Inside The Pulse - Part 2

Inside The Pulse

Volume 1

Part 2 Contents

From DC, CIS, NAS, NLCS:

To What Extent is Sunak’s 15 Year ‘Transfer’ in the NHS Workforce Viable?

- Charlotte Holt_Page. 6

Advances in Ophthalmology Technology: A 2023 Overview

- Eisha Aqil_Page. 9

Phage Therapy: a virus ‘gone good’ and a battle against MRSA

- Ayush Surendran_Page. 11

How Does Smoking Influence Lung Cancer?

- Jimin Park_Page. 14

The Rise of Cryotherapy in Sports Medicine: A Modern Solution for Athletes

- Harrison Cox_Page. 17

NHS Medical Apprenticeships

- Anna Zaman_Page. 19

Peto’s Paradox: Why Blue Whales Can’t Get Cancer

- Prithvi Gupta_Page. 20

How Does Alcohol Influence Liver Cancer?

- Suemin Park_Page. 22

Ethics in Medicine

- Huichan Jung_Page. 25

The Link Between Babies Born by Caesarean Sections and Allergies

- Alexander Gunson_Page. 27

Effects of Climate Change on Ecosystems and Proposed Mitigation Strategies

- Khrysha Arya_Page. 28

How Cocaine Affects the Brain, and How Addiction To It Can Be Treated

- Alexander Mantzavinatos_Page. 30

To Complex Dynamics of Obesity in a Globalized World

- Mishel Kudel_Page. 32

Neurofeedback Therapy

- Sunaina Nambiar_Page. 33

What is CRISPR?

- Elisa Westerhof_Page. 36

Steady Does It: CRISPR- A Peek Of The Future

- Chantille Qi-En Marican_Page. 39

Nanotechnology: Mini Missiles in the War on the Cancer

- Anushree Shah_Page. 41

Alliance for hypocritic medicine

- Delisha Dias_Page. 43

The Prickly Secrete: Sea urchins and cancer

- Leila Ghandour_Page. 47

Principles of Medical Ethics and Their Importance

- Devyansh Pandey_Page. 49 3

Editor’s Notes:

This publication, Inside The Pulse, is the first volume of a collaborative magazine organized by Dubai Medical Society (DMS) with contributions from four schools in Dubai. DMS aims to be a platform for aspiring medics, dentists and scientists to share their research and insights. This magazine is an attempt to reflect our commitment to interdisciplinary approach, bringing together the different perspectives.

As lead coordinator, I had the privilege of curating and editing an impressive collection of articles covering a wide range of topics. Our vision at DMS is to continue supporting students in developing their interests and deepening their insight into their chosen fields. We look forward to publishing the next volume in 2025 which will include even more high-quality contents.

I would like extend my thanks to my fellow DMS coordinators Ayush Surendran and Uddayvir Singh for their support in producing this magazine. Special thanks to Mieke Visser and Anna Zaman for allowing us to include contents from DC’s medical magazine Beneath Our Skin, where some of the articles in this issue were originally published. Lastly, thank you to all the writers from DC, CIS, NAS and NLCS for their contributions!

Jimin Park

[Editor in Chief - Dubai College DMS Coordinator]

[Part 2]

TO WHAT EXTENT IS THE PLAN TO 'TRANSFORM' THE NHS WORKFORCE

VIABLE?

Charlotte Holt

Within the United Kingdom, the National Health Service is both a great source of pride and a system notorious for its flaws. Despite the fact that standardised medicine encourages healthcare equity unseen by the some of the world’s most developed countries, it is true that its quality can be compromised. The NHS has long been a political weapon for many British parties, who pledge support for the system to gain votes. Therefore, it is surprising that such little progress been made in this area if it has clearly been identified by both the public and politicians as a severe point for improvement. The former prime minister, Rishi Sunak, aimed to tackle this issue with a 15-year plan (published June 2023) and the current prime minister has set out new ideas too. But how do their ideas differ? Through each of the three targeted areas of ‘train, retain, and reform’, to what extent is Sunak’s plan to transform the NHS viable and is Starmer’s an improvement on his predecessor’s?

The ‘train’ area of Sunak’s plan had the main aim of growing the workforce, through both recruitment and, of course, training more staff initially. Issues such as geographic and social economic disparity have been presented as reasons for why not all the people who want to work in the NHS are trained to. The plan set out the introduction of apprenticeships from September 2024, enabling doctors to train while earning a salary, thus eliminating financial barriers for many aspiring medics. Additionally, the government hoped to open more medical schools, targeting diverse geographic locations around the country. Both initiatives hope to boost domestic recruitment and lower the costs of employing as many agency recruitment and international staff. Encouraging access into NHS careers in underprivileged areas also aimed to maintain diversity within the workforce. Currently 25% of NHS staff are “Asian, black, or another minority ethnicity, compared to 13% of all working age adults in the UK.”1 The only question remains: what money are these medical schools and apprenticeships being funded with? Unfortunately, the plan does not clearly outline this, simply saying that “NHS England is committed to...develop[ing] a national policy framework that can be used locally to guide the use of funding”2. Therefore, it is not actually said how this money would be obtained, neither does it acknowledge the fact that many students will pursue higher qualifications after their apprenticeship, as opposed to entering the workforce immediately. Within the case study of the Stoke-on-Trent Health and Care course, it is encouraged that the apprenticeship is done alongside university study.3 While lessening the reliance on international staff promises lower expenditure, the means through which this will be done are unclear. Unfortunately, the issue of funding is present throughout Starmer’s plan as well. The government aims to create an additional 7500 medical school places, which would be doubling the current number4. Doctor apprenticeships are also a key idea, although these are controversial among the public and those with concerns about maintaining the quality of care.

Secondly, the ‘retain’ strand centred around embedding the right culture and improving retention (creating a workplace that makes hospitalists want to stay). The system would build on interventions that have previously been successful, like having flexible opportunities for potential retirees and modernising the pension scheme. Such interventions include the NHS emeritus scheme, which connects partially or recently retired doctors with providers that seek the help only an experienced clinician can offer.5 They would also commit to ongoing funding of health and childcare support, with the latter resulting in fewer staff members choosing to not return to work after the end of their paternity/maternity leave. While not confirmed, a “tie in” period was also discussed for junior doctors

1 The NHS workforce in Numbers (no date) Nuffield Trust

2NHS Long Term Workforce Plan - NHS England. (2023)

3 Childcare, Health & Social Care - Stoke-on-trent college (2023)

4 (“DHSC Response to Reporting on Medical School Places – Department of Health and Social Care Media Centre”)

5 Home (2023) NHS Emeritus

to confirm that a certain number of their newly trained years will be spent giving back to the service that trained them. These ideas could help to ensure that a greater percentage of the employees that the NHS funds the training of will remain in the system, making their training a more worthwhile investment. This is significant, as the number of doctors that opt to leave the NHS is increasing, with 4,843 doctors leaving the UK to work abroad during the period of May 2021 and May 2022.6 Enhanced healthcare is also estimated to make a large difference in retaining staff. In particular, mental health support is highly sought from overworked and underpaid employees, with many leaving the workforce entirely due to burnout with a lack of services offered.7 As such, it seemed this strand held promise for retaining more staff members through low-cost initiatives that tackle the harsh culture of the NHS. Labour’s plan differs slightly, in that there is less focus on expanding the workforce by tying in doctors. They also wish to create a healthier environment for their doctors, making the NHS once again a great place to work, and one that many would not choose to leave. In changing the culture, healthcare professionals will have a better work life balance as a result of fewer understaffing issues. The taxing of doctor’s pensions is being re-examined to encourage senior clinicians to continue in the workforce. It is hoped that this money will come from the £3billion8 that the government spends on locum agencies to cover shifts that NHS staff simply cannot.

The third and final strand, ‘reform’ focused on adjusting the way that NHS staff work and train. This includes creating innovative ways in which the multidisciplinary team can support each other so that qualified staff can spend more of their time with patients. Leading on from this, certain professionals will be able to expand their power (e.g. prescribing rights) within General Medical Council guidelines. Furthermore, more staff would be channelled into mental health, primary and communicative care fields to focus on prevention, lessening the severe reliance on secondary care. In an effort to modernise the system, new technological advancements would be harnessed and developed with an experienced team to build upon the Topol Review. This report clearly highlights how artificial intelligence, robotics and genomics can improve efficiency.9 The final change would implement shorter medical school programmes and internships. However, there is reason to believe that this may be an unpopular choice for incoming medics, with many already opting for courses that are longer than necessary to complete an intercalated masters, year abroad or personal project. Approximately one third of UK medical students complete an intercalated degree in addition to their MBChB degree.10 Aside from this, the incorporation of technology has great potential to reduce waiting lists for both surgeries and laboratory tests. Moreover, the shift from secondary to primary care would indicate lower spending due to the cheaper requirements of clinics compared to hospitals. Research conducted by the Health Foundation found that “Over the four-year period studied (2004/05 to 2007/08), it is estimated improvements in primary care for stroke... may have reduced secondary care costs by some £165 million.”11 This reformation of the entire system is unique in that it does not require significantly more funding, but channels existing money into different areas where it will be most effective. Like the Conservative party, the idea of a reformation is key to Labour’s plan as well. There is also a heavy focus on expanding primary care, in order to ensure that it runs more efficiently. The idea that sometimes no medicine is the best medicine is clear throughout both documents, and it appears that prevention of serious illness through social prescribers, improved quality of life and easier access to GP appointments will save a vast sum of money for the taxpayer in the long term. Technology has been presented as an important tool in relieving pressure currently on the NHS. In addition to this, Labour plans to put Britain at the forefront of clinical trials and research by removing unnecessary and outdated bureaucracies that other countries do not face.

These two plans offer hope for the NHS that has not been so prominent in many years. In comparison to each other, they offer greatly similar ideas and are both far more detailed and realistic than the 2019 plan. The ‘train’ strand differs slightly from Labour’s plans to accumulate a greater workforce,

6 (2023) Factcheck: How many UK doctors are going abroad and how does pay compare?

7 Doctors plan to leave NHS in growing numbers due to burnout, Gmc warns (2023)

8 Labour. Build an NHS Fit for the Future

9 (No date) NHS choices.

10 Nicholson, J.A. et al. (2010) ‘Why medical students choose not to carry out an intercalated BSC: A questionnaire study’

11 (No date a) Do quality improvements in primary care reduce ... - the health foundation

7

with the former championing more medical school places with no real proof that there is money for this. However, targeting under-represented demographics has the potential to make the training pathway far more accessible. Secondly, the post-retirement plans may give support to the busiest fields of care offered by the NHS, at a cost lower than full-time employment. By reprogramming the way that seniority is regarded, junior doctors and consultants alike can support one another, which is also a great stride in tackling the stigma surrounding mental health support. Notably, the name ‘junior doctor’ itself has been recently changed under the Labour party to ‘resident doctor’, reflecting better their skill set and training. Finally, the reform strands seems the most pioneering of all. By changing the way that the NHS works and finding new jobs for each member of a multidisciplinary team, its effectiveness can be maximised. By allowing the nursing profession to cover some jobs of doctors, the workforce gap will again be lessened. With these collaborations alongside the use of technology from a heavily researched review, the NHS will be able to function to a fuller extent of its ability. There is no doubt that more funding is needed, but these plans highlight how little changes further down in the system can have a vast impact higher up. As a result of this, Starmer’s plan appears viable, as did Sunak’s, and has the potential to make a real difference to healthcare in the UK.

References

The NHS workforce in Numbers (no date) Nuffield Trust. Available at: https://www.nuffieldtrust.org.uk/resource/the-nhs-workforce-in-numbers (Accessed: 02 January 2024).

NHS Long Term Workforce Plan - NHS England. (2023) Available at: https://www.england.nhs.uk/wp-content/uploads/2023/06/nhs-long-term-workforce-plan-v1.2.pdf (Accessed: 02 January 2024).

Childcare, Health & Social Care - Stoke-on-trent college (2023) Stoke. Available at: https://www.stokecoll.ac.uk/course-areas/childcare-health-social-care/ (Accessed: 02 January 2024).

“DHSC Response to Reporting on Medical School Places – Department of Health and Social Care Media Centre.” Healthmedia.blog.gov.uk, healthmedia.blog.gov.uk/2024/02/27/dhsc-response-toreporting-on-medical-school-places/. (Accessed: 05 October 2024)

Home (2023) NHS Emeritus. Available at: https://www.nhsemeritusconsultants.org/ (Accessed: 02 January 2024).

Johnson, H. (2023) Factcheck: How many UK doctors are going abroad and how does pay compare?, Channel 4 News. Available at: https://www.channel4.com/news/factcheck/factcheckhow-many-uk-doctors-are-going-abroad-and-how-does-pay-compare (Accessed: 02 January 2024).

Doctors plan to leave NHS in growing numbers due to burnout, Gmc warns (2023) The Guardian Available at: https://www.theguardian.com/society/2023/nov/12/doctors-plan-to-leave-nhs-ingrowing-numbers-due-to-burnout-gmc-warns (Accessed: 02 January 2024).

Labour. Build an NHS Fit for the Future. labour.org.uk/wp-content/uploads/2023/05/MissionPublic-Services.pdf. (Accessed: 05 October 2024)

(No date) NHS choices. Available at: https://topol.hee.nhs.uk/the-topol-review/ (Accessed: 02 January 2024).

Nicholson, J.A. Cleland, J. Lemon, J. Galley, H.F. (2010) ‘Why medical students choose not to carry out an intercalated BSC: A questionnaire study’, BMC Medical Education, 10(1). doi:10.1186/14726920-10-25.

(No date a) Do quality improvements in primary care reduce ... - the health foundation. Available at: https://www.health.org.uk/sites/default/files/DoQualityImprovementsInPrimaryCareReduceSecond aryCareCosts_summary.pdf (Accessed: 02 January 2024).

ADVANCES IN OPHTHALMOLOGY

TECHNOLOGY:

A 2023 OVERVIEW

Eisha Aqil

In recent years, ophthalmology has seen significant technological advancements aimed at improving diagnosis, treatment, and patient outcomes. These innovations span areas such as artificial intelligence (AI), gene therapy, drug delivery systems, and advanced imaging techniques, contributing to a new era of precision medicine in eye care.

Artificial intelligence is playing an increasingly prominent role in ophthalmology, particularly in disease detection and progression monitoring. AI algorithms, such as those used in deep learning networks like AVA-Net, have demonstrated high accuracy in diagnosing conditions like diabetic retinopathy by analyzing optical coherence tomography angiography (OCTA) images. This technology allows clinicians to differentiate between healthy and diseased eyes with minimal human input, enhancing early detection and treatment accuracy (Modern Retina, 2023). In addition, AI tools like the iPredict AI Eye Screening System are pushing the boundaries of automation in ophthalmology. iPredict, currently seeking FDA approval, offers fully automated age-related macular degeneration (AMD) screening, which could revolutionize how clinicians approach the early identification of AMD in at-risk populations (Modern Retina, 2023).

Gene therapy is becoming an important treatment option for hereditary eye diseases. One notable advancement is the FDA approval of Luxturna, a gene therapy for treating Leber congenital amaurosis, a rare genetic disorder causing blindness. Luxturna delivers a correct copy of the RPE65 gene directly to the retinal cells, restoring functional vision in affected individuals. This marks a breakthrough in personalized medicine for ocular diseases and could pave the way for further developments in genetic treatments for eye conditions (BrightFocus Foundation, 2023).

Advances in imaging technologies such as swept-source optical coherence tomography (OCT) are significantly improving the diagnosis of retinal diseases. OCT provides high-resolution images of the retina, allowing for earlier detection of conditions such as macular degeneration and diabetic retinopathy. The integration of AI with OCT, as seen in the use of ultra-widefield fundus autofluorescence imaging, has enabled even more precise tracking of disease progression, particularly in disorders like retinitis pigmentosa (Modern Retina, 2023). Another advancement is OCTA, which offers non-invasive imaging of blood flow in the retina. This technology provides detailed visualizations of the retinal vasculature without the need for dye injections, making it safer and more comfortable for patients. OCTA is particularly useful in diagnosing and monitoring diseases like diabetic retinopathy and AMD.

Recent innovations in drug delivery systems have addressed one of the biggest challenges in ophthalmic treatments: medication adherence. Traditionally, glaucoma patients are required to use eye drops daily, leading to compliance issues. In response, the iDose TR implant has been developed to continuously release glaucoma medication for up to three years. This implant ensures consistent drug delivery, reducing the need for daily eye drops and potentially improving long-term outcomes for patients (BrightFocus Foundation, 2023).

Laser treatments in ophthalmology have also seen notable advancements, particularly in the treatment of cataracts and refractive errors. Femtosecond laser-assisted cataract surgery (FLACS) provides greater precision in lens fragmentation and reduces recovery time compared to traditional methods. Meanwhile, SMILE (Small Incision Lenticule Extraction) has emerged as an alternative to LASIK for correcting myopia, offering faster recovery and fewer complications (BrightFocus Foundation, 2023).

The technological advancements in ophthalmology have significantly improved the landscape of diagnosis and treatment for various eye conditions. From AI-driven diagnostics and advanced imaging to gene therapy and innovative drug delivery systems, these technologies are helping clinicians deliver more precise and personalized care. As these innovations continue to evolve, the future of ophthalmology holds even greater potential for improving patient outcomes and quality of life.

References

BrightFocus Foundation. (2023). FDA Approves First-of-its-Kind Glaucoma Treatment. Retrieved from https://www.brightfocus.org

Modern Retina. (2023). AI advancements in ophthalmology: What’s new in 2023 so far. Retrieved from https://www.modernretina.com

White, B., 2017. The truth of Nye Bevan’s words on the NHS. [Online]

Available at: https://www.theguardian.com/politics/2017/jun/02/the-truth-of-nye-bevans-words-on-the-nhs

Anon., 2021. Admissions to Medicine in 2021. [Online]

Available at: https://www.medschools.ac.uk/media/2864/uk-admissions-to-medicine-in-2021.pdf

Anon., 2020. Annual population growth of the United Kingdom from 1970 to 2020. [Online]

Available at: https://www.statista.com/statistics/281956/uk-population-growth/

Anon., 2024a. NHS medical staffing data analysis. [Online]

Available at: https://www.bma.org.uk/advice-and-support/nhs-delivery-and-workforce/workforce/nhs-medicalstaffing-data-analysis#:~:text=High%20vacancies,5.7%25%20of%20all%20medical%20posts.

Anon., 2024b. Pressures in general practice data analysis. [Online]

Available at: https://www.bma.org.uk/advice-and-support/nhs-delivery-and-workforce/pressures/pressures-ingeneral-practice-data-analysis

Anon., n.d. Encyclopedia Britannica. [Online]

Available at: https://www.britannica.com/biography/Aneurin-Bevan

Anon., 2024c. Put pay right and start to solve the NHS’ many problems. [Online]

Available at: https://www.unison.org.uk/news/2024/02/put-pay-right-and-start-to-solve-the-nhs-manyproblems/

Yang, J., 2023. On average, how many additional unpaid hours do you work per week for your organization, over and above your contracted hours?. [Online]

Available at: https://www.statista.com/statistics/883433/nhs-england-staff-working-extra-unpaid-hours/ #:~:text=In%202022%2C%20roughly%2043%20percent,percent%2011%20hours%20or%20more.

Anon., 2024d. UNISON-NHS-pay-position-2024.pdf. [Online]

Available at: https://www.unison.org.uk/content/uploads/2024/02/UNISON-NHS-pay-position-2024.pdf

Moberly, T., 2021. Doctors’ early retirement has trebled since 2008. [Online]

Available at: https://www.bmj.com/content/373/bmj.n1594

Anon., 2022. A third of junior doctors plan to leave NHS to work abroad in next 12 months. [Online]

Available at: https://www.bmj.com/content/379/bmj.o3066 [Accessed 30 March 2024].

Anon., 2023a. NHS Staffing - the role of overseas doctors. [Online]

Available at: https://www.imgconnect.co.uk/news/2023/01/nhs-staffing-the-role-of-overseas-doctors/172

Anon., 2023b. Why British Doctors Move to Australia: A Land of Opportunities and Fulfilment. [Online]

Available at: https://www.jonandjon.com/why-british-doctors-move-to-australia/#:~:text=Over%20the%20past %20decade%2C%20there,over%20the%20next%20twelve%20months.

Goodair, B. & Reeves, A., 2022. Outsourcing health-care services to the private sector and treatable mortality rates in England, 2013–20: an observational study of NHS privatisation. [Online]

Available at: https://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(22)00133-5/ fulltext#seccestitle140

PHAGE THERAPY: A VIRUS ‘GONE GOOD’ AND A BATTLE AGAINST MRSA

Ayush Surendran

Introduction

In the seemingly endless and diverse process of Darwinian evolution, specific bacterial species such as MRSA (Methicillin-resistant Staphylococcus aureus) boldly withstand their selection pressures: The antibiotics. Discovered post the replacement of the penicillin antibiotic with methicillin - to remedy staphylococcus infections-1 in October of 1960,2 MRSA developed resistance at exponential rates to a large pool of beta lactam class antibiotics- inclusive of the aforementioned antibiotics.3

In light of a MRSA outbreak in Boston, 1968,3 Scientists suggested that the transfer of mecA genecontaining plasmids between S.aureus cells, coded for two-fold PBP2a proteins: enzymes that would continue to build the bacterial cell wall (in the presence of antibiotics), and membrane pumps that draw out antibiotics entering the cell.4

In an era where S.aureus gains resistance to the limited range of antibiotics that can treat it, where an annual average of 80,000 MRSA cases and a mortality of 15% of these cases (through endocarditis, sepsis etc) is an actuality,5,6 and where S.aureus is capable of soon resisting all classes of antibiotics,7 it is imperative that we develop effective solutions to lower the presence of MRSA in hospitals and raise the efficacy of hospital care overall.

Felix D’Herelle, the discoverer of the bacteria killing properties of phages15

Bacteriophages- what are they?:

The recent discovery of phages-formally known as Bacteriophages- by William Tort in 1915, led to an epiphany two years later by Felix d’Herelle that they could be used to destroy large populations of bacteria in general,8 as phages selectively infect and produce a battalion of their copies in bacterial cells. Hence, they are typically defined as a ‘‘virus of a bacteria’’.9

According to Brussow and Hendricks,10 there are approximately 1030 phages that occur naturally, though they can be produced through engineering their genes to not just increase specificity to a particular strain, but to allow phage drugs to be manufactured on a mass scale and used therapeutically against MRSA and other resistant species.11

The structure of a bacteriophage16

Phages vs. MRSA:

Once a phage has been introduced into an infected medium, the war between MRSA and the phages begin, but unfortunately this is short lived as MRSA shockingly engenders its own hamartia through its greatest tool: efflux pumps. Complex proteins that are equipped to remove antibiotic molecules that enter a MRSA cell.12

How do phages then overpower the mighty bacteria?. Pursuant to Turner, PhD’s research, they commence by binding to the external end of an efflux pump; thereby entering the cell. Secondly, they penetrate through the biofilm, and after passing into the cell cytosol, repeatedly replicate their genomes, proliferate in number, and secrete lytic enzymes to a point where the enormous number of enzymes are able to digest and ergo weaken the cell wall of MRSA, causing it to explode as a large volume of water rushes into the cell.

Interestingly, Turner’s research has proven that the evolutionary relationship between MRSA and its environment is always desirable, as when cells are exposed to phages for a long duration, the bacteria evolve to decrease the efflux pumps present in the membrane. However, this increases sensitivity to beta lactam antibiotics as they are no longer prohibited from passing into the cell, allowing them to sequester and ultimately kill the bacterial populations.13,14

Bacteriophages attaching to the cell receptors of a bacteria17

Conclusion:

Comprehending the biochemistry and the mechanism of action of bacteriophages has the potential to have a large scale impact on the field of healthcare in the 21st century. Through the introduction of more genetic modification techniques in this technology-run world, the capacity to eradicate MRSA and other resistant species becomes a reality; with the prerogative of lower overall mortality rates within both the existing and future human populations.

References:

1) Cookson, B. (2011) Five Decades of MRSA: Controversy and uncertainty continues - the lancet Available at: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61566-3/ fulltext (Accessed: 19 August 2024).

2) Harkins, C.P. et al. (2017) Methicillin-resistant Staphylococcus aureus emerged long before the introduction of methicillin into Clinical Practice, Genome biology. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5517843/ (Accessed: 19 August 2024).

3) About MRSA (2022) About MRSA - MN Dept. of Health. Available at: https://www.health.state.mn.us/diseases/staph/mrsa/basics.html#:~:text=MRSA%20is %20resistant%20to%20(unable,a%20Boston%20hospital%20in%201968.) (Accessed: 19 August 2024).

4) Gillet, Y. et al. (2018) Fulminant Staphylococcal infections | microbiology spectrum. Available at: https://journals.asm.org/doi/10.1128/microbiolspec.gpp3-0036-2018 (Accessed: 19 August 2024).

5) MRSA: The not-so-famous superbug (2016) Harvard Health. Available at: https://www.health.harvard.edu/blog/mrsa-the-not-so-famous-superbug2016091210191#:~:text=According%20to%20the%20Centers%20for,people%20die%20from %20these%20infections (Accessed: 19 August 2024).

6) Vestergaard, M., Frees, D. and Ingmer, H. (2019) Antibiotic resistance and the MRSA problemASM journals. Available at: https://journals.asm.org/doi/10.1128/microbiolspec.gpp3-0057-2018 (Accessed: 19 August 2024).

7) Team, T.H.E. (2019) Beware: Under the wrong conditions, you can die from MRSA, Healthline Available at: https://www.healthline.com/health/can-you-die-from-mrsa#:~:text=However%2C %20if%20MRSA%20gets%20into,you%20can%20die%20from%20MRSA (Accessed: 19 August 2024).

8) Clokie, M.R. et al. (2011) Phages in nature, Bacteriophage. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109452/#:~:text=Brief%20history%20of %20bacteriophage%20discovery,the%20potential%20to%20kill%20bacteria (Accessed: 19 August 2024).

9) Kasman, L.M. (2022) Bacteriophages, StatPearls [Internet]. Available at: https://www.ncbi.nlm.nih.gov/books/NBK493185/#:~:text=Bacteriophages%2C%20also %20known%20as%20phages,replicate%20only%20in%20bacterial%20cells (Accessed: 19 August 2024).

10) Brüssow, H. and Hendrix, R.W. (2002) Phage genomics: Cell. Available at: https://www.cell.com/fulltext/S0092-8674(01)00637-7 (Accessed: 19 August 2024).

11) Jia, H.-J. et al. (2023) Engineering bacteriophages for enhanced host range and efficacy: Insights from bacteriophage-bacteria interactions, Frontiers in microbiology. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10264812/#:~:text=However%2C%20their %20high%20specificity%20and,free%20production%20of%20phage%20drugs (Accessed: 19 August 2024).

12) Costa, S.S. et al. (2013) Multidrug efflux pumps in Staphylococcus aureus: An update, The open microbiology journal. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3617543/ (Accessed: 19 August 2024).

13) Álvarez, A., Fernández, L. and Gutiérrez, D. (2019) Methicillin-resistant Staphylococcus aureus in hospitals. Available at: https://journals.asm.org/doi/10.1128/jcm.01006-19 (Accessed: 19 August 2024).

14) Turner, P. (2023) Fighting Antibiotic Resistance with Phage Therapy, YouTube. Edited by S.C. Lab. Available at: https://www.youtube.com/watch?v=l2i7T3Eoha0&t=315s (Accessed: 19 August 2024).

15) https://www.cdnmedhall.ca/laureates/felixdherelle

16) https://morgridge.org/community/teaching-learning/virology-immunology/factsheets/ bacteriophage-fact-sheet/

17) https://www.newyorker.com/tech/annals-of-technology/phage-killer-viral-dark-matter

HOW DOES SMOKING INFLUENCE LUNG CANCER?

Jimin Park

Introduction

Being the third most common cancer, lung cancer inflicts around 48,500 new individuals annually in the UK, accounting for 13% of all new cancer cases (2016-2018). [1] It causes 21% of all cancer deaths, reaching its peak number of 34,800 deaths in 2018 (UK). Compared to its survival rate of only 9.5% [2], the general population do not seem to be aware of the high risk of being afflicted, hence it is necessary to explore further and raise awareness of possible causes of this deathly airway disease. The most common types of lung cancer are non-small cell carcinoma (NSCLC) and small cell carcinoma (SCLC): NSCLC is more common and grows slowly, while SCLC is less common but often grows in size very quickly. [3] General symptoms include a constant coughing, chest pain, shortness of breath, haemoptysis and fatigue [3], and although screening high risk individuals can have the potential to allow early detection, most lung cancer is diagnosed at advanced stages when treatment options are very limited. Most importantly, some of the risk factors include genetic susceptibility, poor diet, occupational exposures and air pollution. [4] Nonetheless, the geographic and temporal patterns of lung cancer incidence (as well as cancer mortality) on a population level are chiefly determined by tobacco consumption – responsible for approximately 85% of all cases. The genetic reasoning behind this is to be explored further in this poster.

Discussion

The pie chart on the right is a representation of the frequency of somatic mutations and alterations in NSCLC. The alteration type tend to be mostly mutation but FGFR1 gene undergoes amplification (a copy number increase of a restricted region of a chromosome arm) as its alteration and ALK gene is a rearrangement (DNA recombination event occurs during cellular differentiation) alteration. [5] EGFR mutation is more prominent in non-smokers than frequent smokers until the dosage of smoking goes over 15 pack-years. Whilst, smoking is strongly associated with mutation of the KRAS gene in patients with primary adenocarcinoma of the lung.

Additionally, in recent years, three independent groups of international scientists have identified a region on chromosome 15 that, if mutated, would dramatically increase a smoker’s risk of developing lung cancer by another 30% to 80%. The susceptibility locus has been found as 15q24, susceptibility locus meaning a region on a given chromosome where mutations that affect one or more genes are suspected to be present. Specifically the CHRNA5-A3 region on that locus is a risk factor both for nicotine dependence and for lung cancer. This is due to the cluster of common variants of nicotinic acetylcholine receptor genes (on the chromosome 15q24-25.1) being highly associated with lung cancer risk. [6] On the right is a diagram of chromosome 15 [7] and the area marked with red rectangle is the susceptibility locus.

An alternative view was that from 1950 to late 1970s, the proportion of male to female lung cancer cases has been 5 to 1 and this difference has been decreasing in the recent

years. However, lung cancer tend to be more prevalent in males than females and exhibits sex-specific trends. Considering that lung cancer is not a sex-linked disease, this could be due to sex-differences in behavior such as smoking, diet, sex hormone contributions and differences in immune responses. [8]

Graph 2 and Graph 3 below shows the smoking percentage of the population since 1950 and annual death caused by lung cancer since 1950 respectively. [9] According to the BMJ paper, as the smoking proportion of the population decreases, there is also a decrease (significant for males) in the number of deaths from lung cancer. This could suggest the direct link between cigarette smoking and lung cancer - not necessarily just as a causation factor but also as an exacerbating factor that increases the death rate.

Conclusion

From the studies, it is apparent that smoking is one of the major risk factors of lung cancer, affecting chromosome 15 prominently to cause gene mutation leading to lung cancer. While it is the major causation of lung cancer, it can also be considered as an exacerbating factor which decreases the chances of survival through lung cancer if it is not quit.

However, despite the success in outlining smoking as the major risk factor for lung cancer, this highly preventable disease remains among the most common and most lethal cancers globally. Future preventive efforts and research could focus and try to have a better understanding of risk factors underlying lung carcinogenesis in non-cigarette consumers.

References

[1] “Lung Cancer Statistics.” Cancer Research UK, 7 July 2023, www.cancerresearchuk.org/healthprofessional/cancer-statistics/statistics-by-cancer-type/lung-cancer

[2] “Lung Cancer Statistics.” Cancer Research UK, 7 July 2023, www.cancerresearchuk.org/healthprofessional/cancer-statistics/statistics-by-cancer-type/lung-cancer#heading-Two.

[3] WHO. “Lung Cancer.” World Health Organization, www.who.int/news-room/fact-sheets/detail/lung-cancer. Accessed 24 Jan. 2024.

Graph 2

Graph 3

[4] Malhotra J, Malvezzi M, Negri E, La Vecchia C, Boffetta P. Risk factors for lung cancer worldwide. Eur Respir J. 2016 Sep;48(3):889-902. doi: 10.1183/13993003.00359-2016. Epub 2016 May 12. PMID: 27174888.

[5] Schabath MB, Cote ML. Cancer Progress and Priorities: Lung Cancer. Cancer Epidemiol Biomarkers Prev. 2019 Oct;28(10):1563-1579. doi: 10.1158/1055-9965.EPI-19-0221. PMID: 31575553; PMCID: PMC6777859.

[6] Spitz MR, Amos CI, Dong Q, Lin J, Wu X. The CHRNA5-A3 region on chromosome 15q24-25.1 is a risk factor both for nicotine dependence and for lung cancer. J Natl Cancer Inst. 2008 Nov 5;100(21):1552-6. doi: 10.1093/jnci/djn363. Epub 2008 Oct 28. PMID: 18957677; PMCID: PMC2720751.

[7] Eichler, Evan. “15Q24 Microdeletion Syndrome - Unique.” Rarechromo.Org, 2011, rarechromo.org/media/information/Chromosome%2015/15q24%20microdeletion%20syndrome %20FTNW.pdf. Accessed 24 Jan. 2024.

[8] May L, Shows K, Nana-Sinkam P, Li H, Landry JW. Sex Differences in Lung Cancer. Cancers (Basel). 2023 Jun 8;15(12):3111. doi: 10.3390/cancers15123111. PMID: 37370722; PMCID: PMC10296433.

[9] Peto R, Darby S, Deo H, Silcocks P, Whitley E, Doll R et al. Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case-control studies BMJ 2000; 321 :323 doi:10.1136/bmj.321.7257.323

THE RISE OF CRYOTHERAPY IN SPORTS MEDICINE: A MODERN SOLUTION FOR ATHLETES

Harrison Cox

Cryotherapy has exploded in recent years, claiming to help everything from sports-related injuries to weight loss through to improvements in both mental and physical health. But what is it exactly? How does it work, and most importantly, is it safe? Cryotherapy involves the application of extreme colds, a method that has grown in popularity within sports medicine over the past few decades. Originally rooted from methods like cold water immersion and ice treatments. Modern cryotherapy now embodies a wide range of advanced technologies and approaches, all focused on harnessing colds to enhance athletic performance, aid recovery, and prevent injury. This article explores the evolution of Cryotherapy, its rise in sports medicine, and its greater applications while searching into the benefits and safety concerns surrounding this therapy.

Cryotherapy, traditionally, has been used for many years in the medical field to freeze off unwanted growths such as warts and cancer, these types of treatments have been conducted under a medical professional and have been backed by various medical regulatory bodies such as the FDA. But now the popularity of Cryotherapy has grown so much that private companies have been able to operate without the consent of a medical governing body, the FDA, for example, is one such body who have not approved WBC (whole body cryo) for any medical condition, which begs the question…. Why not?

There are now many types of cryotherapies used in sports medicine – these range from whole-body treatments to the treatment of isolated injuries such as ligaments and joint pain. WBC (whole body cryo) is a treatment that involves using subzero temperatures to treat the ‘whole body’ for a short period of time (usually around 2-4mins). This works by using cold air mixed with Nitrogen to achieve subzero temperatures that is then forced out into an enclosed space such as a chamber. Localized Cryotherapy, like WBC, also involves nitrogen to target specific parts of the body, but unlike WBC, patients are treated via a Cryo laser machine whilst lying on a medical table. This method is used to treat injuries such as sprains, strains, and other localized traumas.

Cold Water Immersion (CWI) acts in the same way. Although the results are comparable, there is a lack of advanced technology and involves athletes submerging themselves into temperature cold water such as ice baths. This older method doesn't allow such controlled cold temperatures as the Cryo Chambers or Cryo laser machines can, but the effects are similar, and thermometers can be used to monitor the chilled water that is set to near freezing.

Research is limited since the technology is relatively new but preliminary research backed by cold enthusiasts, such as Wim Hoff, the self-proclaimed ice man, claim that it reduces inflammation along with other benefits. A recent study was conducted on 10 patients with different active inflammatory rheumatic diseases (four patients had rheumatoid arthritis, three patients with ankylosing spondylitis, and three patients with psoriatic arthritis/spondylitis). All 10 patients underwent 9 sessions of WBC in 5 days, resulting in a significant amelioration, as the pain scores decreased significantly. This study shows the anti-inflammatory benefits WBC offers for those suffering more serious illnesses. This is further backed by an older study done in 2000 which was shown to support the short-term benefits outweighed any long-term lasting benefits and fundamentally showed a reduction in pain amongst a group of arthritic patients. The result concluded that Cryotherapy can be used and is an essential part of rehabilitation programs, but must be carried out alongside other treatments such as physical and occupational therapy. The studies also noted that it was well tolerated by all.

As many sports injuries result in tissue damage, Cryotherapy is particularly helpful in aiding the body in repairing damaged cells by reducing inflammation and speeding up the healing process. This is primarily achieved by additional blood flow to the affected area. For many years Doctors and Health Care professionals around the world have recommended the RICE treatment following a sportsrelated injury, which involves Rest, Ice, Compress, Elevate. Benefits don’t stop with the aiding of reducing inflammation, studies have shown Cryotherapy speeds up weight loss by increasing fat loss

burning and increasing metabolism. As fat cells are injured by the cold temperatures the body is triggered into an inflammatory response which results in the death of them. White blood cells, Macrophages, which are part of the body’s immune system are then sent to the injury location to clean up the dead cells and the body excretes them through sweat, faecal matter and urine.

Today Cryotherapy is in demand, its global market size is $343.62 million and is set to rise by 2029 to $436.43 million, making it one of the most popular complementary therapies in the world. Studies have shown its efficiency in reducing the body’s inflammation response and because the technology is not deemed medical equipment, it is therefore not regulated by the FDA. This is not because it is dangerous, it is purely down to the fact that it is not advertised as a medical treatment.

References:

 0 (2017). What are the benefits of cryotherapy? [online] Medicalnewstoday.com. Available at: https://www.medicalnewstoday.com/articles/319740#safety-and-what-to-expect

 Metzger, D., C Zwingmann, Protz, W. and Jäckel, W.H. (2000). Die Bedeutung der Ganzkörperkältetherapie im Rahmen der Rehabilitation bei Patienten mit rheumatischen Erkrankungen - - Ergebnisse einer Pilotstudie -. Die Rehabilitation, [online] 39(2), pp.93–100. doi:https://doi.org/10.1055/s-2000-14442.

 Lange, U., Uhlemann, C. and Ulf Müller-Ladner (2008). Serielle Ganzkörperkältetherapie im Criostream bei entzündlich-rheumatischen Erkrankungen. Medizinische Klinik, [online] 103(6), pp.383–388. doi:https://doi.org/10.1007/s00063-008-1056-5

 https://www.mordorintelligence.com/industry-reports/cryotherapy-market https://www.wimhofmethod.com/cryotherapy#:~:text=Cryotherapy%20with%20the%20Wim %20Hof,important%20component%20of%20the%20WHM#

NHS MEDICAL APPRENTICESHIPS: WHAT ARE THEY, AND WHAT DO THEY MEAN FOR THE FUTURE OF HEALTHCARE?

Anna Zaman

In January 2023, funding for the Medical Doctor Degree Apprenticeship was confirmed by Health Education England (HEE), enabling 200 medical doctor degree apprentices to begin their course in September 2024. However, what does this actually mean? And how does this affect doctors and healthcare professionals who will undertake the traditional pathway into medicine?

As stated by the NHS, these medical apprenticeships aim to ‘offer routes into many of the more than 350 NHS careers through a mix of on-the-job training and classroom learning.’ It was introduced by the government as a way to combat the NHS workforce crisis, a highly alarming issue. This can be evidenced through the fact that more than 85% of junior doctors say they know other junior doctors who have left to work in a different profession, or to work as a doctor in a different country. These apprenticeships incentivize people to apply because they mean you can become a doctor without actually going to university, and although the course is still 5 years long, you get paid from day one (the National Minimum Wage for apprentices is £5.28 an hour). This is highly attractive as you don’t end up with years of medical school debt as you don’t pay any tuition fees, and you still get the same qualifications as a doctor who undertook the traditional pathway into medicine.

However, these apprenticeships have caused great discontent within the healthcare community, with many believing it will lead to a two-tiered training system. With medical apprentices being entitled to annual leave and a pension as well as pay, many aspiring medics taking the traditional route into medicine feel that their hard work is being undermined. Additionally, the issue of how these apprentices will be able to obtain the same level of expertise knowledge as traditional medical students has been called into question. One critic says, ‘The reason we do a five-, six-year degree is to understand things like why we’re stopping certain medications. If the work side if the apprenticeship is a role where you’re taking instructions, you’ll never understand why you’re doing something, which is what you learn on a placement.’. Another doctor says ‘I’ve done HCA (Healthcare Assistant) work while at medical school. I enjoyed it, but it wasn’t applicable to my medical degree. I learnt more in lectures.’. This shows the possible challenges that apprentices may face, without the proper knowledge and understanding of why specific treatment are given or why one drug is chosen over another, how effective will these apprentice doctors be?

To conclude, although the government has attempted to take action against the NHS workforce crisis, it is difficult to tell whether these medical apprenticeships will have a positive impact on healthcare in the UK. The fact that junior doctors are already unhappy with the scheme and feel that the apprenticeships undermine their hard work and effort, it doesn’t seem likely that they will help solve the depleting numbers of NHS workers. Arguably, the government should be focusing on retention of current NHS workers rather than recruitment. Furthermore, If the training of doctors is not matched to those who have undertaken the traditional medicine pathway, or if a two-tiered system is created then the government seemingly has no back-up plan to address this. Therefore, although advocates for the apprenticeship claim they can ‘widen participation in medicine and help plug hospital workforce gaps in areas struggling to recruit,’ the future is uncertain, and only time will tell how beneficial these medical apprenticeships will be for the NHS.

References

- British Medical Association- https://www.bma.org.uk/news-and-opinion/two-tribes

- Gov UK- https://educationhub.blog.gov.uk/2023/06/30/nhs-doctor-apprenticeships-everythingyouneed-to-know/

NHS- https://www.healthcareers.nhs.uk/career-planning/study-and-training/nhs-apprenticeships

PETO’S PARADOX: WHY BLUE WHALES

DON’T GET CANCER

Prithvi Gupta

We all know about cancer. It has plagued history for millennia, and now haunts the lives of millions, the emperor of all maladies. In the process of better understanding cancer to kill it, scientists discovered a biological paradox in 1977 that still remains a mystery: large animals appear to be resistant to cancer. This phenomenon is known as Peto’s Paradox, named after epidemiologist Richard Peto, who first noticed the apparent inconsistency in cancer rates across different animals. Cells are essentially protein machines and perform various mediated complex chemical reactions which are coordinated, multistep, and fueled by energy from nutrients which form a metabolic pathway. This allows for activities to be carried out such as movement, reproduction, and growth. There are billions of trillions of reactions that happen over years and most of the time function perfectly allowing the organism to thrive; until something goes wrong. Considering that so many reactions are happening over such a long time, one of the reactions is bound to go wrong. Enough mistakes can accumulate and the whole cell will start to mutate. To stop this runaway effect, the cell can undergo apoptosis (programmed cell death), but cancer cells can evade programmed cell death and if the immune system misses them, they can consume resources and multiply.

Every animal can suffer from this, but we can see great abnormalities in the rates of cancer in different animals. Regardless of which animal you look at, cell size is almost the same, ranging from 10 to 100 micrometres – smaller animals just have fewer cells. In theory, since smaller animals such as mice have a smaller lifespan and fewer cells than humans, the likelihood of developing cancerous cells should be lower than a human. Yet the rate of cancer in mice and humans is almost the same; even more interestingly, elephants, who have roughly 100 times more cells than humans, and blue whales, who can have more than 1000 times as many cells as humans, do not suffer higher risks of cancer mortality than humans – they have lower cancer rates than us. This is what Richard Peto initially found during his studies of the relationship between lifespan and cancer onset.

The two most plausible explanations for this are evolution and hyper tumours. Multicellular beings emerged approximately 600 million years ago. As they continued to evolve, they got increasingly bigger, hence increasing the chance of mutations to produce cancer cells. Cancer has always been a challenge for organisms, with one study documenting “bone cancer in a 240-million-year-old reptilian amniote from the Triassic period.” (Haridy , et al., 2019). This means that early organisms had to evolve to develop their cancer defence systems so that they could survive from such a deadly disease through pressure selection, or have the species die out. Cancer is a result of many individual mistakes in specific genes of the same cell. These genes are called proto-oncogenes and are used for controlled cell growth and division normally, but once mutated they become oncogenes and activate when not needed – potentially leading to cancerous growth. They have an ‘opponent’ however, named tumour suppressor genes. There are two categories of these genes: Gatekeeper-genes and Caretaker-genes. Caretaker genes oversee the preservation of genetic information within cells, ensuring its integrity, while gatekeeper genes directly manage tumour growth by encoding proteins that either encourage or impede cell proliferation, differentiation, or apoptosis.

Studies have found that larger-bodied animals have an increased number of tumour-suppressor genes because of evolution: “Proto-oncogene activation decreased steadily will increasing body mass” (Gewin, 2013); “Large, long-lived organisms might have evolved to suppress cancer better than small animals by duplicating tumour suppressor genes” (Caulin & Maley, 2011). This can therefore explain why larger animals have lower cancer rates, animals evolving specific measures to supress cancer development more effectively.

In addition to this, we also have the theory of hyper tumours, which in short are the tumours of tumours. When cancer cells divide, they can form tumours as we know, but this is very difficult to do since it requires lots of resources. The main limiting factor is the amount of nutrients they can plunder from the body. So, it tricks the body to create new blood vessels to the cancer for its growth. As the cancer cells continue to mutate rapidly, new cancer cells may arise which stop cooperating with the

rest of tumour during metastasis. The metastatic subclones (Hyper tumours) can hinder the growth of the tumour through competition as they can be seen as ‘cheaters’ who take advantage of the vascular architecture built by the original tumour. They can cut off the original tumour cells from receiving their supply of nutrients therefore killing the tumour; cancer kills cancer. Larger animals could have more hyper tumours, and this process can repeat continuously which prevents cancer from becoming a problem for a large organism as it prevents the cancer from growing and becoming large enough to cause trouble. Think of a very small cancer that barely compares to the mass of large animals causing harm.

Of course, there are other proposed theories like cellular architecture and metabolism in larger organisms. The multifaceted expanse of theories does show how we still do not have a definite answer, but the real questions is: why do we care?

Understanding the impressive cancer resistance seen in larger animals presents a promising avenue for revolutionizing our approach to combating this deadly disease. By studying the genetic and physiological traits that protect these animals from cancer, researchers envision not only developing more effective treatments but also potentially applying these insights to modify our own genetic makeup. This exploration of nature's mechanisms offers hope for finding innovative solutions to mitigate, or even eradicate, cancer—a disease that continues to pose significant challenges to human health. Perhaps nature holds the answer to transform our fight against cancer.

References

Caulin, A. F., & Maley, C. C. (2011). Peto’s Paradox: Evolution’s Prescription for Cancer Prevention. Retrieved from `National Library of Medicine: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3060950/ Gewin, V. (2013, January 21). Massive animals may hold secrets of cancer suppression. Retrieved from Nature: https://www.nature.com/articles/nature.2013.12258

Haridy , Y., Witzmann, F., Asbach, P., Schoch, R., Fröbisch, N., & Rothschild, B. (2019, February). Triassic Cancer—Osteosarcoma in a 240-Million-Year-Old Stem-Turtle. Retrieved from JAMA Oncology: https://jamanetwork.com/journals/jamaoncology/fullarticle/2723578? guestAccessKey=36a3caee1474-4c66-88e0-e38dc4e8304d

HOW DOES ALCOHOL INFLUENCE LIVER CANCER?

Suemin Park

Approximately 4% of cancers worldwide are caused by alcohol consumption, equating to more than 740,000 cases of cancer globally in 2020. [1] Drinking alcohol increases the risk of several cancer types, including cancers of the upper aerodigestive tract, liver, colorectum, and breast.

Graph 1. Global proportion of cancer cases attributable to alcohol consumption according to cancer type.[2]

Alcohol is classified as a Group 1 carcinogen by the International Agency for Research on Cancer because it induces hepatocellular carcinoma (among other cancers) in humans. An excessive alcohol intake may result in fatty liver, acute/chronic hepatitis, and cirrhosis and eventually lead to hepatocellular carcinoma. [3]

From a clinical perspective, it is well known that alcohol interacts with other factors, such as smoking, viral hepatitis, and diabetes, leading to an increased risk of hepatocellular carcinoma. There are several possible mechanisms through which alcohol may induce liver carcinogenicity, including the mutagenic effects of acetaldehyde and the production of ROS due to the excessive hepatic deposition of iron. Furthermore, it has been reported that alcohol accelerates hepatitis C virus-induced liver tumorigenesis through TLR4 signalling. [4] Worldwide, liver cancer is the second highest cause of cancer-related death in men and the sixth highest cause of cancer-related death in women. [5]

According to the National Cancer Institute, approximately 40 700 cases of liver cancer are expected to be newly diagnosed, and approximately 29 000 patients will die from liver cancer in the USA in 2017. Besides, the incidence of liver cancer is increasing by approximately 3%–4% per year. [6] Hepatocellular carcinoma (HCC), which accounts for around 70%–90% of cases, is the most common type of primary liver cancer. Alcohol consumption is one of the most frequent causes of HCC in developed countries. [7] An excessive alcohol intake has been shown to be a risk factor for liver cirrhosis and HCC. It is considered that there is a linear dose–response relationship between alcohol consumption and the risk of cirrhosis and HCC. [8]

Once ethanol is consumed, almost all of it is absorbed by the small intestine and metabolised by the liver. [9] Ethanol is metabolised to acetaldehyde by ADH in the cytoplasm of hepatocytes, acetaldehyde subsequently enters the mitochondria, and is then oxidised to acetate by mitochondrial aldehyde dehydrogenase (ALDH). When a large amount of ethanol is consumed, cytochrome P450 2E1 (CYP2E1), which mainly exists in the endoplasmic reticulum, and catalase of peroxisomes also contribute to the metabolism of ethanol. The CYP2E1-dependent pathway can catalyse ethanol into acetaldehyde while producing reactive oxygen species (ROS), such as hydroxyethyl, superoxide anion

and hydroxyl radicals. In humans, there are at least seven different isozymes of ADH and four isozymes of ALDH. Several previous studies showed ALDH2 polymorphisms to be significantly associated with the development of HCC [10]; thus, it is possible that the metabolism of alcohol is involved in the mechanisms of HCC development.

Acetaldehyde has been shown to be a carcinogen in animal studies. With regard to direct DNA mutagenic mechanisms, it has been reported that acetaldehyde increases the point mutation frequency in the hypoxanthine phosphoribosyltransferase (HPRT) gene in lymphocytes [11] , and induces sister chromatid exchanges [12]. Furthermore, the formation of protein adducts plays an important role in carcinogenesis. Acetaldehyde interacts with certain amino acids in proteins, for example, the formation of adducts with O6-methylguanine methyltransferase causes DNA repair system dysfunction [13]. The direct DNA mutagenic effect of acetaldehyde and the indirect carcinogenic effect through the formation of adducts may modulate hepatocarcinogenesis and liver fibrosis. The metabolism of ethanol through the CYP2E1-dependent pathway produces ROS. Subsequently, the increase of ROS results in the generation of lipid peroxidation products, such as malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4HNE) [14]. 4HNE, one of the lipid peroxidation products, can cause a mutation at codon 249 of the p53 gene [15] ; this mutation is commonly found in HCC (20%–30%). Chronic ethanol consumption increases intestinal iron absorption and hepatic iron storage. Iron overload has been shown to cause DNA strand breaks and p53 mutation, which could cause hepatocarcinogenesis [16].

From the studies, it is apparent that alcohol is one of the major risk factors of liver cancer, especially hepatocellular carcinoma. Due to multiple genetic factors and chemicals produced during the metabolizing of ethanol, such as the mutagenic effects of acetaldehyde and ROS.

References

[1] Rumgay H, Murphy N, Ferrari P, Soerjomataram I. Alcohol and Cancer: Epidemiology and Biological Mechanisms. Nutrients. 2021 Sep 11;13(9):3173. doi: 10.3390/nu13093173. PMID: 34579050; PMCID: PMC8470184.

[2] Rumgay H., Shield K., Charvat H., Ferrari P., Sornpaisarn B., Obot I., Islami F., Lemmens V.E.P.P., Rehm J., Soerjomataram I. Global burden of cancer in 2020 attributable to alcohol consumption: A population-based study. Lancet Oncol. 2021;22:1071–1080. doi: 10.1016/S14702045(21)00279-5.

[3] Buykx P., Li J., Gavens L., Hooper L., Lovatt M., Gomes de Matos E., Meier P., Holmes J. Public awareness of the link between alcohol and cancer in England in 2015: A population-based survey. BMC Public Health. 2016;16:1194. doi: 10.1186/s12889-016-3855-6.

Graph 2. Hazard ratio to alcohol intake

[4] Matsushita H, Takaki A. Alcohol and hepatocellular carcinoma. BMJ Open Gastroenterol. 2019 Apr 3;6(1):e000260. doi: 10.1136/bmjgast-2018-000260. PMID: 31139422; PMCID: PMC6505979.

[5] Torre LA, Bray F, Siegel RL, et al.. Global Cancer statistics, 2012. CA Cancer J Clin 2015;65:87–108. 10.3322/caac.21262

[6] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. 67 CA: A Cancer Journal for Clinicians, 2017: 7–30.

[7] World Health Organization, a. W. H. O. M. o. S. A. U Global status report on alcohol and health, 2014. World Health Organization, 2014.

[8] Scoccianti C, Cecchini M, Anderson AS, et al.. European code against cancer 4th Edition: alcohol drinking and cancer. Cancer Epidemiol 2016;45:181–8. 10.1016/j.canep.2016.09.011

[9] Holt S. Observations on the relation between alcohol absorption and the rate of gastric emptying. Can Med Assoc J 1981;124:267-77–97.

[10] Chang JS, Hsiao J-R, Chen C-H. ALDH2 polymorphism and alcohol-related cancers in Asians: a public health perspective. J Biomed Sci 2017;24 10.1186/s12929-017-0327-y

[11] He SM, Lambert B. Acetaldehyde-induced mutation at the HPRT locus in human lymphocytes in vitro. Environ Mol Mutagen 1990;16:57–63.

[12] Obe G, Jonas R, Schmidt S. Metabolism of ethanol in vitro produces a compound which induces sister-chromatid exchanges in human peripheral lymphocytes in vitro: Acetaldehyde not ethanol is mutagenic. Mutation Research Letters 1986;174:47–51. 10.1016/0165-7992(86)90075-8

[[13] Collier JD, Bassendine MF, Burt AD, et al.. Characterisation of the DNA repair enzyme for O6methylguanine in cirrhosis. Journal of Hepatology 1996;25:158–65. 10.1016/S0168-8278(96)80068-7

[14] Haorah J, Ramirez SH, Floreani N, et al.. Mechanism of alcohol-induced oxidative stress and neuronal injury. Free Radic Biol Med 2008;45:1542–50. 10.1016/j.freeradbiomed.2008.08.030

[15] Hu W, Feng Z, Eveleigh J, et al.. The major lipid peroxidation product, trans-4-hydroxy-2nonenal, preferentially forms DNA adducts at codon 249 of human p53 gene, a unique mutational hotspot in hepatocellular carcinoma. Carcinogenesis 2002;23:1781–9. 10.1093/carcin/23.11.1781

[16] Asare GA, Mossanda KS, Kew MC, et al.. Hepatocellular carcinoma caused by iron overload: a possible mechanism of direct hepatocarcinogenicity. Toxicology 2006;219:41–52.

ETHICS IN MEDICINE

Huichan Jung

Medical Ethics describes the moral principles which doctors must abide by and conduct themselves. In the field of medicine, professionals frequently face moral questions and ethical dilemmas in their line of work. Although everyone has different sets of values and beliefs when it comes to ethics, there are four principles or pillars of medical ethics that can be used as a framework to help medical professionals make decisions which are morally sound and right.

These four pillars include: Beneficence, Non-maleficence, Autonomy, and Justice. Beneficence relates to always doing ‘good’ or what’s best for the patient. This is important as it ensures that individual circumstances are considered and allows one to acknowledge that what is good for one patient may not necessarily be the case for another. Non-maleficence is a core principle that relates to doing ‘no harm’ to a patient. The concept derives from the Latin phrase ‘primum non nocere’ meaning ‘first, do no harm’ which captures the essence of the pillar, ensuring that risks and burdens need to be weighed against the benefits of an option or treatment of a patient. Patient autonomy is another pillar in medical ethics which recognises the fundamental rights of the patients to make their own decisions about their healthcare. This means that treatments and interventions cannot be imposed on patients without their informed consent, instead, information including potential risks, benefits, and alternatives should be given to the patient so that informed decisions can be made. It is important to realise that patients need to be actively involved in their own treatment and diagnosis and not deferring to the doctor. Finally, justice is the principle that takes the law, patient’s rights, and equity into consideration when making an ethical decision. It ensures that everyone is treated equally and fairly when it comes to healthcare and access to healthcare, which unfortunately is not always the case.

An example of these principles in a reallife scenario is as such. Imagine that a patient with liver failure and the surgeons must make an incision into the liver to make a transplantation. We can consider making this incision is technically causing harm to the patient, however this is done with good will to prevent any further complications like infections, kidney failure, or even death. In this specific instance the principles of nonmaleficence and beneficence clash, but the latter outweighs the former as the benefits outweigh the risks. We can even consider take the other principles into consideration when performing this surgery so that the patient’s autonomy is respected, and they are receiving just treatment.

Alongside these principles of medical ethics, healthcare professionals also have certain ethical ideologies to an extent that helps make them ethical decisions. These ideologies include consequentialism, utilitarianism, and deontology. Consequentialism, as the name states, is an ideology that focuses on the consequences rather than the process when judging the morality of an action – in other words, ‘ends justify the means.’ Despite this ideology being subject to having flaws when viewed in a broader sense, it may prove useful in specific situations such as answering a terminally ill patient who asked if they will be okay undergoing an operation that will most likely be unsuccessful. Ironically, lying to a patient may do more ‘good’ to an emotionally unstable patient even though lying in itself is unethical. Utilitarianism is a well-known ethical theory which strives to always achieve the most ‘utility’ or benefit. The wider society is often considered, and not just the patient. An

example of this is deciding if funds will be used on an expensive treatment for one patient with a rare disease or five patients with a common disease. Utilitarian ethics will encourage the treatment of five patients over the one patient as it derives more utility. Deontology, also known as ‘duty-based ethics’ states that the correct course of action is following your duties and obligations. This opposes the idea of consequentialism as the morality of the action is based on following the rules, no matter what the consequence is.

It is essential to realise that these ideologies aren’t ‘correct’ in fact, it can be argued that no ideology is ‘correct’ in the sense that there will always be an opportunity cost to a decision made. Everyone has a different set of beliefs and ideologies in which they think are right, a unique ‘moral compass’ and that is normal. However, it is important to acknowledge that ‘ethics’ is different to ‘morals’ as medical ethics relate to a conduct that is set at a healthcare work setting which should be aimed to be followed to an extent by taking the four principles into consideration in situations.

THE LINK BETWEEN BABIES BORN BY CAESAREAN SECTION AND ALLERGIES

Alexander Gunson

Food allergies can cause a person’s immune system to overreact to certain foods, triggering mild to life threatening symptoms. The condition affects an estimated 5% of children in the United States and is becoming more prevalent. Research in the past decade have shown that babies delivered by caesarean section (c-section), a surgical procedure for delivering a baby through incisions, have higher rates of food and environmental allergies, compared with those born by vaginal delivery.

From 2003 to 2007, a total of 1258 newborns were involved in research on this matter and were assessed at 4 different times: one month old, six months, one year, and two years. They indicated that c-section babies have a five times greater chance of developing allergies than those born naturally. In 2020, research conducted by Rutgers University and the Copenhagen Prospective Studies on Asthma in Childhood and the University of Copenhagen found that of the 700 children delivered by caesarean section was associated with more than a doubled risk of later asthma and allergies, as well as significant changes in the composition of the gut microbiota. An Australian study which drew data from nearly 500,000 healthy women, saw higher rates of metabolic disorders, such as diabetes or obesity in babies born from emergency c-section.

This has been found to be because caesarean section interferes with a baby’s ability to obtain beneficial germs from the mother’s microbiome. Every generation of mothers hands over its microbiome to the next, as the baby is coated with beneficial germs while being squeezed through the birth canal. This does not happen for babies born through c-section. It takes a while for those babies to develop a normal microbiome. In this time, while the immune system is also developing, they become more at risk to later developing diseases, like asthma, and allergies. Researchers found that delivery by caesarean section was associated with significant changes in the composition of the gut microbiota. Studies look to mitigate this by giving c-section babies probiotics but have not been as successful as hoped. Further research in understanding the role of a child’s microbiota and how this can influence health can lead to new prevention strategies and targeted efforts to fix disturbances in a child’s microbiome. Whilst, caesarean section is often necessary for medical reasons, such as complications during labour, it has also been performed electively in some cases. Therefore, with this research at hand, a parent may choose a different birth mode. It also means that the results indicate that caregivers should be aware of the risks of food allergies in caesarean-born children, reducing the risk of potentially fatal allergic events.

However, it is important to note that not all children born by c-section develop food allergies, and many other factors contribute to the development of food allergies. Genetics, family history of allergies, and early-life environmental factors also play significant roles. In addition, Murdoch Children’s Research Institute reported that 30% of peanut allergies and 90% of egg allergies resolve naturally by the age of 6.

CLIMATE CHANGE'S EFFECTS ON ECOSYSTEMS AND PROPOSED MITIGATION STRATEGIES

Khrysha Arya

Climate change refers to a change in the statistical distribution of weather patterns that lasts for an extended period of time12. In the 4.6 billion years since the earth formed, the climate has changed from hot to cold and cool to warm infinitely many times. There have been 6 major climate periods since then13, each one warmer than the last. Currently, the Earth is the warmest it has been for 140,000 years and we are in a warm interglacial period14

Climate change’s negative effects range from effects on sea levels to food production. In the case of ecosystems, it affects both land based and aquatic organisms. Many species of plants and animals have begun range shifts. Particularly in the northern hemisphere, range shifts are almost wholly northwards and increasing in elevation. As they are moving towards colder weather, this places stress on the cold adapted species already located there as they are forced into smaller ecological niches. As well as that, the water temperatures in lakes and rivers are increasing, impacting economically important cold-water fish through effects on reproduction, food resources and disease. The risk of extinction of these species is increasing rapidly with increases in global temperatures. Another important ecosystem, the wetlands, are shrinking too due to the rising temperatures and anthropogenic activities reducing carbon sequestration capacities. This causes diminishing carbon sinks and buffers against floods15. Climate change also causes the loss of biodiversity, one of its most critical consequences as ecological interactions are disrupted. Invasive species thrive in warmer conditions, outcompete native species and threating biodiversity further. 16

Some proposed strategies can mitigate these effects. EbA or ecosystem-based adaptation for example is an approach which involves restoring and conserving ecosystems to help with adapting to climate change. Tasks such as reforestation and afforestation could help absorb carbon dioxide and provide habitats for species. 17 Additionally, marine protected areas or MPAs can limit human activities and reduce stress on marine habitats to ensure safety of these ecosystems, for example, coral reels. As well as that, transitioning to renewable energy sources will also mitigate climate change’ s most severe impacts.

To conclude, the effects of climate change on ecosystems are profound but several strategies can be used to mitigate the problems. Ecosystem based adaptations, marine protected areas and transitioning to renewable energy sources, when implemented at scale, can reduce greenhouse gas emissions and enhance the resilience of nature to changing climate. This can offer hope for the preservation of biodiversity and ecosystems.

12 B.A. Jerard et al., “Coconut Biodiversity – Nature’s Gift to the Tropical Islands,” in Elsevier eBooks, 2008, 145–185, doi:10.1016/b978-0-12-813064-3.00006-5.

13 Hardy, John T. “Climate Change: Causes, Effects, and Solutions, John Wiley & Sons, 2003, (2336) .

14 Hardy, John T. “Climate Change: Causes, Effects, and Solutions, John Wiley & Sons, 2003, (2336) .

15 C. M. Finlayson et al., “Section 2: Status and Trends. In: Gardner, R.C and Finlayson, C.M. (EDs), Global Wetland Outlook: State of the World’s Wetlands and Their Services to People. Gland, Switzerland: Ramsar Convention Secretariat,” Global Wetland Outlook, October 2018, http://eprints.uwe.ac.uk/38613/.

16 Gian-Reto Walther et al., “Ecological Responses to Recent Climate Change,” Nature 416, no. 6879 (March 2002): 389–395, doi:10.1038/416389a.

17 Bruno Locatelli et al., “Integrating Climate Change Mitigation and Adaptation in Agriculture and Forestry: Opportunities and Trade‐offs,” Wiley Interdisciplinary Reviews Climate Change 6, no. 6 (September 2015): 585–598, doi:10.1002/wcc.357.

References

Finlayson, C. M., N. Davidson, S. Fennessy, D. Coates, R. C. Gardner, W. Darwall, M. Dema, et al. “Section 2: Status and Trends. In: Gardner, R.C and Finlayson, C.M. (EDs), Global Wetland Outlook: State of the World’s Wetlands and Their Services to People. Gland, Switzerland: Ramsar Convention Secretariat.” Global Wetland Outlook, October 2018. http://eprints.uwe.ac.uk/38613/.

Hardy, John T. Climate Change: Causes, Effects, and Solutions. Ebook (John Wiley & Sons, 2003).

Jerard, B.A., V. Damodaran, Iyyappan Jaisankar, Ayyam Velmurugan, and T.P. Swarnam. “Coconut Biodiversity – Nature’s Gift to the Tropical Islands.” In Elsevier eBooks, 2008, 145–185. https://doi.org/10.1016/b978-0-12-813064-3.00006-5.

Locatelli, Bruno, Charlotte Pavageau, Emilia Pramova, and Monica Di Gregorio. “Integrating Climate Change Mitigation and Adaptation in Agriculture and Forestry: Opportunities and Trade ‐offs.” Wiley Interdisciplinary Reviews Climate Change 6, no. 6 (September 2015): 585–598. https://doi.org/10.1002/wcc.357.

Walther, Gian-Reto, Eric Post, Peter Convey, Annette Menzel, Camille Parmesan, Trevor J. C. Beebee, Jean-Marc Fromentin, Ove Hoegh-Guldberg, and Franz Bairlein. “Ecological Responses to Recent Climate Change.” Nature 416, no. 6879 (March 2002): 389–395. https://doi.org/10.1038/416389a.

HOW COCAINE AFFECTS THE BRAIN, AND

HOW ADDICTION TO IT CAN BE TREATED:

Alexander Mantzavinatos

A highly addictive stimulant drug, cocaine has been a major public health concern for decades. It is the second most used illicit drug, with estimates suggesting that 18 million people worldwide use it. The use of cocaine can have severe consequences on an individual's well-being. Specifically, it has a significant impact on the brain, causing long-term changes that can lead to addiction and various neurological disorders.

Cocaine works by raising dopamine, a neurotransmitter associated with pleasure and reward, levels in the brain. It does this by blocking the reuptake of dopamine, causing it to accumulate in the synapses, resulting in a feeling of euphoria. This sudden and intense rush is highly addictive and is what leads addicts to repeatedly seek out the drug for a chance to experience the same effect.

With that said, the increased dopamine levels aren’t sustainable, causing the brain to attempt to restore balance by reducing the number of dopamine receptors. This leads to a decrease in the pleasurable effects of cocaine, causing individuals to take more significant doses to achieve the same high. This vicious cycle of increasing tolerance and dependence can quickly lead to addiction.

The continued use of cocaine also has damaging effects on the brain's structure and function. Regular cocaine use alters the activity and reward circuitry in the brain, which can lead to individuals being more likely to engage in impulsive and risky behaviors. The drug can also cause changes in the prefrontal cortex, the part of the brain responsible for decision-making and impulse control, leading to improper judgment, impulsivity, and a reduced ability to resist drug cravings as long term effects.

Cocaine affects the brain in other ways as well, as use has been linked to various neurological disorders, such as stroke, seizures, and movement disorders. The drug can cause constriction of blood vessels leading to and in the brain, which increase the risk of and can often result in a stroke. The drug also alters the electrical signals sent around the brain, which, in addition to its altering of the sympathetic nervous system, lowers the threshold of stimulation the brain can handle before a seizure occurs. Long-term use of cocaine has also been associated with movement disorders, such as Parkinson's disease, due to the damage it causes to the brain's dopamine-producing neurons. The effects of cocaine on the brain can also extend to an individual's mental health. Chronic cocaine use has been linked to an increased risk of developing mental health disorders such as depression, anxiety, and psychosis. These disorders have a massive negative impact on an individual's overall well-being and most importantly can further perpetuate drug use as individuals turn back to cocaine to self-medicate their symptoms.

As with the vast majority of addictions, the treatment of cocaine addiction is a complex and challenging process, requiring a combination of approaches and a variety of pathways to allow an individual to fully recover. The common procedure for treatment in 2024 involves a number of steps that aim to cleanse the body of the drug and work with the patient to reduce and eventually eliminate reliance on the substance.

The first step in treating cocaine addiction is detoxification, where the drug is flushed out of the body. This process can be especially challenging as individuals may experience intense withdrawal symptoms. These include mental difficulties such as depression, intense cravings, and insomnia as well as more physical challenges such and nausea and vomiting. These symptoms have potential to seriously harm an individual, and because of this detoxification should be done under medical supervision in a controlled environment to ensure the safety and of the patient. After detoxification, behavioral therapies are essential in addressing the psychological aspects of cocaine addiction. These therapies aim to identify and modify the root causes of addiction, develop coping mechanisms, and prevent relapse. Cognitive-behavioral therapy (CBT) is a commonly used

approach that focuses on changing an individual's thought patterns and behaviors related to drug use. It helps individuals develop skills to manage cravings and cope with triggers that may lead to drug use.

Another commonly used effective treatment for cocaine addiction is contingency management. This process involves providing incentives, such as rewards or vouchers, for maintaining abstinence from cocaine use across longer periods of time. This approach has been shown to be effective in reducing drug use and promoting long-term abstinence across many addictions to many different things.

Pharmacological treatments are constantly being researched for treatment of cocaine addiction, although as of yet no specific medication has been approved for this exact purpose by the FDA. However, controlled clinical trials have been conducted using medications marketed for other diseases and show promise in reducing cocaine use. For example, disulfiram, a drug often used to reduce alcoholism, has had some of the most positive results so far. Despite a lack of direct treatment, medicine is still often used to manage specific symptoms of addiction, such as antidepressants for depression and anti-anxiety medications. Furthermore, another promising treatment for cocaine addiction is the use of vaccines. These vaccines aim to producing antibodies abke to bind to cocaine molecules in the bloodstream, preventing them from reaching the brain's reward system and reducing the pleasurable effects of the drug. While still in the early stages of development, research has shown that these vaccines can reduce the amount of cocaine used and increase the chances of successful recovery once the patient is identified.

In conclusion, cocaine has a profound impact on the brain, leading to changes in structure and function, neurological disorders, and mental health issues. Its highly addictive nature makes it challenging to treat, and a combination of approaches is necessary to address the issue; yet, with continued research and advancements in treatment methods, hope continues to grow for individuals struggling with cocaine addiction. Addiction is a serious and pressing issue worldwide, making awareness about the dangers of drug use, with cocaine being a prominent example, and methods of treatment crucial in reducing its impact on individuals and society as a whole as it aims to move towards a healthier, illicit drug free future.

THE COMPLEX DYNAMICS OF OBESITY

IN A GLOBALIZED

WORLD

Mishel Kudel

Obesity is the accumulation of excessive fat that can lead to the presentation of health risks. BMI is the most common measure for obesity (using mass in kg/height meters 2); a calculation above 25 is considered overweight and above 30 is considered obese. The prevalence of obesity has rapidly increased. Obesity is a multifaceted chronic disease which involves genetic and environmental factors of which the genetic factors are arguably more critical to the condition of an individual with this disease. This essay will explore the complex interplay between nature and nurture in influencing obesity.

A critical factor that contributed to the significance of nurture on the development of obesity is the global access to high-calorie and processed foods as they tend to come at a lower cost than more expensive foods. Due to a gradual increase in fast food outlets, this factor has become more prevalent between 1980 to 2000 (The number of fast food outlets has increased by 80% in the UK within this time frame). Consequently, the exposure to food outlets that offer ‘take away’ meals has been associated with the increase in BMI and risk of obesity in the UK.

The genetic component of obesity is also a prevalent factor. Twin studies involving both monozygotic and dizygotic twins (while monozygotic twins share 100% of their genes dizygotic twins only share around 50%) have shown that monozygotic twins tend to share more similarities in BMI than dizygotic twins. Multiple large metaanalysis haves supported this. For example, a study involving 45 cases of twin studies suggested that the heritable nature of BMI ranges from 41% to 85%. Another study with 31 twin studies suggested a heritability of 47%-90% in adults. The similarities in BMI are more apparent in adult life than in adolescence or childhood. However, the range in both tests are over 30% which may suggest the need for a larger sample size to provide less deviation from the mean heritability of BMI. BMI, as a measure, can be good to compare the overall trend of increasing the risk in obesity but it lacks reliability for data as it does not account for muscle to fat ratio, metabolic health, or the distribution of fat in a body.

The exposure to food cues (involves promotion of food through advertisement, smelling food, seeing food or any situation an individual associated with food) has also led to increased energy intake. Specifically, exposure to food cues is more prominent due to the extensive number of food advertisements (that contribute to an estimate of ½ of the commercials on children programmed). An average hour can include up to 11 of which most advertise high calorie and low nutrient foods that are not suitable for a regular/everyday diet.

One might argue that the contribution of leptin (hormone secreted from adipose tissue) and insulin acting as primary signals to regulate food intake and metabolism are crucial to understanding whether genetic or environmental components are more influential to the manifestation of obesity. Leptin is secreted based on the fat content in adipocytes (a storage site for energy in the body). As genetic factors can influence these hormones, an individual’s responsiveness and production of leptin may vary (some people will have leptin resistance) which can directly impact their risk of having obesity. Despite this, the concept of leptin resistance is also affected by environmental aspects. Increased diet and physical activity can change the bodies responsiveness to leptin and may decrease the resistance the individual had towards leptin. This can often override any genetic predisposition.

Lastly, the transition of technology in marketing and production of food have shifted from local markets to larger chains of supermarkets. Notably, these supermarkets are recognized for their cheap prices and the easily accessible processed food which is often considered easier to consume for ‘quick energy’ (foods used to rapidly increase the body’s energy levels). Most foods bought in supermarkets tend to be high in fat, salt, or sugar. The WTO’s deregulatory policies has also reduced barriers to trade food, which can lead to lower prices and possibly an increase in demand for these foods. Demographically, these changes have led to the westernization and increased consumption of refined carbohydrate in many middle-to-lowincome countries. While genetic factors can impact the way that obesity may manifest as well as the risk of developing obesity, heritability is not an absolute concept. However poor lifestyle choices and environmental actors have an impact on obesity to a greater extent. Interventions should therefore be based on these factors including diet modification to accommodate for low-calorie and high nutrition foods, and increased exercise to the development.

NEUROFEEDBACK THERAPY- A OVERVIEW

Sunaina Nambiar

Neurofeedback therapy, also known as electroencephalographic (EEG) biofeedback, is quickly becoming popular as a new form of treatment for mental disorders, particularly anxiety, depression, and ADHD. But what exactly is neurofeedback therapy? How does it work? How does it help treat these mental illnesses? To answer the first question, neurofeedback therapy is a non-invasive form of treatment that encourages the brain to develop new neuronal connections, facilitating healthier patterns of activity. The treatment is founded on the basis of neuroplasticity. Neuroplasticity is the ability of neural pathways in the brain to change and adapt with age and experience. Though this most commonly occurs as a result of learning new information (such as learning a new language), it can sometimes occur due to brain damage. However, neurofeedback therapy seeks to induce such changes in activity via measuring and controlling brain waves, helping the brain self-regulate.

The first stage of neurofeedback therapy is brain mapping. During this stage, EEG scanners are attached to certain points of the head in order to measure the electrical signals in different brain areas. These signals are then statistically analyzed to see brainwave patterns. The EEG data is then recorded and processed by a computer software program. A Quantitative EEG brain map helps detect the brain areas

where there is too little or too much activity. It helps with identifying amplitude, location and dysregulation. This is done to formulate an exact treatment plan using neurofeedback therapy.

Neurons in the brain communicate with each other by electrical activity. This is presented in the form of brainwaves. There are several different types of brainwaves:

Delta waves are the slowest brainwave. These are the most relaxing brainwaves and associated with deep sleep stages and relaxation. It measures from 0-4 Hz and has the highest amplitude. These waves are targeted in neurofeedback therapy to treat sleep disorders, such as insomnia and narcolepsy.

Theta waves are associated with creativity, intuition and daydreaming, and are a repository for memories, emotions, and sensations. The frequency range is between 5-7 Hz. Theta state is seen during light sleep or deep meditation. In this state you may experience vivid visualizations, profound creativity, flow of ideas and exceptional insight. Theta waves are targeted when the patient has ADHD, as those with the disorder tend to have excess theta levels, which results in disorganization, impulsivity, and excessive daydreaming.

Alpha waves are produced naturally during states of calm, allowing the brain to be alert, yet relaxed. Alpha brain waves are in the frequency range of 8 to 13 Hz. Alpha waves are associated with peacefulness and meditation. Alpha waves are typically targeted to combat conditions such as stress and anxiety, in order to induce relaxation.

Beta waves are high frequency, low amplitude waves that are commonly observed while awake. The frequency of these waves is between 14-40 Hz. These involve conscious tasks such as critical thinking, writing, reading, focus, sustained attention, alertness, excitement, and socialization. The brain waves are targeted during neurofeedback therapy to improve attention and focus.

Gamma waves are the fastest brain waves with the highest frequency, their range being between 30100 Hz. These are observed when processing information from different brain areas simultaneously, passing information rapidly. They are associated with alertness, thought, and focus. Gamma waves are targeted during neurofeedback therapy to improve learning, memory, attention span and concentration, and are often targeted with cases of depression.

Brainwaves experiencing over-arousal results in fidgeting, impulsivity, hyperactivity and agitation, while brainwaves experiencing under-arousal is linked to poor concentration, insomnia and daydreaming. In neurofeedback therapy, a computer monitors a person's brain for wave activity, then immediately provides feedback, through either visual or audio cues, such as light or sound. This feedback enables the brain to heal itself and adapt in response to extrinsic stimuli by reorganizing its functions and structure. The therapist in charge of the neurofeedback therapy session will attach sensors to a person's scalp in order to record the brainwaves via EEG. Through neurofeedback, a desired state can be recreated, such as being relaxed and happy, and negative states can be avoided, such as being anxious and agitated. The most common treatment via neurotherapy is allowing the patient to watch a video on a screen while the brain waves are measured. Manifesting the targeted brain waves enables the screen to brighten, enlarge, and allows the audio to become clearer and louder. If the targeted brain waves are inhibited, the screen dims, shrinks, and the audio decreases in volume. The aim of this is to train the brain via positive reinforcement and negative punishment, so that the brain repeats the desirable behavior (producing the targeted brain waves) in order to obtain a reward (a more pleasant viewing experience).

While neurofeedback therapy is a painless procedure, except perhaps extremely mild pain while inserting the sensors, there are often side effects experienced after the procedure. These include dizziness, fatigue, and headaches, though they are relatively minor, and go away a few hours after the session has ended. These side effects decrease as the brain becomes used to neurofeedback therapy.

Neurofeedback therapy can be used to treat disorders both major and minor, from focus and attention, stress, memory, and learning, to depression, anxiety, ADHD, chronic pain, and sleep disorders. However, its effectiveness depends on age. Children would need regular, frequent sessions in order to maintain the new connections formed as a result of the therapy, while adults would need less frequent sessions, and may be able cease them completely once a treatment plan has been established, save from an occasional checkup. Neurofeedback therapy can be combined with other forms of treatment, such as medication or cognitive behavioral therapy, depending on the needs of the patient, though it may be possible to wean off medication in favour of the neurofeedback therapy, due to its effectiveness in managing symptoms, while CBT may still be needed due to its function as a treatment method to address the underlying causes of behaviour itself.

In conclusion, though neurofeedback therapy may not be a relatively new form of treatment for mental health issues, it certainly is gaining in popularity over the last few years for its effectiveness in assisting these conditions and being a relatively hands-off treatment plan, with the patient not having to actively find the motivation to manage their own disorders, such as having to take medication daily or keeping a journal as part of CBT. Of course, while it is important to exercise caution when choosing

it as a treatment method, as with any type of medical help, it certainly presents itself as a new alternative in helping one manage the main different possible mental disorders they struggle with.

References

Chandra, S. What is Neurofeedback? A Psychiatrist’s Perspective: https://chandramd.com/what-isneurofeedback/

Marzbani, H., Marateb, H., & Mansourian, M.

Neurofeedback: A Comprehensive Review on System Design, Methodology and Clinical Applications: https://doi.org/10.15412/j.bcn.03070208/

CLUSTERED REGULARLY INTERSPACED

SHORT

PALINDROMIC REPEATS

Elisa Westerhof

Changing your genome? How is that possible? Where is it needed? Should it be done? Every living organism is determined by their genes. What if we could alter that code to fix a mistake, or change a characteristic? The idea of genetic engineering first arose in 1973, when biochemists Herbert Boyer and Stanley Cohen, invented a method of cloning genetically engineered molecules in foreign cells (1). This was aided by the work of Paul Berg, in 1971, where he conducted a gene-splicing experiment, allowing foreign DNA to replicate naturally in bacteria. These experiments were possible due to prior discoveries (2), such as the discovery of alleles by Gregor Mendel in 1866, and the development of the DNA model by James Watson and Francis Crick with the help of Rosalind Franklins discoveries in the 1950s. CRISPR was first discovered in 1987 in Osaka University by Ishino (3), however, pioneers Jennifer Doudna (professor and biochemist at the University of California, Berkley) and Emmanuelle Charpentier (a microbiologist and director of Max Planck Unit for the Science of Pathogens) further discovered the CRISPR-Cas9 gene editing system, winning the Nobel Prize in Chemistry in 2020 (4). Charpentier discovered tracrRNA, while Doudna mapped the Cas proteins, where their collaboration enabled them to discover and develop the system of gene editing. The scientists became one of the few women to earn the Nobel prize, following 5 other since 1901. Angela Zhou, an information scientist, mentioned how CRISPR has been used to “modify immune cells to make them more effective at destroying cancer cells and to remove the HIV virus when it has integrated itself into the human genome. And CRISPR-based drugs are being developed to treat heart disease, blood disorders and blindness”.

How Does It Work?

CRISPR sequences are crucial for single-celled bacteria and archaea, since they function as their immune system. When a mobile genetic element, particularly a virus (small infectious agents), invades, action is taken to eliminate the threat immediately, protecting the prokaryote (5). Cas proteins cut out a segment of the viral DNA (acting like molecular scissors) to stitch into the bacterium CRISPR region, capturing a ‘chemical snapshot’ of the infection (6). The viral codes are transcribed into short pieces of RNA, which bind to the Cas9 protein (in the CRISPR region). This results in complexes which latch onto free floating genetic material, searching for a match to the virus, resulting in the destruction of the viral DNA. When the immune system has attacked the virus, short CRISPR sequences, called ‘spacers’ are derived (adaption), allowing there to be a ‘genetic memory’, comparable with lymphocytes in the human immune system. This allows CRISPR RNA to be produced within the bacteria (targeting), which will guide the bacterial molecular machinery to destroy the viral material.

Using CRISPR In Labs

This immune system can become a precise gene editing tool, targeting DNA in almost any organism, helping alter the DNA and change specific genes (6):

1. A guide RNA is designed in the lab to match the gene they want to edit

2. This RNA strand is attached to CAS9

3. Guide RNA directs the CAS9 to the target gene

4. The proteins molecular scissors snip the DNA

5. Once it is cut, the cell will try to repair it

Typically, ‘nucleases’ trim and join the ends back together in the process of ‘nonhomologous end joining’. However, this process is prone to mistakes, which can lead to extra or missing bases, often resulting in unusable or turned off genes. If scientists could add an extra template DNA to CRISPR,

cellular proteins could perform a different repair process ‘homology directed repair’, where temporary DNA is used as a blueprint to guide the repairing process (this allows scientists to repair a defective gene or insert a new one). Overall, this produces rDNA (recombinant, meaning it contains a new, different genetic combination).

Applications of CRISPR

This primitive, yet elegant defence system can be used in labs, farms, hospitals and more. CRISPR can lead to critical advances in patient care by drastically changing the trajectory of a disease as scientists learn the effects of turning on and off or changing genes within an organism. The first human clinical trial using CRISPR-Cas9 happened in China in 2016 using lung cancer patients (7) where the PD-1 gene (Programmed Cell Death Protein 1) was inactivated ex-vivo (outside the person), to keep lung cancer in check. This gene normally down-regulates the immune system allowing cancer to multiply, thus the inactivated gene enhances the body’s ability to fight the cancer. However, the success of this trial was kept confidential to the families. Later in July 2019, ex-vivo therapy using CRISPR-Cas9 was performed for a patient with sickle cell anaemia in the US (3), which significantly improved the patient’s condition for months, providing promising results, however the cost has limited further trials, which are estimated to be 0.5-1.5 million USD. Nevertheless, CRISPR can be used as a fast genetic editing system, providing advantageous outcomes.

Currently many clinical trials are taking place for the treatment of diseases such as: hearing loss (Hunter Syndrome), Huntington’s disease (stops part of the brain from working properly over time), Angelman’s syndrome (delayed development, problems with speech and balance), Parkinson’s disease, spinocerebellar ataxia (affects the cerebellum), cystic fibrosis (sticky mucus), turner syndrome (one of the X chromosome is missing or partially missing), muscular dystrophy, sickle cell anaemia, Gaucher disease (missing an enzyme to break down lipids). Promising future applications for CRISPR-Cas9 can be see in HIV and human papillomavirus.

In other settings, gene editing can result in plants that yield larger fruit, improve drought tolerance and drug resistance, and mosquitos that can’t transmit malaria as well as so much more!

Ethics

CRISPR is not a perfect process yet, meaning errors can occur and people may misuse it. One of the largest controversies is in the use of the human embryos, since it may lead to unfair enhancement purposes, but also is affecting the unborn baby who is given no autonomy as to what happens to them. It is believed these concerns should be managed through policy and regulation (8). Ethical discussions are centred around the human germline because these changes will be passed down to future generations, where it is difficult to predict the long-term changes. Gene editing may also lead to offtarget effects (where more cells are affected) or mosaicism (when some cells carry the edit, but others do not). This can lead to an array of unknown consequences. Ethical questions are also raised about genetically edited microbes which may be released into the environment, causing unforeseen changes to the world.

A Recent Study on Heart Disease (9, 10)

Hypertrophic cardiomyopathy (HCM) is the most prevalent genetic heart disease, where the left ventricle heart muscles thicken, leading to stiffness, causing arrhythmia, heart failure or sudden cardiac death. Professor Eric Olsen is conducting a promising study to create in vivo therapy for the treatment of HCM. By editing the gene, he believes this will cause a lifetime fix, as heart cells turnover very slowly, stating it should be a “one-and-done therapy”. A test in mice revealed the editing efficiencies were over 30%, preventing the onset of HCM, showing similar cardiac function to healthy mice. Furthermore, researchers found injecting gene editing reagents to edit the CaMKIIδ gene may lead to protection from ischemia/reperfusion (IRI, cellular dysfunction and death as blood no longer flows to the muscles). Further research is being conducted to repair permanently damaged tissues following a heart attack, which may lead to many exciting opportunities in the advancements of CRISPR-Cas9 gene editing!

References

1. Science History Institute, Herbert W. Boyer and Stanley N. Cohen, no date https://www.sciencehistory.org/education/scientific-biographies/herbert-w-boyer-and-stanley-ncohen/

2. FDA, Science and History of GMOs and Other Food Modification Processes, April 19, 2023, https://www.fda.gov/food/agricultural-biotechnology/science-and-history-gmos-and-otherfoodmodificationprocesses#:~:text=1973%3A%20Biochemists%20Herbert%20Boyer%20and,human %20insulin% 20to%20treat%20diabetes.

3. Irina Gostimskaya, CRISPR-Cas9: A History of Its Discovery and Ethical Considerations of Its Use in Genome Editing, August 15, 2022, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377665/

4. Josh Fischman, Nobel Prize in Chemistry Goes to Discovery of ‘Genetic Scissors’ Called CRISPR/Cas9, October 7, 2020 https://www.scientificamerican.com/article/nobel-prize-inchemistrygoes-to-discovery-of-genetic-scissors-called-crispr-cas911/

5. Ekaterina Pak, CRISPR: A game-changing genetic engineering technique, July 31, 2014, https://sitn.hms.harvard.edu/flash/2014/crispr-a-game-changing-genetic-engineering-technique/

6. Andrea M Henle, How CRISPR lets you edit DNA, January 24, 2019, https://www.youtube.com/watch?v=6tw_JVz_IEc

7. D Cyranoski, CRISPR gene editing tested in a person, 24 November, 2016 https://internationalstudents.unipa.it/dipartimenti/di.chir.on.s./.content/documenti/ IntervistaCRISPR-Nature.2016.20988.pdf

8. National Human Genome Research Institute, What are the Ethical Concerns of Genome Editing?, August 3, 2017 https://www.genome.gov/about-genomics/policy-issues/Genome-Editing/ ethicalconcerns

9. Rebecca Roberts, Base Editing Tackles the Most Common Genetic Heart Disease, May 22, 2023, https://www.science.org/doi/10.1126/science.ade1105

10. Corrie Pelc, Heart disease: CRISPR gene editing may repair damaged tissue after a heart attack, January 13, 2023 https://www.medicalnewstoday.com/articles/heart-disease-crispr-gene-editingmayrepair-damaged-tissue-after-heart-attack

First use of CRISPR https://go.gale.com/ps/i.do?id=GALE %7CA471282615&sid=googleScholar&v=2.1&it=r&linkaccess=ab s&issn=00280836&p=HRCA&sw=w&userGroupName=anon%7Eb1a913aa&aty=open-web-entry

STEADY DOES IT: CRISPR- A PEEK OF THE FUTURE

Chantille Qi-En Marican

What is CRISPR?

CRISPR stands for “Clustered Regularly Interspaced Short Palindromic repeats”. What a mouthful, thank goodness for the abbreviation. It was invented by Jennifer Doudna, a Biochemist, and Emmanuelle Charpentier, a Microbiologist. It was originally proposed to aid in the bacterial immune system to defend against viruses.

Without a doubt, CRISPR is revolutionary in the field of medicine as it enables Scientists to modify the DNA of organisms by editing genes. Why spend time designing your in-game avatar when you can customise your genes?! New year, new you right? Lucky for you, CRISPR was approved in the United Kingdom on November 16th and in the United States on December 8th 2023.

Why is it important?

CRISPR has so much potential to ameliorate medicine as we know it. More and more ways of utilising CRISPR to benefit humanity are being discovered, rendering it invaluable to healthcare. It has the potential to save and improve many lives by reducing symptoms, ailments, and the hardships of medical conditions to allow more individuals to live a more fulfilling life.

Below are some of the breakthroughs and uses of CRISPR:

Treating Sickle cell anemia and thalassemia:

Recently, the FDA has approved the use of CRISPR to aid in treating sickle cell disease (SCD). This is a genetic condition that results in red blood cells taking on a crescent shape instead of its usual more biconcave conformation. This means that less oxygen can be carried effectively throughout the body, causing a great deal of fatigue. As Dr Sharl Azar has noted “It is a disease that really touches every organ in the body”, which emphasises the obstacles those with SCD have to face. Thus, CRIPSR is lifechanging, as it is used to edit stem cells to urge them to produce fetal hemoglobin. After editing, the modified cells are put back into the patient. Thalassemia is another genetic condition affecting the red blood cells that causes hindrance to the daily lives of those afflicted as they require a blood transfusion every 3-4 weeks. CASGEVY is the treatment for these two genetic conditions by correcting haemoglobin genes in the bone marrow stem cells to allow the production of functioning haemoglobin. This is done in a lab and infused into the patient. This can permanently cure the patient, boding for a more satisfying life.

High cholesterol levels can also be reduced using CRISPR 2.0.

Making other viruses harmless:

Genetically engineered viruses by CRISPR are being tested in mice to investigate if viruses can be made less dangerous. The aim is to have the modified viruses alter the other viruses, such as herpes, to extinguish their ability to manifest symptoms.

The key: Gene drives- “parasitic” DNA that is inserted into the chromosomes of another organism. When CRISPR gene drives carrying the modified virus infect a cell simultaneously with the normal virus, it allows the gene drive to copy and paste itself into the DNA. This inhibits co-infections, and in time, all the viruses will carry this same gene drive. It only works with DNA viruses and not RNA viruses, rendering it ineffective against COVID-19 and the flu since it is too small to carry this gene drive. If the gene drive spreads from one person to another, and eventually to the wider population, the viruses in the population will become less harmful. However, this endangers unvaccinated

individuals due to more viruses circulating. Walter, a researcher, is vying to test ways to prevent dormant herpes viruses from reactivation and unwanted transmission.

Preventing the spread of diseases:

Worldwide, there are 200 million cases of malaria each year, with half a million dying. Thanks to CRISPR, a gene drive has been created to make mosquitoes infertile. If a female inherits the gene drive, normal development is halted and male genitalia is created instead. It also shortens the lifespan of the mosquitoes and delays the malaria parasite development by calling forth the mosquito’s death before the parasite can develop. Eventually, the populations of mosquitoes will dwindle, and so will the cases of malaria.

Conclusion:

CRISPR has its pros and cons. It can save lives and improve them by reducing the hassles of a medical condition’s symptoms. Its role in treating neurodegenerative and hereditary diseases is indispensable and its newfangled uses will undoubtedly grace headlines for decades to come. Not only can it offer a helping hand to humans by eradicating diseases, but it can increase crop yields and their quality, making produce more nutritious and resistant to diseases, helping us brave through droughts. However, objectively, it is important to cast light on the ethical concerns of genetic engineering and gene editing for we cannot view things with rose-coloured glasses. Many are against this concept as it goes against their principles and religion due to its genetic meddling. This is probably CRISPR’s largest hindrance to its progression in the medical field. Like any medical treatment, it also carries its own risk as off-target genome editing effects may occur, possibly inducing autoimmune diseases. I would like to encourage you to formulate your own thoughts about CRISPR. Here is a starting point to springboard your exploration: https://www.goodnewsnetwork.org/new-enzyme-allows-crispr-technology-to-accurately-targe talmost-any-human-gene/

References

Hammond, Andrew, et al. “A CRISPR-Cas9 Gene Drive System Targeting Female Reproduction in the Malaria Mosquito Vector Anopheles Gambiae.” Nature Biotechnology, vol. 34, no. 1, 1 Jan. 2016, pp. 78–83, www.nature.com/articles/nbt.3439, https://doi.org/10.1038/nbt.3439. Accessed 5 May 2024.

Kaiser, Jocelyn. “United Kingdom Approves First-Ever CRISPR Treatment, a Cure for Sickle Cell Disease and Beta Thalassemia.” Science.org, 16 Nov. 2023, www.science.org/content/article/united-kingdom-approves-firstever-crispr-treatment-cure-sic kle-cell-disease-and-beta. Accessed 5 May 2024.

Kekatos, Mary. “7 of the Biggest Medical Breakthroughs in 2023.” ABC News, ABC News, 29 Dec. 2023, abcnews.go.com/Health/7-biggest-medical-breakthroughs-2023/story?id=105555925#:~:text= SCD%20is%20a %20genetic%20condition,in%20the%20body%2C%22%20Dr. Accessed 5 May 2024.

Smith, Mike. “CRISPR.” Genome.gov, 2024, www.genome.gov/genetics-glossary/CRISPR#:~:text=CRISPR %20(short%20for%20%E2%8 0%9Cclustered%20regularly,editing%20systems%20found%20in%20bacteria. Accessed 5 May 2024.

Tripathi, Shyam, et al. “A Landscape of CRISPR/Cas Technique for Emerging Viral Disease Diagnostics and Therapeutics: Progress and Prospects.” Pathogens, vol. 12, no. 1, 29 Dec. 2022, pp. 56–56, www.ncbi.nlm.nih.gov/pmc/articles/PMC9863163/, https://doi.org/10.3390/pathogens12010056. Accessed 5 May 2024.

U.S. Food and Drug Administration. “FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease.” U.S. Food and Drug Administration, 8 Dec. 2023, www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patie nts-sickle-celldisease. Accessed 5 May 2024

NANOTECHNOLOGY: MINI MISSILES IN THE WAR ON THE CANCER

Anushri Shah

Introduction

Cancer, an infamous and ubiquitous disease, despite revolutionary medical breakthroughs remains the leading cause of mortality. It is a notoriously tricky disease with a cure more painful than the disease. The cure is more painful than the disease because cancer is caused by uncontrolled replication of your body cells and traditional treatments such as chemotherapy may kill rapidly dividing body cells such as cells in the lining of the gut and hair follicles in the process of destroying cancer cells and may have debilitating symptoms and long term side effects such as nausea, vomiting or even heart attacks.

The use of nanotechnology allows for pinpoint accuracy in targeting cancer cells, reduces harm to healthy cells, and has fewer side effects. It has the potential to revolutionize cancer treatment and diagnosis.

What is Nanotechnology?

‘Nano’ means minuscule - about a billion times smaller than a meter! To put this into perspective, if the diameter of a marble were one nanometer, then the diameter of Earth would be about one meter. Nanotechnology is, therefore, the engineering of nanomaterials. These nanocarriers or nanobots can be engineered to carry and deliver drugs to only cancer cells, allowing for more targeted treatment and overcoming the limitations of traditional treatment methods.

Nanobots attacking cancer cells as a 3D render

Cancer treatment using nanomaterials

Nanocarrier-based drug delivery for cancer cells is achieved through two main avenues: passive and active targeting. Passive targeting takes advantage of the distinguishing features of the target region such as the diameter of capillaries near the targeted region, fostering the accumulation of nanoparticles and allowing targeted release of therapeutic drugs. To enhance passive targeting and improve its efficiency, nanoparticle size is adjusted. The changes in size enhance their circulation, improve accumulation efficiency, and maximize the impact of drugs. Lipid composition and surface characteristics can also be adjusted to optimize the biodistribution of nanoparticles for passive targeting. Conversely, active targeting involves only surface modifications of nanobots with specific ligands that bind with receptors present on the surface of cancer cells, minimizing damage to healthy cells nearby. The advantage of passive targeting is that manufacturing of passively targeting nanoparticles is simple, cost-effective, reduces side effects, and is rapid. Whereas, active targeting can be expensive and not nearly as quick. It does, however, have maximum delivery efficiency.

Passive and active targeting systems for delivery of therapeutics into cancer cells. (A) Heterogenous tumour microenvironment. (B) Passive targeting through the EPR effect for accumulating NCs inside the tumour. (C) Drug transporter internalization into the cytosol via receptor-mediated endocytosis. (D) Blood capillary system of healthy cells vs. cancer cells.

Conclusion

Nanotechnology, in theory, sounds like our miracle cure for cancer. However, there are still numerous problems that need to be overcome before the widespread use of this technology can be achieved such as the possibility of nanoparticles interacting with other systems in the body and the long term biocompatibility and toxicity of nanobots in the body. Another significant challenge is that nanocarriers must go through a stringent pathway before achieving approval which can be difficult due to the unique properties of each carrier. The lack of standardized protocols for nanoparticles such as their characterization, toxicity assessment, and safety protocols slow down the approval process. Many labs and clinics also lack the resources to continue research and go through the whole process and hence, fail to translate their experiments to clinical applications. Nevertheless, with continued research and funding nanotechnology has the potential to be our miracle cure for cancer.

References :

1) Chehelgerdi, M., Chehelgerdi, M., Allela, O.Q.B. et al. Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation. Mol Cancer 22, 169 (2023). https://doi.org/10.1186/s12943-023-01865-0

2) Jin C, Wang K, Oppong-Gyebi A, Hu J. Application of Nanotechnology in Cancer Diagnosis and Therapy - A Mini-Review. Int J Med Sci. 2020 Oct 18;17(18):2964-2973. doi: 10.7150/ijms.49801. PMID: 33173417; PMCID: PMC7646098. Last accessed - 28 September 2024

3) Dessale M, Mengistu G, Mengist HM. Nanotechnology: A Promising Approach for Cancer Diagnosis, Therapeutics and Theragnosis. Int J Nanomedicine. 2022;17:3735-3749

4) https://doi.org/10.2147/IJN.S378074

5) https://www.youtube.com/watch?v=50fAMErAIT0

6) Zhu, Ruirui and Zhang, Fangyuan and Peng, Yudong and Xie, Tian and Wang, Yi and Lan, Yin, 2022, Current Progress in Cancer Treatment Using Nanomaterials, Frontiers in Oncology, Vol. 12, https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.930125 DOI10.3389/fonc.2022.930125

7) Chem. Sci., 2024, 15, 1966 https://pubs.rsc.org/en/content/articlehtml/2024/sc/d3sc05539f DOI: 10.1039/d3sc05539f rsc.li/chemical-science

ALLIANCE FOR HIPPOCRATIC MEDICINE

V. FDA

Delisha Dias

Ahuman soul or just a clump of cells? The debate resurfaces once again after last year’s Roe v. Wade overturn. The question seems simple- the human right to life or the right to choice; but there’s a certain complexity from every angle that this predicament is perceived in. The current problem is posed by a group of doctors and other medical professionals that are represented by a conservative Christian legal group- Alliance for Hippocratic Medicine. They claim that the FDA’s 2000 approval of a popular abortion-inducing medication was a flawed decision, as were the later changes made to the drug's ability to be accessed, wholly because they failed to take into consideration the safety and wellbeing that this medication poses to women.

The FDA's 2000 approval of mifepristone and subsequent actions taken by the agency to make it more accessible were halted by an order from a federal district judge on April 7th 2023. The Biden administration and the drug's manufacturer, Danco Laboratories, formally requested the Supreme Court's intervention and blockade on the same earlier this month.

The reference to the changes includes the FDA’s modification of the usage of mifepristone, including raising the gestational limit from seven to ten weeks of pregnancy, lowering the quantity of in-person clinic visits necessary, and expanding the list of medical professionals qualified to dispense the medication. In addition, the FDA approved a generic version of mifepristone in 2019 and removed the restriction that the pills be administered in person in 2021, enabling telemedicine visits and mailorder prescriptions for the medication.

The Biden administration's decision to apply for emergency relief from the Supreme Court was anticipated; in papers to the 5th Circuit, it stated that it would do so if necessary. This is the next step in its prompt legal response to the Kacsmaryk ruling. The White House press secretary, Karine JeanPierre, told reporters that the government "will prevail because we believe that the law is on our side." President Biden has pledged to defend access to abortion care.

"The Justice Department strongly disagrees with the Fifth Circuit's decision in Alliance for Hippocratic Medicine v. FDA to deny in part our request for a stay pending appeal," Attorney General Merrick Garland said in a statement before the Justice Department formally made its request. "We will be seeking emergency relief from the Supreme Court to defend the FDA's scientific judgment and protect Americans' access to safe and effective reproductive care."

As the Supreme Court deliberated on whether to allow the Biden administration's emergency request to keep the Food and Medicine Administration's approval of the medicine, Justice Samuel A. Alito Jr. issued an order on Friday guaranteeing that a common abortion pill would temporarily remain widely accessible. The decision wasn't meant to determine how the court would decide on the most significant issue involving access to abortion since its conservative majority overturned Roe v. Wade last June; rather, it was intended to stabilize the situation while the justices read the arguments and lower court judgements.

In the meantime, Judge Alito has returned things to as they were before Judge Kacsmaryk issued a decision last week that would have delayed the agency's approval of the pill and severely restricted the supply of mifepristone. Alito went on to further justify his dissent in writing, stressing that he was not debating whether the FDA had broken the law in its handling of mifepristone.

Instead, he spoke about how the conservative majority of the Supreme Court had previously come under fire for how it handled emergency cases on its so-called shadow docket. He also disputed the

manufacturer's and the government's assertions that the 5th Circuit order would have significantly disrupted patient access to the medication.

The administration’s brief asked the court to pause parts of an appeals court ruling that had limited the availability of the pill, which is part of the most commonly used method for ending pregnancies in the United States. “If allowed to take effect, the lower court’s orders would upend the regulatory regime for mifepristone, with sweeping consequences for the pharmaceutical industry, women who need access to the drug, and F.D.A.’s ability to implement its statutory authority,” the brief said. The decision made by a federal appeals court would significantly restrict access to a drug used in medication abortions, which account for over half of all abortions performed in the United States.

The 5th Circuit's order would have imposed limitations on how the abortion medication may be used if the Supreme Court had not intervened as the Biden administration had requested. These restrictions would have limited the drug's gestational duration and mandated that individuals acquire the medication in person from their doctor and attend two additional clinical visits as needed by the protocol.

The Supreme Court has already taken action previously, blocking in its entirety a ruling by Texas U.S. District Judge Matthew Kacsmaryk in April that had overturned the FDA's initial clearance of the medicine more than 20 years prior.

Danco Laboratories, which produces the branded form of mifepristone, submitted a second emergency application, in which the company's attorneys argued that the justices should respect the F.D.A.'s scientific expertise in evaluating whether the drug was safe and effective. The plaintiffs appeared to have standing to file a lawsuit, according to the majority, because they could be confronted with side effects from taking the medication.

The primary issue in the case, according to Danco's submission, was "whether courts can disregard constitutional and statutory limits on judicial review of executive action to overrule an agency decision they dislike." For "the women and teenage girls, health care providers, and States that depend on FDA’s actions to ensure safe and effective reproductive health care is available, this case matters tremendously" it said, echoing the Biden administration's comments. Danco further stated that allowing court review of the FDA's scientific assessments of evidence "for the pharmaceutical and biotechnology industry, permitting judicial second-guessing of FDA’s scientific evaluations of data will have a wildly destabilizing effect.”

Referencing the turmoil that has followed the conflicting court orders regarding mifepristone, Danco said the "result is an untenable limbo, for Danco, for providers, for women, and for health care systems all trying to navigate this uncharted waters-and all after plaintiffs waited years and years before claiming irreparable injury and a need for an emergency injunction voiding the decades-long status quo.”

U.S. Solicitor General Elizabeth Prelogar, representing the federal government, emphasised that the FDA’s original approval had rested on the agency’s “scientific judgment that the drug is safe and effective,” and that the agency had “modified the original conditions of approval as decades of experience have further confirmed the drug’s safety.” She told the justices that allowing the ruling by the 5th Circuit to stand would have “damaging consequences for women seeking lawful abortions and a healthcare system that relies on the availability of the drug under the current conditions of use.” But more broadly, she noted, it was “the first time any court has restricted access to an FDA-restricted drug based on disagreement with FDA’s expert judgment about the conditions required to assure that drug’s safe use—much less done so after those conditions had been in effect for years.” The FDA and Danco say that serious adverse effects are "exceedingly rare." and according to government figures, more than 5 million Americans have used the drugs safely since then.

“We are furious that yet another court would choose to jeopardise the health and futures of the millions of people who rely on mifepristone for abortion care,” said Alexis McGill Johnson, president of the Planned Parenthood Federation of America. “This baseless case is a politically motivated attack to further restrict access to abortion that will place care out of reach for patients — and we will not stand for it.”

A White House spokesperson said if the 5th Circuit decided to take effect, "it would have devastating consequences for women and undermine the FDA’s process for regulating safe and effective medications that patients rely on."

"The biopharma industry, physicians and medical organisations, former FDA and former DOJofficials, and patient advocates have made clear: this lawsuit poses an unprecedented threat to the FDA’s authority to review and approve a wide range of safe and effective drugs," the spokesperson added.

Additionally, In a press conference on Monday, White House Press Secretary Karine Jean-Pierre denounced Friday’s ruling as a “dangerous” attack on women’s rights and FDA authority. She also articulated the Biden administration’s support for the DOJ’s appeal.

“It probably is going to go up to the Supreme Court, which we feel pretty confident that we’re going to win,” Jean-Pierre said.

But Jean-Pierre responded on Monday that disregarding a court decision would set a “dangerous precedent”, echoing a statement that US Department of Health and Human Services (HHS) spokesperson Kamara Jones made “Judge Kacsmaryk’s act of judicial interference has set a precedent for diminishing [the] FDA’s authority over drug approvals, and in doing so, creates uncertainty for the entire biopharma industry,” said the letter, which was signed by high-profile figures including the CEO of Pfizer Inc, Albert Bourla.“Judicial activism will not stop here,” it continued. “If courts can overturn drug approvals without regard for science or evidence, or for the complexity required to fully vet the safety and efficacy of new drugs, any medicine is at risk for the same outcome as mifepristone.”

However, Antiabortion advocates said the legal dispute was about health and safety. March for Life President Jeanne Mancini celebrated the decision with the following statement: “We are pleased that the 5th Circuit Court of Appeals has temporarily reinstated important and commonsense health and safety protections surrounding the use of chemical abortion drugs. The FDA’s elimination of these safeguards shows a reckless disregard for women’s health when it comes to abortion.”

The Justice Department's court petition paves the way for a potential end to a bitter legal battle launched by opponents of abortion rights over the federal approval of the medication mifepristone. The case is brought before the Supreme Court in time for the justices to consider it, hear oral arguments, and make a ruling by the end of the summer. Since overturning Roe v. Wade last year, the case would mark the Supreme Court's first significant abortion-related decision. With minor exceptions, this decision has resulted in bans on abortion at all stages of pregnancy in 15 states and once heart activity can be found, which usually occurs at around six weeks, or in some cases, two.

In conclusion, seeing as access to mifepristone is at risk, Democratic-led states have started their stockpile of supplies of the drug and misoprostol, which can be taken on its own to terminate an early pregnancy. But a misoprostol-only medication abortion is slightly less effective — between 80% and 99% — than the two-drug regimen of mifepristone and misoprostol, which is between 95% and 99% effective.

California Governor Gavin Newsom announced Monday that the state secured an emergency stockpile of up to 2 million misoprostol pills. Massachusetts Governor Maura Healey directed healthcare providers in the state to bank more doses of mifepristone. The University of Massachusetts Amherst purchased roughly 15,000 doses, enough to last the state more than a year, and the doses are set to

arrive this week. New York Governor Kathy Hochul said Tuesday that her state would stockpile 150,000 doses of misoprostol.

Case update: On September 8, the U.S. Department of Justice filed a petition for a writ of certiorari to the U.S. Supreme Court asking it to review the Fifth Circuit Court of Appeals’ August 16 ruling to reinstate significant restrictions on mifepristone. (Due to an earlier order by the Supreme Court, the Fifth Circuit ruling is not in effect.)

References

Chung, A. (2023) Supreme Court’s Alito temporarily blocks abortion-pill curbs | Reuters, Reuters. Available at: https://www.reuters.com/business/healthcare-pharmaceuticals/abortion-pill-maker-asks-us-su preme-courtstop-curbs-access-drug-2023-04-14/ (Accessed: 15 September 2023). Howe, A. (2022) Supreme Court overturns constitutional right to abortion, SCOTUSblog. Available at: https://www.scotusblog.com/2022/06/supremecourt-overturns-constitutional-right-to-abortio n/ (Accessed: 15 September 2023).

Autry, B.M. and Wadhwa, R. (2024) Mifepristone, StatPearls. Available at: https://www.ncbi.nlm.nih.gov/books/NBK557612/ (Accessed: 15 September 2023).

Howe, A. (2023) Biden administration and drug manufacturer ASK court to block suspension of mifepristone approval, SCOTUSblog. Available at: https://www.scotusblog.com/2023/04/supreme-court-bidenadministration-and-drug-manufact urer-ask-court-to-block-suspension-of-mifepristone-abortion-approval/ (Accessed: 15 September 2023).

Anon (2023) Questions and answers on mifeprex, U.S. Food and Drug Administration. Available at: https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/questi ons-andanswers-mifepristone-medical-termination-pregnancy-through-ten-weeks-gestation (Accessed: 15 September 2023).

Chung, A. (2023a) Biden administration takes abortion-pill dispute to US Supreme Court | reuters, Reuters. Available at: https://www.reuters.com/legal/abortion-pill-manufacturer-takes-dispute-over-access-us-supre mecourt-2023-09-08/ (Accessed: 15 September 2023).

Anon (2023b) Statement from attorney general Merrick B. Garland on alliance for hippocratic medicine v. FDA Appeals Decision, Office of Public Affairs | Statement from Attorney General Merrick B. Garland on Alliance for Hippocratic Medicine v. FDA Appeals Decision | United States Department of Justice. Available at: https://www.justice.gov/opa/pr/statement-attorney-general-merrick-b-garland-alliance-hippocr atic-medicinev-fda-appeals (Accessed: 15 September 2023).

Howe, A. (2023b) Federal Government and drug manufacturer ASK court to review ruling restricting access to abortion medication, SCOTUSblog. Available at: https://www.scotusblog.com/2023/09/federal-governmentand-drug-manufacturer-ask-court-t o-review-ruling-restricting-access-to-abortion-medication/#:~:text=In %20its%20own%20filin g%2C%20Danco,argued%20that%20for%20%E2%80%9Cthe%20women (Accessed: 15 September 2024).

Al Jazeera (2023) Biden admin seeks to halt ruling suspending sale of Abortion pill, Al Jazeera. Available at: https://www.aljazeera.com/news/2023/4/10/us-democrats-debate-response-to-court-ruling-on abortion-pill (Accessed: 15 September 2023).

THE PRICKLY SECRETE: SEA URCHINS AND CANCER

Leila Ghandour

Often dismissed as spiky nuisances inhabiting the ocean floor, sea urchins are frequently viewed with disdain and hatred by beachgoers and fishermen alike, and yet just as any prevalent creature, they play a vital role for their local ecosystem. However, a urchins importance goes beyond simple grazing algae and contributing to nutrient cycling, urchins hold the potential to help solve medicine's greatest enigma. A cure for cancer

The longevity of sea urchins surpasses that of most terrestrial animals, with many species living for over a century. This remarkable lifespan tells us that they manage to live free of life-threatening tumors for exorbitant lengths of time, hence suggesting that they must possess effective mechanisms for suppressing tumor development. Unlike many well-known animals, sea urchins lack an adaptive immune system and rely solely on innate immunit. This characteristic provides scientists with a unique opportunity to investigate cellular processes related to cancer and aging without the complications introduced by adaptive immune responses.

Regenerative Abilities and Their Role in Cancer Research

One of the most significant traits of sea urchins in cancer research is their remarkable regenerative abilities, which enable them to repair and regenerate their tissues and organs. These organisms can regenerate lost spines, tube feet, and even parts of their internal organs, showcasing an extraordinary capacity for healing. This regenerative capability is largely attributed to specialized cells called coelomocytes, which play a crucial role in tissue repair and regeneration. Understanding the underlying mechanisms of this regeneration may provide valuable insights into tumor development and progression.

Research has shown that the regenerative process in sea urchins is tightly regulated by specific signaling pathways, including those involving growth factors and hormones. These pathways control critical processes such as cell growth, division, and differentiation—mechanisms that are often disrupted in cancerous cells, leading to uncontrolled proliferation and tumor formation. For instance, studies have highlighted the role of the Wnt signaling pathway, which is essential for regulating cell fate during development and is also implicated in various cancers when misregulated.

Cytotoxic sea urchin extracts as potential cancer medicine

Research has demonstrated that certain extracts derived from sea urchins exhibit cytotoxic effects against various cancer cell lines. These compounds can inhibit cancer cell multiplication and induce apoptosis (programmed cell death), making them promising candidates for developing new anticancer drugs. As researchers delve deeper into the biochemical properties of these extracts, there is potential for discovering effective treatments that could complement existing cancer therapies.

Recent research has found that specific sea urchin extracts could trigger a cascade of cellular events that lead to apoptosis. This involves the activation of certain proteins called caspases, which play a vital role in the execution phase of cell death. Additionally, these extracts may disrupt the signaling pathways that cancer cells rely on for survival, making it harder for them to grow and divide.

The biochemical properties of these sea urchin extracts, captivate scientests as they could lead to the development of new anticancer drugs, possible providing an alternative to synthetic drugs, possibly eliminating the harsh side effects that come attached. By isolating and studying the active compounds within these extracts, scientists can better understand how they interact with cancer cells and the mechanisms by which they exert their effects. This could pave the way for innovative therapies that enhance the effectiveness of existing cancer treatments, such as chemotherapy and radiation.

The Journey Ahead for Sea Urchin Research

Although still in moderately preliminary stages, as the research progresses, potential is uncovered not only for new anticancer drugs but also for developing combination therapies that improve treatment outcomes for patients facing numerous types of cancer.

The journey is far from over, scientists still need to conclude extensive biochemical analyses to isolate and characterize the specific compounds within sea urchin extracts that exhibit cytotoxic effects and even then, they must further conduct preclinical studies to evaluate the safety and efficacy of these extracts in vivo. However, the exploration of sea urchins in medicine represents a promising frontier in the ongoing battle against cancer, showcasing how the unique biology of marine organisms can lead to groundbreaking medical advancements. The research serves as a reminder that the teaching of the natural world is a school that everyone is still taking to this day. In the fight against cancer our nature might hold the key to unlocking new therapies, and these small prickly creatures are helping to lead the way.

References

1. Matray, T. J., Coffman, A. S., & Shapiro, M. D. (2021). Regeneration in sea urchins: Insights into regenerative biology and its application to human health Frontiers in Genetics, 11, 627259. https://doi.org/10.3389/fgene.2020.627259

2. Unuma, T., & Moriyama, A. (2015). Sea urchins as model organisms in studies of cell biology and regeneration. Nature Genetics, 440, 1295–1302. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534296/

3. Gloucester Marine Genomics Institute. (2021). Lessons from the sea: Unlocking the secrets of sea urchin longevity and cancer resistance NEB Expressions. Retrieved from https://gmgi.org/wp-content/uploads/2021/04/Lessons-from-the-sea_NEB-expressions.pdf#:~:text= %3C%20The%20red%20sea%20urchin%20(Mesocentrotus,no%20reported%20cases%20of%20cancer

4. Rizzo, V., & Ferrando, R. (2005). Sea urchin immune response: A tool for the study of evolutionary and comparative immunology Nature Genetics, 440(1295), 1295-1302. https://www.nature.com/articles/4401295

5. Albuquerque, D., & Almeida, J. (2023). Pharmacological insights into sea urchin extracts: The next frontier in marine biomedicine BMC Pharmacology and Toxicology, 23(6). https://doi.org/10.1186/s40360-023-00651-4

WHAT ARE THE PRINCIPLES OF MEDICAL ETHICS

AND WHY ARE THEY IMPORTANT?

Devyansh Pandey

There are four core principles of medical ethics, and each one of them has a significant role in the treatment of a patient. The four core principles consist of autonomy, beneficence, non-maleficence, and justice. Implementing these four ethical principles to their finest extents can be a tough decision for a physician at times18, but before I explain why they are important, let me inform you about each of them.

Autonomy is usually expressed as the right of competent adults to make informed decisions about their own medical care. The principle underlies the requirement to seek the consent or informed agreement of the patient before any investigation or treatment takes place19 .

Beneficence is understood as a principle requiring that physicians provide, and to the best of their ability, positive benefits such as good health, prevent and remove harmful conditions from patients20 . Non-maleficence is the principle of refraining from causing intentional harm toward another human being. Maleficence is the deliberate infliction of a negative act or effect on another individual or a group. Non-maleficence, therefore, indicates that a person genuinely works for a positive outcome for those with whom they come in contact. This principle especially applies to healthcare, particularly the field of nursing. Non-maleficence has four key components: An action must not be intrinsically wrong; a good effect must be intended by the action; the good outcome must not be a byproduct of a bad effect; if there are negative outcomes of an action, the good outcomes of the action must outweigh the bad21 .

Justice – in the context of medical ethics – is the principle that when weighing up if something is ethical or not, we must think about whether it’s compatible with the law, the patient’s rights, and if it’s fair and balanced. It also means that we must ensure no one is unfairly disadvantaged when it comes to access to healthcare22

18 Medicine, D. (2019). Core ethical principles (part 1). YouTube. YouTube. Retrieved December 29, 2022, from https://www.youtube.com/watch?

v=7JkRncMz9xc&list=PL5rTEahBdxV5szNYtMDCm7YuiG51WUnZV&index=1

19 BMA, T. (2020). Autonomy or self-determination as a medical student - ethics toolkit for medical studentsBMA. The British Medical Association is the trade union and professional body for doctors in the UK. Retrieved December 29, 2022, from < https://www.bma.org.uk/advice-and-support/ethics/medical-students/ethicstoolkit-for-medical-students/autonomy-or-self-determination#:~:text=What%20do%20we%20mean %20by,investigation%20or%20treatment%20takes%20place.>

20

Munyaradzi, M. (2012). Critical reflections on the principle of beneficence in biomedicine. The Pan African medical journal. U.S. National Library of Medicine. Retrieved December 29, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325067/#:~:text=More%20commonly%20in %20medical%20ethics,remove%20harmful%20conditions%20from%20patients.

21 Hepler, R. (2022). Take online courses. earn college credit. Research Schools, Degrees & Careers. Study.com | Take Online Courses. Earn College Credit. Research Schools, Degrees & Careers. Retrieved December 29, 2022, from <https://study.com/learn/lesson/principle-nonmaleficence-examples.html>

22

Medical ethics guide one’s decision-making, interactions and conduct with patients. Violations of medical ethics can threaten one’s job, medical license, or even constitute a crime. Ethics provide us a moral compass to use in situations that may not be straightforward23. Having a system of medical ethics gives one a starting point for tackling the dilemmas put forward by medicine24 .

References

BMA, T. (2020). Autonomy or self-determination as a medical student - ethics toolkit for medical studentsBMA. The British Medical Association is the trade union and professional body for doctors in the UK. Retrieved December 29, 2022, from https://www.bma.org.uk/advice-and-support/ethics/medical-students/ethics-toolkitfor-medical-students/autonomy-or-self-determination#:~:text=What%20do%20we%20mean %20by,investigation%20or%20treatment%20takes%20place

Bolin, P. (2018). Basic principles in medical ethics - CRASH! Medical Review Series. YouTube. YouTube. Retrieved December 29, 2022, from https://www.youtube.com/watch?v=sQTrPIwtWaw&t=193s

Hepler, R. (2022). Take online courses. earn college credit. Research Schools, Degrees & Careers. Study.com | Take Online Courses. Earn College Credit. Research Schools, Degrees & Careers. Retrieved December 29, 2022, from https://study.com/learn/lesson/principle-nonmaleficence-examples.html

Medicine, D. (2019). Core ethical principles (part 1). YouTube. YouTube. Retrieved December 29, 2022, from https://www.youtube.com/watch?v=7JkRncMz9xc&list=PL5rTEahBdxV5szNYtMDCm7YuiG51WUnZV&index=1 MSAG, the. (2019). The importance of medical ethics. theMSAG. Retrieved December 29, 2022, from https://themsag.com/blogs/medical-school-interviews/the-importance-of-medical-ethics

Munyaradzi, M. (2012). Critical reflections on the principle of beneficence in biomedicine. The Pan African medical journal. U.S. National Library of Medicine. Retrieved December 29, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325067/#:~:text=More%20commonly%20in%20medical %20ethics,remove%20harmful%20conditions%20from%20patients

Nineham, L. (2021). Medical ethics: Justice. The Medic Portal. Retrieved December 29, 2022, from https://www.themedicportal.com/application-guide/medical-school-interview/medical-ethics/justice/ #:~:text=Justice%20%E2%80%93%20in%20the%20context%20of,if%20it's%20fair%20and%20balanced

Nineham, L. (2021). Medical ethics: Justice. The Medic Portal. Retrieved December 29, 2022, from <https://www.themedicportal.com/application-guide/medical-school-interview/medical-ethics/ justice/#:~:text=Justice%20%E2%80%93%20in%20the%20context%20of,if%20it's%20fair%20and %20balanced.>

23 Bolin, P. (2018). Basic principles in medical ethics - CRASH! Medical Review Series. YouTube. YouTube. Retrieved December 29, 2022, from <https://www.youtube.com/watch? v=sQTrPIwtWaw&t=193s>

24 MSAG, the. (2019). The importance of medical ethics. theMSAG. Retrieved December 29, 2022, from &lt; https://themsag.com/blogs/medical-school-interviews/the-importance-of-medical-ethics&gt;