Dubai College Medical Journal - May 2020

DUBAI COLLEGE MEDICAL JOURNAL 2020 Edition

DIABETES This year's edition includes an in-depth article about diabetes and how it is managed by patients.

ETHICS: VACCINES Based on a legal case from the US, read about the different perspectives on whether children should be allowed to consent to vaccinations without their parents' approval.

AUTHORS AND EDITORS Thank you to everyone who contributed to this edition of the Dubai College Medical Journal.

Editor-in-chief: Tricia Chua Editors: Aparna Sridhar, Mikail Khawaja and Raphaelle Landais.

Pictures on pages 14, 16 and 20 are illustrated by Ciara Corroon.

01

DIABETES Isobel Thompson

02

WHY GUT BACTERIA IS MORE IMPORTANT THAN WE THINK Hannah Dawson

03

NEGELCTED TROPICAL DISEASES Mikail Khawaja

04

HEALTHCARE AT THE SPECIAL OLYMPICS WORLD GAMES ABU DHABI 2019 Ciara Corroon

05

DARAPHIM Noa Consiglio-Cockle

06

LIQUID BIOPSIES Raphaelle Landais

07

COLOUR CODED SURGERY Tricia Chua

08 SHOULD CHILDREN BE ABLE TO CONSENT TO VACCINATIONS WITHOUT THEIR PARENTS' APPROVAL? Zainab Kashif

DIABETES ORIGINS In the year 1550 BC

The first ever record of a disease was created by the ancient Egyptians.

Their papyrus depicted a condition in which a person would rapidly lose weight and urinate excessively. The urine produced by sufferers attracted ants because of its sweetness. Roughly a thousand years later, the ancient Greek physician Apollonius of Memphis identified the same disease and dubbed it ‘Diabetes Mellitus’ – two words in Greek which translate to ‘to pass through’ and ‘to sweeten with honey.’

Diabetes Mellitus (DM) is a complex disease that can present itself in many different forms. There are both genetic and lifestyle related risk factors that contribute to its development in a person. Despite the ever-growing body of research on the disease, DM is still a major threat to the global population. 415 million people currently live with it and that number is expected to rise to 642 million by 2040. DM and its side effects are the seventh largest killer in Europe, so it is important to understand it in order to know how to best treat its sufferers and prevent further unnecessary complications caused by the disease.

How the healthy body processes glucose A healthy body breaks down food in the gut. Carbohydrates and sugars are broken down into glucose which is absorbed into the blood stream, causing an increase in the glucose level or ‘glycemia’ in the blood. Glucose is needed by the cells, especially in the muscles and brain, for energy. When active (i.e. during exercise), these cells absorb glucose from the blood, inducing a drop in glycemia.

The body tries to maintain glucose levels in the blood at a constant level and the pancreas is the organ primarily responsible for this. Medical student Paul Langerhans identified small structures in the pancreas called ‘Islets of Langerhans’. These structures produce the hormones which are responsible for glycemia control. There are three types of cell in each islet: Alpha, Beta and Delta.

Alpha cells produce a hormone called ‘glucagon’.

When a person has not eaten for a long time or undergoes physical activity, the alpha cells detect the resultant glucose drop in the blood and release glucagon.

This causes cells, particularly hepatocyte cells, to convert glycogen into glucose and release it into the blood, thus preventing low blood sugar or ‘hypoglycaemia’.

Beta cells are the opposite of alpha cells and they produce the hormone ‘insulin’.

This hormone causes cells (mainly hepatocyte) to absorb glucose from the blood and store it as glycogen for later use. Beta cells also synthesise the proteins Cpeptide, amylin and GABA (y amino butyric acid) – all of which play important roles in regulating glucose in the bloodstream. Glucose is transported into beta cells by facilitated diffusion where it is then metabolised to create ATP. An increase in ATP:ADP ratio closes the KATP channels of the cell which transport potassium ions and this depolarises the cell membrane. This triggers the opening of VDCC channels which transport calcium ions. An influx of calcium ions causes the cell to release stored insulin by exocytosis. This means that when a healthy person consumes food, the glucose levels in the blood will rise. In order to prevent high blood sugar or ‘hyperglycaemia’, the beta cells release insulin, causing cells to remove glucose from the blood and store it.

The relationship between the pancreas and glycemia is known thanks to the work of researchers like Joseph von Meringa and Oskar Minkowski, who removed the pancreas of a dog only to discover diabetes-like symptoms after removal.

Type 1 Diabetes Type 1 diabetes is an autoimmune disease where the immune system attacks the beta cells of the body and destroys them - as though the person is allergic to their own pancreas. It is a lifelong disorder that can be treated but has no reliable cure yet. It is not known why the disease occurs, though there is a strong genetic component. A possible cause is zinc deficiency because zinc is required by beta cells to produce insulin and it also reduces inflammatory responses caused by the immune system. Type 1 diabetics make up about 8% of all DM sufferers.

As the beta cells are destroyed, the pancreas of a type 1 diabetic cannot produce insulin, GABA, amylin or C – peptide. GABA represses the production of glucagon from the alpha cells, so the loss of GABA causes the cells to convert glycogen to glucose and release it into the blood, causing hyperglycaemia. The loss of insulin is the most important feature of type 1 diabetes as it means that, even after a large meal, the sufferer’s cells will not take in glucose and as a result they will be constantly tired. The blood sugar levels of a type 1 diabetic will continue to rise if left untreated and the sufferer will die in a matter of weeks.

To obtain energy, the body of a type 1 diabetic will break down fat stores, resulting in rapid weight loss. The body tries to filter out the glucose from the blood in the kidneys – hence the excessive urination and presence of glucose in the urine. A person can start to suffer from type 1 diabetes at any point in life and the symptoms present themselves very quickly after a person starts to develop the disease.

Type 2 diabetes Type 2 is the most common diabetes, comprising 90% of DM sufferers. It is thought to be primarily caused by obesity given that 60% to 90% of those affected are also obese. Some are also genetically predisposed to it. Unlike type 1, type 2 diabetes develops slowly. Patients often do not notice their symptoms and can go undiagnosed for up to 10 years. It is estimated that almost half of type 2 pre-diabetics do not know that they have it.

T2 Diabetes occurs when the beta cells cannot produce enough insulin to meet the metabolic demand. Adipose cells release hormones called adipokines and these can induce inflammatory responses and insulin resistance. The more fat a person has, the more insulin resistant they become.

Insulin resistance causes an increased metabolic demand for insulin which is met by the beta cells and these compensate with hypersecretion of insulin. If the hypersecretion continues for too long, the beta cells will start to fail and gradually the person will become more and more hyperglycaemic as their pancreas produces less and less insulin.

Type 2 diabetes is a spectrum. The more insulin resistant a person is, the higher on the spectrum they are. There is a phase between normal and diabetic called ‘pre-diabetic’. A person who is diagnosed as a pre-diabetic should use this warning as an opportunity to improve their diet and exercise to avoid the damage that diabetes can do to the body. Luckily, it is possible for a person to move around on the spectrum. It is possible for a T2 diabetic to regulate their glucose levels without medication simply through diet and exercise and it is even possible for a diabetic to reverse their insulin resistance entirely.

Other types of diabetes Most people are not aware that there are more than two types of diabetes.

Type 3 diabetes or ‘Alzheimer’s’ as it is more commonly known occurs when the brain becomes insulin resistant. The cause is unknown, though type 2 diabetes is a major risk factor (sufferers have 50-65% increased risk) and genetics are also important.

Type 1.5 diabetes is the unofficial term used to describe a rare form of T1 diabetes called Latent Autoimmune Diabetes in Adults (LADA). It is slow onset, much like T2, and displays itself in adulthood but is not the result of poor lifestyle. A tenth of the sufferers of LADA are misdiagnosed with type 2 due to the slow onset of their symptoms.

Secondary diabetes is when the pancreas is destroyed by another disease such as cystic fibrosis, hemochromatosis (excess iron absorption), pancreatitis, PCOS and cancer. The symptoms and treatment of secondary diabetes are the same as T1.

Neonatal diabetes can occur in infants under six months. It usually dissipates within a year but can return in adolescence.

MODY , or Maturity Onset Diabetes of the Young, is a genetic form of diabetes that occurs in patients that are under 25 years old. It can be induced by renal cysts, impaired insulin production or glucokinase. MODY has similar symptoms to type 2 diabetes and is therefore frequently misdiagnosed.

Testing for diabetes Diabetes is diagnosed with a blood test.The glucose and HbA1c levels in a patient after fasting are recorded several times over a period of time.

HbA1c is the molecule formed when haemoglobin binds with glucose. The molecules can survive in the blood stream for 8 – 12 weeks so they provide more long-term data about a patient’s glycemia than just the glucose concentration in the blood. A person with diabetes will have an elevated concentration of HbA1c and glucose.

How diabetes can affect the body Hyperglycaemia reduces the vasodilation of blood vessels which in turn increases blood pressure. The molecule O-GLcNAc (which is derived from glucose) suppresses the phosphorylation of nitric oxide synthase which reduces the rate at which nitric oxide – a vasodilator – is produced in the blood. Therefore, if untreated/poorly treated, diabetics are in danger of every type of cardiovascular risk factor.

Neuropathy is when nerves become damaged due to insufficient nutrients for growth and repair. This occurs in untreated diabetics because the blood vessels around the nerves are too damaged to supply the nerves properly. There are three types of diabetic neuropathy: sensory, autonomic and motor.

Sensory neuropathy causes tingling, numbness and loss of ability to detect pain.

Autonomic neuropathy causes irregular heartbeat and loss of bladder control amongst other things.

Motor neuropathy effects muscle control and strength.

Retinopathy can be caused when the capillaries in the retina bulge due to diabetes. They become damaged and can leak which in turn causes scar tissue to form on the retina. Ultimately this leads to blindness.

The kidneys are put under a lot of strain in diabetics as they must filter out massive quantities of waste products. This puts stress on the blood vessels in the kidney, causing significant damage. When this happens, the nephrons are not able to carry out filtration and reabsorption properly so waste fluid builds up in the body. This is called an oedema. If this goes on for prolonged periods of time, it can cause kidney failure. Luckily, these effects can be prevented if the patient takes their medication and is treated with the same blood pressure medication that would be administered to a patient displaying symptoms of heart disease.

How diabetes is managed

A person with T1 diabetes needs to take insulin since their pancreas cannot produce it. It is administered either as shots that are injected into the fat of the abdomen or by an insulin pump. Shots of insulin should be taken after meals – times when a spike in glucose would be expected. Prior to 1970, the insulin used to treat T1 diabetics came from pigs. Nowadays, it is synthesised artificially.

Insulin pumps are becoming more and more sophisticated. They can automatically detect raised glycemia and administer insulin accordingly without the patient having to do anything. Even though most diabetes-related health problems are caused by hyperglycaemia, sufferers are also at risk of becoming hypoglycaemic if their medication is administered incorrectly or if they exercise/inject insulin without eating before or after. To avoid this, diabetics use glucose monitors to ensure that their glucose levels are never too high or too low. If they become hypoglycaemic, they need to eat food. If they are hyperglycaemic, they can administer insulin.

Dr Edward Damiano created the first bionic pancreas or ‘iLet’ as it was named in 2015. Other treatments for T1 (such as stem cell replacement therapy of the pancreatic islets) are currently being developed.

Type 2 diabetics should be able to regulate their symptoms through diet and exercise – the ketogenic diet has delivered promising results in the reversal of insulin resistance. If a change of lifestyle is not possible, there are a plethora of alternate medications that can be taken orally to aid weight loss and glycaemic control. Some examples are the sulphonylureas (drugs that stimulate the pancreas to produce more insulin) and the glinides (drugs that reduce post meal glucose spikes). Though diabetes is on the rise, so are the methods by which it can be treated, but the number one enemy facing the health of diabetics is the sufferers themselves. It is not necessarily the disease itself that does damage to the body but the poor management of it.

Isobel Thompson

DIABETES IN THE UAE The UAE has the tenth highest prevalence of diabetes in the world with almost a fifth of the population affected. Many other conditions, such as hypolipidemia and PCOS, carry similar statistics. In fact, 18% of hospital visits and 20% of infant mortalities in the UAE are due to genetic disorders.

Working in a Diabetes clinic in Abu Dhabi gave me the opportunity to observe the population affected by these statistics. Â Several of the cases I observed involved genetic analysis.

The family tree of the couples looking to conceive would be drawn up by the endocrinologist and the probability of the offspring being affected by a certain genetic disorder (i.e.mature onset diabetes of the youth) would be calculated. Consanguineous couples existed in many of the families and patients usually had many siblings and half siblings.

The Emirati population is sparse and therefore possesses a small gene pool. With such complex family trees, it is not surprising that a large percentage of the population shares the same mutated genes.

Most of the patients I observed displayed no improvement or decline in their HbA1c and LDL concentrations since diagnosis, despite receiving medication, counselling and lifestyle instructions from doctors.

This was usually because the medical advice was not followed. Patients were either overwhelmed with the quantity of medication they needed to consume daily, confused as to how to calculate and inject their insulin or simply not worried about the potential damage that diabetes could do to their bodies.

I do not think this is because the population of the UAE is lazy, untrusting of medicine or uneducated. In fact, all the patients I met were likable people who were respectful to the doctors. It was upsetting to see such a warm and friendly population suffering from this disease. As easy as it is to blame sufferers of lifestyle related diseases for creating their own problems, I saw that this is not always fair. When facing the population behind the statistics, it becomes much easier to sympathise with them. Many patients wanted to lose weight but were struggling because they had become dependent on food to cope with stress or depression. These patients would greatly benefit from seeing a councillor, but many seemed uncomfortable with the idea. Indeed, there was a psychologist at the clinic where I was working but they were not in as there had been no appointments to see him.

Some patients did not understand how to administer their medication correctly.

Many explained that the doctor who prescribed them their drugs was too busy to explain how to administer them properly. Furthermore, many of the patients had a seemingly endless list of prescribed medications and as a result they could easily have been mixed up.

In recent years there has been a lot of improvement in the UAE with an emphasis being placed particularly on health and fitness in schools. Initiatives such as the Dubai 30x30 challenge and moral education have been launched in schools.

There is also the ever-growing expat population, which is becoming increasingly integrated within the local population. This will hopefully lead to greater diversity within the gene pool and foster a greater awareness amongst the younger generations due to the introduction of different perspectives on health and wellbeing.

Though changing the lifestyle of a region takes time, I believe we are headed in the right direction and I am optimistic about the future of diabetes in the UAE.

Isobel Thompson

Bibliography for Diabetes and Diabetes in the UAE: 1. Linetsky, E., Ricordi, C. and Inverardi, L. (2013). 'Cell Replacement Therapy in Type 1 Diabetes', INTECH Open Access Publisher.

2. Nepton, Soltani (2012). 'Beta-Cell Function and Failure', INTECH Open Access Publisher.

3. Linetsky, Elina; Inverardi, Luca; Ricordi, Camillo (2012). 'Cell Replacement Therapy in Type 1 Diabetes', INTECH Open Access Publisher.

4. Marković- Jovanovic, SneŞana (2012). 'Nutritional Management in Type 1 Diabetes Mellitus', INTECH Open Access Publisher.

5. Penn Medicine News (2012). Brain Insulin Resistance Contributes to Cognitive Decline in Alzheimer's Disease. [online] Available at: https://www.pennmedicine.org/news/news-releases/2012/march/brain-insulinresistance-contr 6. Diabetes UK (n.d.). Maturity onset diabetes of the young (MODY). [online] Available at: https://www.diabetes.org.uk/diabetes-the-basics/other-types-ofdiabetes/mody 7. Diabetes UK (n.d.). Nerves (neuropathy). [online] Available at: https://www.diabetes.org.uk/Guide-todiabetes/complications/Nerves_Neuropathy 8. Diabetes UK (n.d.). Diabetic nephropathy (kidney disease). [online] Available at: https://www.diabetes.org.uk/guide-todiabetes/complications/kidneys_nephropathy 9. Diabetes UK (n.d.). Sulphonylureas. [online] Available at: https://www.diabetes.org.uk/Guide-to-diabetes/Managing-yourdiabetes/Treating-your-diabetes/Tablets-and-medication/Sulphonylureas 10. Leutholtz, Brian C. & Ripoll, Ignacio (2011). Exercise and Disease Management, 2nd edition, CRC Press Taylor & Francis Group, Boca Raton.

11. Kwon, Hyokjoon & Pessin, Jeffrey E. (2013). 'Adipokines Mediate Inflammation and Insulin Resistance', Frontiers in Endocrinology (Lausanne), 4, pp. 71.

12. Kasuga, Masato (2006). 'Insulin resistance and pancreatic β cell failure', The Journal of Clinical Investigation, 116(7), pp. 1756-1760.

13. Wikipedia (n.d.). Fatty acid metabolism. [online] Available at: https://en.wikipedia.org/wiki/Fatty_acid_metabolism 14. Wikipedia (n.d.). Gluconeogenesis. [online] Available at: https://en.wikipedia.org/wiki/Gluconeogenesis 15. World Health Organization Regional Office for Europe (n.d.). Data and Statistics. [online] Available at: http://www.euro.who.int/en/healthtopics/noncommunicable-diseases/diabetes/data-and-statistics 16. Khaleej Times (2017). Pre-marital screening must to avoid genetic diseases in UAE. [online] Available at: https://www.khaleejtimes.com/nation/pre-maritalscreening-must-to-avoid-genetic-diseases-in-uae 17. Diabetes in Control (2009). How High Blood Sugars Damage Blood Vessels. [online] Available at: http://www.diabetesincontrol.com/how-high-blood-sugarsdamage-blood-vessels/ 18. Diabetes.co.uk (2019). Alpha Glucosidase Inhibitors. [online] Available at: https://www.diabetes.co.uk/diabetes-medication/alpha-glucosidaseinhibitor.html 19. Centers for Disease Control and Prevention (2017). Leading Causes of Death. [online] Available at: https://www.cdc.gov/nchs/fastats/leading-causes-ofdeath.htm 20. The Free Dictionary (n.d.). acinar cell. [online] Available at: https://medicaldictionary.thefreedictionary.com/acinar+cell

WHY GUT BACTERIA IS MORE IMPORTANT THAN WE THINK We already know that our genetic differences can influence our response to drugs and this can explain why the efficacy and side effects of drugs vary from person to person (Newscientist.com, 2019). However, there is still very little clarity surrounding exactly what happens when a drug is digested. A study using human gut bacteria and a mouse model has led to an investigation into why our gut bacteria plays a more pivotal role in drug metabolism than previously believed (Newman, 2019).

Our microbiome has been discovered to contain over 100 times more genes than our own genome (Goodman, 2019).

As most drugs are taken as pills or via another oral method, and very often as a result of this, they are not absorbed completely by the body. The ‘remains’ of the drugs that are not absorbed, subsequently encounter enormous numbers of microbes in our guts (Newscientist.com, 2019).

In order to investigate what happens to these ‘remains’, a Team at Yale University and ETH Zurich led by Dr. Andrew Goodman mapped how 76 different strains of human gut bacteria break down 271 different drugs (Newman, 2019).

The result of this investigation showed that 176 out of the 271 drugs (64.9%) could be metabolised by gut bacteria (Goodman et al., 2019). This was noted as a rather high proportion by Michael Zimmermann at Yale University. The results also showed that each strain of bacteria could metabolise 11–95 types of drugs.

When drugs are broken down by microbes, substances with unwanted side effects can be produced alongside chemicals, which can even render the drug’s active ingredient ineffective. “I think it’s a big step forward. People can start to predict, based on someone’s gut microbes, how they might respond to a drug.” says Tim Spector of King’s College London (Newscientist.com, 2019). In light of this new finding it is likely that in the future, methods of changing our microbiomes to reduce side effects and increase drug efficacy will become an option (Newscientist.com, 2019).

It is becoming increasingly clear that variation in the human microbiome has important consequences for health. The overall goal of the Goodman Lab at Yale School of Medicine is to dissect the mechanisms that commensal gut microbes use to compete, cooperate, and antagonize each other in the gut and to explore how microbiome variation impacts our response to external perturbations, including pathogenic infection and medical drugs (Goodman, 2019).

The group has explained that earlier studies have shown how microbes can influence the way that specific drugs work. For example, sulfasalazine, a drug used as a treatment for ulcerative colitis, relies on gut bacteria to activate it.

On the other hand, digoxin, a drug used to treat various heart conditions, can be inactivated by Eggerthella lenta, a bacteria found in the colon (Newman, 2019).

Although scientists have described the microbiome’s impact on specific drugs, Goodman and his colleagues explain that “the molecular mechanisms remain largely unknown” as this area of science is still in its infancy. With that said, “This [discovery] could provide a means to mechanistically connect microbiome information to interpersonal variation in drug metabolism and toxicity."

(Newman, 2019).

Hannah Dawson

Bibliography: 1. Goodman, A. (2019). Microbial Pathogenesis | Microbes metabolising drugs. [online] Medicine.yale.edu. Available at: https://medicine.yale.edu/lab/goodman/ [Accessed 14 Jun. 2019].

2. Goodman, A., Zimmermann, M., Zimmermann-Kogadeeva, M. and Wegmann, R. (2019). Mapping human microbiome drug metabolism by gut bacteria and their genes. https://www.nature.com/articles/s41586-019-1291-3.

3. Newman, T. (2019). Gut bacteria may help explain why drugs don't work for everyone. [online] Medical News Today. Available at: https://www.medicalnewstoday.com/articles/325366.php [Accessed 14 Jun. 2019].

4. Temming, M. (2019). Gut bacteria may change the way many drugs work in the body. [online] Science News. Available at: https://www.sciencenews.org/article/gut-bacteria-may-change-way-manydrugs-work-body [Accessed 14 Jun. 2019].

5. Newscientist.com. (2019). Your gut bacteria may influence whether you get drug side effects. [online] Available at: https://www.newscientist.com/article/2205127-your-gut-bacteria-mayinfluence-whether-you-get-drug-side-effects/ [Accessed 14 Jun. 2019].

NEGLECTED TROPICAL DISEASES (NTD) Neglected Tropical Diseases (NTDs), are a subclass of infectious diseases that majorly impact the lives of individuals in countries with underdeveloped healthcare systems. They affect an estimated 149 countries, and infect 1 in 7 people every year according to the WHO. Unlike other infectious diseases, NTDs are defined by their high rates of infection and gruesome symptoms shown by those who are infected. Considering this, the lack of attention they receive from the media is startling. This article will act to increase awareness on the problem that NTDs pose to tropical countries, and what we have done to combat them.

The term NTDs was coined by Peter Hotez and his colleagues in early 2003 to differentiate them from other tropical diseases in the limelight such as malaria and tuberculosis (Winkler, 2018). The umbrella of NTDs covers a vast range of vectors, including bacteria, viruses, worms and amoeba.

However, the various means by which these diseases can be transmitted in is not the only factor causing alarm. Like predators, these diseases are most common in smaller, isolated communities. The lack of sanitation – of both water and food – paired with the restricted access to drugs allows these pathogens to conquer entire regions. To make matters worse, the individuals affected can exhibit chronic symptoms which prevent them from contributing to their local economy (Lenk, 2016). This reduces the size of the workforce, meaning the region will sink into deeper poverty– perpetuating a cycle of infection and harm for anyone within the deadlocked region.

The Guinea Worm (Dracunculiasis) is an example of such a disease. In fact, the native Dogon people (Mali) named it the “Disease of the empty granary” because of its long lasting effects on the agricultural abilities of farmers (Yoro, the empty Granary, 1995). Infection can occur from the ingestion of non-potable or contaminated water, which results in the eggs entering the digestive tract.

Symptoms go relatively unnoticed for around a year, after which the worm will attempt to burrow out of the skin near the lower extremities – usually below the knee (Cairncross, 2002). In 1986, the WHO reported 3.5 million cases of Dracunculiasis, the epicenter of these cases originating from sub-Saharan

Africa. Treatment after lesions have developed generally includes slowly pulling the worm out through the skin over several weeks, after which patients will remain bedridden for an equal length of time. This painful process essentially rendered a significant portion of farmers temporarily disabled, and meant that children were unable to attend schools. The measurable impact this had on the then-suppressed economy of Africa alerted the WHO, causing it to call for an eradication program (Hopkins, 2017).

The Guinea Worm posed a greater threat than first anticipated, as the pharmaceutical industry quickly found that none of the drugs developed were effective enough to be used in practice (Biswas, 2013). To combat this, other methods were employed which made use of knowledge concerning the spread of Dracunculiasis. Campaigns to sanitise local drinking water, removing the worm from human hosts and health education became the norm to the 20 countries where the pathogen had become endemic (Netshikweta, 2017).

The eradication program proved to be one of the biggest successes in the suppression of infectious diseases in the past century. Compared to the 3.5 million cases of Dracunculiasis in 1986, the number reported in 2016 had dropped to just 22 – as well as only being confined to 3 countries (Ruiz-Tiben, 2017). It has been estimated that the Guinea Worm will be the first parasite to be eradicated in the near future.

Dracunculiasis stood as a perfect example to the type of infections lurking in areas beyond the reach of modern medicine, but more importantly how simple awareness and action can combat that. It is not the first, nor the last, NTD on the loose. However, campaigns like the London Declaration enacted by the WHO are working to eradicate more neglected tropical diseases by 2020. To learn more about what is being done to fight NTDs, you can visit the World Health Organization's website, where they have regular updates about their progress and development; or visit other supporters of the effort contributing to a better future.

Mikail Khawaja

Bibliography: 1. Biswas, G. (2013). Dracunculiasis (guinea worm disease): eradication without a drug or a vaccine. Philos Trans R Soc Lond B Biol Sci. 2. Cairncross, S. (2002). Dracunculiasis (Guinea Worm Disease) and the Eradication Initiative. Clin Microbiol Rev. 3. Hopkins, D. R. (2017). Progress Toward Global Eradication of Dracunculiasis.

MMWR Morb Mortal Wkly Rep. 4. Lenk, E. J. (2016). Productivity Loss Related to Neglected Tropical Diseases Eligible for Preventive Chemotherapy: A Systematic Literature Review. PLoS Negl Trop Dis. 5. Netshikweta, R. (2017). A Multiscale Model for the World's First Parasitic Disease Targeted for Eradication: Guinea Worm Disease. Comput Math Methods Med. 6. Ruiz-Tiben, E. (2017). Progress Toward Global Eradication of Dracunculiasis, January 2016–June 2017. MMWR Morb Mortal Wkly.

7. Winkler, A. (2018). Neglected tropical diseases – the present and the future.

Tidsskr Nor Laegeforen.

HEALTHCARE AT THE SPECIAL OLYMPICS WORLD GAMES ABU DHABI 2019

The Special Olympics is an international sporting event for people with intellectual disabilities. It was started by Eunice Kelly Shriver in the early 1960s; she founded a summer camp in her backyard, encouraging children of determination to engage in sports and to socialise. It was an instant success, and after only four years there were approximately 100 campers attending. It has since blossomed into a worldwide event with over 10 000 athletes representing 170 different countries competing in 24 different sports. In the modern day, people with intellectual disabilities are a lot more widely accepted due to increasing awareness and education, however even in 2019 there is unfortunately still a lot of prejudice they face daily.

The Special Olympics offers free health services to all athletes competing, the initiative is called ‘Healthy Athletes'. This started due to the fact that many people with intellectual disabilities do not receive equal healthcare, and are denied it altogether in some instances. The services offered are as follows: Podiatry Physical therapy Better health and well-being Audiology Sports physical exam Vision Dentistry Emotional well-being

In addition to these services, athletes also received items such as properly fitting shoes and hearing aids free of cost. For many of these athletes, especially those in third world countries, these items are invaluable. There are a few particular instances in which the significance of these services is highly evident, such as when Sanatou Diara, a gold medalist 100m runner, was fitted with hearing aids, allowing her to hear for the first time at the age of 21. She was believed to be permanently deaf, despite never having been formally examined, however the high cost of hearing aids would likely mean that even if she was aware they would be unaffordable.

I was assigned to the ‘Fit Feet’ (podiatry) department of the Healthy Athletes initiative. As I am not currently a healthcare practitioner, my job was to manage the floor and direct athletes to each of the different stations within ‘Fit Feet’.

The athletes would first have their feet examined by a doctor that would look for common foot deformities and abnormalities. They would first examine the skin; if it was dry, cracking or had any fungal growth. They would then analyse the range of motion of the foot, to detect if there was any restricted movement.

Afterward, they would examine the athletes feet whilst standing still, to check for fallen or high arches (pes planus and pes cavus), they would also check for knocked-knees or bow leggedness (genu valgum and genu varum). Lastly they would examine the athletes' gait to look for any pronation or supination of the feet. This information was recorded on an online database and was made available to all athletes.

After this station the athletes then moved on to a foot measuring station as many of them wore incorrectly sized shoes, which could have detrimental impacts later on in their lives. The athletes then received their medical information, and if needed were advised to follow up with a doctor afterwards.

They also received a pair of properly fitting, laceless sports shoes shown in Fig. 1 which, to many of the athletes competing, was an invaluable item to receive and I am sure is appreciated beyond understanding by many.

Figure 1 - Concept art for laceless sports shoes The Special Olympics is more than just a sporting event. It is an opportunity for athletes with intellectual disabilities all over the world to come together and demonstrate their capabilities, and it is a chance for social biases and judgements to be broken, for the topic to become less taboo. Most importantly however, it is a chance for a group of people looked down upon in many places to be at the forefront of an event such as the Special Olympics.

Ciara Corroon

Bibliography: 1. NHS (2017). Hearing Aids. [online] Available at: https://www.nhs.uk/livewell/healthy-body/hearing-aids/ 2. CenturyHearingAids (2015). Types of Hearing Aids. [online] Available at: https://www.youtube.com/watch?v=IfMUhW1J6Mc 3. U.S. Food and Drug Administration. 2018. Types Of Hearing Aids. [online] Available at: https://www.fda.gov/medical-devices/hearing-aids/types-hearingaids 4. Audika.com.au. n.d. Types Of Hearing Aids: Find The Right Model For Your Needs. [online] Available at: https://www.audika.com.au/hearing-aids/hearingaid-styles

DARAPHIM Daraprim is a drug that has gained notoriety amongst the medical and drug industries thanks to one man: Martin Shkreli. Daraprim is an anti-parasite that is used for two main diseases: malaria and toxoplasmosis, both two deadly diseases caused by parasites. Daraprim works by preventing parasites from growing and reproducing in the body. As an anti-malarial, it is usually used in tandem to either prevent or treat malaria by stopping the reproduction of the parasite within the body, suppressing most strains of malaria and initiating transmission control. It is also recommended when the patient has a compromised immune system. When used to treat toxoplasmosis it is the standard, most effective treatment that is prescribed. Toxoplasmosis mainly affects those who have compromised immune systems; those who have cancer or HIV are the most susceptible to the parasite. The active ingredient is pyrimethamine, and the small tablets contain some other inactive ingredients.

However, it is not the drug itself that earned Daraprim its notoriety. When the drug was bought by Turning Pharma, there was a price hike of 5000% - a shift from $13.50 to $750 per pill, meaning any of the sick individuals who rely on it to be able to survive must pay hundreds of thousands of dollars a year in the US. Whereas, in Australia and most other countries, it costs only $1-$2 per pill. As the price of the pills were raised, the number of prescriptions shrank, though the profits of Turning Pharma continued to rise. There was a 50% decrease for hospitals, but this still leaves the prices as $375, meaning that many hospitals find it too expensive to stock and cannot obtain enough of it, especially in lowincome areas.

Upon learning this, a group of students at Sydney Grammar decided to try to recreate the production of Daraprim, guided by three professors. The students started out with 17g of 2,4-chlorophenyl acetonitrile, and had to come up with their own way to produce Daraprim as the (formerly) patented route used in industry involves too many dangerous reagents.

This led to several different failed experiments which the students and their teachers documented on malaria.ourexperiment.org. Eventually, after 12 months, the students were able to create their own, safer way to create the drug. They were able to make 3.7g of the active ingredient, pyrimethamine, for $20. This would average out to about $2 a pill made from this mass of the active ingredient, which would sell in the US for $35,000-$110,000.

“And not only have they done it, it’s super pure.

It’s A-grade.”

DR ALICE WILLIAMSON

This is what one of their professors, Dr Alice Williamson, explained upon viewing the spectrograph of the compound that they used to test their successful attempt at recreating Daraprim. To be able to do this in a new way, without any change in the composition of the compound is seen to pose a new way to be able to potentially produce the drug commercially.

On the contrary, this new method created by the students, would pose no competition or threat towards Turing due to the intrinsically complex nature of the US approval system.

As the production method and the product itself would have to undergo very expensive clinical trials which would end up costing much more than could ever be returned in profits. Instead, it should be seen for what it is: an achievement that has continued to spark the debate over the prices and ethics of selling important medication in America.

The ability of these students to recreate Daraprim is important in bringing the increasing lack of access to the drug due to its price to the surface and providing a way for those who need Daraprim to be able to fight for more affordable, life-saving medication.

Noa Consiglio-Cockle

Bibliography: 1. Binns, D., Sheridan, D. and Of Sydney Grammar, T. (2017). Daraprim Synthesis. [online] Malaria.ourexperiment.org. Available at: https://malaria.ourexperiment.org/daraprim_synthesis/group/Summary [Accessed 12 Jun. 2019].

2. RxList. (2017). Daraprim (Pyrimethamine): Side Effects, Interactions, Warning, Dosage & Uses. [online] Available at: https://www.rxlist.com/daraprimdrug.htm#description [Accessed 11 Jun. 2019].

3. Davey, M. (2016). Australian students recreate Martin Shkreli price-hike drug in school lab. [online] The Guardian. Available at: https://www.theguardian.com/science/2016/dec/01/australian-studentsrecreate-martin-shkreli-price-hike-drug-in-school-lab [Accessed 12 Jun. 2019].

4. Hunjan, R. (2016). Students recreate Daraprim, drug that sells for thousands in US, for $20. [online] ABC News. Available at: https://www.abc.net.au/news/2016-11-30/daraprim-nsw-students-create-drugmartin-shkreli-sold/8078892 [Accessed 12 Jun. 2019].

5. MacDonald, F. (2016). Students Have Made Martin Shkreli's $750 Drug in Their Chem Lab For Just $2. [online] ScienceAlert. Available at: https://www.sciencealert.com/students-have-made-martin-shkreli-s-750-drugin-their-chem-lab-for-just-2 [Accessed 12 Jun. 2019].

6. Multum, C. (2017). Daraprim Uses, Side Effects & Warnings - Drugs.com. [online] Drugs.com. Available at: https://www.drugs.com/mtm/daraprim.html [Accessed 11 Jun. 2019].

7. Pollack, A. (2015). Drug Goes From $13.50 a Tablet to $750, Overnight. [online] Nytimes.com. Available at: https://www.nytimes.com/2015/09/21/business/a-huge-overnight-increase-ina-drugs-price-raises-protests.html [Accessed 11 Jun. 2019].

8. SEIDMAN, B. (2015). Drug price increases 5,000 percent overnight. [online] Cbsnews.com. Available at: https://www.cbsnews.com/news/generic-drug-priceincreases-5000-percent-overnight/ [Accessed 11 Jun. 2019].

LIQUID BIOPSIES What is a liquid biopsy?

A liquid biopsy is a minimally invasive procedure involving the withdrawal of a blood sample or other bodily fluids in order to identify and isolate circulating free floating cancer cells (FFCC’s) or DNA (Castro-Giner et al., 2018). While it was initially used for prognostic purposes, such as predicting how the cancer would respond to treatment, research is being done into its use as a tool for diagnosis. The identification of different mutations in the target genes can also aid in guiding treatment and evaluating its appropriateness. (Silvestris et al., 2018).

Mechanism Cancer, a molecular disease associated with changes and mutations in the genome, can be identified in cell-free DNA (cfDNA) (A. Barrera-Saldaña et al., 2018). It was in 1938 that researchers first detected and quantified cfDNA (DNA that freely circulated in the bloodstream that is not necessarily of tumour origin) in both healthy and diseased patients. However, they were not able to differentiate between tumour and healthy cfDNA. By 1994, scientists were able to identify specific mutations in the cfDNA. The first liquid biopsy test (cobas® EGFR Mutation Test) was approved by the FDA as a cfDNA test for the EGFR gene mutation in blood from lung cancer patients in 2016 (Labce.com, n.d.).

Current progress and limitations In order to ensure that liquid biopsies enter the wide use clinical stage, scientists will have to ensure that it can reliably identify different types of cancer at an early stage, distinguish between benign and malignant tumours and determine if the tumour is fast or slow growing (Kostuk, n.d.).

One challenge is that even with a medium-sized tumour, there is very little cfDNA in the blood. In addition, cfDNA is an umbrella term for many different types of DNA found in the blood. For example, foetal DNA may be found in the blood of pregnant mothers and people who have had strokes or heart attacks may also have DNA fragments in their blood (McDowell, 2018). Researchers need to be able to reliably differentiate ctDNA (tumour DNA) from other types of cfDNA in order to avoid false positives.

In addition, not every cancer is dangerous and lethal, and scientists need to be able to identify between slow growing and more aggressive tumours. Some slow growing cancers may never need treatment. Treating these relatively harmless tumours may in fact do more harm than good to the patient (R. Speicher et al., 2017). Furthermore, finding a tumour early on may not be enough if the tumour is aggressive, furthering the need for liquid biopsies being able to make that distinction (McDowell, 2018).

It is also important for the liquid biopsy technology to be able to identify where the tumour is located. The aim of this technology is to be able to detect the tumour before it can easily be identified by current screening techniques. In a recent study, scientists combined the technologies, managing to identify and sort for ctDNA. They then matched these up with protein markers to give them an idea of where the tumour may be located (McDowell, 2018).

The liquid biopsy test could potentially be used alongside MRIs and tissue biopsies in order to increase the accuracy of the diagnosis and allow the doctor to begin treatment more quickly. There is also the hope that this test would allow the doctor to pick a treatment that works well the first time before the cancer grows out of control (Kostuk, n.d.).

Raphaelle Landais

Bibliography 1. A. Barrera-Saldaña, H., G. Domínguez-Vigil, I., K. Moreno-Martínez, A., Y. Wang, J. and H.A. Roehrl, M. (2018). The Dawn of the Liquid Biopsy in the Fight Against Cancer. [online] NCBI. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788692/ [Accessed 8 Jun. 2019].

2. Castro-Giner, F., Gkountela, S., Donato, C., Alborelli, I., Quagliata, L., Ng, C., Piscuoglio, S. and Aceto, N. (2018). Cancer Diagnosis Using a Liquid Biopsy: Challenges and Expectations. [online] NCBI. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023445/ [Accessed 8 Jun. 2019].

3. Kostuk, M. (n.d.). Liquid Biopsy and Cancer Detection - BioChain Institute Inc. [online] BioChain Institute Inc. Available at: https://www.biochain.com/general/liquid-biopsy-cancer-detection/ [Accessed 8 Jun. 2019].

4. Labce.com. (n.d.). The History of Liquid Biopsy Assays - LabCE.com, Laboratory Continuing Education. [online] Available at: https://www.labce.com/spg1560905_the_history_of_liquid_biopsy_assays.aspx [Accessed 8 Jun. 2019].

5. McDowell, S. (2018). Liquid Biopsy: Past, Present, Future. [online] Cancer.org.

Available at: https://www.cancer.org/latest-news/liquid-biopsies-past-presentfuture.html [Accessed 8 Jun. 2019].

6. R. Speicher, M., Heitzer, E., Perakis, S. and B. Geigl, J. (2017). The potential of liquid biopsies for the early detection of cancer. [online] nature.com. Available at: https://www.nature.com/articles/s41698-017-0039-5 [Accessed 8 Jun. 2019].

7. Silvestris, F., Palmirotta, R., Lovero, D., Cafforio, P., Felici, C., Mannavola, F., Pellè, E., Quaresmini, D. and Tucci, M. (2018). Liquid biopsy of cancer: a multimodal diagnostic tool in clinical oncology - Raffaele Palmirotta, Domenica Lovero, Paola Cafforio, Claudia Felici, Francesco Mannavola, Eleonora Pellè, Davide Quaresmini, Marco Tucci, Franco Silvestris, 2018. [online] SAGE Journals.

Available at: https://journals.sagepub.com/doi/full/10.1177/1758835918794630 [Accessed 8 Jun. 2019].

COLOUR CODED SURGERY Activatable cell-penetrating peptides (ACPPs) have been developed by Quyen Nguyen and her team in order to identify structures in the body (TEDMED, 2011).

This discovery is primarily used to locate and identify tumors in the body in order to fully extract them from the patient. Â Tumors are normally identified using radiographic imaging or ultrasounds and are then outlined using guide wire by surgeons. However, due to the low spatial resolution as well as difficulties in transforming a 2D image into a 3D image, the tumor may not be fully outlined and identified. This means that groups of cancerous cells may not be removed during the surgery. To prevent this from occurring, surgeons typically send biopsies of the tissue removed during the surgery to pathologists to identify if there are any malignant cells left in the body. However, this process is lengthy and increases the duration of time the patient has to stay in surgery, which also makes anesthesia-related complications more likely. Even with this arduous process, at times tissues may test positive for cancerous cells after the operation; this results in the patient having to potentially undergo a second surgery, chemotherapy or radiotherapy (Chelsey, 2012). Â A cell-penetrating peptide (CPP) is a type of polycationic sequence that is able to fully penetrate mammalian cells without needing specific receptors (Aroui & Kenani, 2019).

These molecules are covalently bonded to molecules of various kinds, such as iron oxide nanoparticles which are then carried to cells.

In this case, the molecule is Cy5, which is a type of fluorophore that creates the property of fluorescence in the molecule. Unlike antibodies, which are more difficult to penetrate mammalian cells due to their size, CPPs are able to reach cells and deposit covalently attached payloads. The polycationic sequence allows the molecule to bind to any cell surrounding it. However, when injecting it into tissues, this property would cause the molecules to bind to every cell (Chelsey, 2012).

To ensure that this does not happen, activatable cell-penetrating peptides (ACPPs) were developed. These molecules are similar to cell-penetrating peptides but the polycationic sequences in these molecules are attached to a polyanionic sequence by a cleavable link. The polyanionic sequence neutralises the polycationic sequence, preventing it from binding to any cells surrounding it (Nguyen et al., 2010). The cleavable link is specifically designed so that it can only be severed by a matrix metalloproteinase (type of protease enzyme) that tumours secrete (National Cancer Institute, n.d.). Once the cleavable link is separated, the polyanionic segment dissociates from the rest of the molecule and the polycationic segment of the molecule is able to attach itself to the tumour cell. Due to the covalently bonded fluorophore, the cell can be seen when a surgeon shines a light on the area (Chelsey, 2012). Â As discussed in the introductory paragraph, this molecule can be injected into patients with tumours in order to fully identify the affected area. As shown in Figure 1, after a light is shone on the area, the cancerous cells will fluoresce, which allows the surgeon to easily identify the cancerous cells (Nguyen et al., 2010). In addition to the identification of tumours, this technique can be replicated and Figure 1 - Examples of tumors without the (A and D), with the fluorophore modified to identify nerves (TEDMED, 2011). fluorophore (B and E) and after the surgery (C and F) (Nguyen et al., 2010).

There are several advantages to this new method of viewing tumours and specific cells. Through this method, the number of follow up surgeries can be reduced in the future as this method is able to allow surgeons to see the tumour and cancerous cells. In turn, this can also reduce costs as follow up surgeries, chemotherapy and other treatments may not be required if the tumour if fully removed (Präger et al., 2018).

Currently, better methods are being investigated and discovered to further the development of colour coded surgery. Through the discovery of new potential fluorescent tracers and development in the biomarkers used, this will hopefully improve the detection and removal of tumours in the future.

Tricia Chua

Bibliography: 1. H., Chelsey (2012). Colour-Coded Surgery: Lighting the Way for Surgeons. [online] Available at: https://cr4.globalspec.com/blogentry/19320/ColorCoded-Surgery-Lighting-the-Way-for-Surgeons [Accessed 15th May 2019].

2. TEDMED (2011). Color-coded surgery. [online] [Accessed 12th May 2019].

Available at: https://www.ted.com/talks/quyen_nguyen_color_coded_surgery/transcript? language=en. [Accessed 11th May 2019].

3. Nguyen, Quyen T.; Olson, Emilia S.; Aguilera, Todd A.; Jiang, Tao; Scadeng, Miriam; Ellies, Lesley G.; Tsien, Roger Y. (2010) 'Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves cancer survival', Proc Natl Acad Sci USA, vol 107, no. 9, pg. 4317-4322.

4. Aroui, Sonia; Kenani, Abderraouf (2019). 'Cell-Penetrating Peptides: A Challenge for Drug Delivery', Cheminformatics and its Applications, InTechOpen, viewed 12th of May 2019, DOI: 10.5772/intechopen.91684.

5. Präger, Maximilian; Kiechle, Marion; Stollenwerk, Björn; Hinzen, Christoph; Glatz, Jürgen; Vogl, Matthias; Leidl, Reiner (2018). 'Costs and effects of intraoperative fluorescence molecular imaging – A model-based, early assessment', Plos One. 6. National Cancer Institute (n.d.). matrix metalloproteinase. [online]. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/matrixmetalloproteinase [Accessed 15th May 2019].

SHOULD CHILDREN BE ALLOWED TO CONSENT TO VACCINATIONS WITHOUT THEIR PARENTS' CONSENT? The anti-vaccination movement is led by the growing number of parents in western societies that are refusing to vaccinate their children due to issues they have concerning their perceived side effects, out of which, the most substantial one being the so-called link to the development of autism. This demonisation of vaccinations has caused outbreaks of diseases that were otherwise almost eradicated globally. In fact, more measles cases were reported in the first 5 months of 2019 than in any full year since 1992. Parents’ resistance to vaccination is leaving more children vulnerable to measles and various other preventable illnesses. Some of these children have begun to seek opportunities to revisit vaccine-refusal decisions made on their behalf by their parents and are now pursuing vaccination.

In March 2019, Ethan Lindenberger, a senior in high school in Ohio, shared his experiences on the battle he fought, trying to become vaccinated despite his mother being an anti-vaccine supporter . She did not vaccinate her child as she believed that vaccinations cause autism and brain damage, even though such opinions have been debunked numerous times by the scientific community.

His case, and those of numerous others has raised the question of whether adolescents should be allowed to seek and consent to receiving vaccinations without their parents’ permission. For this to be a reality, changes need to be made to the laws regarding medical consent in most countries and US states.

Currently, the law considers those under 18 as not autonomous, meaning their parents have a substantial role in making their medical decisions. This is due to a number of reasons, partly due to the fact that parents know their children best, and also to respect the wishes of the family and how they choose to raise their children. Despite this, out of respect for their developing autonomy, children are regularly made aware of treatment plans and procedures by their doctors, to broaden their understanding of health related issues. On top of this, their confidentiality interests are protected.

Aside from the ethical principles, the state law in the US also supports an adolescent’s autonomy in the circumstance that failure to provide it could foreseeably result in substantial risk to the minor or to public health. For instance, all states have laws permitting minors to make independent clinical decisions regarding certain health care services, such as those related to sexual health, reproduction, mental health, and substance use disorders. Yet, despite this, most states, however, don’t authorise adolescents to independently consent to vaccination.

Recently, however, bills have been proposed in at least two jurisdictions in 2019 to grant adolescents independent authority to consent to vaccination. New York’s bill would allow anyone 14 or older to consent to any vaccine required for school or daycare entry (measles, rubella, diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, varicella, and meningitis vaccines).

Granting minors the right to vaccinations without parental consent will allow them to catch up on any missed childhood vaccines. Although this is not a panacea for all vaccine uptake and access problems, such laws would improve rates of vaccination against highly infectious diseases, and hopefully lead to a complete eradication of these in the tangible future.

The next question that arises is, if minors are able to consent to vaccination, at what age should this be permissible?

On average, professionals responding to a recent survey reported that they were comfortable with patients at least 14 years of age consenting to vaccines recommended for adolescents, including vaccines against pertussis, meningitis, HPV, and influenza.

It is also important to note that parent involvement in vaccination decisions should continue to remain of utmost importance, and everyone’s first priority.

Many vaccine-hesitant parents ultimately agree to vaccination; they just need a few visits to the doctor to be completely convinced. It is only when doctors use their professional judgment to conclude that individuals are at harm due to parents having misinformation or disinformation, that adolescents should seek vaccinations without their consent. Ultimately, allowing children to give their own consent promotes the minor’s health, poses minimal personal risk, and offers substantial social benefits, including reinforcement of the norm of vaccination and enhancement of community protection against the spread of dangerous and costly, yet preventable diseases.

Zainab Kashif