Looking at p53 mutations and cancer predisposition Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Decoding p53: the guardian against cancer 09/07/25, 15:03 Last updated: Published: 23/11/23, 11:38 Looking at p53 mutations and cancer predisposition Being a tumour suppressor protein, p53 encoded by the TP53 gene plays a critical role in regulating cell division and preventing the formation of tumours. Its function in maintaining genome stability is vital in inhibiting cancer development. Understanding p53 Located on chromosome locus 17p13.1, TP53 encodes the p53 transcription factor 1. Consisting of three domains, p53 can directly initiate or suppress the expression of 3661 different genes involved in cell cycle control and DNA repair 2. With this control, p53 can influence cell division on a massive scale. Cancer is characterised by uncontrolled cell division, which can occur due to accumulated mutations in either proto-oncogenes or tumour suppressor genes. Wild-type p53 can repair mutations in oncogenes such that they will not affect cell division. However, if p53 itself is mutated, then its ability to repair DNA and control the cell cycle is inhibited, leading to the emergence of cancer. Mutations in TP53 are actually the most prevalent genetic alterations found in patients with cancer. The mechanisms by which mutated p53 leads to cancer are manifold. One such mechanism is p53’s interaction with p21. Encoded by CDKN1A , p21 is activated by p53 and prevents cell cycle progression by inhibiting the activity of cyclin-dependent kinases (CDKs). Therefore, we can see that a non-functional p53 would lead directly to uncontrolled cell division and cancer. Clinical significance The importance of p53 in preventing cancer is highlighted by the fact that individuals with inherited TP53 mutations (a condition known as Li-Fraumeni syndrome or LFS) have a significantly greater risk of developing any cancer. These individuals inherit one defective TP53 allele from one parent, making them highly susceptible to losing the remaining functional TP53 allele, ultimately leading to cancer. Loss of p53 also endows cells with the ability to ignore pro-apoptotic signals such that if a cell becomes cancerous, it is far less likely to undergo programmed cell death 3. Its interactions with the apoptosis-inducing proteins Bax and Bak, are lost when mutated, thus leading to cellular apoptosis resistance. The R337H mutation in TP53 is an example of the founder effect at work. The founder effect refers to the loss of genetic variation when a large population descends from a smaller population of fewer individuals. The descendants of the initial population are much more likely to harbour genetic variations that are less common in the species as a whole. In southern Brazil, the R337H mutation in p53 is present at an unusually high frequency 4 and is thought to have been introduced by European settlers several hundred years ago. It is responsible for a widespread incidence of early-onset breast cancers, LFS, and paediatric adrenocortical tumours. Interestingly, individuals with this mutation can trace their lineage back to the group of European settlers that set foot in Brazil hundreds of years ago. Studying p53 has enabled us to unveil its intricate web of interactions with other proteins and molecules within the cell and unlock the secrets of cancer development and potential therapeutic strategies. By restoring or mimicking the functions of p53, we may be able to provide cancer patients with some relief from this life-changing condition. Written by Malintha Hewa Batage Related articles: Zinc finger proteins / Anti-freeze proteins Project Gallery

Unmasking the complexities of the condition Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Crohn's disease 09/07/25, 15:01 Last updated: Published: 22/03/24, 20:16 Unmasking the complexities of the condition Introduction Crohn's disease is a chronic inflammatory condition that primarily targets the gastrointestinal tract. While it commonly afflicts individuals aged 20 to 50, it can also manifest in children and older adults, albeit less frequently. Symptoms of Crohn's disease vary widely and may include skin lesions spanning from the mouth to the anus, along with prevalent issues such as diarrhoea, abdominal pain, weight loss, rectal bleeding, fatigue, and fever. Diagnosis Diagnosing Crohn's disease can be challenging due to its similarity to other conditions. However, specific symptoms like bloody diarrhoea, iron deficiency, and unexplained weight loss are significant indicators that warrant further investigation by a gastroenterologist. Many tests that can confirm Crohn’s disease: Endoscopy: endoscopy, including procedures like colonoscopy and upper endoscopy, is a dependable method for diagnosing Crohn's disease and distinguishing it from other conditions with similar symptoms. During an endoscopy, a thin tube called an endoscope is inserted into the rectum to visually inspect the entire gastrointestinal tract and collect small tissue samples for further analysis. Imaging: Computed tomography (CT), magnetic resonance imaging (MRI), and ultrasonography are valuable tools for assessing disease activity and detecting complications associated with Crohn's disease. These imaging techniques can examine areas of the gastrointestinal tract that may not be accessible via endoscopy, providing comprehensive insights into the condition's progression and associated issues. Laboratory testing: various laboratory tests, including complete blood count, C-reactive protein levels, pregnancy tests, and stool samples, are conducted to screen for Crohn's disease. These tests are typically the initial step in diagnosis, helping to avoid the necessity for more invasive procedures like endoscopies and imaging. Additionally, laboratory testing may involve assessing inflammatory markers such as erythrocyte sedimentation rate (ESR) and faecal calprotectin to further aid in diagnosis and monitoring of the condition. Treatment and prevention While there is currently no cure for Crohn’s disease, numerous treatments have been developed over time to effectively manage symptoms and sometimes even induce remission. When determining a treatment plan for patients, factors such as age, specific symptoms, and the severity of inflammation are taken into careful consideration. Corticosteroids and immunomodulators are medications commonly used to manage Crohn’s disease. Corticosteroids work by reducing inflammation and suppressing the immune system, typically employed to address flare-ups due to their rapid action. However, they are not suitable for long-term use as they may lead to significant side effects. In contrast, maintenance therapy often involves immunomodulators such as azathioprine, methotrexate, or biologic agents like anti-TNF drugs (such as infliximab or adalimumab). These medications target specific immune pathways to enhance the effectiveness of the immune system. Research indicates that immunomodulators are associated with fewer adverse effects compared to corticosteroids and are effective in maintaining remission. Monoclonal antibody treatment is another approach used to manage symptoms and sustain remission in Crohn's disease. These therapies are categorised as biologic treatments, targeting precise molecules involved in inflammation and the immune response. Despite carrying certain risks, such as infections, the likelihood of developing cancer with these treatments is typically deemed low. Crohn’s disease frequently leads to complications that may necessitate surgical intervention. Gastrointestinal surgeries can greatly alleviate symptoms and enhance the quality of life for patients. However, surgery is usually considered only when medical therapy proves insufficient in controlling the disease or when complications arise. Although the exact cause of Crohn’s disease remains uncertain, factors such as genetics, immune system dysfunction, and environmental influences are believed to contribute to its development. While there is no definitive evidence pinpointing specific causative factors, numerous studies suggest potential links to an unhealthy diet and lifestyle, dysbiosis (imbalance of healthy and unhealthy gut bacteria), smoking, and a family history of the disease. Therefore, it is crucial to minimise exposure to these risk factors in order to decrease the likelihood of developing Crohn’s disease. Written by Sherine Abdul Latheef Related articles: the gut microbiome / the dopamine connection / Diverticular disease / Mesenchymal stem cells REFERENCES Veauthier B, Hornecker JR. Crohn's Disease: Diagnosis and Management. Am Fam Physician. 2018;98(11):661-669. Torres J, Mehandru S, Colombel JF, Peyrin-Biroulet L. Crohn's disease. Lancet. 2017;389(10080):1741-1755. doi:10.1016/S0140-6736(16)31711-1 Mills SC, von Roon AC, Tekkis PP, Orchard TR. Crohn's disease. BMJ Clin Evid. 2011;2011:0416. Published 2011 Apr 27. Sealife, A. (2024) Crohn’s disease, Parkland Natural Health. Available at: https://wellness-studio.co.uk/crohns-disease/ (Accessed: 09 March 2024). How to stop anxiety stomach pain & cramps (2022) Calm Clinic - Information about Anxiety, Stress and Panic. Available at: https://www.calmclinic.com/anxiety/symptoms/stomach-pain (Accessed: 09 March 2024). Project Gallery

From foe to ally Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Herpes vs devastating skin disease 09/07/25, 15:16 Last updated: Published: 06/01/24, 11:14 From foe to ally This is article no. 3 in a series on rare diseases. Next article: Epitheliod hemangioendothelioma . Previous article: Breast cancer in males . Have you ever plucked loose skin near your nail, ripping off a tiny strip of good skin too? Albeit very small, that wound can be painful. Now imagine that it is not just a little strip that peels off, but an entire sheet. And it does not detach only when pulled, but at the slightest touch. Even a hug opens wounds, even a caress brings you pain. This is life with recessive dystrophic epidermolysis bullosa (RDEB), the most severe form of dystrophic pidermolysis bullosa (DEB). Herpes becomes a therapy DEB is a rare genetic disease of the skin that affects 3 to 10 individuals per million people (prevalence is hard to nail down for rare diseases). A cure is still far off, but there is good news for patients. Last May, the US Food and Drug Administration (FDA) approved Vyjuvek (beremagen geperparvec) to treat skin wounds in DEB. Clinical studies showed that it speeds up healing and reduces pain. Vyjuvek is the first gene therapy for DEB. It is manufactured by Krystal Biotech and - get this- it is a tweaked version of the herpes virus. Yes, you got that right, the virus causing blisters and scabs has become the primary ally against a devastating skin disease. This approval is a milestone for gene therapies, as Vyjuvek is the first gene therapy - based on the herpes virus, - to apply on the skin as a gel, - approved for repeated use. This article describes how DEB, and especially RDEB, affects the skin and wreaks havoc on the body; the following article will explain how Vyjuvek works. DEB disrupts skin integrity We carry around six to nine pounds of skin. Yet we often forget its importance: it stops germs and UVs, softens blows, regulates body temperature and makes us sensitive to touch. Diseases that compromise the skin are therefore devastating. These essential functions rely on the organisation of the skin in three layers: epidermis, dermis and hypodermis ( Figure 1 ). Typically, a Velcro strap of the protein collagen VII firmly anchors the epidermis to the dermis. The gene COL7A1 contains the instructions on how to produce collagen VII. In DEB, mutations in COL7A1 result in the production of a faulty collagen VII. As the Velcro strap is weakened, the epidermis becomes loosely attached to the dermis. Mutations in one copy of COL7A1 cause the dominant form of the disease (DDEB), mutations in both copies cause RDEB. With one copy of the gene still functional, the skin still produces some collagen VII, when both copies are mutated, little to no collagen VII is left. Therefore, RDEB is more severe than DDEB. In people with RDEB, the skin can slide off at the slightest touch and even gentle rubs can cause blisters and tears ( Figure 2 ). Living with RDEB Life with RDEB is gruelling and life expectancy doesn't exceed 30 years old. Wounds are very painful, slow to heal and get infected easily. The risk of developing an aggressive skin cancer is higher. The constant scarring can cause limb deformities. In addition, blisters can appear in the mouth, oesophagus, eyes and other organs. There is no cure for DEB for now; treatments can only improve the quality of life. Careful dressing of wounds promotes healing and prevents infections. Painkillers are used to ease pain. Special diets are required. And, to no one's surprise, physical activities must be avoided. Treating RDEB Over the past decade, cell and genetic engineering advances have sparked the search for a cure. Scientists have explored two main alternatives to restore the production of collagen VII in the skin. The first approach is based on transferring skin cells able to produce collagen VII. Despite promising results, this approach treats only tinyl patches of skin, requires treatments in highly specialised centres and it may cause cancer. The second approach is the one Vyjuvek followed. Scientists place the genetic information to make collagen VII in a modified virus and apply it to a wound. There, the virus infects skin cells, providing them with a new COL7A1 gene to use. These cells now produce a functional collagen VII and can patch the damage up. We already know which approach came up on top. Vyjuvek speeds up the healing of wounds as big as a smartphone. Professionals can apply it in hospitals, clinics or even at the patient’s home. And it uses a technology that does not cause cancer. But how does Vyjuvek work? And why did scientists choose the herpes virus to build Vyjuvek? We will find the answer in the following article. And since perfection does not belong to biology, we will also discuss the limitations of this remarkable gene therapy. NOTES: 1. DEB is part of a group of four inherited conditions, collectively named epidermolysis bullosa (EB), where the skin loses integrity. EB is also known as “Butterfly syndrome” because the skin becomes as fragile as a butterfly’s wing. These conditions are EB simplex, junction EB, dystrophic EB and Kindler EB. 2. Most gene therapies are based on modified, or recombinant in science jargon, adenoassociated viruses, which I reviewed for Scientia News. 3. Over 700 mutations have been reported. They disrupt collagen VII and its function with various degrees of severity. Consequently, RDEB and DDEB display several clinical phenotypes. 4. Two studies have adopted this approach: in the first study, Siprashvili and colleagues (2016) grafted ex vivo retrovirally-modified keratinocytes, the main cell type in the epidermis, over the skin of people with RDEB; in the second study, Lwin and colleagues (2019) injected ex vivo lentivirally-modified fibroblasts in the dermis of people with RDEB. Written by Matteo Cortese, PhD Related article: Ehlers-Danlos syndrome Project Gallery

Health inequalities and inequities amid the ongoing civil war Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Healthcare challenges during civil war in Sudan Last updated: 03/05/26, 18:15 Published: 17/04/25, 08:00 Health inequalities and inequities amid the ongoing civil war This is article no. 2 in a series about global health injustices. Next article: Yemen: a neglected humanitarian crisis . Previous article: Life under occupation in Palestine Introduction Welcome to the second article of the Global Health Injustices Series. My previous article focused on the Palestinians and the injustices they face, notably the blockade of food, water and medical supplies in Gaza. This one will focus on Sudan by examining the health inequalities and inequities the wider Sudanese population faces, mainly due to the ongoing civil war between the Sudanese Armed Forces (SAF) and the Rapid Support Forces (RSF). This carries direct and indirect consequences ( Figure 1 ); some of these will be discussed in this article, along with ways forward to advocate and support the Sudanese people after an overview of Sudan’s history and current state. Sudan: a rich history to modern challenges Sudan is a country in North Africa bordered by South Sudan, Egypt, the Central African Republic, Libya, Chad to the northwest, Eritrea and Ethiopia. Sudan has had shifts in political power over centuries, notably the joint Egyptian-Ottoman rule beginning over 200 years ago, before the British government took control of Sudan during the first half of the 20th century. After that, Sudan became independent, and South Sudan gained independence in the 21st century. Through these different shifts, there has been a struggle for representation and power in Sudan, leading to various crises, including the current civil war ( Figure 2 ). Despite this, Sudan maintains its multiple languages and cultural traditions through its resilient population. Aside from the SAF and RSF, the civil war in Sudan has arms trade and exports from external governments, particularly the United Arab Emirates (UAE), Russia, and China, have accelerated the civil war. This expansion is crucial because it illustrates how much geopolitics has severe consequences on the health and wellbeing of the Sudanese people. Health in Sudan: the consequences of civil war and geopolitics In a public health situation analysis (PHSA) by the World Health Organisation (WHO) published in 2026, they highlighted four major emergencies in Sudan: food insecurity, displacement, epidemics and conflicts, which are intrinsically linked to detrimental health outcomes like non-communicable diseases (NCDs), trauma and injury, measles and malaria. Moreover, several mortality indicators were noted in the PHSA. For example, the mortality rate among infants is 39.1 per 1000 people and for children, it is 50.1 per 1000, both originating from the United Nations Children's Fund (UNICEF). These outcomes among infants and children are attributed to health conditions, such as those occurring neonatally and lower respiratory infections. Nonetheless, there has been increased vaccine coverage in Sudan to fight the spread of infectious diseases. For example, COVID-19 vaccination reached approximately 12.6 million people (28% of the population) in March 2023, along with improved polio and rotavirus vaccination. However, all of these outcomes highlight the magnitude of the civil war in Sudan, with the impact of the arms trade adding fuel to it. Looking at Sudan’s healthcare system, there are several pressures to highlight. One commentary article noted that in conflict areas, less than one third of hospitals are operational, while 70% of them are not. Additionally, the operating hospitals stopped for various reasons, mainly shortages in electricity, medical equipment and healthcare workers. With the aforementioned geopolitical context, these gaps in the healthcare system are amplified and lead to the worsening health outcomes outlined in the PHSA, such as the rise in NCDs. Not only are NCDs rising in Sudan, but infectious diseases are exacerbated in Sudan with the civil war. One of them is drug-resistant tuberculosis (DR-TB), caused by bacteria. One systematic review found that the prevalence of TB with resistance to drugs was 47%; the ones that are not working on TB with the highest resistance include isoniazid at 32.3%, streptomycin at 31.7% and rifampicin at 29.2% resistance. These values are likely to be higher nowadays, given that arms trade exports into Sudan are increasing and leading to more patients not getting sufficient care to manage or treat DR-TB. Another infectious disease that is a significant health problem in Sudan is schistosomiasis, which is caused by parasites. One systematic review included two categories of the disease: Schistosoma haematobium (S. haematobium) and Schistosoma mansoni (S. mansoni) . S. haematobium prevalence was 24.83%, and for S. mansoni , it was 19.13%. These signify that although devising preventative strategies against these infections is crucial, it is paramount to consider the broader picture in Sudan: tackling schistosomiasis and other infections begins with understanding the geopolitical context. Looking at undernutrition among children in Sudan it is another significant health problem. For instance, a meta-analysis found that Sudan had the highest prevalence of stunting among North African countries at 36%; this was also true for wasting, where Sudan had a prevalence of wasting at 14.1% and a prevalence of underweight at 24.6%. Therefore, in a similar sentiment to tackling infectious diseases, understanding the geopolitical context in Sudan is vital to minimising the prevalence of undernutrition among children. Reflecting on all the data and sources I used above, gaps and perspectives still need to be addressed and highlighted, specifically in places within Sudan where the ongoing civil war severely impacts research. This signifies the importance of obtaining reliable information to support communities in Sudan facing numerous injustices. In turn, filling these information and perspective gaps may apply to other crises similar to Sudan. Protecting health in Sudan: crucial ways forward from NGOs To move forward, several NGOs, particularly Amnesty International, have made recommendations to protect the Sudanese people: As a part of their obligation to respect and ensure respect for international humanitarian law (IHL), all states are prohibited from transferring or permitting private actors to transfer weapons to a party to an armed conflict In light of the substantial risk that all arms and ammunition being transferred to Sudan….. will be used by parties to the conflict to commit grave human rights abuses, companies must immediately cease their involvement in this supply of arms to avoid causing or contributing to these abuses. If a company identifies that the products they sold have contributed to such abuses, they should provide for or cooperate in the remediation process to any persons harmed as a result. Therefore, taking these steps on board is essential to upholding human rights and ensuring that the health and wellbeing of the Sudanese people are sustained, particularly during the ongoing civil war. If not, these health inequities and inequalities will only be exacerbated. Moreover, the health outcomes from infectious and chronic diseases outlined are likely worse now, given how much weapons trading has occurred. Conclusion: call to action for the international community Overall, the civil war in Sudan has had devastating impacts on the health and wellbeing of the whole population, particularly the infants and children, among the other injustices. Unfortunately, this crisis has not received a lot of mainstream attention compared to others currently, such as Palestine, which is also a significant injustice. Therefore, Sudan must be addressed just as openly through discussions of justice and advocacy through the voices of the Sudanese people. Moreover, my statement in the previous article on Palestine rings true: It is crucial always to nudge those in positions of power worldwide to fulfil their responsibilities as civil servants and defend human rights for everyone. This is essential to maintain the health and wellbeing of the Sudanese people, particularly to facilitate the recommendations from NGOs such as Amnesty International. In my next article, I will discuss Yemen because this population is also encountering civil war as one of the many injustices which have been occurring for more than a decade, and Yemen is considered to be going through one of the worst humanitarian crises of our time. Similarly, these impacts on the health and wellbeing of the Yemeni people still need awareness and discussion. Written by Sam Jarada Related articles: A perspective on well-being / Understanding health through different stances / Impacts of global warming on dengue fever REFERENCES Crisis in Sudan: What is happening and how to help. The IRC. 2025. Available from: https://www.rescue.org/article/crisis-sudan-what-happening-and-how-help Khogali A, Homeida A. Impact of the 2023 armed conflict on Sudan’s healthcare system. Public Health Challenges. 2023 Oct 28;2(4). Available from: https://onlinelibrary.wiley.com/doi/full/10.1002/puh2.134 Elamin A, Abdullah S, ElAbbadi A, Abdellah A, Hakim A, Wagiallah N, et al. Sudan: from a forgotten war to an abandoned healthcare system. BMJ Global Health. 2024 Oct;9(10):e016406. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC11529772/ New weapons fuelling the Sudan conflict. Amnesty International. 2024. Available from: https://www.amnesty.org/en/latest/research/2024/07/new-weapons-fuelling-the-sudan-conflict/#:~:text=Shipment%2Dlevel%20trade%20data%20indicates,into%20lethal%20weapons%20in%20Sudan . PHSA -Sudan Complex Emergency 030424 SUDAN CONFLICT. World Health Organisation (WHO); 2024. Available from: https://cdn.who.int/media/docs/default-source/documents/emergencies/phsa--sudan-complex-emergency-030424.pdf?sfvrsn=81039842_1&download=true Alaa Dafallah, Osman, Ibrahim ME, Elsheikh RE, Blanchet K. Destruction, disruption and disaster: Sudan’s health system amidst armed conflict. Conflict and Health. 2023 Sep 27;17(1). Available from: https://conflictandhealth.biomedcentral.com/articles/10.1186/s13031-023-00542-9 Hajissa, K., Marzan, M., Idriss, M.I. and Islam, M.A. (2021). Prevalence of Drug-Resistant Tuberculosis in Sudan: A Systematic Review and Meta-Analysis. Antibiotics, 10(8), p.932. doi: https://doi.org/10.3390/antibiotics10080932 . Yousef Alsaafin, Omer, A., Osama Felemban, Sarra Modawi, Ibrahim, M., Mohammed, A., Ammar Elfaki, Abushara, A. and SalahEldin, M.A. (2024). Prevalence and Risk Factors of Schistosomiasis in Sudan: A Systematic Review and Meta-Analysis. Cureus. doi: https://doi.org/10.7759/cureus.73966 . Nagwa Farag Elmighrabi, Catharine, Dhami, M.V., Elmabsout, A.A. and Agho, K.E. (2023). A systematic review and meta-analysis of the prevalence of childhood undernutrition in North Africa. PLoS ONE, 18(4), pp.e0283685–e0283685. doi: https://doi.org/10.1371/journal.pone.0283685 . Project Gallery

This requires a strategy accounting for different factors, as well as other wider determinants of health Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Addressing Health Inequalities Last updated: 03/05/26, 18:09 Published: 02/04/26, 08:00 This requires a strategy accounting for different factors, as well as other wider determinants of health This is the fourth and final article in a series on health inequalities. Previous article: Ethnic health equalities. Welcome to the final article in a series of articles about health inequalities. This article will look more in detail at how to address health inequalities. Introduction Health inequalities are systematic and avoidable differences in health outcomes. They carry heavy human and economic costs, including over £31bn in lost productivity annually. Previous articles in this series explored how factors like geography, income, and ethnicity drive these disparities. However, addressing healthcare inequalities requires a strategy accounting for these factors, as well as other wider determinants of health. The impact of the environment Scientists have published research which found that environmental factors, including smoking, physical activity, and socioeconomic status, have a greater impact on a person’s health and premature death compared to their genes. They analysed data from the UK Biobank, a dataset of biological, health and lifestyle information. Their analysis showed that environmental exposure explains 17% of the variation in risk of death, while genetic predisposition explains less than 2%. Of the 25 factors that were analysed, smoking was linked to 21 diseases, followed by 19 diseases for socioeconomic factors like household income, home ownership, and employment status. While genetics still dominates for specific conditions like dementia and breast cancer, these findings emphasise that the vast majority of health outcomes are determined by our environment rather than our biology. Therefore, to address health inequalities, targeted strategies and collaborative methods like co-design need to be used to ensure interventions meet the genuine needs of the most vulnerable communities. Core20PLUS5 The NHS’s Core20PLUS5 is one of these targeted strategies, defining a target population (the “Core20PLUS”) and identifying 5 areas of healthcare that require improvement. For both groups (adults, children and young people), the target population is the same: CORE20 refers to the most deprived 20% of the population identified by the national Index of Multiple Deprivation, while the PLUS population includes those who experience health inequalities the most, such as ethnic minority groups, individuals with a learning disability, autistic individuals, and individuals with multiple long-term health conditions. The differences between the strategy for adults and that for children and young people are in the 5 areas of healthcare requiring improvement. As seen in Figure 1 , for adults, the 5 areas are continuity and improvement of maternity care (specifically for women from Black, Asian and ethnic minority groups and from the most deprived groups), improved services for individuals with severe mental illness, improved services for those with chronic respiratory disease, early cancer diagnosis, and improved management of hypertension. Smoking cessation is another area of focus that covers all the 5 priorities. For children and young people, the 5 areas of healthcare improvement are specific to this population: asthma care, diabetes care, epilepsy care, oral health, and mental health, as seen in Figure 2 . Co-design for addressing health inequalities Another method to address health inequalities is through co-design, which is a participatory methodology where stakeholders, including service users (e.g., patients, their carers, etc) and providers (healthcare professionals and other staff), collaborate to jointly create and refine services, products, or solutions. A diagram of three key factors needed in co-design can be seen in Figure 3 . This joint approach helps to ensure that interventions align with the genuine needs and preferences of the people who will be using that service, and the findings that providers see coming up frequently from comments by service users. Co-design can be used to address health inequalities by co-producing strategies with people from those communities and backgrounds. For example, individuals from ethnic minority groups can participate, so researchers can genuinely understand and try to address racism's impact on health. This is supported by research published in the BMJ , where co-design with service users and providers from ethnic minority groups found that more culturally appropriate mental healthcare was needed, and that there needed to be more open discussions about the impacts of ethnicity, culture and racism in mental health. In the context of Figure 3 , this study involved “committed” ethnic minority groups with the “capability” of sharing their lived experience with researchers. This shows how co-design can be used as a tool that allows others to share their experiences for the benefit of themselves and others. Conclusion There needs to be a cross-government strategy that aligns current policy, funding, and practice around health equity. Because these inequalities are systematic and avoidable failures, they require a holistic approach that moves beyond clinical care to address the PLUS populations who experience the greatest disadvantage. Trust in the healthcare system has been eroded among ethnic minority groups due to repeated negative experiences, cultural insensitivity, and discriminatory treatment. To rebuild it, lived experiences need to be accounted for, and solutions need to be co-designed. Furthermore, determinants of good health, like stable housing, fair pay, and high-quality education, must be provided to the people most affected by health inequalities. These inequalities must be addressed to ensure everyone has the ability and opportunity to have a long and healthy life. Written by Naoshin Haque Related article: Reflection on global health injustices Project Gallery

Establishing causation through Randomised Controlled Trials and Instrumental Variables Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Proving causation: causality vs correlation Last updated: 03/06/25, 14:43 Published: 12/06/25, 08:00 Establishing causation through Randomised Controlled Trials and Instrumental Variables Does going to the hospital lead to an improvement in health? At first glance, one might assume that visiting a hospital should improve health outcomes. However, if we compare the average health status of those who go to the hospital with those who do not, we might find that hospital visitors tend to have worse health overall. This apparent contradiction arises due to confounding – people typically visit hospitals due to existing health issues. Simply comparing these two groups does not tell us whether hospitals improve health or if the underlying health conditions of patients drive the observed differences. A similar challenge arises when examining the relationship between police presence and crime rates. Suppose we compare two cities—one with a large police force and another with a smaller police force. If the city with more police also has higher crime rates, does this mean that police cause crime? Clearly not. Instead, it is more likely that higher crime rates lead to an increased police presence. This example illustrates why distinguishing causation from correlation is crucial in data analysis, and that stating that two variables are correlated does not imply causation. First, let’s clarify the distinction between causation and correlation. Correlation refers to a relationship between two variables, but it does not imply that one causes the other. Just because two events occur together does not mean that one directly influences the other. To establish causation, we need methods that separate the true effect of an intervention from other influencing factors. Statisticians, medical researchers and economists have ingeniously come up with several techniques that allow us to separate correlation and causation. In medicine, the gold standard for researchers is the use of Randomised Controlled Trials (RCTs). Imagine a group of 100 people, each with a set of characteristics, such as gender, age, political views, health status, university degree, etc. RCTs randomly assign each individual to one of two groups. Consequently, each group of 50 individuals should, on average, have similar ages, gender distribution, and baseline health. Researchers then examine both groups simultaneously while changing only one factor. This could involve instructing one group to take a specific medicine or asking individuals to drink an additional cup of coffee each morning. This results in two statistically similar groups differing in only one key aspect. Therefore, if the characteristics of one group change while those of the other do not, we can reasonably conclude that the change caused the difference between the groups. This is great for examining the effectiveness of medicine, especially when you give one group a placebo, but how would we research the causation behind the police rate and crime example? Surely it would be unwise and perhaps unethical to randomise how many police officers are present in each city? And because not all cities are the same, the conditions for RCTs would not hold. Instead, we use more complex techniques like Instrumental Variables (IV) to overcome those limitations. A famous experiment using IV to explain police levels and crime was published by Steven Levitt (1997). Levitt used the timings of mayoral and gubernatorial elections (the election of a governor) as an instrument for changes in police hiring. Around election time, mayors and governors have incentives to look “tough on crime.” This can lead to politically motivated increases in police hiring before an election. Crucially, hiring is not caused by current crime rates but by the electoral calendar. So, by using the timing of elections to predict an increase in police, we can use those values to estimate the effect on crime. What he found was that more police officers reduce violent and property crime, with a 10% increase in police officers reducing violent crime by roughly 5%. Levitt’s paper is a clever application of IV to get around the endogeneity problem and takes correlation one step further into causation, through the use of exogenous election timing. However, these methods are not without limitations. IV analysis, for instance, hinges on finding a valid instrument—something that affects the independent variable (e.g., police numbers) but has no direct effect on the outcome (e.g., crime) other than through that variable. Finding such instruments can be extremely challenging, and weak or invalid instruments can lead to biased or misleading results. Despite these challenges, careful causal inference allows researchers to better understand the true drivers behind complicated relationships. In a world where influencers, media outlets, and even professionals often mistake correlation for causation, developing a critical understanding of these concepts is an essential skill required to navigate through the data, as well as help drive impactful change in society through exploring the true relationships behind different phenomena. Written by George Chant Related article: Correlation between HDI and mortality rate REFERENCE Steven D. Levitt (1997). “Using Electoral Cycles in Police Hiring to Estimate the Effect of Police on Crime”. American Economic Review 87.3, pp. 270–290 Project Gallery

Through AI Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Revolutionising sustainable agriculture 11/07/25, 10:51 Last updated: Published: 27/06/23, 16:34 Through AI Artificial Intelligence (AI) is taking the world by storm. Recent developments now allow scientists to integrate AI into sustainable farming. Through transforming the way we grow crops, manage resources and pests, and most importantly- protect the environment. There are many applications for AI in agriculture. Outlined below are some of the areas in which the incorporation of AI systems improves sustainability: Precision farming Artificial intelligence systems help improve the overall quality and accuracy of harvesting – known as precision farming. Artificial intelligence technology helps detect plant diseases, pests, and malnutrition on farms. AI sensors can detect and target weeds, then decide what herbicide to use in an area. This helps reduce the use of herbicides and lower costs. Many tech companies have developed robots that use computer vision and AI to monitor and precisely spray weeds. These robots can eliminate 80% of the chemicals normally sprayed on crops and reduce herbicide costs by 90%. These intelligent AI sprayers can drastically reduce the amount of chemicals used in the field, improving product quality, and lowering costs. Vertical farming Vertical farming is a technique in which plants are grown vertically by being stacked on top of each other (usually indoors) as opposed to the ‘traditional way’ of growing plants and crops on big strips of land. This approach offers several benefits for sustainable agriculture and waste reduction. The use of AI brings even more significant advancements making vertical farming more sustainable and efficient- Intelligent Climate Control: AI can use algorithms to measure and monitor temperature, humidity, and lighting conditions to optimise climate control in vertical farms. Thus, reducing energy consumption and improving resource efficiency. Creating an enhanced climate-controlled environment also allows for repeatable and programmable crop production. Predictive Plant Modelling: the difference between a profitable year and a failed harvest can just be the specific time the seeds were sowed. By using AI, farmers can use predictive analysis tools to determine the exact date suitable for sowing seeds for maximum yield and reduce waste from overproduction. Automated Nutrient Monitoring: to optimise plant nutrition, AI systems monitor and adjust nutrient levels in hydroponic (plants immersed in nutrient containing water) and aeroponic setups (plants growing outside the soil, with nutrients being provided by spraying the roots). Genetic engineering AI plays a pivotal role in genetic engineering, enhancing the sustainability and precision of crop modification through- Targeted Gene Editing: AI algorithms help in gene editing to produce desirable traits in crops, such as resistance to disease or improved nutritional content. This allows genetic modification without the need to conduct extensive field trials. Thus, saving time and resources. Computational Modelling: by combining AI modelling with gene prediction, farmers will be able to predict which combinations of genes have the potential to increase crop yield. Pest management and disease detection Artificial intelligence solutions such as smart pest detection systems are being used to monitor crops for signs of pests and diseases. These systems detect changes in the environment such as temperature, humidity, and soil nutrients, then alert farmers when something is wrong. This allows farmers to act quickly and effectively, taking preventive measures before pests cause significant damage. Another way to achieve this is by using computer vision and image processing techniques. AI can detect signs of pest infestation, nutrient deficiencies and other issues that can affect yields. This data can help farmers make informed decisions about how to protect their crops. By incorporating AI into these aspects of sustainable agriculture, farmers can achieve high yields, reduce waste and enable more sustainable farming practices, reducing environmental impacts while ensuring efficient food production. Written by Aleksandra Zurowska Related articles: Digital innovation in rural farming / Plant diseases and nanoparticles Project Gallery

Looking at the option of nuclear fusion to generate renewable energy Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Unleashing the power of the stars: how nuclear fusion holds the key to tackling climate change 14/07/25, 16:08 Last updated: Published: 30/04/23, 11:55 Looking at the option of nuclear fusion to generate renewable energy Imagine a world where we have access to a virtually limitless and clean source of energy, one that doesn't emit harmful greenhouse gases or produce dangerous radioactive waste. A world where our energy needs are met without contributing to climate change. This may sound like science fiction, but it could become a reality through the power of nuclear fusion. Nuclear fusion, often referred to as the "holy grail" of energy production, is the process of merging light atomic nuclei to form a heavier nucleus, releasing an incredible amount of energy in the process. It's the same process that powers the stars, including our very own sun, and holds the potential to revolutionize the way we produce and use energy here on Earth. Nuclear fusion occurs at high temperature and pressure when two atoms (e.g. Tritium and Deuterium atoms) merge together to form Helium. This merge releases excess energy and a neutron. This energy an then be harvested inform of heat to produce electricity. Progress in the field of creating a nuclear fusion reactor has been slow, despites the challenges there are some promising technologies and approaches have been developed. Some of the notable approaches to nuclear fusion research include: 1. Magnetic Confinement Fusion (MCF) : In MCF, high temperatures and pressures are used to confine and heat the plasma, which is the hot, ionized gas where nuclear fusion occurs. One of the most promising MCF devices is the tokamak, a donut-shaped device that uses strong magnetic fields to confine the plasma. The International Thermonuclear Experimental Reactor (ITER), currently under construction in France, is a large-scale tokamak project that aims to demonstrate the scientific and technical feasibility of nuclear fusion as a viable energy source. 2. Inertial Confinement Fusion (ICF) : In ICF, high-energy lasers or particle beams are used to compress and heat a small pellet of fuel, causing it to undergo nuclear fusion. This approach is being pursued in facilities such as the National Ignition Facility (NIF) in the United States, which has made significant progress in achieving fusion ignition, although it is still facing challenges in achieving net energy gain. In December of 2022, the US lab reported that for the first time, more energy was released compared to the input energy. 3. Compact Fusion Reactors: There are also efforts to develop compact fusion reactors, which are smaller and potentially more practical for commercial energy production. These include technologies such as the spherical tokamak and the compact fusion neutron source, which aim to achieve high energy gain in a smaller and more manageable device. While nuclear fusion holds immense promise as a clean and sustainable energy source, there are still significant challenges that need to be overcome before it becomes a practical reality. In nature nuclear fusion is observed in stars, to be able to achieve fusion on Earth such conditions have to be met which can be an immense challenge. High level of temperature and pressure is required to overcome the fundamental forces in atoms to fuse them together. Not only that, but to be able to actually use the energy it has to be sustained and currently more energy is required then the output energy. Lastly, the material and technology also pose challenges in development of nuclear fusion. With high temperature and high energy particles, the inside of a nuclear fusion reactor is a harsh environment and along with the development of sustained nuclear fusion, development of materials and technology that can withstand such harsh conditions is also needed. Despite many challenges, nuclear fusion has the potential to be a game changer in fight against not only climate change but also access of cheap and clean energy globally. Unlike many forms of energy used today, fusion energy does not emit any greenhouse gasses and compared to nuclear fission is stable and does not produce radioactive waste. Furthermore, the fuel for fusion, which is deuterium is present in abundance in the ocean, where as tritium may require to synthesised at the beginning, but once the fusion starts it produce tritium by itself making it self-sustained. When the challenges are weighted against the benefits of nuclear fusion along with the new opportunities it would unlock economically and in scientific research, it is clear that the path to a more successful and clean future lies within the development of nuclear fusion. While there are many obstacles to overcome, the progress made in recent years in fusion research and development is promising. The construction of ITER project, along with first recordings of a higher energy outputs from US NIF programs, nuclear fusion can become a possibility in a not too distant future. In conclusion, nuclear fusion holds the key to address the global challenge of climate change. It offers a clean, safe, and sustainable energy source that has the potential to revolutionize our energy systems and reduce our dependence on fossil fuels. With continued research, development, and investment, nuclear fusion could become a reality and help us build a more sustainable and resilient future for our planet. It's time to unlock the power of the stars and harness the incredible potential of nuclear fusion in the fight against climate change. Written by Zari Syed Related articles: Nuclear medicine / Geoengineering / The silent protectors / Hydrogen cars Project Gallery

The role of CRISPR-Cas9 technology Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Reaching new horizons in Alzheimer's research 09/04/26, 18:09 Last updated: Published: 12/10/23, 11:50 The role of CRISPR-Cas9 technology The complexity of Alzheimer’s Alzheimer's disease (AD) is a formidable foe, marked by its relentless progression and the absence of a definitive cure. As the leading cause of dementia, its prevalence is expected to triple by 2050. Traditional therapies mainly focus on managing symptoms; however, advances in genetics research, specifically CRISPR-Cas9 gene-editing technology, offer newfound hope for understanding and treating this debilitating condition. The disease is characterized by progressive deterioration of cognitive function, with memory loss being its hallmark symptom. Primarily affecting individuals aged 65 and over, age is the most significant risk factor. Although this precise cause remains elusive, scientists believe that a combination of genetic, lifestyle and environmental factors contributes to its development. CRISPR’s role in Alzheimer’s research After the discovery of using CRISPR-Cas9 for gene editing, this technology is receiving interest for its potential ability to manipulate genes contributing to Alzheimer’s. Researchers from the University of Tokyo used a screening technique involving CRISPR-Cas9 to identify calcium, proteins, and integrin-binding protein 1, which is involved in the formation of AD. Furthermore, Canadian researchers have edited genes in brain cells to prevent Alzheimer’s using CRISPR. The team identified a genetic variant called A673T, found to decrease Alzheimer’s likelihood by a factor of four and reduce Alzheimer’s biomarker beta-amyloid (Aβ). Using CRISPR in petri dish studies, they managed to activate this A673T variant in lab-grown brain cells. However, the reliability and validity of this finding are yet to be confirmed by replication in animal studies. One final example of CRISPR application is targeting the amyloid precursor protein (APP) gene. The Swedish mutation in the APP gene is associated with dominantly inherited AD. Scientists were able to specifically target and disrupt the mutant allele of this gene using CRISPR, which decreased pathogenic Aβ peptide. Degenerating neurons are surrounded by Aβ fibrils, the production of Αβ in the brain initiates a series of events which cause the clinical syndrome of dementia. The results of this study were replicated both ex vivo and in vivo and demonstrated this could be a potential treatment strategy in the future. The road ahead While CRISPR technology’s potential in Alzheimer’s research is promising, its therapeutic application is still in its infancy. Nevertheless, with the aid of cutting-edge tools like CRISPR, deepening our understanding of AD, we are on the cusp of breakthroughs that could transform the landscape of Alzheimer’s disease treatment. Written by Maya El Toukhy Related articles: Alzheimer's disease (an overview) / Hallmarks of Alzheimer's / Sleep and memory loss Project Gallery

Exploring the genetic roots of a neurological tragedy Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Breaking down Tay-Sachs 15/05/25, 11:43 Last updated: Published: 20/04/24, 12:29 Exploring the genetic roots of a neurological tragedy This is article no. 9 in a series on rare diseases. Next article: Ehlers-Danlos Syndrome . Previous article: Pseudo-Angelman Syndrome . Tay-Sachs disease is a heritable metabolic condition that affects the neurons in the brain. The disease is more common in infants and young children as well as people of Ashkenazi Jewish descent, although it can occur in any ethnicity. Symptoms of the disease most commonly manifest themselves in children around six months of age. However, it is possible to develop symptoms from five years old to the teenage years. There are three different forms of the disease, each appearing at different stages of life: infantile, juvenile, and adult. The adult form is much rarer and non-fatal but can still cause neuron dysfunction and psychosis. Early symptoms of the disease include mobility issues such as difficulty crawling, and as the disease progresses, the child may suffer from seizures, vision, and hearing loss. In the classic infantile form, the disease is fatal within the first few years of life or by three to five years old. In infants, infection and respiratory complications, such as pneumonia, are the most common cause of death. Being categorised as an autosomal recessive disease means that in order to display the phenotype, two copies of the mutated HEXA gene must be present in an individual. This HEXA gene is located on chromosome 15 and is responsible for producing enzymes that affect the nerve cells. The carrier frequency of Tay-Sachs is highly dependent on ethnic backgrounds, with carrier frequency being 1 in 30 for those of Ashkenazi Jewish descent and 1 in 300 for others. The chance of developing the disease early or late is predicated on the specific type of HEXA mutation that is inherited within the family. Meaning, if one child in a family possesses the infantile form, all other members of the family will also possess the infantile form (if they express the phenotype). When both parents are carriers of the Tay-Sachs gene mutation, there is a 25% chance with each pregnancy that the child will inherit two mutated copies of the HEXA gene and thus be affected by the disease. Also, there is a 50% chance the child will be a carrier like the parents and a 25% chance the child will inherit two normal copies of the gene and be unaffected. Furthermore, this particular type of gene mutation results in the disease being commonly labelled as a hexosaminidase A deficiency. The HEXA gene’s significance in the disease is further highlighted due to its ability to code for specific alpha subunits in the enzyme β-hexosaminidase A. This enzyme is involved in breaking down molecules that can be recycled in a cell through the use of lysosomes. This key cellular function helps a cell undergo apoptosis (programmed cell death) or help evade bacteria that can damage a cell. However, in individuals with this HEXA gene mutation, less of the enzyme β-hexosaminidase A is produced, which results in less degradation of GM2 ganglioside. GM2 ganglioside is a lipid involved in a host of processes such as membrane organisation, neuronal differentiation, and signal transduction. In addition, due to its lack of degradation, it accumulates inside the body. The rate at which the lipid accumulates inside the cell ultimately determines the form of Tay-Sachs an individual will possess. It is worth noting that this GM2 ganglioside pathology also includes other diseases, such as Sandhoff disease and the AB variant, which have similar disease prognoses. Furthermore, the disease specifically targets the brain as gangliosides are the main lipids that compose neuronal plasma membranes. Their expression is specific to brain regions, impacting key neurodevelopmental processes like neural tube formation and synaptogenesis. Furthermore, ganglioside synthesis is a highly regulated process facilitated by glycosyltransferases during transcription and post-transcription. They also modulate ion channels and receptor signalling, which are crucial for neurotransmission, memory, and learning. The exact mechanism of how this ganglioside accumulation due to HEXA malfunction leads to neuronal death remains unclear. Figure 1 illustrates the dysfunction of the alpha subunit in HEXA as it cannot break down GM2 gangliosides. This results in an accumulation of GM2 within the liposome, contrasting with its concentration in the external environment. This accumulation of GM2 causes lysosomal dysfunction and eventually cell damage, which leads to the symptoms commonly associated with Tay-Sachs. Mouse models have been created to understand this GM2 pathway in greater detail to develop treatments. However, this is quite limited as mice do not have the same pathway of breaking down GM2 as humans. Also, since the disease may be prevalent before birth, it is hard to establish the damage done to a baby inside the womb, making reversing this disease in infants very challenging. However, the later onset types of Tay-Sachs disease might respond to treatment. Implementing ganglioside synthesis inhibitors in combination with existing DNA and enzymatic screening programs holds promise for eventually managing and controlling this condition. Parents can undergo genetic screening to assess their risk of carrying the Tay-Sachs gene, which is done by doing a simple blood test that examines the DNA for mutations in the HEXA gene. Genetic screening is particularly important for couples who have a family history of Tay-Sachs disease or who belong to ethnic groups with a higher prevalence of the condition. Early detection through genetic screening allows couples to make informed reproductive decisions, such as pursuing in vitro fertilisation with preimplantation genetic testing or opting for prenatal testing during pregnancy to determine if the foetus has inherited the mutated gene. Utilising the acronym SHADES as a mnemonic to recognise potential signs of Tay-Sachs disease in their child can help parents get a prompt medical evaluation if any symptoms arise. SHADES: S tartle response H earing loss A ffecting vision D evelopmental delay E pileptic seizures S wallowing difficulties Written by Imron Shah REFERENCES Center, N. (2015). Tay-Sachs disease. Nih.gov . Available at: https://www.ncbi.nlm.nih.gov/books/NBK22250/ . Leal, A.F., Benincore-Flórez, E., Solano-Galarza, D., Garzón Jaramillo, R.G., Echeverri-Peña, O.Y., Suarez, D.A., Alméciga-Díaz, C.J. and Espejo-Mojica, A.J. (2020). GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies. International Journal of Molecular Sciences, 21(17), p.6213. doi: https://doi.org/10.3390/ijms21176213 . Ramani, P.K. and Parayil Sankaran, B. (2022). Tay-Sachs Disease. PubMed. Available at: https://www.ncbi.nlm.nih.gov/books/NBK564432/ . Project Gallery