It is our privilege as the new editorial team to present the final edition of the B-word journal for this academic year This Summer edition, we have had numerous varied articles covering an interview with Kit Yates, evolution, poisons, and much more! We would like to thank the writers for all their hard work and contributions- we know this has been a very busy year!
Enjoy your summer and enjoy reading!
The B-Word Editorial Team
Avnika, Elizabeth, and Lucia
An Interview with Kit Yates
By Willow Craig and Niamh Trigwell
Who is Kit Yates?
Kit Yates is co-director of the Centre for Mathematical Biology at the University of Bath and a senior lecturer in the Department of Mathematical Sciences. Having completed his PhD in mathematics at the University of Oxford (2011), Yates went on to research the application of maths and statistics in everyday life
During the Covid-19 pandemic, he was a member of the independent SAGE group who voluntarily advise the government and general public on how to minimise Deaths and help Britain's recovery by using their individual scientific thinking and knowledge to provide transparency. SAGE aims to provide the public with the relevant facts and untainted data allowing them to make their own conclusions in the hope of leading to more discussion and better outcomes for the country.
When we spoke to Yates, he emphasised the importance of using Mathematical modelling to form predictions while also recognising that they are bound to real-world limitations. The danger of focusing solely on a model is that a model can lead to misinformation Yates stated it was important to remember that models are simplifications which hopefully capture the fundamentals of a situation, Demonstrating the necessity for open conversation.
The Maths of Life and Death
Kit Yates released his first book ‘The Maths Of Life and Death’ in 2019 and it was named by The Sunday Times as one of the Best Science Books the same year
We would like to thank Kit Yates for giving his time so willingly to allow us to conduct this interview.
The Interview
What A-levels did you take and did you always like the subjects you chose?
I did the pretty classic combination of maths, further maths, physics and chemistry. A lot of people, I found, when I got to University did something pretty similar I was really disappointed that I couldn’t do biology. I really liked it at GCSE level but I also wasn’t very good at the cutting up stu I fainted after we had to dissect an eyeball or a fish head or something I’m quite squeamish So, when I had to make that choice about what sciences to do, I steered away from biology not because I didn’t like it and actually I was a bit gutted because I actually think understanding biology gives you the secrets to understanding life which is really important ultimately. So, I was disappointed about that, but I did enjoy my other ones Chemistry I found hard, big step up from GCSE Everything they tell you at GCSE is a lie and probably everything they tell you at A-level is a lie, so you have to relearn it I enjoyed maths and further maths. I never planned to be a mathematician earlier on but because I had done those two subjects it led me down that path.
What made you decide to go into Mathematical biology instead of just maths?
After my A-levels in maths and further maths, I thought that it would be a bit of a waste not to go on and do that at uni. But I was sad because I thought I had said goodbye to biology forever But then I got to university and I found out that maths, especially applied maths, is this amazing tool that you can use to understand physics and chemistry and surprisingly for me, biology So, I did a really great course that a professor called Philip Maini in Oxford called mathematical ecology in biology, and I was hooked from there Again, I never had this plan to go on and do a masters or PhD or to become an academic, but each step along the way I suppose I got
more and more interested and specialised, it was the natural thing to sort of go on and keep doing
From reading your book it is clear you have a lot of interest and knowledge of all sciences, has this helped you in your chosen field?
Yes it has, firstly in terms of popular science writing, it's good to be super broad because actually no science exists on its own, they’re all interlinked You might have heard the famous saying ‘all biology is chemistry, and all chemistry is physics, and all physics is maths, and maths is the language of science.’ They’re not unrelated to each other and if we’re talking applications of mathematics you have to understand the other sciences particularly maths and physics are really strongly linked
That said, in terms of my research it was important to understand biology, but it wasn’t like I came into it understanding the biological areas that I work on I had to work after I got my maths degree, whenever I started a new project with a new collaborator, I have to talk with them and understand at least enough biology that I could extract the most important parts of it so I could model it So I don’t need to have a degree in biology but I do need to have an interest and ask the right questions and, to some degree, be able to speak the language the biologist speaks.
In maths we have lots of technical words and phrases, they have the same in biology, so it’s important to learn some of those On the flip side, because you have to be inter disciplinary to be a mathematical biologist you maybe don’t go as deep into your research area as other scientists do, so in some senses that holds you back. For example, I’m never going to win a Fields medal, I’m never going to do that sort of deep level thing, I just concentrate on one thing for years and years, I’m not Andrew Wilds I’m not going to solve Fermat's last theorem I’m more widely spread but less deep so in a sense that’s a disadvantage, but for me that’s what I enjoy doing
Do you feel using maths in your daily life has benefited you significantly or given you an advantage over others?
Yes! I think being quantitative and numerate helps in a variety of areas. It’s not like I go about doing maths all the time, it’s about maybe having the confidence to question the numbers that I see in the media headlines, all the numbers coming out of the mouths of politicians not just taking them at face value, but find the data they’re talking about to dig into it and to check
It’s partly a matter of confidence, I think there’s this illusion with numbers that people think the numbers are truths that can’t be questioned but actually that’s not really the case. People who are giving the numbers to the politicians, sometimes even the doctors who are giving the details on the risks on particular diseases or outcomes, maybe they don’t have the strongest grasp of maths, and part of what I try to do in my books is to empower people to question numbers that are being thrown at them
What’s your favourite area of crossover between maths and biology?
Anywhere really, I suppose particularly the areas I work on I work in developmental biology which is understanding the way embryos form where the cells migrate in an embryo, pattern formation, how mammals get their patterns, specifically humans, and other animals which have clearer patterns We just got a grant to work on the spots on Dalmatian dogs, understanding how cows' patterns work, patterns in mice and more broadly mammalian patterns but also zebrafish we have a big project on their stripes.
I like all of those that I work on and to some degree the good thing about being in research is that you get to choose what you work on so I have chosen those areas because they’re the things I was most interested in but there are lots of other areas that people work in
Is there any niche or not Largely known areas where maths and biology crossover?
I don’t have a good perspective on what people do and don’t know about mathematical biology I suspect not much is really known, like maths biology is used anywhere you have a biological system you can try and describe it mathematically, so we use it to understand cancer, heart disease, drug discovery and the things already mentioned like biology pattern formation.
I have also done projects understanding locus migration. of course probably the area people will know most is disease spread, epidemiology, because of the pandemic you know all of the models we used to try and predict what was going to happen in the future, it’s another area I work on a little bit I don’t know who knows what but certainly there are some areas where maths is being used really frequently to change the world.
When there were all the statistics about coronavirus what did you think when you were sitting at home watching the TV?
What I would try to do during the pandemic was to get out there and to actually communicate the ideas because I figured that a lot of people wouldn’t understand what was going on so because I’m a mathematical biologist, I teach mathematically epidemiology to my undergraduate students, I’m familiar with the basic principles so tried to get out there onto the news and the radio and be the person who was explaining those sorts of thing to people so that everyone could get an understanding of the models that were being used to suggest what was going to happen in the future and were being used by politicians to justify why they were having to put restrictions in place
Getting people to understand the models and question them. The best way to predict the future, don’t let anyone tell you otherwise, is using mathematics. You form a model and then you run it forward and your model hopefully captures the important dynamics of the system but people don’t like that sometimes models go wrong depending on
the assumptions you put into them, so you can feel free to disagree with a model, that’s not a problem, but you can’t just say I don’t believe it because it’s not the real world because if you built a model that was as complicated as the real world you could never interrogate that model, you might as well just watch what happens in real time
The point of models is they are simplifications so consequently, they are to some degree falsifications
The point is that you hope you’re capturing everything that’s important So, it's fine to say I disagree with the results of this model because I disagree with this one event because of the assumptions that go into this model, but it’s not fine to say it’s a model so it’s not real so I disagree with it.
So the message I have been trying to get across to people is that it’s fine to disagree with the model, but you have to have a reason beyond it just being a model because actually anytime you look at data you’re using a model whether you realise it or not and the job of mathematical modellers is to write down the assumption clearly and to show how the predictions of the models follow from those assumptions so you can go back and question the assumptions So that’s the sort of message I was trying to put across during the pandemic.
In your book you explained about the limitations of believing statistics and obviously you’re very interested in not believing everything the media shows us, do you think there is any way to overcome those limitations or do you think we will always just have to trust those people or research it ourselves?
To some extent it will always be there and I worry that it may be getting worse with the rise of misinformation on social media but one way to combat it, is to produce a more numerate society so that’s to encourage people to do maths and to encourage them that maths is fun and useful and relevant
You know the prime minister has put forward a proposal to make everyone do maths until the age of eighteen. I personally don’t think that is necessarily the right way to do it Firstly, we don’t have the
number of teachers needed to teach it and secondly, we need to look at what we’re currently providing and ask whether that’s the appropriate thing that we want to be teaching kids Whether we’re inspiring people in the right way to realise that maths is important and that it's going to make a di erence and that being numerate means that you can question the stats and the figures that are put in front of you So, I think it’s a problem that will inherently be there but there are ways to mitigate it.
If evolution always finds the most e cient route, do you think we could use maths to predict the future of evolution?
Yes, so there are evolutionary mathematicians. I have former students who work in mathematical evolution so there are absolutely ways of doing that They are often looking at pathogens and how they evolve, particularly because they evolve on a much faster time scale. you can do experiments, at most they tend to look at flies, it would be unethical to do experiments like that with humans of course.
The other thing I would say about that is that evolution doesn’t always find the best solution, It finds a solution that works. it finds a solution that’s better than all the other solutions that are out there, but it doesn’t have to be the best, it just has to be fractionally better than the previous solutions for it to spread throughout the population and to take over. So, I think it's a really interesting question In fact, there are plenty of places where animals have come to a dead end because either their environment has changed, or something's happened and the traits that they have evolved become less useful. Sometimes it doesn't even solve the problems that are out there but often it manages to find a solution, it’s just not always the best one. So yes, absolutely mathematicians are really interested in evolutionary biology for sure.
What challenges will your field face in the near future?
Mathematical biology is actually a big growth area There are lots of people who are coming through maths degrees who want to be applied
mathematicians and mathematical biology is a great place to do that you can get funding from all sorts of research councils and so, I think mathematical biology at least in the short term is going to go from strength to strength, I hope. We face the same challenges that all scientific fields face I suppose, which is we're always fighting for funding to make sure we’re properly funded to make sure we've got the money to take the people who are interested in the field and to get them into the field. These are the same problems as any scientific field faces, which is coming up against the reality of the real world and the money that has to be there to support people in our field
Do you believe we live in a binary world currently?
I mean that’s quite an open question I think we live in an increasingly polarised world. Yes, I think social media in particular has damaged the discourse and it's allowed tribalization, it's allowed people to just hear opinions that they want to hear and have their opinions reinforced and reinforced to the point of certainty. I think we also have a number of populist leaders like Boris Johnson, Donald Trump, like Bolsonaro (Brazil), who tell people the things that they think they want to hear and are, perhaps, afraid of making di cult decisions. Then the reverse side of that is that there are reactions against that which push people in the other direction, so I think there is a lot of polarisation. I don't know about complete binarization, but certainly I can see there is more and more polarisation in the world.
Obviously in maths there are lots of questions we don't necessarily have answers to, and problems that we don’t understand. Do you think there will be a point where we can know the answers to all these questions?
So, there are a lot of theorems and conjectures, I should say, in maths that we don't know whether are true or false So, a theorem is a conjecture which we know to be true, and so we should call them conjectures to be careful There are some questions in maths which are called undecidable, so there genuinely will never be a solution to those problems There’s a really interesting book by Marcus du Sautoy
who is a maths populariser. I don’t know if you’ve come across him, it's called ‘What we Cannot Know’ and deals with exactly this topic from a maths perspective, but also from a number of di erent scientific perspectives.
‘Are there questions we just can't answer?’ There is this way of thinking about it: there are things that we know, there are things that we know that we know, there are things that we don't know, and other things that we don't know that we don't know. These ‘unknown unknowns’, are things we don't even know that we need to know, so it’s probably quite a deep philosophical question, but I think there are certainly questions that we will never be able to answer both in science and in maths.
I know you studied later at Oxford University, but is that where you went initially?
Yes I did, I did my undergraduate and my masters and my PhD all in Oxford. My first job was there as well, then I got a job here almost ten years ago which is a bit alarming for me. I actually used to live in Oxford because my wife is more important than me
and she has a job there, so we don’t live in Bath, we live in Oxford
Finally, do you have a favourite maths trick or joke?
I do, and I wrote it down a few years ago for a di erent interview that I did as well. I don't know, it might not be received particularly well, I don’t know
‘So, there are infinitely many mathematicians and they walk into a bar and the first says i’ll have a pint, the second says i'll have half a pint, the third says i'll have a quarter of a pint, but before the fourth one can ask for their eighth of a pint, the bar man stops him or her and pours out two pints. The mathematicians complain ‘is that all you're going to give us? How drunk do you expect us to get on that?’ and the bartender says ‘come on guys, know your limits’
Geometric series, adds up to two, there you go. It’s not a great one but it probably works better written down than it does said out loud.
Causes of the “Globesity” Crisis
By Avnika Mittal
“Globesity” and its Consequences
In 2001, the WHO coined the term “globesity1” to refer to the global obesity epidemic - one of the most visible, yet most neglected, public health concerns in modern society Obesity is the second-most prevalent cause of preventable illness across the globe today, closely following smoking2 . As of 2023, 25% of all adults in the UK live with obesity whilst, alarmingly, over 20% of children under the age of 11 are overweight or live with obesity For a time, the highest rates of obesity were limited to countries with higher standards of living, as you might expect with obesity typically considered a condition of plenty, however rates of obesity in central Africa have increased by almost 25% in children under 5 from 2000 to 20213 . Globally, obesity has been found to disproportionately a ect the most disadvantaged of society4.Type II Diabetes, a range of cardiovascular diseases and cancers5 as well as multiple mental
health disorders, can all be linked to obesity6 . Additionally, treatment of this vast array of ailments is time-consuming and expensive to healthcare providers and governments; as of 2021, the estimated annual costs of obesity to the NHS was £19bil , with a further £16bil. to wider society as a result of lower productivity7 However, since the worst consequences of many of these diseases are often not pronounced in earlier stages, the focus has typically been on treatment or management of symptoms and later e ects rather than addressing their root causes. In this article I will explore the significance of three risk factors for developing obesity as the potential, primary causes of the globally rising obesity rates
Sedentary Lifestyles
1Aetna International, ‘ The rise of globesity: a short introduction to a big problem,’ Aetna International [website], 2024, available at: https://www aetnainternational com/en/about-us/explore/h ealth-care/prevent-manage-conditions/the-rise-of-globesi ty html#:~:text=Tackling%20the%20problem,term%20“glob esity”%20in%202001 (accessed 09 June 2024)
2Health Matters: Obesity and the Food Environment, GOV.UK [website] , 2024, available at: https://www gov uk/government/publications/health-matter s-obesity-and-the-food-environment/health-matters-obesi ty-and-the-food-environment--2 (accessed 26 February 2024)
3 J Zheng, ‘The Obesity Crisis #1: How Did We Get Here?’, at Medic Network - Medium, 05 April 2021, [website], https://medium com/that-medic-network/the-obesity-crisi s-1-how-did-we-get-here-12146f5144cd, (accessed 06 March 2024)
4 V Raleigh, ‘Why Do Health Outcomes in the UK Compare Poorly with Peers?’, King’s Fund [website], 08 November 2023, available at: https://www.kingsfund.org.uk/insight-and-analysis/blogs/u npacking-health-outcomes-uk-with-peersn (accessed 06 March 2024)
5 Controlling the global obesity epidemic (who int)
Increasingly fewer people regularly engage in rigorous physical activity8 yet now more than ever we have access to plenty of energy-dense food9 Obesity is the result of a higher caloric intake than expenditure - if we consume more than is burnt, we will gain weight - and it has been suggested that, rather than access to excess being to blame for rising obesity rates, it is our sedentary lifestyles which are the culprits. Rigorous, physical activity requires a
6 Obesity, NHS [website], available at: https://www nhs uk/conditions/obesity/ (accessed 26 February 2024)
7 M Bell, et al , ‘The rising cost of Obesity in the UK,’ Frontier Economics [website], 21 November 2023, available at: https://www frontier-economics com/uk/en/news-and-insi ghts/news/news-article-i20358-the-rising-cost-of-obesityin-the-uk/#:~:text=We%20estimated%20the%20total%20an nual,billion%20(see%20Figure%201) (accessed 09 June 2024)
8 P T Katzmarzyk, et al , ‘Relationship between lifestyle behaviours and obesity in children ages 9-11: results from a 12-country study,’ Obesity, 2015;23:1696-702
9 J Zheng, ‘The Obesity Crisis #1: How Did We Get Here?’, at Medic Network - Medium, 05 April 2021, [website], https://medium com/that-medic-network/the-obesity-crisi s-1-how-did-we-get-here-12146f5144cd, (accessed 06 March 2024)
greater energy input thus more calories are burnt10 , and the excess we consume would surely be removed. In the absence of the hunt as civilisations have progressed, we must therefore exercise regularly to maintain a healthy physique. Athletes have higher basal metabolic rates, do they not?
“Exercise is medicine,” the famous proverb goes, but if indeed this is true, increasing one’s level of physical activity ought to reverse overweight which various studies have concluded is not the case; whilst exercise is useful to maintain healthy weight, it is incredibly di cult to lose weight through exercise alone. In fact that phrase is trademarked by Coca-Cola11 , likely the last organisation any of us would associate with sparkling health12 .
Additionally, a study conducted by Herman Pontzer in Tanzania13 (with similar studies concluding the same since) comparing caloric expenditure of Hadza hunter-gatherers, with obesity prevalence under 5%14 , to that of the average Western adult, found increased physical activity makes little di erence to caloric expenditure15 in the long-term At the time, those involved in the investigation were quite as ba ed as I believe you must be now, however this is evolutionary sensible: in times of scarcity, one does not want to waste energy during periods of intense
physical activity inevitably required of the search for food16
Similarly, obesity is not observed in wild animals, even those in environments of plenty because, just as we regulate pH and water levels and temperature and all other aspects of our internal physiology, so too do we regulate caloric intake and expenditure17 . Our bodies must expend a set value of calories no matter what; if not through physical activity, then by potentially toxic increases in hormonal activity that could be to blame for stress and inflammation18
Indeed, it is possible to temporarily increase one’s caloric expenditure, as you may observe in any athlete who has undergone rigorous training19 , however this is rarely sustainable. Exercise is beneficial then, not because it increases calorie expenditure but because it prevents calories fuelling anxiety or inflammation, perhaps part of the reason that regular physical activity has often been found to improve overall mental well-being20 21 .
Dietary Fats, High-Sugar Diets and Nutritionism
The idea that sources of dietary fats22 - particularly saturated fats - were to blame for ostensibly uncontrollably rising obesity rates was popularised in the 1980s23 Fat contains more calories per gram
10 G A Hand, S N Blair, ‘Energy flux and its role in obesity and metabolic disease,’ European Journal of Endocrinology, 2014;10:131-35
11Coca-cola, ‘Exercise is the best medicine,’ Coca-cola, 2009, available at: https://investors.coca-colacompany.com/news-events/press -releases/detail/392/exercise-is-the-best-medicine, (accessed 09 June 2024)
12A O’connor, ‘Coca-cola funds scientists who shift blame for obesity away from bad diets,’ New York Times, 09 August 2015
13H. Pontzer, et al., “Energy expenditure and activity among Hadza hunter-gatherers ” American journal of human biology : the o cial journal of the Human Biology Council vol 27,5 (2015): 628-37 doi:10 1002/ajhb 22711
14 H Pontzer, et al , ‘Hunter-gatherers as models in public health,’ Obesity reviews : an o cial journal of the International Association for the Study of Obesity vol 19 Suppl 1 (2018): 24-35. doi:10.1111/obr.12785
15 H Pontzer, et al , ‘Hunter-gatherer energetics and human obesity.’ PloS one vol. 7,7 (2012): e40503. doi:10 1371/journal pone 0040503
16H Pontzer, ‘The crown joules: energetics, ecology and evolution in humans and other primates,’ Evolutionary Anthropology, 2017;26:410-17
17 H Pontzer, ‘The Exercise Paradox,’ Scientific American, 01 February 2017
18 C. V. Tulleken, Ultra Processed People (Penguin 2023)
19‘The Harsh Reality of Ultra Processed Food,’ e Royal Institution [podcast], presentation by Chris Van Tulleken, December 2023, https://www youtube com/watch?v=5QOTBreQaIk (accessed 26 February 2024)
20 A. Sharma, V. Madaan & F. D. Petty. ‘Exercise for mental health,’ Primary care companion to the Journal of clinical psychiatry, (2006), 8(2), 106.
21K Mikkelsen, et al , ‘Exercise and mental health ’ Maturitas, 01 December 2017;106: 48-56.
22N G Forouhi et al , ‘Dietary fat and cardiometabolic health: evidence, controversies, and consensus for guidance’ BMJ 2018;361:k2139
23 C V Tulleken, Ultra Processed People (Penguin 2023)
than either carbohydrate or protein24 , and often we find the diets of those with overweight or obesity to consume great quantities of high-fat foods. Yet obesity was not slowed25
Towards the late ‘90s, Gary Taubes widely publicised the idea that sugar, not fats, ought to take most of the blame for increasing obesity. The science seemed sound: consumption of carbohydrates causes a spike in insulin levels. This promotes lipid storage, increases risk of insulin-resistance26 , and the crash in insulin levels and period of rebound hypoglycemia following the spike leaves us feeling dissatisfied and fatigued27 As a result we are not only driven to eat more but also are less active due to reduced glucose availability for respiration in muscle tissues Thus, Taubes suggested eating fewer carbohydrates would encourage burning of fat-stores28 , prevent overconsumption and increase activity levels, all contributing to weight loss and preventing obesity29 .
He had confirmed what Dr Robert Atkins proposed in 1972 with his - most imaginatively titled, I’m sure you’ll agree - ‘Dr. Atkins’ Diet Revolution,’ suggesting a virtually zero-carb diet30 . Sugar was out and fats back in It was during this time that non-nutritive sweeteners began to increase
24 S. N. Bhupathiraju., & F. Hu, ‘Carbohydrates, Proteins and Fats,’ MSD Manual, December 2023, available at: https://www.msdmanuals.com/en-gb/home/disorders-of-n utrition/overview-of-nutrition/carbohydrates,-proteins,-an d-fats, (accessed 09 June 2024)
25 C V Tulleken, Ultra Processed People (Penguin 2023)
26 M C Petersen, G I Shulman, ‘Mechanisms of insulin action and insulin resistance,’ Physiological Reviews, 2018;98:2133-223
27 I A Hainerová, & J Lebl, ‘Mechanisms of appetite regulation,’ Journal of paediatric gastroenterology and nutrition, (2010), 51, pp S123-S124
28 Harvard Medical School,’Ketogenic diet: Is the ultimate low-carb diet good for you?’Harvard Health Publishing, 09 August 2022, available at: https://www.health.harvard.edu/blog/ketogenic-diet-is-the -ultimate-low-carb-diet-good-for-you-2017072712089, (accessed 05 June 2024)
29 C. V. Tulleken, Ultra Processed People (Penguin 2023)
30 B Liebman, ‘Big Fat Lies - The Truth about the Atkins Diet,’ Centre for Science in the Public Interest - Nutrition Action [website], 29 November 2002, available at: https://cspinet.org/sites/default/files/attachment/bigfatlies. pdf, (accessed 09 June 2024)
in popularity, yet, despite decreased consumption of sugar, obesity rates continued to rise, much in the same fashion that they had done so throughout the ‘90s, when low-fat substitutes for common residents of the kitchen had their fifteen minutes of fame31 . Convinced sugar was the villain however, Taubes devised an experiment in 2012, carried out by sceptics including Kevin Hall32 , hoping to prove conclusively that calories from carbohydrates promote weight gain to a greater extent than calories from fats Unfortunately for Taubes, while it was found that low-carb diets resulted in decreased insulin in the volunteers, it was found that, overall there was no di erence in the e ects of lipids versus sugar on metabolism.
While there is evidence that, for those who are able to sustain them, low-carb diets do promote weight loss, this is largely anecdotal and humans have evolved to eat carbohydrates as our primary energy source making such diets rather di cult to sustain33 Primarily, increased consumption of sugars is harmful not because it causes spikes in insulin levels, but because it promotes tooth decay and drives overconsumption simply by increasing the palatability of items of food
As it was found that varying levels of dietary fats and carbohydrates does not significantly impact energy expenditure34 , one might argue the main flaw in hypotheses seeking to blame singular components of food for epidemic obesity is that the validity of these relies on nutritionism: the pervading paradigm that the nutritional value of food can be determined solely
31 C V Tulleken, Ultra Processed People (Penguin 2023)
32K D Hall , ‘A review of the carbohydrate-insulin model of obesity,’ European Journal of Clinical Nutrition, vol. 71,3 (2017): 323-326 doi:10 1038/ejcn 2016 260
33 Harvard Medical School,’Ketogenic diet: Is the ultimate low-carb diet good for you?’Harvard Health Publishing, 09 August 2022, available at: https://www health harvard edu/blog/ketogenic-diet-is-the -ultimate-low-carb-diet-good-for-you-2017072712089, (accessed 05 June 2024)
34K D Hall , ‘A review of the carbohydrate-insulin model of obesity,’ European Journal of Clinical Nutrition, vol. 71,3 (2017): 323-326 doi:10 1038/ejcn 2016 260
by the sum of that of its constituent parts, an idea that is increasingly discredited by researchers35 36
Ultra-processed Foods
By virtue of cooking (a necessary, human evolutionary phenomenon37), almost everything we eat has undergone some degree of processing as per the NOVA Food Classification system:
❖ Group 1 - Unprocessed/minimally processed
❖ Group 2 - processed culinary ingredients
❖ Group 3 - processed, including cheeses
Processing of food only becomes an issue when its individual ingredients might not otherwise be recognised as food at all This is NOVA Group 4, ultra-processed food38 and is often defined as: ‘plastic-wrapped containing at least one non-standard culinary ingredient39 ’
UPF is harmful for three main reasons:
- UPF is soft, dry and energy dense40
As a result we consume UPF products much faster than we would whole foods; when we eat UPF, we obtain far more calories from it in a much shorter space of time than we would from whole food. UPF interferes with homeostatic mechanisms to regulate energy intake and expenditure so UPF consumption leaves us feeling hungry and dissatisfied, associated with overconsumption
- Additives drive excess consumption. Additives commonly used to increase palatability of UPF mimic beneficial molecules without providing their benefits It has been suggested that the
35S. Strauss, ‘Clara M. Davis and the wisdom of letting children choose their own diets,’ CMAJ 2006;175(10):1199 doi:10 1503/cmaj 060990
36 B Goldacre, Bad Science (HarperCollins, 2008)
37 C. V. Tulleken, Ultra Processed People (Penguin 2023)
38British Nutrition Foundation ‘The Concept of Ultra Processed Food (UPF)’, 24 April 2023, available at: https://the-concept-of-ultra-processed-food-background-i nformation-24-04-23-branded pdf (nutrition org uk), (accessed 13 March 2024)
39Soil Association, ‘What are Ultra-processed Foods (UPFs)?’ Soil Association 2022, available at: https://www.soilassociation.org/media/26694/upf-faqs.pdf, (accessed 09 June 2024)
40C. A. Monteiro, E. Martinez-Steele, G. Cannon, ‘Reasons to avoid ultra-processed foods,’ BMJ 2024;384:q439
disconnect caused by these prevalent additives and artificial flavourings - provoking a sensation associated with a given beneficial molecule which is not, in fact, present - is a large factor in driving excess consumption, ultimately leading to obesity41 . It has been suggested that perhaps the reason low-carb diets appear e ective is that often, high-sugar foods are UPF so following a low-carb diet may indirectly result in reduced UPF in one’s diet42 .
- UPF is designed to be addictive43
Created as a means of adding marketing value to agricultural and other industrial waste, UPF is not designed with potential benefits to public health in mind44 It is designed to drive overconsumption to increase manufacturers’ profits, and is often inexpensive requiring little to no preparation; these are foods of convenience which is why they are beginning to dominate food environments across the globe, and perhaps also why obesity and related conditions so disproportionately a ect some of the most disadvantaged in society45
To conclude, of the factors explored, at present it would seem food environments saturated in ultra-processed foods are the most significantthough not necessarily the sole- cause of the “globesity” crisis.
41 ‘The Harsh Reality of Ultra Processed Food,’ e Royal Institution [podcast], presentation by Chris Van Tulleken, December 2023, https://www youtube com/watch?v=5QOTBreQaIk (accessed 26 February 2024)
42 C V Tulleken, Ultra Processed People (Penguin 2023)
43 N D Volkow, et al , ‘Overlapping neuronal circuits in human obesity and addiction,’ Philosophical Transactions of the Royal Society B, 2008;363:3191-200
44 K Chang, et al , ‘Association between childhood consumption of ultra processed food and adiposity trajectories in the Avon Longitudinal Study of Parents and Children birth cohort JAMA Paediatrics 2021; 175; e211573
45 V Raleigh ‘Why Do Health Outcomes in the UK Compare Poorly with Peers?’, King’s Fund, 08 November 2023, https://www kingsfund org uk/insight-and-analysis/blogs/u npacking-health-outcomes-uk-with-peers (accessed 06 March 2024)
Spina Bifida: How Surgical Innovations Can Treat A Debilitating Disease
By Lucia Amaral
What is spina bifida?
Spina bifida is a defect of the neural tube in a foetus, it occurs when the neural tube doesn’t close properly, resulting in abnormalities in the spinal cord and the vertebrae46 The traditional method for treatment of this disease involves postnatal surgery, however, in 2018 the first operations to treat spina bifida in the womb in the UK took place at Great Ormond Street Hospital and University College London Hospitals47 This new type of foetal surgery shows great advancements in the way we treat this disease and has been shown to have significantly better outcomes than the traditional postnatal operations.
Types of spina bifida
There are 3 types of spina bifida, ranging in severity and rarity The most severe is myelomeningocele, a condition where the infant’s spinal cord is left open along multiple vertebrae, causing the spinal cord and surrounding membranes (meninges) to be pushed out, forming a sack on the baby’s back The second, meningocele, is less severe as, though the spinal meninges are pushed outwards, the spinal cord itself often remains undamaged which also allows easier surgical removal of excess membrane. Finally, the most common, and least severe: spina bifida occulta where incorrect vertebral formation results in a small, often unnoticeable spinal gap48
46 NHS ‘spina bifida,’ NHS, [website], available at: https://www nhs uk/conditions/spina-bifida/, (accessed 04 June 2024)
47‘First UK surgery in the womb for baby with spina bifida,’ NHS - GOSH, 24 October 2018, available at: https://www gosh nhs uk/news/first-uk-surgery-womb-bab y-spina-bifida/, (accessed 05 June 2024)
48 NHS ‘spina bifida,’ NHS, [website], available at: https://www.nhs.uk/conditions/spina-bifida/, (accessed 04 June 2024)
Why this is dangerous
Spina bifida is associated with lifelong morbidity, with only half of patients being able to live independently. Myelomeningocele can cause neurological defects due to chemical trauma caused by the spinal cord’s exposure to amniotic fluid (liquid that surrounds the baby in the womb) which damages the neural tissue Su erers of myelomeningocele may struggle with mental retardation49 as well as damage to the nervous system, causing paralysis, weakness or lack of heat sensation in the legs and both bowel and urinary incontinence. Another significant issue facing infants born with myelomeningocele is congenital hydrocephalus (hydrocephalus in babies from birth)50 . Hydrocephalus is caused by cerebro-spinal fluid leaking through the myelomeningocele The cerebral ventricles become enlarged, causing neural complications51 , and the fontanelle area on the baby’s scalp bulges, resulting in thin skin and visible veins
Risk factors for spina bifida
Several risk factors are implicated in spina bifida, such as low folic acid levels during pregnancy, family history of spina bifida and taking medicines such as valproic acid during pregnancy52 . As a result, improvements have been made to prevent myelomeningocele by giving pregnant mothers folic
49 N S Adzick, ‘Fetal surgery for spina bifida: past, present, future,’ Seminars in pediatric surgery, (2013), 22(1), 10–17. https://doi org/10 1053/j sempedsurg 2012 10 003
50 NHS ‘spina bifida,’ NHS, [website], available at: https://www nhs uk/conditions/spina-bifida/, (accessed 04 June 2024)
51 N S Adzick, ‘Fetal surgery for spina bifida: past, present, future,’ Seminars in pediatric surgery, (2013), 22(1), 10–17 https://doi.org/10.1053/j.sempedsurg.2012.10.003
52 NHS ‘spina bifida,’ NHS, [website], available at: https://www.nhs.uk/conditions/spina-bifida/, (accessed 04 June 2024)
acid supplements. However, spina bifida still a ects 1 out of 3000 babies born, with another 25 to 40 % of foetuses su ering with myelomeningocele being aborted53 (statistics taken from multiple studies in the United States). Advancements in the treatment of spina bifida may aid in reducing fear of this disorder and help to give infants with this disease a better quality of life as well as the ability to become independent
Use of foetal surgery
The use of antenatal surgery to treat spina bifida gives significantly better results than the traditional post-natal surgery which is used after birth to cover the exposed spinal cord and treat hydrocephalus54 . The reason for surgical intervention before birth is the “two- hit hypothesis” which suggests the developmental defects in the spinal cord allow it to be further damaged by amniotic fluid as well as direct trauma and hydrodynamic pressure, as the hole in the neural tube means that the spinal cord is exposed in the womb By carrying out foetal surgery, the length of time the spinal cord is exposed is lessened, minimising the harm caused to the foetus by this disorder55 . Surgery increases the probability of the child being able to walk unaided (with 44 8 percent of those who underwent antenatal surgery walking independently, compared to 23 9 percent in the postnatal group) and reduces neurological damage to the child. The child’s developmental outcomes are improved regarding incontinence and hindbrain herniation - when the lower brain area at the rear of the head comes down, herniating, into the spinal canal. Open foetal surgery does, however, show an elevated chance of premature birth and maternal morbidity56
53 N S Adzick, ‘Fetal surgery for spina bifida: past, present, future,’ Seminars in pediatric surgery, (2013), 22(1), 10–17. https://doi org/10 1053/j sempedsurg 2012 10 003
54 ‘About Foetal Surgery for Spina Bifida,’ Children’s Hospital of PhiladelphiaI [website], available at: https://www chop edu/treatments/fetal-surgery-spina-bifid a/about, (accessed 05 June 2024)
55 N S Adzick, ‘Fetal surgery for spina bifida: past, present, future,’ Seminars in pediatric surgery, (2013), 22(1), 10–17. https://doi org/10 1053/j sempedsurg 2012 10 003
56A. Sacco et al. “Fetal surgery for open spina bifida.” e obstetrician & gynaecologist : the journal for continuing
This type of foetal surgery can take place between 23 and 25 weeks of pregnancy The mother is given general anaesthetic (to anaesthetise the foetus and relax the uterus) before laparotomy (incision crossing the abdomen. An intraoperative ultrasound will then be performed to locate the placenta and foetus and a uterine stapling device opens the uterus, secures membranes to muscle, and pinches o blood vessels. The myelomeningocele sac is removed, the spinal cord is placed back into the spinal canal and surrounding skin and tissues closed to protect the area from amniotic fluid before the incisions are closed too57 .
First UK foetal surgery for spina bifida
In 2018, two 90-minute surgeries were conducted by a team of 30 doctors58 to treat spina bifida in foetuses- this being the first of this type of surgery to be carried out in the UK. Previously, for mothers with infants diagnosed with the disorder the only available options were postnatal surgery (with worse developmental outcomes) or foetal surgery abroad The benefits of international collaboration health care are exemplified in these successful surgeries, as it was through cooperation with the Children’s Hospital of Philadelphia and Belgian foetal Professor Deprest and his team that piloted this advancement in British medicine59 .
professional development from the Royal College of Obstetricians & Gynaecologists vol 21,4 (2019): 271-282 doi:10.1111/tog.12603
57 ‘About Foetal Surgery for Spina Bifida,’ Children’s Hospital of PhiladelphiaI [website], available at: https://www chop edu/treatments/fetal-surgery-spina-bifid a/about, (accessed 05 June 2024)
58 ‘Two unborn babies’ spines repaired in womb in UK surgery first,’ BBC News, 24 October 2018, available at: https://www bbc co uk/news/health-45958980, (accessed 05 June 2024)
59‘First UK surgery in the womb for baby with spina bifida,’ NHS - GOSH, 24 October 2018, available at: https://www.gosh.nhs.uk/news/first-uk-surgery-womb-bab y-spina-bifida/, (accessed 05 June 2024)
How Does HIV Interact with the Body in Co-infection?
By Finley Calderbank
What is co-infection?
In simple terms, co-infection is the term used when two or more infections are present in your body60 . Using the main subject of this article as an example, if you had mycobacterium tuberculosis and HIV, you would have a co-infection of tuberculosis and HIV. People with HIV are more susceptible to infections, due to the low count of CD4 cells (T-Cells). When someone with HIV/AIDS contracts an infection that would not cause disease in a healthy person, it is known as an ‘opportunistic infection61’ .
What exactly is HIV?
HIV (human immunodeficiency virus) is a virus that damages T-Cells in your immune system and makes it less strong and more susceptible to infections. It is transmitted through all bodily fluids, apart from sweat, saliva, and urine62 . When the T-Cell count drops below 200 cells/mm3, HIV becomes AIDS (acquired immune deficiency syndrome), and this means that most infections are life-threatening to you
HIV in co-infection
The most common pathogens to be in co-infection with HIV globally are tuberculosis, cryptococcosis, hepatitis B and C, and malaria63 This article will only detail two of these - tuberculosis and malaria The symptoms of these pathogens in co-infection are
60 Va gov: Veterans A airs (2005) /AIDS Basics Available at: https://www.hiv.va.gov/patient/basics/index.asp (Accessed: 22 April 2024)
61 What is an opportunistic infection? (2021) National Institutes of Health Available at: https://hivinfo.nih.gov/understanding-hiv/fact-sheets/what -opportunistic-infection (Accessed: 22 April 2024)
62 National Health Service (2021) Overview - HIV and AIDS [online] NHS Available at: https://www nhs uk/conditions/hiv-and-aids/ [Accessed 4 Jun 2024]
63 Chang, C C , Crane, M , Zhou, J , Mina, M , Post, J J , Cameron, B.A., Lloyd, A.R., Jaworowski, A., French, M.A. and Lewin, S R (2013) HIV and co-infections Immunological Reviews, 254(1), pp.114–142. doi:https://doi org/10 1111/imr 12063 [Accessed 5 Jun 2024]
di erent from each other, as the pathogens alone have di erent symptoms
HIV and Tuberculosis
Tuberculosis is known as an AIDS-defining infection64 When infected with tuberculosis (TB), the cellular immune response is heavily slowed in HIV patients, likely due to the low amount of CD4 cells in the blood. It was found that as CD4 count lowered, the rate of infection increased It was also found that in patients that had developed AIDS, disseminated TB (where the infection that started in the lungs spreads to other parts of the body through the blood or lymph system) was common as granuloma formation is poor when the HIV infection is this advanced When cART (a way to treat HIV infection by preventing replication) is used, the number of memory cells in the blood increases, improving the function of the cellular immune response, slowing the rate of TB infection and reactivation of latent TB by around 65%65
The increase in HIV-TB infections is likely the result of either the increase of reactivation of latent TB or the increased susceptibility to TB due to the weakened immune system. Usually, patients infected with the tuberculosis bacteria do not develop active TB as it stays dormant, but HIV is the greatest factor in TB becoming an active infection, and this increased risk is e ective soon after the co-infection, before the T-Cell count drops drastically66 .
64 hivinfo nih gov (2021) HIV and Tuberculosis (TB) [online] Available at: https://hivinfo nih gov/understanding-hiv/fact-sheets/hiv-a nd-tuberculosis-tb#: :text=healthy%20immune%20system s - [Accessed 5 Jun 2024]
65 Chang, C C , Crane, M , Zhou, J , Mina, M , Post, J J , Cameron, B A , Lloyd, A R , Jaworowski, A , French, M A and Lewin, S R (2013) HIV and co-infections Immunological Reviews, 254(1), pp 114–142 doi:https://doi org/10 1111/imr 12063 [Accessed 5 Jun 2024]
66 Bruchfeld, J., Correia-Neves, M. and Källenius, G. (2015). Tuberculosis and HIV Coinfection Cold Spring Harbor Perspectives in Medicine, [online] 5(7), p.a017871. doi:https://doi org/10 1101/cshperspect a017871
HIV and Malaria
Malaria alone is very dangerous in underdeveloped countries and is, in fact, one of the leading causes of death globally However, co-infection with HIV is very common and has large public health risks. In 2007, over 3 million deaths were caused by the HIV/malaria co-infection The most common consequence of it is anaemia67 .
In Brazil, it was found that HIV patients were 6 48 times more likely to develop a malaria infection68 , though, interestingly HIV was found to tend to protect against a recurrence of a malarial episode
Furthermore, it was also found that malaria commonly speeds up HIV progression, however this correlation was only found in terms of a viral load increase in pregnant women. This was not common to just malaria and was found in many parasitic diseases Parasitemia has not been found to increase progress to an AIDS-related death. It is theorised that malaria may be more damaging to a person with low levels of immunosuppression as more T-Cells are available for HIV replication after cytokine stimulation (activation of a T- or B-Cell) by malaria69
The co-infection exacerbates the symptoms of malaria during pregnancy, and commonly leads to an increase in anaemia, clinical disease, and low birth weights, which results in low infant survival.
67 Sanyaolu, A , Fagbenro-Beyioku, A , Oyibo, W , Badaru, O , Onyeabor, O and Nnaemeka, C (2013) Malaria and HIV co-infection and their e ect on haemoglobin levels from three healthcare institutions in Lagos, southwest Nigeria African Health Sciences, 13(2). doi:https://doi org/10 4314/ahs v13i2 14 [Accessed 18 Jun 2024]
68 Guerra, C V C , da Silva, B M , Müller, P , Baia-da-Silva, D.C., Moura, M.A.S., Araújo, J.D.A., Silva, J.C.S. e, Silva-Neto, A V , da Silva Balieiro, A A , da Costa-Martins, A G , Melo, G.C., Val, F., Bassat, Q., Nakaya, H.I., Martinez-Espinosa, F E , Lacerda, M , Sampaio, V S and Monteiro, W (2022) HIV infection increases the risk of acquiring Plasmodium vivax malaria: a 4-year cohort study in the Brazilian Amazon HIV and risk of vivax malaria Scientific Reports, 12(1) doi:https://doi org/10 1038/s41598-022-13256-4 [Accessed 18 Jun 2024]
69 Medscape. (n.d.). HIV and Malaria Interactions: Where Do We Stand? - Page 5 [online] Available at: https://www.medscape.com/viewarticle/759555 5?form=fpf [Accessed 18 Jun 2024]
Children and adults who have HIV or AIDS are more likely to experience severe malaria and require hospitalisation
A Brief Overview of Dental Tourism
By Elizabeth Haseldine
What is Dental Tourism?
A subcategory of medical tourism (the practice of travelling overseas to receive medical treatment), dental tourism is a rapidly growing sector of the healthcare industry involving the intentional pursuit of dental treatment abroad In the UK, this can refer to either non-UK-residing patients requesting NHS dental care upon visit, or patients travelling to destinations outside their home country to receive treatment70; in this article I will be focusing on the latter. The number of Britons seeking treatment abroad has reportedly increased from 48,000 patients in 2014 to 144,000 in 201671 , with popular destinations including (but not limited to): Malaysia, Thailand, Hungary, and Romania, and common treatments encompassing crowns, bridgework, implants and veneers
Reasons for Dental Tourism
Concerning dental tourism, there are a multitude of factors contributing to the rising number of cases where patients may seek treatment abroad, each being classified as either a pushing or pulling factor; quality, e ciency, and hospital reputation can be considered pulling factors whereas long waiting lists, lack of availability, and high-cost treatments are categorised as pushing factors. Pertaining to the UK, the lengthy waiting lists concerning dental treatment from the NHS is a significant pushing factor, with the alternative route of private treatment regarded as
una ordable for the vast majority.72 In the case where certain NHS treatments are available, and the patient is eligible for funding, the timescale for procedures involving appointments and multidisciplinary consultations can become extensive, and patients may instead choose to undertake treatment abroad where a limited number of appointments at a lower price are o ered Increasingly, dental clinics have begun to o er ‘dental tourism packages’ for foreign patients, incorporating features such as accommodation and transportation into the cost of treatment, improving the cost-e ectiveness and ease of the pursuit of treatment abroad, further incentivising patients to consider dental tourism Another contributing factor to dental travel may be the unwillingness of local practitioners to perform certain procedures; for both ethical and medico-legal reasons, UK clinicians may feel uncomfortable providing controversial treatment options for fear of being sued or receiving complaints For some patients, there is a lack of trust towards NHS dentists and the quality of their results and, in the case of immigrants, they are able to instead follow the recommendation of family or friends for treatment whilst visiting their home country- being in a familiar environment where they may be able to communicate better (possibly in their mother language) with a potentially greater trust in the clinician also influences the decision to receive treatment abroad 73
Risks of Dental Tourism
70 J Iqbal et al, ‘International Rescue? Managing the dental tourist’ Dental Update [online] 29 May 2024
https://www dental-update co uk/content/dental-tourism /international-rescue-managing-the-dental-tourist
71 L Donnelly and K Morley, ‘Soaring numbers flying abroad for medical care as NHS lists lengthen’ The Telegraph [online] 29 May 2024
https://www telegraph co uk/news/2017/10/22/soaring-nu mbers-flying-abroad-medical-care-nhs-lists-lengthen/?I CID continue without subscribing reg first,
In the event that patients travel to unfamiliar destinations, problems with communication are likely to arise; due to language barriers,
72 J Zoltan and R Maggi, ‘What is Tourism in Dental Tourism?’ [online] 30 May 2024 https://ssl lu usi ch/entityws/Allegati/pdf pub5354 pdf
73 S. Ashiti and C. Moshkun, ‘Dental tourists: treat, re-treat or do not treat?’ British Dental Journal [online] 30 May 2024 https://www nature com/articles/s41415-020-2591-6#Sec3,
communication between the clinician and patient can become di cult and misunderstandings may occur, resulting in a lack of knowledge for patients when choosing their treatment options For this reason, informed consent may not be fully obtained, and patients are likely to undergo treatments they do not fully understand or even need. Furthermore, procedures and practices di er between countries so any comparisons in treatments that patients may make are unlikely to be reliable, and so they are still uninformed about the di erences and extent of their treatment. Unlike the UK, not all countries have professional dental regulators like the GDC- as such, there is not always a guaranteed standard for the quality of treatment abroad, which can result in patients being subjected to low quality procedures. The risk of such is that it is probable for complications to emerge and, in the case that treatment goes unexpectedly, patients may struggle in seeking help from UK dentists who feel as though they are competent enough to manage these concerns When care has been provided abroad, there is often little to no contact between dentists and a lack of record sharing in regard to treatments, further complicating any remedial work for patients. The lack of dental regulators abroad also means that patients may experience di culty in finding opportunities to report poor practice, and any legal proceedings may be hard to undertake due to di erences in legislation between countries
Possible benefits of dental tourism
Being a main motivator for dental tourism, the reduced cost of treatments is a notable benefit for any patient considering dental tourism; the same could be said of the shorter wait lists. For dental tourism destination regions, dental travel can bring economic benefits to the country- often, dental tourists travel from developed nations, o ering employment and business opportunities for the local residents, providing financial benefits to the countries visited 74 As mentioned previously,
74 A RJ et al , ‘Benefits of Medical and Dental Tourism- A Review’ IOSR Journal of Dental and Medical Sciences (IOSR-JDMS) e-ISSN: 2279-0853, p-ISSN:
when the subjects of dental tourism are immigrants, it is often more beneficial to receive treatment in their home countries; if the patients face a language barrier in their country of residence, communication may be more prone to misunderstanding and travelling to a more familiar environment may be more favourable When considering the quality of dental tourism, and how it often varies depending on location, it is important to note that high quality treatments can be found abroad and that, whilst undergoing treatments abroad may pose a risk, there is the potential for successful treatments
The Role of Dental Practitioners in
Dental Tourism
Although the final decision to travel ultimately resides with the patient, it is crucial for local dentists, when consulted, to inform patients to the best of their ability on the matter, including both long and short-term impacts of the treatment. Additionally, after treatment is received, there is arguably an ethical obligation to help patients, regardless of opinion on the sensibility of overseas treatment. In the UK, any acute problems are (at a minimum) managed by either NHS or private dentists however there is no obligation to perform any elective treatments.75 From an ethical standpoint, it may be argued that responsibility also falls upon the foreign dentists providing these treatments to ensure informed consent is obtained and that their patients are knowledgeable enough on the treatments to make a well-informed decision.
75 S. Ashiti and C. Moshkun, ‘Dental tourists: treat, re-treat or do not treat?’ British Dental Journal [online] 01 June 2024 https://www nature com/articles/s41415-020-2591-6#Sec3 2279-0861 Volume 19, Issue 3 Ser 12 (March 2020), PP 26-31 www iosrjournals org [online] 01 June 2024
Conclusion
In conclusion, the advantages and disadvantages of dental tourism must be considered by any patient intending to travel abroad for dental care, and any potential treatments should be thoroughly researched. For example, using information provided by the NHS or GDC on treatment abroad (as shown in figure 176). The responsibility of collecting this knowledge lies upon the patient however there is also a duty for dentists to provide su cient knowledge to aid the patient’s decision
76 General Dental Council ‘Going abroad for your dental care?’ [online] 01 June 2024 https://www.gdc-uk.org/standards-guidance/information -for-patients-public/going-abroad-for-dental-treatment
Oral Mucosa: A Brief Overview
By Ruby Hughes
Structure
The basic structure of an oral mucous membrane consists of a multilayer of epithelial cells called squamous stratified epithelial cells. The degree of keratinisation of these cells is dependent on its location and function within the oral cavity. This is later explored in the classification of the di erent oral mucosa tissues. Followed by this, there is a layer of lamina propria which is attached to submucosa or can be directly bound to bone in the absence of submucosa. The role of lamina propria is to act as a blood supply to epithelial cells77 Due to the secretions of saliva, the oral mucous membrane remains a wet, moist lining in the oral cavity
Oral Classification
Each oral mucosa tissue has its own clinical and histological characteristics due to their di erent functions within the oral cavity, such as di erent epithelium cells or locations The classification of oral mucosa consists of three main types: masticatory mucosa, lining mucosa and specialised mucosa.
Masticatory mucosa makes up 25% of the total mucosa78 and is found in gingivae, along with the hard palate This membrane is tough and rigid to remain bound to underlying bone, whilst being exposed to chewing and abrasion Therefore, masticatory mucosa contains keratinised or pre-keratinised stratified squamous epithelium to provide strength and support
77 M Brizuela and R Winters, ‘Histology, Oral Mucosa ’ StatPearls [Internet] Treasure Island (FL): StatPearls Publishing; [updated] 08 May 2023, [published] 2024 JanAvailable from: https://www ncbi nlm nih gov/books/NBK572115/
78 T. A. Winning, G. C. Townsend, ‘Oral Mucosal Embryology and Histology,’ Elsevier, 2000;18:499 –511, available from: https://web.unicz.it/admin/uploads/2014/03/Oral-MucosalEmbryology-and-Histology pdf, (accessed 03 June 2024)
Lining mucosa is found in the lips, cheeks, floor of the mouth and the ventral surface of the tongue, resulting in 60% of the total mucosa being lining mucosa79 These are structures that are mobile and therefore lining mucosa is also known as moveable mucosa. The epithelium found in lining mucosa is non-keratinised stratified squamous epithelium, resulting in more susceptibility to damage and swelling
Specialised mucosa is in the dorsum of the tongue and in taste buds with non-keratinised or keratinised squamous epithelial cells. The total mucosa consists of 15% of specialised mucosa80 The idea of this mucosa being specialised relates to its contrasting function of providing the sensation of taste Its ability to carry out this function is due to containing taste buds or papillae. There are two types of papillae known as fungiform papillae or filiform papillae
Our oral cavities are lined with oral mucosa, a soft tissue membrane made wet due to serous or mucosa secretions
Functions
- Protection
Underlying tissues can be protected from harmful diets (diets containing tobacco, alcohol and carcinogenic substances) and from stretching, compression and abrasion during mastication81 . Microorganisms can also result in the infection of deeper tissues; however, the oral mucosa acts as a
79 L L Hurjui,, et al , ‘Oral Mucosa - Pathophysiological and Pharmacotherapeutic Aspects,’ Romanian journal of Oral Rehabilitation, December 2021, Vol 13, No 4, available from: https://www rjor ro/wp-content/uploads/2022/01/ORAL-MU COSA-PATHOPHYSIOLOGICAL-AND-PHARMACOTHERAP EUTIC-ASPECTS pdf, (accessed 03 June 2024)
80 N A L Ghaban ‘Oral Histology,’ CoDental, [web document] available at: mucous-membrane-lecture-1 pdf (uobaghdad edu iq) (accessed 03 June 2024)
81D Nischwitz, ‘It's all in your mouth,’ (Chelsea Green Publishing, 18 March 2020)
physical and immune barrier to prevent this. The presence of T helper 17 cells, dendritic cells and layers of epithelial cells provides oral mucosa with the characteristics to carry out its function82 Destruction of this barrier can lead to gingivitis, oral mucosal diseases or more severe diseases like periodontitis, highlighting the importance of the oral mucosa being healthy in the oral cavity. Factors in the oral cavity can a ect the susceptibility to these diseases. Saliva, proteins and immune components can play a role in forming an altered mucosal structure
- Sensation
Specialised mucosa, located on the dorsa of the tongue, contains a sensory function for temperature, touch pain and taste, Taste receptor cells can perceive salty, sweet. sour and bitter sensations. Recent research has also suggested that fat can also be detected ³ . The ability of being able to sense touch allows us to be able to identify food or objects within the oral cavity, recognise if food is too hot to prevent scalding and can also be used as indication for when to initiate the swallowing reflex Without this function everyday tasks like speaking and chewing may be more di cult
- Secretion
Saliva is vital for oral health which is released by ducts in the minor salivary glands of the submucosa. Saliva has many roles itself and without the oral mucosa providing secretions, this can lead to a dry mouth The lower the salivation rate, the lower the proportion of calcium, inorganic phosphates and bicarbonates. These are nutrients that supply the teeth in remineralisation Saliva can assist this process83 .
- As a marker of general, physical health
Oral mucosa has a wide range of functions within the oral cavity. The oral mucosa can be useful within dental check-ups as a dentist can utilise the oral mucosa to identify signs of other health problems, such as oral cancer, diabetes, vitamin deficiency and coagulopathies84 . The oral mucosa therefore acts as a gateway to general physical well-being as well as oral health
82 Cleveland Clinic, ‘Mucosa,’ Cleveland Clinic, [website], available from: https://my.clevelandclinic.org/health/body/23930-mucosa (accessed 04 June 2024)
84M Handa, ‘Anatomy and Classification of Oral Mucosa,’ Department of Oral and Maxillofacial Surgery, University of Cincinnati Medical Center,
Toxoplasma gondii: A Brief Overview of “The Mind-Control Parasite”
By Hilda Koko
What is it?
Toxoplasma gondii, or T. gondii, is a fascinating parasite known for its mind-bending ability to manipulate its hosts, primarily aiming to reproduce and thrive in cats85
186
How is it spread?
This crafty parasite, found in about one-third of the global population, spreads through contact with cat faeces or undercooked meat.
To make its way back to feline hosts, T gondii targets the natural prey of cats – rats
How does it a ect rats?
Once a rat is infected, T. gondii works its magic, forming cysts in the rat’s brain, especially in areas associated with fear and anxiety, like the amygdala.
This brain-hijacking act strips the rat of its natural fear of cats, making it oddly attracted to the scent of feline urine87
86 The Native Antigen Company ‘SAG2 Protein,’ e Native Antigen Company, [website], https://thenativeantigencompany com/products/toxoplasma -gondii-sag2-protein/ (accessed 12 June 2024)
87 M Bates, ‘This parasite manipulates the minds of wolves, rats - and maybe even you,’ National Geographic, 29 November 2022
88Mavink com, [website], available at: https://mavink.com/post/87E3EBD4C4A295D532E4EFFF9408 2F84DAAM19F228/toxoplasma-gondii-parasite (accessed 12 June 2024)
Figure
Figure
But wait, it gets even more intriguing!
Studies show that T gondii boosts dopamine levels in the rat’s brain
This neurotransmitter surge further reduces the rat’s fear response and alters its behaviour, making it more likely to approach its deadly predator.
And what about humans?
While we don't become prey to cats, T gondii can still have some fascinating e ects on us Some studies suggest that infected humans may exhibit subtle changes in behaviour and personality.
For instance, there’s evidence linking T. gondii infection to increased risk-taking and altered response to fear
Researchers have also explored potential connections between T. gondii and certain mental health conditions, like schizophrenia and bipolar disorder, due to the parasite's influence on brain chemistry, linking T gondii infection to higher levels of neuroticism, which includes traits like anxiety, moodiness, and emotional instability91
In humans, T. gondii typically remains in a latent state, with the immune system keeping it in check.
Thus, the bewitched rat, drawn to the cat’s scent, becomes an easy meal, allowing T gondii to complete its life cycle within the feline host Figure 4
However, in individuals with weakened immune systems, such as those with HIV/AIDS or undergoing chemotherapy, the parasite can reactivate and cause serious complications92 . Figure 593
91 H Baker, ‘10 surprising facts about the ‘mind-control’ parasite, Toxoplasma gondii, ’ Live Science, 01 February 2023
89A J Ghiadaa , ‘Use of real time polymerase chain reaction (PCR) and histopathological changes for detection of the Toxoplasma gondii parasite in male rats (experimental study),’ African Journal of Bacteriology Research, 2015;7(1), 8-13
90 C. Marie & W. A. Petri, ‘Toxoplasmosis - Infectious Diseases,’ MSD Manual, December 2022
92 GOV UK, ‘Toxoplasmosis,’ GOV UK, [website], 19 December 2016, available at: https://www gov uk/guidance/toxoplasmosis (accessed 13 June 2024)
93 Mayo Clinic, ‘Toxoplasmosis,’ MayoClinic, [website], available at: https://www.mayoclinic.org/diseases-conditions/toxoplasm osis/symptoms-causes/syc-20356249 (accessed 13 June 2024)
Infection during the first trimester (being infected for the first time during pregnancy) is less common but can lead to the most severe outcomes, including miscarriage or stillbirth94 .
Infection later in pregnancy, during the second or third trimesters, can cause the parasite to cross the placenta and infect the developing foetus, making it more likely to result in the baby being born with congenital toxoplasmosis
Further studies show that these babies su ering from congenital toxoplasmosis can su er from neurological issues: seizures, an enlarged head (hydrocephalus), or a smaller than normal head (microcephaly)
So, while T. gondii might not turn us into cat-seeking zombies, its impact on our brains and health can be dangerous and understanding and mitigating the risk of infection through preventive measures can help ensure better health outcomes
The Heloderma Lizards consist of 5 species; The Gila Monster (Heloderma suspectum), the Mexican Beaded Lizard (Heloderma horridum), Rio Fuerte beaded lizard (Heloderma exasperatum), Guatemalan beaded lizard (Heloderma charlesbogerti) and the Chiapan beaded lizard (Heloderma alvarezi), (see cladogram below,Fig 195)
Figure 1 : Phylogenetic model of the Heloderma genus.
They inhabit southern Nevada and Utah, the deserts of Arizona and Sonora and the Pacific coastline of Mexico to south Guatemala96 Helodermatids have long been the only known true venomous lizards (the existence of Varanid venom is controversial)
Unusually - and unlike snakes - Helodermatid venom is used exclusively for defensive purposes This may be because they are generally slow-moving lizards and have an extremely low metabolism relative to any
96 M E Douglas et al , Conservation phylogenetics of Helodermatid Lizards using multiple molecular markers and a supertree approach, 2010, PubMed, Research Gate 95 Wikimedia Commons, 2021, Kladogramm Heloderma jpg, Wikipedia
other lizard, thus the venom could be used to warn o any predators that ignore its aposematism (bright colouring to deter predators)
Anatomical Adaptations
Helodermatids have a di erent method of venom delivery to that of vipers and elapids. They have mandibular salivary glands adapted to produce venom which spans the length of their mandibular dentistry. Venom ducts branching from these mandibular glands conduct venom to labial grooves next to the mandibular teeth. Their mandibular and maxillary teeth are grooved but, unlike those of vipers, are not hollow. This may help the flow of venom into the prey’s wound once the lizard has latched on (see fig 297) Once the lizard has a hold on the animal, it will start to chew the venom into the animal causing most excruciating pain If the prey is small enough, venom may lead to paralysis and death
97 S. Weinstein et al., Reptile venom glands: Form, Function and Future, 2019, Research Gate
Figure 2: Transverse cross section of Helodermatid jaw.
Venom Composition and Function
All venom, including that of a Helodermatid, is a mixture of proteins Of special interest are the polypeptide neurotoxins such as the Cysteine-rich Secretory Proteins (CRiSP) One such CRiSP is Helothermine, a toxin isolated from H.horridum venom; studies in rats have shown that application causes rear limb paralysis and death. These e ects are attributed to the helothermine binding to ryanodine receptors, located on the internal side of the sarcoplasmic reticulum in striated muscle98 , thereby inhibiting Ca2+ e ux from the sarcoplasmic reticulum and into the sarcomere. A lack of Ca2+ ions in the sarcomere would prevent the troponin from changing shape and exposing the binding site on the tropomyosin Due to the binding sites not being exposed, actin-myosin cross bridges cannot be formed between the actin and myosin filaments, preventing any ratcheting action between the 2 filaments in the sarcomere, causing muscular paralysis in the a ected area
Helodermatid venom also contains hemo- and cytotoxic proteins - most likely metalloproteinases (fig 4) and phospholipases respectively The metalloproteinases induce haemorrhaging by the cleaving of polypeptides of collagen and perlecan in the extracellular matrix around microcirculatory vessels
The phospholipases cause localised necrosis through the cleavage of phospholipids in the cell surface membrane, eventually leading to apoptosis Whilst the e ects of hemotoxins and cytotoxins would be
98 J A Raszewski, et al , Physiology, Ryanodine Receptor, 2022, NIH, National Center for Biotechnology Information
99N Cerdà-Costa, Architecture and function of metallopeptidase catalytic domains, 2024, Protein Sci, PubMed
painful, they do not compare to the neurotoxins. This is because neurotoxins act on the peripheral nervous system and overstimulates nerves, causing intense pain and localised paralysis, compared to relatively mild, localised internal bleeding. If the dosage is high enough, the venom could act upon muscle fibres of the diaphragm The diaphragm regulates atmospheric pressure within the thoracic cavity (controlling exhalation and inhalation) so paralysis of the diaphragm leads to loss of voluntary breathing, weaker and shallower breaths and, eventually, asphyxiation One death has been attributed to Helodermatid venom when an illegally-owned, captive specimen bit its owner (12 02 2024)100 However there have been suggestions from herpetologists that an H suspectum bite is so painful to a human it may drive the victim to suicide.
Implementation
Common predators of Helodermatids include hawks, owls, coyotes and snakes, all of which weigh less than humans If Helodermatid venom causes such excruciating pain in humans, one can only imagine the pain and damage it would inflict on these, smaller species who would receive the same injection volume yet experience greater nerve stimulation.
found itself in a rather unfortunate situation
There is a debate as to whether venom is primarily for subduing prey, as the physical strength of the lizard (especially the jaw) should be su cient to prevent prey from escaping, however the general consensus amongst most herpetologists is that it is
100Travers S , A Scientist Explains e Rare Dangers Of Gila Monster Venom, Forbes, 2024
101J Cancalosi, Gila Monster eating a mouse, ThoughtCo, 2024
Figure 4: Catalytic process of monometallic proteinase99
Figure 5101: A Cactus mouse (Peromyscus eremicus) that has
solely used for defensive purposes. It is also theorised that the cytotoxic proteins in the saliva (such as Phospholipases) could aid in digestion as it breaks apart the phospholipid bilayer of the cell surface membranes.
Medical Significance
Venoms have always been a resource for drug discovery and development, due to their rich and varied polypeptide contents The venom of H.suspectum is no exception. Gila Monster venom contains exendin-4, an analogue of Glucagon-like peptide 1 (GLP-1) (Figure 5)
5:
102 (top) and Exendin-4103 (bottom)
Synthetic exendin-4 is now used alongside exenatide (the primary GLP-1 receptor agonist in the medication) in Byetta® to treat Type 2 diabetes104 . As an analogue of GLP-1, synthetic exendin-4 modulates blood sugar levels by activating GLP-1 receptors in the pancreas Activation causes increased insulin
102Glucagon Like Peptide-1 GLP-1 1DOR, 2024, Biologic Models
104 L R Aramadhaka, Connectivity maps for biosimilar drug discovery in venoms: the case of Gila monster venom and the anti-diabetes drug Byetta®, 2013, PubMed
secretion and decreased glucagon secretion, thus lowering the risk of hypoglycaemia in the patient105
Conclusion
Overall, Helodermatids are a relatively small genus of squamates with much yet to learn, especially regarding their behavioural habits and molecular physiology; at present, it is only H horridum and H.suspectum that have had a significant volume of research attributed to them Further venom gland transcriptomic analysis of the remaining 3 species (H exasperatum, charlesbogerti and alvarezi) would give us a more holistic view of Helodermatid venom composition and from this we might be able to produce immunoglobulins to mitigate the pain caused by a Helodermatid bite. Additionally, further analysis could lead to development of more e ective treatments for type 2 diabetes After all, one who researches STEM must never lose sight of the reason. Research for research’s sake is irrelevant We have a responsibility to implement said research in such a way that it improves the human condition
105 C F Shaefer Jr , et al , User's guide to mechanism of action and clinical use of GLP-1 receptor agonists, 2015, PubMed.
Figure
GLP-1
The Perfect Poison: Nature’s Deadly Nature…
By Bethany Jones
What is a Poison?
The Royal Society of Chemistry defines poison as:
‘any substance which when introduced into or absorbed by a living organism, destroys life or injures health106’
A poison may be synthetic, natural, a liquid, gas or solid, so long as it harms living organisms.
Poison has been used in murders and suicides throughout human history, from appearing in famous novels by authors such as Agatha Christie, to featuring in News stories covering assassinations of political figures. The human race has been using both natural and synthetic chemicals to kill one another for nearly as long as we have existed As our ancestors discovered long ago, nature o ers some of the fastest and easiest ways to end a human life, often hidden in charming, ostensibly harmless packages - think of the alluring belladonna107 or beautiful foxgloves108 that feature in many home gardens
In the media, famous poisons such as arsenic often appear to act instantly, though in truth this is rarely the case. There are only a few poisons e cient enough to make for e ective tools of assassination, the majority of which are found in nature, most likely due to the fact that they are
106 Royal Society of Chemistry (n d ) What is a poison? [online] Available at: https://www rsc org/images/What-is-a-poison-2015 tcm1 8-12694.pdf [Accessed 10/06/24]
107 The Editors of Encyclopaedia Britannica (2020) Belladonna | plant | Britannica. In: Encyclopædia Britannica [online] Available at: https://www britannica com/plant/belladonna [Accessed 11/06/24]
108 Ramlakhan, S L and Fletcher, A K (2007) It could have happened to Van Gogh: a case of fatal purple foxglove poisoning and review of the literature European Journal of Emergency Medicine, 14(6), pp.356–359.[online] doi:https://doi org/10 1097/mej 0b013e3280bef8dc Available at: https://pubmed.ncbi.nlm.nih.gov/17968204/ [Accessed 10/06/24]
used to ward o predators109 , and a prey item hasn’t got three to five business days to wait for their attacker to die. Whilst a select few synthetic poisons such as VX110 could act quickly enough111 , they are not easy to access or buy making them unsuitable for the majority of cases Therefore, after extensive research, I have narrowed down a list of three fact-acting, extremely potent, relatively easy to obtain toxins, all of which appear in nature.
Features of the Ideal Poison
If we are using a poison to kill someone, then it must be potent enough to do so in relatively small quantities as it would be rather noticeable to lug a large vat of poison into a public space to kill someone. Not characteristic of the subtlety required in an assassin’s line of work The poison must also be easy to administer, ideally leaving no evidence of crime in the form of needle punctures, for example. Additionally, the poison should be fast-acting so that the person has little to no time to seek medical help; if it is not fast acting it should be near-untraceable so it takes time to work out the treatment Even better if there is no direct cure or treatment. Finally, the poison should be readily available to minimise the possibility of it being traced back to the assassin.
109 Jackson, T (2020) e Toxin Resistance Tango (part 1) [online] School of Biomedical Sciences. Available at: https://biomedicalsciences unimelb edu au/departments/ department-of-biochemistry-and-pharmacology/engage/ avru/blog/the-toxin-resistance-tango-part-1#:~:text=Thi s%20means%20that%20the%20function [Accessed 12 /06/24]
110 Vaughan, D (2023) VX | nerve gas [online] Encyclopedia Britannica Available at: https://www britannica com/technology/VX [Accessed 12/06/24]
Perhaps the world’s best-known poison, occurring in apple seeds112 and worldwide murders, cyanide is famous as a way to kill people and a classic choice of poison. Cyanide or a derivative can be manufactured with relatively common chemicals in a lab113 or bought from various sources such as mining companies114 It is therefore relatively easy to acquire, with many modes of administration, including subcutaneous injection, oral ingestion, inhalation of gas or skin contact115
Additionally, according to the American National Library of medicine, cyanide ‘is rapidly absorbed,’ with symptoms beginning ‘a few seconds after exposure and death usually occurs in <30 min116’
Treatment for cyanide should be administered within thirty minutes or will almost definitely be fatal,117 due to how fast acting it is, increasing the likelihood of successful assassination
Cyanide works by interrupting respiration in the mitochondria so that ATP cannot be synthesised, and this leads to cell death, particularly in heart
112 Petruzzello, M. (2019). Can Apple Seeds Kill You? | Britannica In: Encyclopædia Britannica [online] Available at: https://www britannica com/story/can-apple-seeds-kill-y ou. [Accessed 12/06/24]
113 camachem com (n d ) How to Buy Sodium Cyanide [online] Available at: https://camachem com/vn/blog/post/how-to-buy-sodium -cyanide [Accessed 10/06/24]
114 Anon, (2016) How to Make Cyanide [online] Available at: https://www.911metallurgist.com/blog/how-to-make-cya nide [Accessed 10\06\24]
115 Graham, J. and Traylor, J. (2018). Cyanide Toxicity. [online] Nih gov Available at: https://www.ncbi.nlm.nih.gov/books/NBK507796/. [Accessed 10\06\24]
116 Jethava, D., Gupta, P., Kothari, S., Rijhwani, P. and Kumar, A (2014) Acute cyanide Intoxication: A rare case of survival Indian Journal of Anaesthesia, [online] 58(3), pp 312–314 doi:https://doi org/10 4103/0019-5049 135045 Available at: Acute cyanide Intoxication: A rare case of survival - PMC (nih gov) [Accessed 10/06/24]
117 Jethava, D , Gupta, P , Kothari, S , Rijhwani, P and Kumar, A. (2014). Acute cyanide Intoxication: A rare case of survival Indian Journal of Anaesthesia, [online] 58(3), pp.312–314. doi:https://doi.org/10.4103/0019-5049.135045. [Accessed 10/06/24]
muscle cells and neurones. Therefore, the symptoms of cyanide poisoning can include low blood pressure, a slowed heart rate, convulsions and a coma 118 These symptoms are useful as stabilisation of the patient’s airways, breathing and circulation is often necessary before an antidote, typically Hydroxocobalamin, may be administered119 .
Cyanide is, however, easily traceable in an autopsy, using the relatively simple Cyantesmo colour test. It has a sensitivity of around 0 2mg120; the average lethal dose is 250mg121 so a homicide by cyanide would be easy to prove. This and its antidote are major drawbacks of its use as a tool of murder If treated in time, according to MedicalNewsToday ‘Out of 3165 human exposures, from 1993 to 2002, only 2.5% were fatal’.122
Batrachotoxin
This next poison is one you can find hopping around in the Colombian jungles: found in the skin of Poison Dart Frogs, batrachotoxin is extremely potent123 Once poisoned, death occurs in less than
118 ThoughtCo (2015) Why Cyanide Is so Lethal -- and How It Kills so Quickly. [online] Available at: https://www thoughtco com/overview-of-cyanide-poison -609287. [Accessed 10/06/24]
120 Docplexus (n d ) Docplexus [online] Docplexus Available at: https://www docplexus com/posts/cyanide-poisoning-an d-its-forensic-implications [Accessed 10/06/24].
121 Jethava, D , Gupta, P , Kothari, S , Rijhwani, P and Kumar, A. (2014). Acute cyanide Intoxication: A rare case of survival Indian Journal of Anaesthesia, [online] 58(3), pp.312–314. doi:https://doi.org/10.4103/0019-5049.135045. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4090999/ [Accessed 10/06/24]
122 Lloyd, W (2022) Cyanide poisoning: Symptoms, causes, and treatment [online] www medicalnewstoday com Available at: https://www medicalnewstoday com/articles/cyanide-poi soning [Accessed 10/06/24]
123 ED BluePlanet (2021). All About the Poison Dart Frog. [online] Blue Planet Aquarium Available at: https://www.blueplanetaquarium.com/education/all-abou t-the-poison-dart-frog-weird-and-wonderful-facts/#:~:
ten minutes and there is no cure124 , though tetrodotoxin (a poison in its own right - that of pu erfish as a connoisseur of Japanese cuisine might know) has been used as an antidote to varying degrees of success125 Still, even if you were to survive this poison, you would experience convulsions, muscle contractions, salivation and respiratory muscle paralysis126 as the toxin prevents the formation of action potential127 preventing nerves from contacting each other.
Batrachotoxin is alarmingly also relatively simple to obtain on the internet, from both labs and independent companies, at £286 for 10 µg128 - the minimum dose for fatality in humans129 - on one site. Overall, Batrachotoxin is one of the easiest poisons that is so lethal to acquire, but once you have done so, how should it be administered? Batrachotoxin, like many toxins found in nature, is to ward o predators130 and thus is lethal via both
124 Farrows (n.d.). Golden Poison Frog. [online] World Land Trust Available at: https://www.worldlandtrust.org/species/amphibians/gold en-poison-frog/#:~:text The%20poison%20permanently %20prevents%20nerves. [Accessed 10/06/24] text=Despite%20severe%20habitat%20destruction%2C%2 0poison [Accessed 12/06/24]
125 www sciencedirect com (n d ) Poison Dart Frog - an overview | ScienceDirect Topics. [online] Available at: https://www sciencedirect com/topics/agricultural-and-b iological-sciences/poison-dart-frog#: :text=While%20th ere%20are%20currently%20no [Accessed 10/06/24]
126 Dodd-Butera, T , Broderick, M and Meza, C (2024) Animals, poisonous and venomous [online] ScienceDirect Available at: https://www sciencedirect com/science/article/abs/pii/B9 780128243152010319 [Accessed 11/06/24]
127 Dodd-Butera, T., Broderick, M. and Meza, C. (2024) Animals, poisonous and venomous [online] ScienceDirect. Available at: https://www sciencedirect com/science/article/abs/pii/B9 780128243152010319.
128 www scbt com (n d ) Batrachotoxin | CAS 23509-16-2 | SCBT - Santa Cruz Biotechnology. [online] Available at: https://www scbt com/p/batrachotoxin-23509-16-2 [Accessed 10/06/24]
129 O ce for Science and Society (n d ) South American Poison Dart Frog [online] Available at: https://www mcgill ca/oss/article/health-you-asked/whycan-you-die-just-picking-south-american-poison-dart-f rog#: :text=There%20are%20several%20species%20of. [Accessed 10/06/24]
130 Dumbacher, J.P. (2014). Batrachotoxin. [online] ScienceDirect Available at:
ingestion and dermal contact. This means that it must be handled with care when being used, as a drop of batrachotoxin on the skin could be fatal131 , however this does allow an easy route of exposure for an assassin
The primary drawback of its use in murder is that Batrachotoxin is not entirely untraceable during autopsy. According to Oregon university ‘Batrachotoxin can be assayed using a modified Ehrlich reagent’132 , this means that if there is evidence of purchase you may still be found as the culprit
Hemlock
Finally, the poison responsible for the execution of famous Greek philosopher Socrates: water hemlock133 . Found all around various rivers, marshes and streams right here in the UK, it is Britain’s most toxic plant134 This means that there could be absolutely no purchase trial and an assassin could destress with a nice foraging session between jobs, as long as they ensure they get around eight leaves135 per target to guarantee the desired e ect. As with batrachotoxin, there is no cure and water hemlock poisoning and may lead to death within fifteen minutes.136 As there is no cure,
131 Danai, M and Ray, S D (2024) Batrachotoxin [online] ScienceDirect Available at: https://www sciencedirect com/science/article/abs/pii/B9 780128243152011271 [Accessed 11/06/24]
132 Grimes, H (2020) Batrachotoxin [online] Wou edu Available at: https://people.wou.edu/ courtna/ch350/Projects 2006/Gr imes/index html [Accessed 10/06/24]
133 Petruzzello, M. (2023). 7 of the World’s Deadliest Plants | Britannica [online] www britannica com Available at: https://www.britannica.com/story/7-of-the-worlds-deadl iest-plants [Accessed 10/06/24]
135 Vallie, S (2022) Poison Hemlock Poisoning [online] WebMD Available at: https://www.webmd.com/first-aid/poison-hemlock-poiso ning [Accessed 11/06/24]
136 www.webmd.com. (n.d.). Water Hemlock: Uses, Side E ects, Interactions, Dosage, and Warning [online]
stomach pumping and aggressive supportive care is the only chance someone with hemlock poisoning has at survival137; however, how likely this treatment is to help when the victim may die in fifteen minutes is questionable Whilst the mortality rate of hemlock poisonings is only 30%,138 This may be due to the fact that most exposures are not over the lethal amount. The higher the amount the more likely that the seizures caused by the interruption to the central nervous system will cause death 139
The Perfect Poison
Taking everything discussed into account, it appears batrachotoxin could act as the ‘perfect’ poison to carry out an assassination Whilst water Hemlock is a close second due to the advantage that it can be harvested locally and discreetly, it can (like the other two) still be identified in autopsy,140 and has a lower mortality rate than batrachotoxin Unlike cyanide and Hemlock, batrachotoxin does not seem to have a mortality rate but rather the resounding agreement that to
Available at: https://www webmd com/vitamins/ai/ingredientmono-94 8/water-hemlock. [Accessed 11/06/24]
137 Hemlock Poisoning Treatment & Management: Prehospital Care, Emergency Department Care, Consultations (2024) eMedicine [online] Available at: https://emedicine medscape com/article/821362-treatmen t?form=fpf [Accessed 11/06/24]
138 Hemlock Poisoning: Practice Essentials, Background, Pathophysiology (2021) eMedicine [online] Available at: https://emedicine medscape com/article/821362-overview ?form=fpf. [Accessed 11/06/24]
139 Schep, L J , Slaughter, R J , Becket, G and Beasley, D.M.G. (2009). Poisoning due to water hemlock. Clinical Toxicology, 47(4), pp 270–278 doi:https://doi.org/10.1080/15563650902904332. Available at: https://pubmed.ncbi.nlm.nih.gov/19514873/#: :text=Ingest ion%20of%20even%20a%20small,care%2C%20can%20resu lt%20in%20death [Accessed 11/06/24]
140 Labay, L M , Chan-Hosokawa, A , Homan, JW , McMullin, M M , Diamond, F X , Annand, M M , Marco, S M and Hollenbach, J M (2022) Poison hemlock determination in postmortem samples Forensic Science International, [online] 341, p.111500. doi:https://doi org/10 1016/j forsciint 2022 111500 Available at: https://pubmed.ncbi.nlm.nih.gov/36335848/ [Accessed 11/06/24]
survive would be a miracle.141 This being said, we should take into account that both cyanide and hemlock have a history of usage as suicide drugs142143 , therefore those using them may not have known the correct lethal dosage Even with this, batrachotoxin is the fastest acting of the three poisons and has no cure or e ective treatment
Batrachotoxin can act as a powerful reminder that whilst humanity has come far, nature was here first and in the case of poison we have yet to overtake it. Our ancestors that inhabited the jungles the frogs that harbour batrachotoxin live in, knew, even then, that it was a force to be reckoned with144 .
141 Chemistry World (2019) Batrachotoxin [online] Available at: https://www chemistryworld com/podcasts/batrachotoxin /7073 article [Accessed 11/06/24]
142 Rodríguez Padilla, C (2021) Cyanide poisoning as a suicide method: case report. Medicina Legal de Costa Rica, [online] 38(1), pp 29–37 Available at: https://www.scielo.sa.cr/scielo.php?pid=S1409-001520210 00100029&script sci abstract&tlng en [Accessed 12/06/24].
143 www stoa org (n d ) Punishment in Ancient Athens [online] Available at: https://www stoa org/demos/article punishment@page=5 &greekEncoding=UnicodeC html#: :text=From%20the% 20end%20of%20the [Accessed 12/06/24]
144 Research News (2017) Behold, the ancient ones [online] Available at: https://www floridamuseum ufl edu/science/behold-theancient-ones/#: :text=Some%20native%20tribes%20in%2 0the [Accessed 12/06/24]
Chemical Structures of ‘Biological Catalysts’
By Conner J. Evans
What is a ‘biological catalyst’?
Enzymes are sometimes known as biological catalysts, weakening substrate bonds thus lowering activation energy of the chemical breakdowns they catalyse Without them, metabolic reactions such as those involved in digestion would be extremely ine cient, life as we know it would not be sustainable; it is therefore of great importance that there are no errors in the polypeptide chain(s) or changes to conditions which could result in denaturation of the enzyme.
In this article, I will explore the chemical structure of enzymes and their mechanisms of binding
What are the di erent types of enzymes?
There are six main categories of enzymes145 146:
- Oxidoreductases (e.g: lactate dehydrogenase), - catalyse redox reactions in which oxygen or hydrogen are gained or lost from a molecule.
- Transferases (e g: acetate kinase) - involved in transfer of functional groups between molecules.
- Hydrolases (e,g: sucrase) - these catalyse hydrolysis of polymers into their constituent monomers.
- Lyases (e g: oxalate decarboxylase)involved in removal of groups of atoms without hydrolysis.
- Isomerases (e g: glucose-phosphate isomerase) - involved in rearrangement of atoms of a given molecule.
145 Lewis, T and Stone, W L (2022) Biochemistry, Proteins Enzymes [website] Available at: https://www ncbi nlm nih gov/books/NBK554481/#: :text=T he%20first%20model%20called%20the, (accessed 23 May 2024)
146 University of Maryland, ’Classes of Enzymes,’ [website]. Available at: https://science.umd.edu/classroom/bsci424/BSCI223WebSite Files/ClassesofEnzymes htm, (accessed 15 May 2024)
- Ligases (e g: DNA ligase) - catalyse joining of pairs of molecules through the use of ATP hydrolysis.
Why are there di erent types of enzymes?
Each distinct type of enzyme is complementary to a di erent substrate The substrate to which a given enzyme will bind is determined by the shape of its active site as formed by the 4 levels of protein structure:
- Primary structure - a polypeptide chain formed by condensation reactions between adjacent amino acids to form peptide bonds
- Secondary structure - folding of the primary structure into either an α helix or β pleated sheet as a result of hydrogen bonding between amino acids.
- Tertiary structure - further folding due to hydrogen or ionic bonding, or disulphide bridge formation between the variable groups of the amino acids of a polypeptide chain Tertiary structure determines the shape of the active site.
- Some enzymes may also have quaternary structure, with multiple polypeptide chains bonded together.
Di erent enzymes carry out di erent- but often synergistic - functions in living organisms, for example, the coordination between DNA helicase and RNA primase: DNA helicase breaks the hydrogen bonds between complementary base pairs of opposing DNA nucleotides to create 2 template strands RNA primase then ‘synthesises a primershort nucleic acid sequence that provides a starting point for DNA synthesis147’ The primer is made of
147 www nature com (2014) primer | Learn Science at Scitable, [website]. Available at: https://www nature com/scitable/definition/primer-305/#:~ :text=A%20primer%20is%20a%20short, (accessed 18 June 2024)
RNA nucleotides, basically a small mRNA that carries the complementary codons of DNAs triplet codes
Both enzymes are di erent structurally and functionally, but both catalyse reactions vital for DNA synthesis for mitosis in healthy cells
How do enzymes form an enzyme-substrate complex?
There are two suggested models to explain enzyme-substrate complex formation:
Why and how do non-optimal pH levels denature enzymes?
1 Lock & Key148 (fig 2) - the enzyme’s active site is exactly complementary to the substrate5.
Figure 1149
2. Induced Fit150 (fig. 3) - the enzyme and substrate are not, initially, complementary, so the active site of the enzyme must instead be altered slightly to accommodate the substrate
pH is hydrogen potential; the lower the pH value, the more acidic (therefore less alkaline) a solution as acids are H+ ion (proton) donors. Di erent enzymes require di erent conditions for optimal function and changes to these conditions may bring about denaturation152 . In the case of a pH change specifically, denaturation occurs because changes to H+ ion concentration impairs ionic bond interactions in the enzyme’s tertiary structure, thus a ecting the shape of the active site
Imagine, for example, an enzyme whose optimum pH is 7.0. At this pH value, a substrate will attach itself to the enzyme via ionic bonds - there will be anions and cations Now if the pH value were to decrease, there would be a greater concentration of H+ ion available to react with the enzyme’s anions and vice versa if the pH were to increase; in other words, ionic bond potential formation decreases. As a result the tertiary structure is unravelled and the shape of the active site changes so it is no longer complementary to its typical substrate(s); the denatured enzyme cannot form an enzyme-substrate complex and the rate of this hypothetical enzyme-controlled reaction increases, potentially fatal for the organisms.
148 Lewis, T and Stone, W L (2022) Biochemistry, Proteins Enzymes. [website] Available at: https://www ncbi nlm nih gov/books/NBK554481/#:~:text=T he%20first%20model%20called%20the, (accessed 23 May 2024)
149 The Science Hive (2021) Enzymes (A-Level) [website] Available at: https://www thesciencehive co uk/enzymes-alevel (accessed 18 June 2024)
150 Lewis, T and Stone, W L (2022) Biochemistry, Proteins Enzymes. [website] Available at: https://www ncbi nlm nih gov/books/NBK554481/#:~:text T he%20first%20model%20called%20the, (accessed 23 May 2024)
151 The Science Hive (2021) Enzymes (A-Level) [website] Available at: https://www thesciencehive co uk/enzymes-alevel (accessed 18 June 2024)
152 Encyclopedia Britannica (2018). Denaturation | biology, [website] Available at: https://www.britannica.com/science/denaturation, (accessed 18 June 2024)
Mysteries of Reproductive Evolution
By Luby Kou Hoi Kiu
Excessively Large Eggs
The kiwi, as depicted above, is a flightless bird endemic to New Zealand All species of kiwi birds are classed as vulnerable as per the IUCN155 and it wasn’t until 1991 that management action was taken to prevent them becoming extinct with the help of Kiwi Recovery Programme.
With adult size varying from 38-85cm you probably wouldn’t think that their eggs could reach up to 20% of the mother's body weight. For comparison, a human baby at birth weighs only 5% of mother's body weight, while an ostrich egg is just 2%. Various suggestions have been made as to why kiwis lay such large eggs: some believe that kiwi and its egg have always existed in this unfortunate size ratio; others suggest that adult kiwis were once much larger, their size proportional to the eggs, but have shrunk over the millennia, egg size failing to catch-up
Despite the pain that surely arises from laying such large eggs, the Kiwi is known to be very productive: females may lay up to 100 eggs in their lifetime, and
153 Animal Club, How big are kiwi eggs?’ Animal Club, [website] Available at: https://animal-club co uk/how-big-are-kiwi-eggs/
154 Robertson L, ‘7 Curious Facts That Prove Kiwis Are Amazing Little Birds’ (2014) Available at: https://www thedodo com/7-curious-facts-that-prove-kiw638917637 html (Accessed 13 June 2024)
155 M. Ganguly, (2017) Two kiwi species no longer endangered in new red list, CNN Available at: https://edition.cnn.com/2017/12/05/world/kiwi-red-list-intl/ index html (Accessed: 13 June 2024)
there are some advantages with such an enormous size. While most bird eggs are 35-40% yolk, kiwi’s egg is 65% yolk156 The nutritious yolk produces fully-feathered chicks and sustains hatchlings for their first week of life, by which point they may already provide for themselves
In addition to this obvious advantage, Kiwis have a few adaptations to allow them to produce and care for their large eggs with relative ease:
Behavioural
- Often forming lasting pair-bonds, the male broods the egg inside a nest built in a burrow for 75-84 days, one of the longest incubation periods among birds
Anatomical
- Kiwi’s ribs are enlarged to support body weight when leaning on the egg4 their brood patch - a 10cm by 12cm area of featherless skin on the ventral side of an incubating bird to enable heat transfer to egg with superficial blood vessels.
- Sternal ribs and the sternum pushed forward 4 to allow the kiwi to carry the egg ventrally below the narrow pelvis This is because kiwis cannot carry their large eggs between the ilium and pubis, close to the rachis, as is the case in other birds
156 Anonymous , A. (2021) Enormous egg, Save the Kiwi. Available at: https://savethekiwi.nz/about-kiwi/kiwi-facts/enormous-egg / (Accessed: 27 May 2024)
Female Hyenas’ Pseudo-penises
Figure 7157
Figure 8158
Both male and female hyenas possess fully functioning penises and thus are often di cult to distinguish between
However, a female hyena’s “penis” is in fact an extended clitoris, approximately 90% the length of that of a male with the same diameter (17mm long and 22mm in diameter) The labia are fused to form a scrotum containing fat and connective tissue resembling testicles The urogenital canal runs the length of the clitoris, rather than venting from below so females urinate via their pseudo-phalluses, which also contain erectile tissue so both males and females may experience erections 11
During mating, the female hyena must fold her ‘penis’ into her body to allow the male to insert his penis into hers.10
(A) e male mounts the female, who stands still, with her head lowered and her clitoris retracted into her abdomen
(B) e male shows penile 'flips, ' as indicated by arrows
(C) Underside view
(D) lateral view of a female spotted hyena, with arrows showing the site of the clitoral opening, which is located far anterior to the point of entry in other female mammals
(E) Once the male locates the opening, he squats down and scoots forward to enable intromission, which is followed by pelvic thrusting
Whilst this information is fascinating, females must endure an agonising birth through the tiny, clitoral opening of their pseudo-phalluses.
Mother hyenas would be in an unimaginable amount of pain while giving birth to foetuses of 6-7 cm -
160Drea. C, et al., ‘Hyenas’ (2018) Available at: https://www researchgate net/figure/The-mating-sequence -in-spotted-hyenas-A-The-male-mounts-the-female-who -stands-still fig3 340879586 (Accessed: 27 May 2024) -penis-A-and-clitoris-B-Note-the-distinctive-shapes-of-t he fig5 7825103 (Accessed:27 May 2024)
much larger than the clitoral opening (2.2cm) so frequently results in clitoral tears With a 9-18% chance of death during childbirth and a 25% survival rate of cubs, it’s di cult to understand the purpose for which female hyenas have evolved as such. Moreover, considering that the birthing process can last up to 48 hours, female hyenas should be put on the top list for animals su ering because of their evolution161
Eaten Alive by O spring
Figure 4162
Figure 5163
As part of the life cycle of the female sea-louse, having been impregnated, her children proceed to devour her from the inside out The male invertebrate captures every female he encounters (up to 25 at a time) to impregnate, often causing the females’ abdomens to rip, potentially even resulting in death.
“As a dioecious species, sea lice reproduce sexually, with adult male typically forming mate-guarding pre-copulatory pairs with pre-adult females ”164
161 Liek@outinafrica.com, A. (2020) Not fun becoming a hyena mother, Kwambili Safari Lodge Available at: https://www.kwambilisafarilodge.com/not-fun-becoming-h yena-mother/ (Accessed: 01 June 2024)
162Budd.G.C, ‘Speckled sea louse’ (2007) Available at: https://www marlin ac uk/species/detail/1663 (Accessed: 01 June 2024).
163 Iannone, J (2014) 5 terrible ways nature turns pregnancy into a horror movie, Cracked com Available at: https://www cracked com/blog/5-terrible-ways-nature-turn s-pregnancy-into-horror-movie (Accessed: 01 June 2024)
164 R Cox, M L Groner, C D Todd, G Gettinby, T Patanasatienkul, C W Revie (2017) Mate limitation in sea lice infesting wild salmon hosts: the influence of parasite sex ratio and aggregation, ESA, Available at: https://esajournals.onlinelibrary.wiley.com/doi/10.1002/ecs2 2040 (Accessed: 17 June 2024)
Now, as the newborns start to grow inside the mother, there’s a lack of space Instead of giving birth like other organisms, the newborns feast on the remains of their mother’s body, a cruel but e ective reproduction strategy which does, in fact, increase newborns’ survival rate165 .
165 Iannone, J. (2014) 5 terrible ways nature turns pregnancy into a horror movie, Cracked com Available at: https://www.cracked.com/blog/5-terrible-ways-nature-turn s-pregnancy-into-horror-movie (Accessed: 01 June 2024)