The Role of Crystallins in Maintaining Lens Transparency

Crystallins are adapted not to crystallise; the eye lens needs to be a highly concentrated solution, but it needs to avoid small crystals or aggregates, since they would scatter light and make the lens opaque. Our lenses achieve this by mixing together several different crystallins, which together form a uniform, glassy solution. The protein molecules are arranged in a way which means that their refractive index is nearly the same as glass- which makes the lens transparent. This is due to the small size of the protein molecules, less than 10 nm in diameter, and their close packing at high concentration

The lens contains three major types of crystallins, making up about 90% of the protein. Alpha crystallins are the most common. They are composed of two similar types of protein chain, which associate to form large spherical complexes containing about 40 chains. These large spheres repel one another and distribute themselves throughout the lens cells. Beta crystallins, shown here from, also form oligomeric complexes (contains a limited number of monomers), typically formed of two or six copies of the chain. There are several similar beta crystallins, which can mix and match to form a bunch of different types of oligomers. Finally, gamma crystallins are monomeric, and serve as a weak glue to gently bind the alpha crystallins together.

Our crystallin proteins need to last our entire life, so the lens contains a powerful method to protect them. Alpha crystallin acts as chaperone, finding damaged proteins and binding to them before they can form translucent or opaque complexes. Unfortunately, in spite of this protection, the damage builds up as we age, as crystallins are broken or unfolded or oxidized. Slowly, the damage leads to progressive build-up of opaque aggregates, leading to cataracts. 

Forensic psychiatry

Psychiatry is defined as the study and treatment of mental illness, emotional disturbance, and abnormal behaviour. Psychiatry is a medical specialty, and so psychiatrists need to be medically trained to perform this type of medicine. This is the main difference between psychiatry and psychology; which can be defined as the study of behaviour and the mind, and can be thought of more as a social science. Forensic psychiatry is a specialised branch of psychiatry which deals with the assessment and treatment of mentally ill offenders in prisons, secure hospitals and the community. It is a particular aspect of psychiatry which I find interesting as it has extreme consequences in terms of the threat posed to society.

Forensic psychiatrists provide psychiatric treatment in a secure environment or where patients are subject to legal restrictions- meaning that the doctor needs an in-depth understanding of criminal, civil and case law as it relates to patient care in these settings. Treatment areas can vary from high security rural prisons to community centres. Referrals can range from those who have committed minor offences to serious and violent offenders, and for this reason the day of a forensic psychiatrist is never the monotonous. Forensic psychiatrists may also assess non-offenders displaying high-risk behaviour. Forensic psychiatrists also provide specialist advice to courts, probation services, and the prison service. They also prepare reports for mental health review tribunals, hospital managers’ hearings, other practitioners and criminal justice agencies.

Expert opinions given to court:

• ·         defendant’s fitness to plead and fitness to stand trial
• ·         capacity to form an intent
• ·         advice to the courts on the available psychiatric defences
• ·         appropriateness of a mental health disposal at the time of sentencing
• ·         nature of a particular mental disorder and link to future risks
• ·         prognosis and availability of “appropriate treatment”
• ·         level of security required to treat a patient and manage risk

Trichromatic vision in Humans

The human eye is the visual pathway to the world around us, and enables most of us to see thousands upon thousands of different colours. As shown in figure 1, the human eye is a very complex organ, with many different structures help us get the best vision in different situations- dim or bright etc. - and when all of these parts perform in harmony, we are able to see clearly.

In order to understand how we see different colours, it is first imperative to understand how the eye works as a unit: the starting point of vision is when light rays reflect off an object and enter the eyes through the cornea-the outermost, transparent layer of the eye. The rays are then refracted by the cornea and pass through the pupil- a whole created by the iris to control the amount of light passing through it. After that the rays pass through the lens- which can bulge or shrink to further refract the rays in order to focus them on the retina at the back of the eye.

The retina is an extremely thin layer of cells at the back of the eye which contains millions of light-sensitive cells called rods and cones- and are also known as photoreceptors. Cones are concentrated in the center of the retina (the macula) and in bright light conditions, they provide precise vision and detect colours. Rods however, are located outside the macula and extend all the way to the outer edge of the retina. They provide peripheral vision and allow the eyes to detect motion and help us see in dim light and at night. These photoreceptors then convert the light into electrical impulses which are sent to the brain via the optic nerve at the back of the eye, and create an image in our head.

As previously mentioned, we are able to see colours due to cone photoreceptors, of which there are 6-7 million of in the retina of each eye. Most of them are located in a 0.3mm spot on the retina called the fovea centralis, and over the last few centuries experiments have given evidence that amoung these cones there are three different types of colour reception: red (64%), blue (2%) and green (34%). This was proved by two different groups of scientists: Wald and Brown at Harvard, and Marks, Dobelle and MacNichol at Hopkins in 1959. However, the first original theory of there being three different light sensitive ‘particles’ was put forward by Thomas Young in 1802, 136 years after Sir Isaac Newton’s famous discovery that white light contained thousands of different colours (due to their different wavelengths on the electromagnetic spectrum), and so enabled us to understand where colour ‘comes from’.

"Colour is the visual effect that is caused by the spectral composition of the light emitted, transmitted, or reflected by objects” and when a light ray of a certain wavelength hits the fovea centralis, it activates the three different types of cone to varying degrees, and with an infinite amount of varying combinations, we are able to see thousands of different colours. This is shown in a simplified diagram in figure 3, but in reality this diagram would be a lot more complex because of the ranging number of shades which belong to each colour. To prove that any colour visible to humans can be created from this trichromatic system, we can use the example of TV sets; if you look at a normal television up close when it is switched on, the tiny pixels contain just 3 colours: red, blue and green (as shown in figure 4).

The human eye can perceive many more variations in warmer colours than cooler ones due to the fact that almost 2/3 of the cones process longer light wavelengths and so we are able to see more yellows, oranges and reds. Additionally, the reason we can’t see colours in the dark is because the rods ‘take over’ to control the amount of light that we see, and so the cones aren’t in control anymore. Furthermore, about 8% of men and 1% of women have some type of colour impairment; the most common of which is red and green dichromatism, which causes the colours red and green to appear indistinguishable.

In conclusion the reason why humans can see thousands upon thousands of different colours is that, despite only having 3 types of cone photoreceptor, the cones send-off varying amounts of blue, red and green to the optic nerve to be carried to the brain, and by changing these amounts of light, all of the colours in the visible spectrum can be produced.

Analgesics and Anaesthetics

An analgesic is a drug acting to relieve pain, and this group of drugs include aspirin, paracetamol and ibuprofen[1]. These three drugs all fall under the most common type of analgesic- non-opioid analgesics. This group of simple painkillers work by blocking the COX-2 enzyme which is responsible for pain and inflammation[2]. The stronger groups of painkillers are compound and opioid analgesics, and these are widely used in hospitals for severe pain.

Aspirin is one of the most common analgesics used today[3]- the very first use of this drug dates back to ancient Asian records 2400 years ago, as a related compound from willow bark had been used to relieve pain and treat fevers[4]. The use of this compound then grew in the 18^th Century, with Edward Stone reading a paper to the Royal Society of London on the effect of willow bark on Malaria. In the 1840s, nearly 100 years later, organic chemists identified this active ingredient as salicin- which was found to be converted into salicylic acid in the body by Pr. Von Nencki in 1870. This was then given to patients to help with fevers, however a common and unpleasant side effect was soon discovered; severe irritation of the lining of the mouth, gullet and stomach.

To combat this chemists made sodium salicylate to cause less painful side effects, but it tasted awful and so patients were not keen on taking it. This also caused patients to vomit and so was not an ideal painkiller. In the 1890s Felix Hofmann of the Bayer (a German pharmaceutical company) synthesized a similar drug which was found to have good medicinal properties and be less irritable towards membranes in the body; aspirin had now been made.

Aspirin, or 2-Ethanoyloxybenenecarboxylic acid, was sent off for clinical trials and was finally patented by Bayer in 1898[5]. John Vare won the Nobel Prize for medicine in 1982 for discovering that aspirin inhibits the COX-2 enzyme in the prostaglandin pathway, and this drug is now one of the most manufactured in the world, with 10 million kilograms being made in the US each year.

An anaesthetic is a drug that causes anaesthesia, which is a reversible loss of sensation[6]. These contrast with analgesics, which relieve pain without eliminating sensation. These drugs are generally given to perform surgery or an invasive surgery, which would be very painful if the area could be felt by the patient. The main two types of anaesthetic are local and general anaesthetics.

Local anaesthetic is a form of medication that causes reversible absence of pain sensation in a localised area, although other senses can also be affected. Paralysis can also be achieved by this type of anaesthetic when used on specific nervous pathways[7] (this is known as an epidural, and is commonly used during a caesarean section during childbirth). The other two main types of local anaesthetic are topical and subcutaneous anaesthesia. Topical anesthesia is a local anesthetic which is applied directly to the skin- mostly in the form of a gel or a cream. Subcutaneous anesthesia as local anesthetic applied directly under the skin, mostly in the form of an injection, targeted at the nerves which stimulate pain in that specific area.

A common local anaesthetic is lidocaine[8], and we can use this example to see how many other local anaesthetics work. The main action of this drug is to inhibit the movement of sodium into nerve cells, but why does this effectively stop the feeling of pain? Figure 5 shows a representation of an electrical signal inside a nerve cell (axon), and how sodium ions move through sodium channels to stimulate the feeling of pain[9]. It then shows how lidocaine- represented as a red circle- blocks these channels and so does not allow the sodium to pass through the channel, and does not allow the electrical signal travel to the brain.

Figure 6 is a magnified version of figure 5 and shows the cellular membrane interactions with the lidocaine molecules. The 'sodium channel' spans the phospholipid bilayer on the membrane of the cell and is extremely narrow.  The anaesthetic binds much more tightly to the channel when charged due to electrostatic interactions, and so helps block the sodium channels and make the area temporarily numb[10].

For more serious circumstances, when a patient has to be completely unaware, doctors use general anaesthesia. This renders patients unconscious with no perception or memory of the surgery while it is happening. It also limits the physiological responses to invasive procedures and surgical cuts, keeping blood pressure, stress hormone release and heart rate constant during the operation.

General anaesthesia is still quite a mystery to the scientific world[11], as the biochemical mechanism which controls it is still speculated about. To induce unconsciousness, anaesthetics have different sites of action and affect the central nervous system at varying levels of severity. Common areas of the CNS whose functions are often interrupted or changed during general anaesthesia include the cerebral cortex, thalamus, and spinal cord.

Paul Ehrlich stated that drugs act only when they are bound to their receptors; however, this concept does not seem to apply in the case of general anaesthetics. There are two main reasons to support this concept:

·      

            The molecular structures of these anaesthetics are very simple and different to one another

, and so there is no obvious structure-activity relationship

      Most general anaesthetics have very weak affinities for their targets acting at much higher concentrations than most other drugs

In 2015, roughly 15 million operations and minor procedures were carried out in the UK alone, and this would never have been able to happen without anaesthetics.

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[1] http://www.nhs.uk/ipgmedia/national/Arthritis%20Research%20UK/Assets/Painkillers-analgesics.pdf

[2] http://www.arthritisresearchuk.org/arthritis-information/drugs/painkillers.aspx

[3] http://www.drugs.com/aspirin.html

[4] https://en.wikipedia.org/wiki/Aspirin

[5] https://en.wikipedia.org/wiki/History_of_aspirin#World_War_I_and_Bayer

[6] http://www.nhs.uk/Conditions/Anaesthesia/Pages/Introduction.aspx

[7] http://patient.info/doctor/practical-local-anaesthesia

[8] http://www.drugs.com/pro/lidocaine.html

[9] https://www.evidence.nhs.uk/formulary/bnf/current/15-anaesthesia/152-local-anaesthesia

[10] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2075196/

[11] https://www.newscientist.com/article/mg21228402-300-banishing-consciousness-the-mystery-of-anaesthesia/

The Use of Maths in Medicine

Maths is used every day in hospitals, surgeries and many more healthcare facilities around the world. As a prospective medical student, I wanted to know more about the huge role that this discipline plays in the world of medicine, and so I did some research and came up with the following conclusions.

One of the most basic and common use of maths in medicine is prescriptions and drug dosing. Most medications have guidelines for dosage amounts in mg/kg, and so doctors need to figure out how many milligrams of medication each patient will need, depending on their weight. There is a big role here for conversions, as sometimes patients will only know their weight in pounds or stone, and so this will have to be changed quickly by the doctor or nurse to the right units. This is extremely important as a wrong drug dosage could mean a life or death decision, especially if the drug being administered to the patient is especially potent and so could be toxic if given in high amounts, or if a patient is desperately in need of a drug, and not enough is given to that patient. Doctors must also determine how long a prescription will last, as this figure can be in days, weeks or months, and so healthcare professionals must be able to give the right amount of drug to a patient over a specific period of time, without the patient needing to come back as they don’t have enough of their medication.

Another important factor to consider is how long the medication needs to stay inside the patient.  This will determine how often the patient needs to take their medication in order to keep a sufficient amount of the medicine in the body. The amount of medicine in the body decreases by a certain amount in a specific time (e.g. 10%hour^-1), and this can be expressed as a rational number- 1/10. This rational constant creates a geometric sequence, as the amount decreases by a fixed ratio each time unit, and so doctors can use this concept to decide how often a patient needs to take their prescribed medication.

Another common use of maths in the medical field is for the calculation of one’s BMI, which is a number derived from an adults weight and height to judge whether they are of a healthy weight. This is a very common equation, used to test people’s weight all around the world, and shows that healthcare professionals have to be able to use equations with the right units; however, one’s BMI is not a very good indicator of healthy weight. I say this as, when you ‘plug’ weight into the equation to calculate a patient’s BMI, it doesn’t consider whether the weight is muscle or fat, and so a bodybuilder could be classified as ‘obese’ on the BMI scale even though they are healthy.

One of the more less-commonly known uses of maths in this field is through Extracorporeal Shockwave Lithotripsy, which is used to treat kidney and gallstones non-invasively. This technique is all thanks to the reflective properties of an ellipse, which can be seen in the diagram to the left. Shockwaves are generated at one focus and will reflect off the ellipse and pass through the second focus- creating a unique property which allows ESWL to take place. In order for the lithotripter to work, the patient’s stone must be at one focus point of the ellipsoid and the shockwave generator at the other focus.  The patient is then laid on the table and moved into position next to the lithotripter. Doctors then use a fluoroscopic x-ray machine to get a visual on the stone, allowing the focus to be at the precise location of the stone.  A water-filled cushion is then wrapped around the machine and rests on the patient’s side; this acts as a sort of buffer for the machine, as the water allows the shockwaves to travel through the body’s tissues safely because water and the soft tissue have the same density. The stone has a larger density and so is then shattered by the shockwaves. This is a popular choice for patients as it is quick, relatively safe and non-invasive, and so is available on the NHS.

In conclusion, mathematics plays a crucial role in medicine as it directly impacts people’s lives, and so it is very important for healthcare professionals to be very accurate in their mathematical calculations.

The Junior Doctor Strike: What You Need To Know

In the last few months junior doctors all over the UK have been heavily objecting the proposed changes to the junior doctor contract proposed by the government, which has led to a 24-hour strike of over 90% of the UK's junior doctors, leaving the NHS in a state of distress.

This opposition has arisen as the government has decided that the current contracts are ‘unfair’ and too old-fashioned, and even though the initial plans for a new contract were first drawn up in 2012, talks only started breaking down in 2014. The government has indicated it will impose the new contract in England and the British Medical Association (BMA) has responded by initiating the industrial action process.

So, what exactly is a ‘junior doctor’? The term ‘junior doctor’ refers to doctors which have just graduated from medical school up to doctors which have had up to 10 years’ worth of experience being a fully qualified doctor- to most people a 32-year old hospital specialist would seem to be a ‘senior’ and well-qualified doctor. The starting salary for a junior doctor is currently just under £23,000 a year, but with additional payments for extra services such as unsociable hours, this can quite easily top £30,000.

Junior doctors at the top end of the spectrum can earn just over £70,000 per year. However, it's important to remember these doctors often make life-and-death decisions and carry out surgery, in addition to having over 10 years’ worth of professional experience as a qualified doctor.

Given that 1/3 of all doctors in England are junior doctors, this contract change will directly affect around 55,000 doctors, making it a lot harder so earn more money and work healthy hours.

The proposed changes to the contract will change the standard working hours for junior doctors in England, which are currently set at 0700-1900 Monday-Friday, which is already quite long and is certainly a strain on the NHS. What the new contract proposes is that these standard hours would change to 0700-2200 Monday-Friday in addition to 0700-1900 on a Saturday- which is, in my opinion, quite ridiculous as this implies that working on 0800 on a Monday morning is the same as working on a 1900 on a Saturday evening.  As the standard number of hours has increased, it means that junior doctors will have to work practically all week to earn a decent pay for the first few years or their careers.

Another problem which will almost certainly arise is extreme tiredness and fatigue, which is already a problem within much of the NHS and will be made even more common with these new changes. With this proposed change, therefore, comes the question of patient safety, as it has been proven that doctors make more mistakes practicing medicine whilst being tired than drunk, which ultimately poses the question: to what extent would you be comfortable with an exhausted surgeon operating you who is more likely to make a mistake than a surgeon under the influence of alcohol?

The main problem the government is trying to solve here is timings: in an ideal world, they would like to see a 24/7 NHS which everyone has complete access to; however, they are trying to do this without spending huge amounts of money by employing more doctors, and so, there is only one foreseeable solution without spending huge amounts of money- to stretch the capacity of NHS doctors.

Personally, as a prospective medical student I think that this change in contract has very few proper advantages, as, even if we have a fully running 24/7 NHS, what is the point if barely any of the doctors are working to their full potential and putting the lives of thousands of patients at risk every day?

Should we ban smoking?

Smoking tobacco is the most expensive social burden in the UK, costing the government roughly £65 billion per year. It also indirectly accounts for up to 20% of deaths in the UK, as it is the main causing factor of lung cancer and smoker's illnesses, such as chronic bronchitis and emphysema. Despite 65% of regular smokers dying from some form of respiratory disease, 20% of the English adult population still smoke; causing huge strains on both a personal and national scale, which raises the question: should we ban smoking?

The reasons for the ban of smoking are pretty simple if you think about it: increased life expectancy, quality of life and a less-stressed NHS. On average, the life expectancy of a smoker is roughly 5-10 years lower than a non-smoker, and in addition to this the DALYs (disability-adjusted life years) of smokers can add up to around 15 years- about 1/5 the average life. Furthermore, 1/3 of cigarettes in Britain are smoked by people with mental illnesses, seriously worsening their physical health, in addition to their mental issues. 

COPDs (Chronic obstructive pulmonary diseases) are found in around 58% of smokers, and this includes diseases such as chronic bronchitis, emphysema and lung cancer; the former two of which cause permanent and irreversible lung damage. Emphysema is a condition in which the phagocytes in the blood move to the inflamed lung tissue when smoking and release the enzyme elastase (in order to reduce swelling), which then digests the walls of alveoli- therefore reducing their surface area, meaning that gas exchange happens less efficiently and so people who have this often have to have a constant flow of oxygen going into their blood stream (often an oxygen tube) so that their body has enough oxygen to function. 

In addition to this, countries where tobacco is farmed are extremely poor, and often the average worker on tobacco farms is a child. This is the case in Malawi, where almost all of the workers have gained a nicotine addiction from handling the tobacco leaves every day, but they are often forced to carry on as, for many, this is their only source of income (this often results in nicotine poisoning). Furthermore, there are also many environmental impacts which tobacco farming has, including deforestation, of which 26% is due to tobacco farming in Malawi. 

In conclusion, there are simply no advantages of smoking tobacco - apart from the social factor of thinking its 'cool'-, so why not just ban it? Well, its not as simple as that.

Many people argue that every human being has the right to do what they want with their own body- which I partially agree with, as I think that one's body is truly one's own; however, I think that if one is harming themselves or the people around them this belief is partially compromised. This belief is applicable to not only smoking but a huge range of other medical issues and diseases, such as obesity, substance abuse and alcoholism, and, such as with many other ethical issues surrounding medicine, there is no prefect solution to this problem.

As with any other damaging burden, the government and the NHS are trying to persuade people to stop and try to live a healthy lifestyle, however I don't think that there will ever be a complete ban on smoking due to the belief that everyone can do what they want with their body; but, I do think that this raises questions such as: why is prostitution illegal if everyone can do what they want with their own body?

In a nutshell, theoretically a ban on smoking would do more good than bad, as it would improve millions of lives across the UK, but due to ethical issues it is simply not feasible in the real world that we live in.