits, and hospitalizations6.

3. Prevents Spread of Infectious Disease

Remote patient monitoring is crucial in preventing infectious disease as patients would no longer need to visit in person to receive care and be unnecessarily exposed to healthcare settings where they could easily contract infections6. This was highlighted by the COVID-19 pandemic as limiting human contact was crucial in preventing the spread of the virus. Remote patient monitoring would also enable providers to monitor patients with infectious diseases without coming into direct contact with them. For instance, spirometers can be used to measure airflow and as a result are useful for remotely assessing how well the patient’s lungs works, this could be useful for vulnerable patients experiencing COVID-19 or lung conditions.

4.  Enhance Patient Education and Engagement

Health care practitioners can send educational resources that are catered to patient needs, along with information that can help them improve lifestyle behaviours such as different exercises to follow or different foods that they can incorporate into their diet 6. This allows patients to be more educated about their health and in turn feel empowered to make changes or manage their health more carefully.

References

  1. Government of Ontario, Ministry of Health and Long-Term Care. Preventing and Managing Chronic Disease [Internet]. [cited 2022Dec22]. Available from: https://www.health.gov.on.ca/en/pro/programs/cdpm/
  2. Siwicki B. How remote patient monitoring improves care, saves money for chronic care [Internet]. Healthcare IT News. 2022 [cited 2022Dec20]. Available from: https://www.healthcareitnews.com/news/how-remote-patient-monitoring-improves-care-saves-money-chronic-care
  3. Dolan S. Remote Patient Monitoring Trends & Health Devices in 2022 [Internet]. Insider Intelligence. 2022 [cited 2022Dec22]. Available from: https://www.insiderintelligence.com/insights/remote-patient-monitoring-industry-explained/
  4. Prevounce. A comprehensive guide to Remote Patient Monitoring [Internet]. [cited 2022Dec22]. Available from: https://www.prevounce.com/a-comprehensive-guide-to-remote-patient-monitoring
  5. March of Dimes Canada. National Survey Shows Canadians Overwhelmingly Want to Age at Home; Just One-Quarter of Seniors Expect to Do So [Internet]. 2021 [cited 2022Dec22]. Available from: https://www.marchofdimes.ca/en-ca/aboutus/newsroom/pr/Pages/Aging-at-Home.aspx
  6. Scott J. The benefits of remote patient monitoring are wide ranging [Internet]. HealthTech. 2022 [cited 2022Dec2]. Available from: https://healthtechmagazine.net/article/2021/06/benefits-remote-patient-monitoring-are-wide-ranging-perfcon
Categories
3D Printing Precision Medicine Startups

How 3D Printing will Shape the Future of HealthCare

Mariam Abdel-Baset—McMaster Life Sciences 2023

Close your eyes and think of a hospital. What is the first thing that comes to mind? Is it doctors and nurses running around from room to room? Do you think of a hospital drama and your favourite character? Or is it a big and modern building filled with a bunch of high-tech equipment.

It is no secret that hospitals are rely on many types of high-tech equipment to ensure that patients are provided with the best of care. From robots that perform remote concussion evaluations, to proton beam therapy that can be used to treat cancer, to labs that can process over 1,000 COVID-19 tests in a single day, it’s safe to say that technology and healthcare go hand in hand (1). As the largest demographic group in many countries is older adults, hospitals are in constant need of novel and innovative technology to treat them. To top, the increasing number of COVID-19 cases has strained hospital staff and resources, increasing the need for innovative technology.

Medical professionals must ask themselves what piece of technology has such potential to be the key in solving many of these medical problems? What tool has the potential of shaping the future of healthcare?

The answer to this question is 3D printing.

3D printing has come a long way in the last couple decades. It has evolved from a novel and unheard-of tool to a machine that can be found in many hospitals, offices and even homes. Today, 3D printing is used in numerous ways throughout hospitals. For example, it is used to cost effectively print materials such as bandages, stents, casts, and various surgical tools (2)! 3D printing is also used to make prosthetics, lowering the financial burden on patients from tens of thousands of dollars, to only hundreds of dollars. This makes medicine more accessible to many more individuals around the world (3). This amazing tool has also played a major role in supporting hospitals during the COVID-19 pandemic, as 3D printing was used to mass produce additional respirators – a device essential in the treatment of patients suffering from respiratory symptoms associated with severe COVID-19 infection.

Today, many researchers and doctors are looking at 3D printing to bridge the gap between patients requiring organ transplantation and the absence of suitable organ donors. As a result, organ transplantation waitlists can be eliminated, and individuals in need can receive a heart, lung, or kidney. Some researchers are even looking to print tissue, bones, heart valves and much more (4). At the University of Madrid, researchers have begun developing a prototype 3D printer that can print skin, which could potentially be used for accident or burn victims (5).  Researchers across the world are pushing the limits of 3D printing every day. With printing costs being much cheaper than acquiring a donated organ, millions of more people may be able to afford such procedures.

At this rate, printing parts of organs is not a question of “if”, but rather “when”. In 2020, the 3D printing market was valued at $12.6 billion, and it is only estimated to keep growing (6). The value of the 3D printing is expected to increase by 17% by 2023, and with it more advances in health care are predicted to follow (6). Time will only tell what will happen to the future of healthcare, but my guess is that 3D printing will play a huge role in it.

SOURCE: Advanced Solutions

References

  1. Upkeep. What are the Most Technologically Advanced Hospitals and How Are They Taking on Covid-19? 2020. [Internet] Available from: https://www.upkeep.com/answers/healthcare/top_technologically_advanced_hospitals
  2. Manufacturing Tomorrow. The Massive Potential of 3D Printing in the Healthcare Industry. 2020. [Internet] Available from: https://www.manufacturingtomorrow.com/story/2020/04/the-massive-potential-of-3d-printing-in-the-healthcare-industry/15155/
  3. General Electric. How 3D Printing Could Bend the Cost Curve in Healthcare. 2017. [Internet]. Available from: https://www.ge.com/news/reports/3d-printing-bend-cost-curve-healthcare
  4. The Medical Futurist. 3D Printing in Medicine and Healthcare – The Ultimate List In 2021. 2021. [Internet]. Available from https://medicalfuturist.com/3d-printing-in-medicine-and-healthcare/
  5. University of Madrid. 3-D bioprinter to print human skin. ScienceDaily. 2017. [Internet]. Available from: https://www.sciencedaily.com/releases/2017/01/170123090630.htm
  6. Statistica. Global 3D printing products and services market size from 2020 to 2026. 2021. [Internet]. Available from: https://www.statista.com/statistics/315386/global-market-for-3d-printers/
Categories
Precision Medicine

Personalized Cancer Vaccines

Danielle Zak—McMaster Life Sciences OOD 2024

Cancer is a disease, resulting from a mutation which causes cells to divide uncontrollably1 and skip cell cycle checkpoints. This results in a tumor, a mass of damaged cells 1left undestroyed.  Tumors are classified as either benign or malignant. Benign tumors are not able to spread 1to  other regions of the body as they grow. Conversely, malignant tumors can metastasize, spread to  other parts of the body as pieces of the original tumor break off and travel through the  bloodstream.1 Cancers are predominately categorized as either carcinomas, sarcomas, leukemias or lymphomas, depending on the original cancerous tissue.1  

Immunotherapy is a cancer treatment which attempts to boost the immune response of the human  body.2 An example of such treatment are cancer vaccines, which administer cancer-specific  antigens, molecules for which antibodies are produced, found exclusively on the surface of  cancerous cells.2 Personalized cancer vaccines are created using the cancer-specific antigens  found on tumor cells of a specific patient.2 Once a patient’s tumor is partially removed during  surgery, a vaccine may be tailored using the specific antigens present on the surface of the  removed cancerous cells.2  

Personalized cancer vaccines contain patient-specific tumor derived epitopes,3 which are regions  of the cancer-specific antigens that are recognized by the immune system.4 The immunoresponse  to the epitopes is produced by cytotoxic T cells, also known as killer T cells. Cytotoxic T cells  are lymphocytes (type of white blood cell) that respond to cytokines and kill cancer cells.5  

One type of personalized cancer vaccine is the neoantigen cancer vaccine,3 that uses the specific  neoantigens from different mutations of individual patients’ tumors as a component of the  vaccine. These neoantigens can be mRNA, DNA, and peptides.3 The synthesis of such vaccines  uses next-generation sequencing which maps all the mutations relevant to the patient’s cancer,  and gives a neoantigen prediction.3 Then, algorithms and techniques are used to determine which  neoantigens3 are specific to the malignant tumors, and which are also present on non-cancerous cells.  

Another type of vaccine uses autologous tumor cells, which are cancer cells directly from the  patient’s tumor.3 These cells are extracted from the patient, are treated, and then re-administered  as either components of cells or as whole cells.3 As a result, autologous tumor cell vaccines  contain all the patient-specific tumor-derived antigens, making this type of vaccine faster to  produce.3  

Personalized cancer vaccines can be injected subcutaneously (under the skin) or intramuscularly (into the muscle), depositing a mass of antigens in the interstitial fluid (fluid surrounding cells).3 The injected antigens are only processed by the immune system once they diffuse into capillary  vessels, therefore only a small percentage of the injected antigens are processed.3 As a  

consequence, dosage and frequency of administering the vaccine must be increased for the T cell  response to be sufficient.3 Therefore, various delivery vectors, including cell vesicles, liposomes,  cells and synthetic carriers are used to increase the strength and duration of the immune  response.3 Additionally, there are three types of vaccine delivery strategies based on the location  of antigen introduction.3 These strategies are LN-targeting (through lymph nodes), intratumoural  action (into tumor) and depot-forming (injects vaccine in scaffold to form a depot).3 

There are many human clinical trials testing different personalized vaccines. A trial conducted  by Moderna and Merck study mRNA-4157, which is in Phase 1.6 The personalized cancer  vaccine will be synthesized using the information from specific mutations in 20 neoepitopes to  create a single mRNA vaccine that will be injected into the patient.6  Ultimately, personalized cancer vaccines indicate to the immune system which antigens should  be targeted, since various malignant tumors have different cell surface antigens.2 The field of  immuno-oncology is ever growing with new personalized vaccine types, delivery vectors and  delivery methods constantly being tested and researched. 

References

1. What is Cancer? [Internet]. Cancer.Net. 2019 [cited 2021 Dec 10]. Available from:  https://www.cancer.net/navigating-cancer-care/cancer-basics/what-cancer

2. What are Cancer Vaccines? [Internet]. Cancer. Net. 2020 [cited 2021 Dec 10]. Available from: https://www.cancer.net/navigating-cancer-care/how-cancertreated/immunotherapyand-vaccines/what-are-cancer-vaccines 

3. Ye T, Li F, Ma G, Wei W. Enhancing therapeutic performance of personalized cancer  vaccine via delivery vectors [Internet]. Advanced Drug Delivery Reviews. Elsevier; 2021  [cited 2021 Dec 10]. Available from:  https://www.sciencedirect.com/science/article/pii/S0169409X21003203

4. Kogay R, Schönbach C. Epitope [Internet]. Epitope – an overview | ScienceDirect Topics.  Encyclopedia of Bioinformatics and Computational Biology; 2019 [cited 2021 Dec 10].  Available from: https://www.sciencedirect.com/topics/neuroscience/epitope

5. Augustyn A. T cell [Internet]. Encyclopædia Britannica. Encyclopædia Britannica, inc.;  2020 [cited 2021Dec10]. Available from: https://www.britannica.com/science/T-cell

6. Moderna, Inc. mRNA Personalized Cancer Vaccines and Immuno-Oncology [Internet].  Moderna. 2021 [cited 2021Dec10]. Available from:  https://www.modernatx.com/pipeline/therapeutic-areas/mrna-personalized cancervaccines-and-immuno-oncology

Categories
Blockchain

Blockchain and its Applications in Medicine

Alicia Tran—McMaster Software and Biomedical Engineering, 2023

With the fast rate at which technology is developing during today’s day and age, many novel digital solutions are making their way to solve problems in new contexts. Blockchain is one such buzzword being thrown around in recent years.

A Surface-Level Look

The main characteristic of a blockchain system is the distribution of data in a peer-to-peer network rather than through a centralized server (1). Due to its numerous features and advantages, it is especially desirable for use in implementing cryptocurrency systems, its most well-known application, the process of which is shown below.

SOURCE: Biomedical Journal of Scientific & Technical Research

What’s the Big Deal?

As mentioned in the example above, data in the blockchain is immutable, meaning it cannot be changed, due to sheer amount of computational power that would be required to change data in all nodes of the network (2). This immutability leads to many advantages of the blockchain, namely, but not limited to, traceability, integrity, and security (3). As the data cannot be changed, transactions can be tracked through the system. In addition, the system verifies the authenticity of transactions against all data sources throughout the blockchain network, reducing likelihood of fraud (3). Lastly, the very nature of a decentralized system results in no single data source for malicious users to target (2).

Uses in Healthcare

There are many opportunities to implement blockchain the health sector. The main requirements of any health-related system being developed today are security and data sharing (3). Medical information is bound by Health Insurance Portability and Accountability Act of 1996 (HIPAA) and thus needs to be secure to ensure patient privacy (4). On the other hand, patients may wish to have access to their own data and physicians may need to share information with other doctors should a patient require expanded care, so it is imperative that information can be shared only with those permitted access (3). By leveraging the security and mobility of a decentralized blockchain system with many data sources, this general problem can be solved with the use of smart contracts, whereby records can only be accessed if users have the required signatures (or keys) (2).

SOURCE: Biomedical Journal of Scientific & Technical Research

Through this system, MedRec, developed as part of the digital currency initiative at MIT Media Lab, seizes on the opportunity for interoperability in healthcare systems by having a decentralized hub of medical records of which all healthcare providers would have access (5). Smart contracts are used to map patient-provider relationships, with a contract containing a list of references detailing the relationships between nodes (patients and healthcare providers) (5). This allows the patient to accept, reject, or modify relationships with healthcare providers, putting themselves in control of their own information (5).

Uses can also become more niche. In the case of clinical trials, it can be used to maintain a log of patient consent. Due to the immutability of data in the system, one can easily monitor trial standards and prevent falsification of consent forms, thereby reducing clinical fraud and preserving the integrity of the data (5). A smart contract system would prevent study investigators from accessing patient information unless they are provided with consent at each stage of the trial (5).

Drug tracking is another avenue of blockchain application. It prevents theft and fraud by making use of the immutability of the system to track the chain of custody of pharmaceuticals, from when it is manufactured to when it is in the possession of a patient (5). The Counterfeit Medicines Project, created by Hyperledger, the Open-Source Blockchain Working Group tackles the problem of counterfeit pharmaceuticals by tracing and removing counterfeit medicine from the supply chain (5).

It is clear to see how blockchain has many uses outside of cryptocurrency, with which it is commonly associated. As the technology is further developed, it will no doubt continue to become more widespread in the healthcare sector.

References

  1. Oderkirk J, Slawomirski L. Opportunities and challenges of blockchain technologies in Healthcare [Internet]. Organisation for Economic Co-operation and Development. 2020 [cited 2021Dec12]. Available from: https://www.oecd.org/finance/Opportunities-and-Challenges-of-Blockchain-Technologies-in-Health-Care.pdf
  2. Huang X. Blockchain in Healthcare: A patient-centered model. Biomedical Journal of Scientific & Technical Research [Internet]. 2019Sep27 [cited 2021Dec11];20(3). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764776/
  3. McGhin T, Choo K-KR, Liu CZ, He D. Blockchain in healthcare applications: Research challenges and opportunities. Journal of Network and Computer Applications [Internet]. 2019Jun1 [cited 2021Dec11];135:62–75. Available from: https://www.sciencedirect.com/science/article/pii/S1084804519300864
  4. (OCR) Office for Civil Rights. Summary of the HIPAA security rule [Internet]. HHS.gov. 2021 [cited 2022Jan11]. Available from: https://www.hhs.gov/hipaa/for-professionals/security/laws-regulations/index.html
  5. Bell L, Buchanan WJ, Cameron J, Lo O. Applications of blockchain within healthcare. Blockchain in Healthcare Today [Internet]. 2018 [cited 2021Dec11];1. Available from: https://blockchainhealthcaretoday.com/index.php/journal/article/download/8/29&hl=en&sa=X&ei=f7ehYZPYMIGEmgGSwISoAw&scisig=AAGBfm0Crm9y6UcKNWw50TQDjdIvrx-R4A&oi=scholarr