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Research confirms anxiety disorders do have a genetic side Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Does anxiety run in families? Here's what genetics tells us Last updated: 10/07/25, 18:26 Published: 19/06/25, 07:00 Research confirms anxiety disorders do have a genetic side Have you ever noticed anxiety can pop up in several members of the same family? Maybe your sister worries constantly, or your brother gets nervous around people. It might feel like anxiety is passed down through generations. But is that really how it works, or is it just a coincidence? Here's what science has to say. Your DNA can affect anxiety Research confirms anxiety disorders do have a genetic side. That means you're more likely to have anxiety if someone in your family, like your mum, dad, sibling, or even a grandparent, has it too. But this doesn't mean anxiety is certain. Instead, genes increase your chances, accounting for about 30% to 40% of your risk. Scientists work this out by comparing identical and fraternal twins and by following anxiety diagnoses across generations; those studies repeatedly find that roughly one-third to two-fifths of a person’s risk is genetic. So, if genetics only make up part of the picture, what's the rest? That's where your environment steps in. Your life experiences matter a lot. Things like your relationships, stressful situations, and even your physical health can tip the scales one way or another. Genes set the stage, but they don't control the outcome. Think of your genes as nudging you towards anxiety rather than pushing you into it completely. The rest depends on what happens to you. How genes shape your brain Scientists have pinpointed several genes linked to anxiety. One of these genes affects serotonin, a brain chemical that helps regulate your mood and manage stress. When serotonin works well, you feel calm and can handle stressful events better. But if your genes make serotonin less effective, stress hits you harder. This can make anxiety more likely during tough times, even when others around you seem okay. There's another important point: your brain structure. Genes influence parts of your brain, especially the amygdala. Think of the amygdala as your internal alarm system. It warns you when something feels dangerous. In people with certain genes, the amygdala is extra sensitive. That means their "alarm" goes off more easily, causing anxiety even when there's no real danger present. However, not everyone with these genetic variations experiences anxiety. Your brain adapts throughout life, changing how genes affect you. This ongoing flexibility is called neuroplasticity: experience can strengthen or weaken neural circuits and can even add or remove chemical tags, such as DNA methylation, that switch genes on or off, reshaping how your stress system responds. Anxiety isn't just genetic; here's why It's tempting to blame your genes entirely if anxiety runs in your family. But life is more complicated. Even if you inherit genes that make anxiety more likely, the disorder usually develops when certain environmental conditions come into play. Stressful life events like losing a loved one, ongoing conflict at home, bullying, or trauma can trigger anxiety symptoms. Someone might have anxiety-related genes but never experience anxiety if their life stays relatively stress-free. On the other hand, someone without these genes can still develop anxiety if they experience severe stress or trauma. Lifestyle choices also make a big difference. Regular exercise, healthy eating, good sleep, and support from friends and family can protect against anxiety. Studies show these lifestyle habits are powerful, even if your genes are pushing in the opposite direction. Can you change your genetic destiny? Understanding that anxiety has a genetic basis can help. It means anxiety isn't just a character flaw or personal weakness. It's something partly built into your biology, something real and valid. Realising this can reduce shame and make people more willing to seek help. And here's another benefit: knowing your family history allows you to spot anxiety sooner. If you understand that anxiety might run in your family, you can pay attention to early signs, like trouble sleeping, excessive worry, or panic in social settings. Catching anxiety early means getting support earlier, making treatments like therapy or lifestyle changes more effective. Anxiety might run in your family, but you get to decide how far it goes. Written by Rand Alanazi Related articles: Depression / South Asian mental health / Physical and mental health / Does insomnia run in families? REFERENCES National Institute of Mental Health. Anxiety disorders [Internet]. Bethesda (MD): National Institute of Mental Health; 2024 [cited 2025 May 29]. Available from: https://www.nimh.nih.gov/health/topics/anxiety-disorders Mayo Clinic. Anxiety disorders [Internet]. Rochester (MN): Mayo Foundation for Medical Education and Research; 2018 [cited 2025 May 29]. Available from: https://www.mayoclinic.org/diseases-conditions/anxiety/symptoms-causes/syc-20350961 Leyfer O, Woodruff-Borden J, Mervis CB. Anxiety disorders in children with Williams syndrome, their mothers, and their siblings: implications for the aetiology of anxiety disorders. J Neurodev Disord . 2009 Feb 13;1(1):4-14. Martin EI, Ressler KJ, Binder EB, Nemeroff CB. The neurobiology of anxiety disorders: brain imaging, genetics, and psychoneuroendocrinology. Psychiatr Clin North Am [Internet]. 2009 Sep;32(3):549-75. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684250/ McEwen BS, Eiland L, Hunter RG, Miller MM. Stress and anxiety: structural plasticity and epigenetic regulation as a consequence of stress. Neuropharmacology . 2012 Jan;62(1):3-12. Xie S, Zhang X, Cheng W, Yang Z. Adolescent anxiety disorders and the developing brain: comparing neuroimaging findings in adolescents and adults. Gen Psychiatry [Internet]. 2021 Aug 4;34(4):e100542. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340272/ Zhang K, Ibrahim GM, Venetucci Gouveia F. Molecular pathways, neural circuits and emerging therapies for self-injurious behaviour. Int J Mol Sci [Internet]. 2025 Feb 24;26(5):1938. Available from: https://www.mdpi.com/1422-0067/26/5/1938 Chaves T, Fazekas CL, Horváth K, Correia P, Szabó A, Török B, et al. Stress adaptation and the brainstem with focus on corticotropin-releasing hormone. Int J Mol Sci [Internet]. 2021 Jan 1;22(16):9090. Available from: https://www.mdpi.com/1422-0067/22/16/9090 Project Gallery

Beyond sugarcane fields and dreamy beaches, Mauritius secures first place in mobile connectivity Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Mauritius's rise as African leader of mobile networks Last updated: 08/06/25, 11:12 Published: 05/06/25, 07:00 Beyond sugarcane fields and dreamy beaches, Mauritius secures first place in mobile connectivity Background: GSMA ranking In the bustling capital city of Port Louis, commuters check the latest news updates using mobile data on their phones. Across the busy, connecting streets, a handful of tourists video call their family back home, asking them what souvenirs they would like- also on mobile data. Apart from idyllic holiday scenes and solid sugar exports, the island nation of Mauritius has recently become number one in Africa for mobile connectivity- as scored by the Global System for Mobile Communications Association (GSMA). The small island is now at the forefront of telecommunication development, with the increasing rollout of 5G networks. How did this touristic country become a leader in mobile connectivity? On the 13th of August 2024, the GSMA announced its yearly index for mobile connectivity. The GSMA looks at 41 African countries and ranks them based on: internet accessibility, prices of mobile devices, relevant services and political environments. Scoring 62.7 points out of the possible 100, Mauritius took the first spot, in front of South Africa. This result also places the island country 76th in the world. Remarkably, this is the third consecutive year that Mauritius is leading in mobile connectivity in Africa. Moreover Mauritius, with a population of 1.26 million, boasts an average of 1.7 phones per person, compared to only 1.2 phones per person in the US (according to 2023 data). Connecting the island: 5G is nearly everywhere Three companies provide mobile phone networks on Mauritius island: Emtel, MTML (Chili) and state-owned My.t. At present, 5G is widely available in Mauritius, thanks to Emtel supplying it to approximately 80% of the island for both residential and commercial usage. Though Emtel is the biggest network in the country, My.t is the most popular provider currently, and it also offers 5G to its users. A closer look at 4G and 5G 3G (and 3G High-Speed Packet Access, HSPA), 4G (Long Term Evolution, LTE) and 5G are wireless mobile networks, where the ‘G’ in these networks means ‘generation’ and indicates the strength of the signal on the mobile device. Hence, each mobile network is an improvement since the last generation of network. These mobile networks aim for high quality, reliable communication, and are based on radio signals. Each generation has evolved to achieve this. Table 1 compares the differences between all of these networks. The original 1G network from 1979 used analogue radio signals, while subsequent network generations use digital radio signals. Table 1: A comparison of 2G, 3G, 4G and 5G mobile networks 2G 3G HSPA+ 4G LTE 5G Speed 64Kbps 8Mbps 50Mbps 10Gbps Bandwidth 30- 200 kHz 15- 20 MHz 100 MHz 30- 300 GHz Features Better quality video calls than before Can send and receive larger emails Higher speeds and capacities Much faster speeds and capacities; high resolution video streaming SMS and MMS Larger capacities Low cost per bit Low latency Interactive multimedia, voice, video Allows remote control of operations e.g. vehicles, robots, medical procedures It is evident from Table 1 that not only have speeds and capacities increased with each generation, but new features have also been implemented such as video calls, interactive multimedia, streaming, and remote control of operations. Introduced in 2019, 5G is thought to be the most ambitious mobile phone network- almost revolutionary in its benefits since 1G. Usually, mobile carriers operate on a 4G LTE and 5G coexistence. This means that 5G phones can switch to 4G if 5G isn’t available in the region. Top of the tower- how? Since the 5G rollout in 2021, Mauritius has been enjoying the larger capacities and speeds of the network. The same question arises: how did this touristic country become a leader in mobile connectivity? There are several factors: - Tourist hotspot - Government initiatives - Improving local infrastructure - General advancements in mobile network technologies - High penetration rates and mobile ownership - Increasing number of connections - Geography Each factor will be considered in turn. Factor 1- Tourist hotspot Every year, Mauritius attracts visitors far and wide to enjoy its mesmerising beaches, luscious escapes and tantalising wildlife. Therefore, over time, mobile network technology has had to improve to meet the communicative needs of tourists. Put differently, tourism significantly supports the telecom industry on the island. Factor 2- Government initiatives As well as providing free, public WiFi hotspots around the island, the government is committed to bridging the digital divide and increasing access to all of its population. Thus, it was announced that, eligible citizens between the ages of 18 and 25 will receive a free, monthly mobile data package (with 4G and 5G capabilities)- starting from the 1st of September 2024. It is an endeavour to include young people in the government’s digital plans, i.e. digital inclusion. Factor 3- Improvements in local infrastructure In recent years, My.t and EmTel have been upgrading their equipment to ensure better coverage and access to 5G in the country. Infrastructure must have improved so that the three mobile operators on the island were granted the license for 5G rollout in June 2021. The current goal is to fully expand 5G coverage in Mauritius. Factor 4- General advancements in mobile network technologies Since its inception in 2019, 5G has had a profound impact on consumers around the globe with its low latency, high resolution streaming, and insanely high speeds and capacities. This pioneering mobile network has rolled out to millions of people, including the citizens of Mauritius island. The government has utilised this new technology to empower its people and pave a way for the country to become a leader in mobile connectivity. Factor 5- High penetration rates and mobile ownership Early 2025 data shows that the East African nation has over 2.1 million active mobile connections, when its population is half of that, a mere 1.261 million. (More mobile connections is not a usual thing as people may have separate connections for personal and work use, for example. Embedded SIMs – eSIMs- have made this possible recently). With this statistic, Mauritius has a high degree of mobile ownership and network connection density. Factor 6- An increase in the number of connections Another recent event is that the number of mobile connections in the nation has been increasing gradually: between 2024 and 2025, the number has increased by 1.9%. Factor 7- Geography It is known that less land- especially less rural land- makes deployment of cell phone towers and installation of masts much easier. Therefore, spanning an area of 2,040 squared kilometres, the main island of Mauritius can enjoy adequate mobile coverage- being one of the smallest African countries. Small island, big signal. To summarise, the above factors contribute to the number one ranking in mobile connectivity for Mauritius. What does Mauritius’s rise mean for the future? If these advancements in infrastructure and technology continue on the island, then there is a brighter outlook for the future. 5G coverage in Mauritius is on its way to completion, ensuring all districts have access to the latest mobile network. Geography, government initiatives, improvements in infrastructure by mobile operators, high number of mobile connections and ownership, are some of the factors that enabled 5G rollout in Mauritius in the first instance. Mauritius is leading by example to the other countries in Africa and is additionally performing well on the global stage for mobile networks. This small island country, usually known for its exotic sights and sugarcane landscape, is quickly overtaking its African neighbours in the race to become the leader in mobile phone connectivity. Written by Manisha Halkhoree Related articles: The future of semiconductor manufacturing / Wireless electricity Project Gallery

Arginine, the key to metabolic reprogramming in liver cancer Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Linking arginine and tumour growth: a breakthrough in cancer research Last updated: 20/02/25, 15:29 Published: 27/02/25, 08:00 Arginine, the key to metabolic reprogramming in liver cancer Unpicking the secrets of tumour growth: arginine, the key to metabolic reprogramming in liver cancer. We will look at how unleashing the power of arginine and elevating levels of this amino acid drive metabolic reprogramming and fuel tumour growth. Introduction In recent years, the field of cancer research has made significant progress in unravelling the complexities of this devastating disease. Scientists at the University of Basel have made a groundbreaking discovery regarding the role of the amino acid arginine in promoting tumour growth. Their findings shed light on the mechanisms underlying metabolic reprogramming in cancer cells and present new avenues for improving liver cancer treatment. Elevated levels of arginine: a surprising revelation An intriguing aspect of the study conducted by the researchers is the observation that tumour cells accumulate high levels of arginine despite producing less or none of this amino acid. Through careful analysis of liver tumour samples from both mice and patients, the team discovered that the tumour cells achieve this accumulation by increasing the uptake of arginine and suppressing its consumption. The role of arginine in tumorigenicity Upon further investigation, the scientists at the University of Basel found that high concentrations of arginine bind to a specific factor, triggering metabolic reprogramming in the tumour cells. This reprogramming, in turn, promotes tumour growth by regulating the expression of metabolic genes. The tumour cells revert to an undifferentiated embryonic cell state, enabling them to divide indefinitely. Immune system escape: a beneficial effect for tumour cells Another fascinating discovery made by the researchers is the role of arginine in aiding tumour cells in evading the immune system. Immune cells rely on arginine to function properly. By depleting arginine in the tumour environment, the tumour cells can escape immune surveillance. This finding opens up new possibilities for targeted therapies. Targeting the arginine-binding factor: a novel approach Instead of depleting arginine levels overall, which can have unwanted side effects, the scientists propose targeting the specific arginine-binding factor responsible for promoting metabolic reprogramming. By inducing the degradation of this factor, the researchers were able to prevent metabolic reprogramming in liver tumours. This approach offers a promising alternative to liver cancer treatment. Metabolic changes as biomarkers for early cancer detection Furthermore, the study suggests that metabolic changes, such as increased arginine levels, may serve as biomarkers for the early detection of cancer. Early detection is crucial for successful cancer treatment and patient survival. This finding provides hope for the development of non-invasive diagnostic methods that can detect elevated arginine levels. By measuring arginine levels in patients, these diagnostic methods can potentially identify liver cancer at an early stage. By identifying the elevated levels of arginine in liver tumour cells, these diagnostic methods could potentially use metabolic changes, such as increased arginine levels, as biomarkers for detecting cancer. Therefore, this would be crucial for successful cancer treatment and patient survival, as early detection allows for prompt intervention and improved outcomes. Conclusion The discovery of the role of arginine in driving metabolic reprogramming and promoting tumour growth opens up new avenues for liver cancer treatment. Additionally, the elevated levels of arginine observed in liver cancer patients suggest the potential for using arginine as a biomarker for non-invasive cancer detection. Further research is needed to explore the full potential of arginine as a diagnostic marker and to develop targeted therapies that exploit the metabolic vulnerabilities of cancer cells. With continued advancements in our understanding of cancer metabolism and the role of arginine in tumour growth, further research is needed to explore the full potential of arginine as a diagnostic marker and to develop targeted therapies that exploit the metabolic vulnerabilities of cancer cells. By studying the specific arginine-binding factor and its role in promoting metabolic reprogramming, scientists may be able to develop new treatments that selectively target tumour cells while minimising harm to immune cells that rely on arginine. Additionally, investigating the metabolic changes associated with increased arginine levels may lead to new biomarker designs for early cancer detection, which is crucial for successful treatment and patient survival. Written by Sara Maria Majernikova Related articles: Immune signals and metastasis / Cancer research treatment / Prostatate cancer treatment REFERENCE MOSSMANN, D., MÜLLER, C., PARK, S., RYBACK, B., COLOMBI, M., RITTER, N., WEISSENBERGE, D., DAZERT, E., COTO-LLERENA, M., NUCIFORO, S., BLUKACZ, L., ERCAN, C., JIMENEZ, V., PISCUOGLIO, S., BOSCH, F., TERRACCIANO, L. M., SAUER, U., HEIM, M. H. & HALL, M. N. Arginine reprograms metabolism in liver cancer via RBM39. Cell . DOI: https://doi.org/10.1016/j.cell.2023.09.011 Project Gallery

Implementing established physical theories into the constructions of the future Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Building Physics Last updated: 03/04/25, 10:39 Published: 20/02/25, 08:00 Implementing established physical theories into the constructions of the future From the high rise establishments that paint the expansive London skyline to the new build properties nestled within thriving communities, buildings serve as a beacon of societal needs. The planned and precise architecture of buildings provides shelter and comfort for individuals, as well as meet business agendas to promote modern day living. Additionally, buildings serve a purpose as a form of protection where, according to the World Health Organisation (WHO), the design and construction of buildings is to create an environment suitable for human living: more favourable than the state of the natural environment outdoors construction and building protects us from: extremes of temperature moisture excessive noise To sustain these pivotal agendas, a comprehensive analysis of the physical factors within the environment of buildings, including temperature, light and sound are required for design and legislation for a building to function. The field of ‘Building Physics’ primarily addresses these physical factors to innovate ‘multifunctional solutions’, be more efficient, and build upon present designs, which can be adapted for future use. Moreover, the built environment is regarded as one of the biggest carbon emissions on the planet, so using building physics as an early design intervention can reduce energy consumption and minimise carbon emissions. This supports global manifestos of moving towards net zero and decreasing the likelihood of the detrimental effects caused by climate change. The main components of Building Physics Building Physics is composed of examining the functions of an interior physical environment, including air quality, thermal comfort, acoustics comfort (sound), and light : Air quality: Ventilation is needed for maintaining a safe environment and reducing the quantity of stale air - consisting of carbon dioxide and other impurities - within an interior environment. Air infiltration also contributes to a significant heat loss, where it is important to provide intentional ventilation to increase the efficiency of energy transfers within the building. Thus, good ‘airtightness’ of a building fabric, which can be considered as the building’s resistance to unintentional air infiltration or exfiltration, can enable planned airflows for ventilation. Thermal: The biggest influence within the field of Building Physics stems from an understanding of heat conductivity depending on the density and moisture content of the material, as well as heat transfers - conduction, convection, radiation and transition - to determine the suitability of materials used for construction. For example, a material such as a solid wood panel for walls and ceilings is favourable as it can be installed in layers, providing even temperature fields across the surface. It is important that a building has the ability to isolate its environment from external temperature conditions and have the correct building envelope - a barrier that separates the interior and exterior of a building. Acoustics: A regulated control of sound within buildings contributes towards maintaining habitable conditions for building users to make sure that sound is loud, undistorted, and the disturbances are reduced. Acoustics can be controlled and modified through material choices, such as installing sound-absorbing material. These materials can be adapted to reduce sound leakage, which are common in air openings, such as ventilators and doors, that are more likely to transmit sound than adjacent thicker walls. Light: Light provides an outlook of viewing an environment in an attractive manner, particularly using daylight as a primary source of enhancing the exterior of a building, whilst also functioning within a building. One strategy used to fulfil the purpose of light in buildings is designing windows for the distribution of daylight to a space. The window design has a divisive effect on the potential daylight and thermal performance of adjacent spaces, so it needs to be closely checked using the standardised methods, in order to be suitable for use. Additionally, as windows are exposed to the sky, daylighting systems can adapt windows to transmit or reflect daylight as a function of incident angle, for solar sharing, protection from glare and redirection of daylight. Overall, a key objective of sustaining a safe and eco-friendly building is to ensure that the space has proper heat and humidity aligning with a suitable degree of acoustic and visual comfort in order to sustain the health of the people using the building. Particularly within modern society, a combination of Building Physics principles and digitalised software, such as Building Information Modelling (BIM), can enhance the design process of a building to provide healthy environments for generations to come. Written by Shiksha Teeluck Related article: Titan Submersible REFERENCES Unsplash. A construction site with cranes [Internet]. [Accessed 2 January 2025]. Available from: https://unsplash.com/photos/a-construction-site-with-cranes-mOA2DAtcd1w . Katunský D, Zozulák M. Building Physics . 2012. ISBN: 978-80-553-1261-3. Partel. Building Physics [Internet]. [Accessed 2 January 2025]. Available from: https://www.partel.co.uk/resources/building-physics/#:~:text=According%20to%20WHO%20(World%20Health,%3A%20in%20contrast%2C%20allows%20productions . RPS Group. A day in the life of a senior building physics engineer [Internet]. [Accessed 4 January 2025]. Available from: https://www.rpsgroup.com/insights/consulting-uki/a-day-in-the-life-of-a-senior-building-physics-engineer/ . Cyprus International University. What is Building Physics and Building Physics Problems in General Terms [Internet]. [Accessed 6 January 2025]. Available from: /mnt/data/What_Is_Building_Physics_and_Building_Ph.pdf. Centre for Alternative Technology. Airtightness and Ventilation [Internet]. [Accessed 6 January 2025]. Available from: https://cat.org.uk/info-resources/free-information-service/eco-renovation/airtightness-and-ventilation/#:~:text=With%20good%20airtightness%2C%20effective%20ventilation,won't%20work%20as%20intended . KLH. Building Physics [Internet]. [Accessed 6 January 2025]. Available from: https://www.klh.at/wp-content/uploads/2019/10/klh-building-physics-en.pdf . Watson JL. Climate and Building Physics [Internet]. [Accessed 6 January 2025]. Available from: https://calteches.library.caltech.edu/98/1/Watson.pdf . Ruck N, Aschehoug Ø, Aydinli S, Christoffersen J, Edmonds I, Jakobiak R, et al. Daylight in Buildings - A source book on daylighting systems and components . 2000 Jun. Synergy Positioning Systems. How BIM Saves Time & Money for Construction Businesses [Internet]. [Accessed 6 January 2025]. Available from: https://groupsynergy.com/synergy-positioning-news/how-bim-saves-time-money-for-construction-businesses . Project Gallery

'Manis pentadactyla' is the dominant pangolin species in China Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Pangolins: from poached to protected Last updated: 27/03/25, 11:15 Published: 27/02/25, 08:00 'Manis pentadactyla' is the dominant pangolin species in China This is article no. 4 in a series on animal conservation. Next article: How Gorongosa National Park went from conflict to community . Previous article: Beavers are back in Britain Pangolins are a group of eight scaled mammal species from Asia and Africa. They are being poached mainly for their scales and meat, driving them to dangerously low numbers. Although commercial trade is banned for all species, pangolins are the most illegally trafficked animals in the world. One pangolin species has a fascinating story because of its appeal to traditional medicine and demand in a populated country. That species is the Chinese pangolin Manis pentadactyla , and this article will describe its threats and conservation efforts. About pangolins in China Manis pentadactyla is the dominant pangolin species in China, living south of the Yangtze River ( Figure 1 ). The Sunda pangolin Manis javanica has a tiny habitat in southwest China ( Figure 1 ). Pangolins prefer natural forests, with an ambient temperature of 18-27°C and plenty of termites and ants to eat. Both Chinese species were classified as critically endangered in 2014, though accurately estimating pangolins' distribution and population size is complex. This is because they are nocturnal, solitary, and live underground. Pangolins also make no obvious sounds, or leave no apparent traces, for scientists to detect their presence. Despite these challenges, Chinese scientists are learning more about pangolin habitat to improve conservation strategies. Threats facing Chinese pangolins Chinese pangolins are critically endangered for various human-caused reasons ( Figure 2 ). The biggest reason is poaching because pangolin meat is a local delicacy, and its scales, bones, and blood are used in traditional Chinese medicine. Pangolin scales have recently been removed from the official list of ingredients for Chinese medicine, but that has not stopped hospitals from selling them. In a recent study, only a third of Chinese hospitals selling roasted pangolin scales had the required permit. Permits are also needed to sell or manufacture patented medicines containing pangolin scales, considered the gold standard for treating many conditions. Because these medicines and pangolin meat are so revered, one hunted pangolin sells for up to 90,000 yuan (≈£9800). This has incentivised the hunting and illegal trafficking of non-native pangolin species into China - where they could outcompete, or spread diseases to native species. Thus, illicit trade for traditional medicine threatens Chinese pangolins. Habitat destruction has made Chinese pangolins more vulnerable to poaching. Natural forests are being destroyed to grow crops, grow economic trees like rubber, or build human infrastructure. Farms or rubber plantations have fewer ants and termites than natural forests, so pangolins cannot survive there. As a result, in some parts of China, the pangolin geographical range halved in 30 years. With acres of this unsuitable habitat separating fragments of forest, pangolins may struggle to find mates, and inbreeding could be an issue. Thus, habitat loss is contributing to the decline of the Chinese pangolin. Conservation Conservation measures were taken in the last few decades in response to the pangolin population decline. In China, hunting pangolins was first restricted in 1987, and they were given legal protection in 1989. The Chinese government tightened this protection in 2020 after suggestions that pangolins were an intermediate species for SARS-CoV-2 to transmit from bats to humans. In addition to national restrictions, international authorities restricted pangolin trade, and the Chinese government ran public awareness campaigns about their endangered status ( Figure 3 ). Pangolins also have 100,000 squared kilometres of protected habitat in China, though this is only 9% of what models predict as a suitable pangolin habitat. Habitat protection and trade restrictions are essential to protect pangolins because captive breeding has either failed or acted as a front for illegal trafficking. Although Chinese pangolin conservation has come far in the last 40 years, more can be done. Conclusion Humans have driven Chinese pangolins to near extinction, mainly by hunting for traditional medicine ingredients and destroying native habitats. Conservation efforts have primarily involved legal and habitat protection, but pangolins are challenging to monitor and impossible to breed in captivity. Hopefully, public awareness and a clampdown on illegal trafficking will help to save this unique mammal species. Written by Simran Patel Related articles: Conservation of marine iguanas / Galapagos tortoises REFERENCES Challender, D. et al. (2013) IUCN Red List of Threatened Species: Manis pentadactyla . IUCN Red List of Threatened Species . Available from: https://www.iucnredlist.org/en (Accessed 23rd October 2024). Convention On International Trade In Endangered Species Of Wild Fauna And Flora (2017) Appendices I, II and III valid from 4 October 2017 . Available from: https://cites.org/sites/default/files/eng/app/2017/E-Appendices-2017-10-04.pdf . Mammoser, G. (20th February 2017) Chinese Police Go After ‘Pangolin Princess’ Who Proudly Eats Endangered Species. VICE . Available from: https://www.vice.com/en/article/chinese-police-go-after-pangolin-princess-who-proudly-eats-endangered-species/ (Accessed 23rd October 2024). Wang, Y., Turvey, S.T. & Leader-Williams, N. (2023) The scale of the problem: understanding the demand for medicinal pangolin products in China. Nature Conservation . 52: 47–61. Available from: https://doi.org/10.3897/natureconservation.52.95916 (Accessed 23rd October 2024). Xinhua News Agency (2015) Opinions of the Central Committee of the Communist Party of China and the State Council on Accelerating the Construction of Ecological Civilization . Beijing: The Central Government of the People’s Republic of China. Available from: https://www.gov.cn/xinwen/2015-05/05/content_2857363.htm (Accessed 23rd October 2024). Zhang, F., Chen, Y., Tang, X., Xi, F., Cen, P., Pan, Z., Ye, W. & Wu, S. (2024) Predicting the distribution and characteristics of Chinese pangolin habitat in China: Implications for conservation. Global Ecology and Conservation . 51: e02907. Available from: https://www.sciencedirect.com/science/article/pii/S2351989424001112 (Accessed 23rd October 2024). Zhang, F., Wang, W., Mahmood, A., Wu, S., Li, J. & Xu, N. (2021) Observations of Chinese pangolins ( Manis pentadactyla ) in mainland China. Global Ecology and Conservation . 26: e01460. Available from: https://www.sciencedirect.com/science/article/pii/S235198942100010X (Accessed 23rd October 2024). Zhang, F., Wu, S. & Cen, P. (2022) The past, present and future of the pangolin in Mainland China. Global Ecology and Conservation . 33: e01995. Available from: https://www.sciencedirect.com/science/article/pii/S235198942100545X (Accessed 19th October 2024). Project Gallery

Immunosenescence and related therapies Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Ageing and its association with immune decline Last updated: 24/02/25, 11:28 Published: 20/02/25, 08:00 Immunosenescence and related therapies Introduction Ageing is a profoundly complex and integral part of human life. As pharmaceutical developments have occurred, introducing new medicines and therapies such as biologics and antibiotics within the last 100 years, research has begun to look at malignancy at a more macro scale. To be clear, while it has become easier to combat infectious diseases in recent times, the combating of diseases tied to our genetic composition is far more complicated, whether it be autoimmune diseases or onset conditions such as cases of dementia. Ageing is one such case of a process that is hard to combat because the mechanisms that cause it are diverse and currently not fully understood. Strides have been made under a concept known as senescence, which continues to enlighten researchers and the anti-ageing pharmaceutical industry. This article provides a short summary of what immunosenescence is and how we can utilise our understanding to develop therapies for human immunity. What is immunosenescence? Immunosenescence is the change from a healthy, active immune cell phenotype to one that is no longer conventionally active and begins to secrete inflammatory chemical messengers known as the senescence-associated secretory phenotype (SASP) ( Figure 1 ). A most important aspect of senescence is that a cell undergoes cell cycle arrest, meaning it cannot proliferate. You may now question why cells are programmed to senesce if the outcomes are detrimental to the host? It prevents the continued proliferation of old or damaged cells, including cells with uncontrolled proliferation (such as cancer cells). If we stop senescence altogether, we run the risk of accumulating damaged and/or mutated cells, increasing the chances of disease progression, such as through fibrosis and tumorigenesis, so specific targeting and dosage of drug interventions have to be considered. The immune system in particular, displays biological changes that are indicative of senescent progression. These include thymic involution (shrinking of the thymus associated with a decrease in T cell production), inflammaging (chronic inflammation associated with SASP), an increase in mitochondrial stress through metabolic changes, and an increase in differentiated memory T cells (EMRA T cells). Knowledge of these changes can give insight into potential mechanisms to target for therapeutics. Current and developing therapies for immunosenescence Given our expanding understanding of senescence, as of the time of writing, there are no clinically approved drugs for senescence specifically. The development of therapies for diseases such as cancer, heart disease and diabetes (diabetic patients tend to exhibit increased levels of cellular senescence owing to “accelerated ageing”) have been implicated with suppressing senescence. These drugs would be mTOR inhibitors such as Rapamycin, statins, P13K inhibitors, as well as immune checkpoint inhibitors for T cells, such as anti CTLA-4 PD-L1 and PD-L2, and the anti-diabetic metformin, which have all shown in vitro to be effective against high levels of senescent cells. There was also the development of the recent first senolytic drugs dasatinib and quercetin in 2015 that kill senescent cells selectively against non-senescent cells and stand to provide a proof of concept for targeting disease through senescent mechanisms. Conclusion The field of senescence is certainly one to keep an eye on, with a bibliometric analysis in 2023 showing an increase every year in the number of published papers ( Figure 2 ). It may be sooner rather than later that we see this become a trending topic of discussion for treating an array of disease states. Continuous research into specific immune cell subtypes (B, T and NK cells) and their relation to a decline in immunity in response to age can tell us more about potential therapeutic pathways or lifestyle choices that can improve the health of the immunocompromised elderly. One such example of this is Treg-mediated increased glucose consumption in the tumour microenvironment leading to an increase in cell senescence in effector T cells, suggesting that high sugar diets can accelerate tumorigenesis. Our understanding of ageing through senescence will help reduce the mortality rates of elderly groups in decades to come through knowing that mechanisms such as the SASP and altered immune cell function, which can promote disease states. Written by Yaseen Ahmad Related articles: Genetics of ageing and longevity / Accelerated ageing REFERENCES Henson, S.M. and Aksentijevic, D. (2021) ‘Senescence and type 2 diabetic cardiomyopathy: How young can you die of old age?’, Frontiers in Pharmacology , 12. doi:10.3389/fphar.2021.716517. Wang, R. et al. (2017) ‘Rapamycin inhibits the secretory phenotype of senescent cells by a NRF2-independent mechanism’, Aging Cell , 16(3), pp. 564–574. doi:10.1111/acel.12587. Henson, S.M. et al. (2012) ‘Reversal of functional defects in highly differentiated young and old CD8 T cells by PDL blockade’, Immunology , 135(4), pp. 355–363. doi:10.1111/j.1365-2567.2011.03550.x. Islam, M.T. et al. (2023) ‘Senolytic drugs, dasatinib and quercetin, attenuate adipose tissue inflammation, and ameliorate metabolic function in old age’, Aging Cell , 22(2). doi:10.1111/acel.13767. Li, C., Liu, Z. and Shi, R. (2023) ‘A comprehensive overview of cellular senescence from 1990 to 2021: A machine learning-based bibliometric analysis’, Frontiers in Medicine , 10. doi:10.3389/fmed.2023.1072359. Herranz, N. and Gil, J. (2018) ‘Mechanisms and functions of cellular senescence’, Journal of Clinical Investigation , 128(4), pp. 1238–1246. doi:10.1172/jci95148. Li, L. et al. (2019) ‘TLR8-mediated metabolic control of human Treg function: A mechanistic target for cancer immunotherapy’, Cell Metabolism , 29(1). doi:10.1016/j.cmet.2018.09.020. 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, 13:43 Published: 12/06/25, 07:00 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

The current conflict has caused unfathomable mental distress and health problems for the Kashmiri people Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Health gaps in conflict-affected Kashmir Last updated: 18/09/25, 08:41 Published: 17/07/25, 07:00 The current conflict has caused unfathomable mental distress and health problems for the Kashmiri people This is article no. 5 in a series about global health injustices. Previous article: Syria and Lebanon ’s diverging yet connected struggles . Next article: Health inequalities in Bangladesh . Introduction Welcome to the fifth article of the Global Health Injustices Series. The previous article was a collaborative endeavour focused on the populations in Syria and Lebanon. Now, I will focus on the people living in Kashmir, who are currently experiencing a lot of health and wellbeing challenges, primarily attributed to conflict. For example, on top of the enduring conflict in Kashmir, the COVID-19 pandemic had worsened the mental health of the Kashmiri population, where 1.8 million adults were living with any type of mental distress. Despite these concerns, the Kashmiri people have not had their voices heard as clearly in mainstream discourse compared to other vulnerable populations discussed in previous articles. Kashmir: a rich history to current conflict Kashmir (also known as Jammu & Kashmir) is a region within the Northern Indian subcontinent, bordered mainly by Pakistan and China. Kashmir is a disputed territory between the militaries of India and Pakistan since the Indian subcontinent was divided up by the British Empire in 1947. Even before that, conflicts were driven by issues with local governments and tensions between cultural and ethnic groups within the region. These issues, among others, have contributed to the instability and health challenges encountered by the Kashmiri people. In recent years, tensions and violence have accelerated, particularly in 2024, due to the Indian government wanting to maintain control of the Kashmiri region. This has led to vast protests and friction between civilians and armed forces. In turn, this has weakened ties within the region, particularly between India and neighbouring nations. Another overlooked impact (which I will be discussing further) of this current conflict is on Kashmiri women, who encounter certain challenges, which include loss of family members, displacement and Gender-Based Violence. Considering this background of Kashmir is crucial because it will help with understanding the current geopolitical climate and how it detrimentally affects the health of the Kashmiri people. Geopolitics and health in Kashmir Similar to the populations discussed in previous articles, the Kashmiri people are encountering a lot of mental distress attributed to the ongoing conflict. One study from 2009 found that the prevalence of depression was 55.72%. Meanwhile, another study from 2017 uncovered that approximately 45% of adults experienced mental distress, with specific rates of 41% for depression, 26% for anxiety, and 19% for post-traumatic stress disorder (PTSD). This difference presumably came from wider geopolitical factors, as measuring mental health is challenging during conflict. As such, the healthcare system in Kashmir needs urgent improvement to better support mental health. Even though it does better in some areas compared to the national average, the demand for services, especially in conflict-affected areas, is overwhelming. There are not enough mental health professionals, and many healthcare providers lack the training to handle trauma-related issues properly. Investing in training, community mental health initiatives, and integrating mental health services with regular healthcare could help improve the overall mental health of the Kashmiri people. Focusing on mental health just as much as physical health to build resilience in Kashmir is essential. As for the health infrastructure in Kashmir, noted in one review, they have 4433 government health institutions and a doctor-patient ratio of 1:1880, which is lower than the World Health Organisation (WHO) recommendation of 1:1000, yet higher than the national level of 1:2000. Moreover, the state of Kashmir was shown to have better health indices compared to the national average, including life expectancy, infant mortality rate, and crude birth and death rates. Despite these improvements, challenges persist, such as the inadequate health infrastructure and a shortage of financial resources and technical staff, despite relatively stable trends ( Table 1 ). In one study, the authors noted that among the Schedule tribes in Kashmir, they encounter significant health challenges attributed to illiteracy, poverty, and inadequate healthcare facilities and infrastructure, leading to increased non-communicable diseases (NCDs). There is a high prevalence of poor nutrition and undernutrition, which contributes to the susceptibility of these populations to NCDs (7). Moreover, a lack of access to clean water and sanitation worsens health issues, which increases their risk of infectious diseases. Social taboos and beliefs hinder healthcare service utilisation among the population, which impacts health outcomes and even awareness of NCDs ( Figure 1 ). Focusing on violence exposure in Kashmir, another study among households found that respondents documented high levels of violence, which include: exposure to crossfire (85.7%), round-up raids (82.7%), witnessing torture (66.9%), experiences of rape (13.3%) and forced labor (33.7%). What this study also found was that males noted more violent confrontations and had higher odds of experiencing different forms of maltreatment compared to females. Given that this study was conducted in 2008, these figures are likely to be either higher or lower now, depending on the magnitude of violence and warfare. Nonetheless, the high frequency of violence has led to substantial health issues, specifically mental health problems among the affected Kashmiri population. A severely overlooked impact of conflict in Kashmir is on the women, who encounter specific tragedies, including loss of family members and displacement. Moreover, the use of rape as a weapon in conflict stresses the convergence of gender and political power, particularly in Kashmir. Unfortunately, there have been some researchers who usually depict Kashmiri women as solely victims, which can undermine their autonomy and political involvement. Therefore, addressing the plight of Kashmiri women by allowing them to discuss their experiences openly and actively involving them in key decisions regarding Kashmir can be a vital stepping stone towards supporting their health and well-being. To truly understand all of the various health challenges illustrated above impacting the Kashmiri population, it is vital to cite the various geopolitical factors I discussed in previous articles on Yemen, Sudan and Palestine. The most notable factor is the continuous international weapons/ arms trade, which I firmly believe must be thwarted because of how much damage it has caused, particularly through the sale of bombs and other explosives used to target the most vulnerable populations. However, stopping this trade requires actual political will and legislation, which is unlikely to happen anytime soon because our leaders make a lot of profit from selling weapons. NGOs: their role in supporting Kashmir International non-governmental organisations (INGOs), notably Aakar Patel, chair of board at Amnesty International India, shared this statement in 2024 regarding Kashmir: The Indian authorities are using arbitrary restrictions and punitive actions to create a climate of fear in Jammu and Kashmir. Anyone daring to speak out – whether to criticize the government or to stand up for human rights – faces a clampdown on their rights to freedom of expression and association and cannot move freely within and outside the country. Amnesty International also shared testimonies from a few Kashmiri people: I feel a deep responsibility to be the voice of my people, who are currently voiceless. There are no stories coming out of Kashmir anymore. - Masrat Zahra, an award-winning Kashmiri photojournalist. My freedom of movement is a right enshrined in the Indian Constitution, but I had to really struggle to exercise this right. - Iltija Mufti, daughter and media advisor to ex-chief minister of Jammu & Kashmir. To address the complex health and social issues previously discussed, international organisations and local communities need to come together for solutions. Programs focusing on building mental health support, improving healthcare availability, and creating safe spaces for women and young people can make a difference. The Kashmiri people need to have their voices heard in discussions about their health and wellbeing. Otherwise, their challenges will continue to affect their lives. Conclusion Overall, the health and well-being issues in Kashmir are closely linked to the long-standing conflict and warfare. Although this region has a rich cultural history and shows a lot of resilience, the current conflict has caused unfathomable mental distress and health problems for the Kashmiri people. The rise in mental health issues and the inadequate healthcare infrastructure illustrate that reforms are urgently needed. There is a real shortage of support for mental health, particularly when dealing with the trauma from ongoing violence. Moreover, marginalised groups face tremendous health challenges because of various factors ranging from poverty to a lack of education to limited access to basic needs. Living in violence and conflict not only affects physical health, but also leads to ongoing psychological trauma that is often ignored. Tackling these health inequalities and inequities requires a comprehensive approach incorporating mental health care into the standard healthcare system, improving access to clean water and food, and building communities. Listening to the Kashmiri people and focusing on their health needs is key to achieving peace and better living standards in the region. Therefore, national and international players must recognise these issues and take real action to ensure they receive the support they need and deserve. Only with continued efforts can we expect a healthier future for Kashmir. The following article in the Global Health Injustices series will focus on Bangladesh and the plight of the Rohingya population, which will also be a collaborative endeavour. Written by Sam Jarada Related articles: Impacts of global warming on dengue fever / Understanding health through different stances / South Asian famine / South Asian mental health REFERENCES Sheikh Shoib, Arafat SMY. Mental health in Kashmir: conflict to COVID-19. Public Health. 2020 Sep 1;187:65–6. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC7484691/ Center for Preventive Action. Conflict Between India and Pakistan. Global Conflict Tracker. 2015. Available from: https://www.cfr.org/global-conflict-tracker/conflict/conflict-between-india-and-pakistan Zeeshan S, Hanife Aliefendioğlu. Kashmiri women in conflict: a feminist perspective. Humanities and Social Sciences Communications. 2024 Feb 12;11(1). Available from: https://www.nature.com/articles/s41599-024-02742-x Amin S, Khan A. Life in conflict: Characteristics of Depression in Kashmir. International Journal of Health Sciences. 2009 Jul;3(2):213. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC3068807/ Housen T, Lenglet A, Ariti C, Shah S, Shah H, Ara S, et al. Prevalence of anxiety, depression and post-traumatic stress disorder in the Kashmir Valley. BMJ Global Health. 2017 Oct;2(4):e000419. Available from: https://gh.bmj.com/content/2/4/e000419 Mir A, Bhat S. Health Status and Access to Health Care Services in Jammu and Kashmir State. Asian Review of Social Sciences [Internet]. 2018;7(3):52–7. Available from: https://www.trp.org.in/wp-content/uploads/2018/11/ARSS-Vol.7-No.3-October-December-2018-pp.52-57.pdf Habib A, Iqbal A, Rafiq H, Shah A, Amin S, Suheena, et al. Trends in the Magnitude of NCDs among Schedule Tribe Population of Kashmir with Special Reference to Health and Nutritional [Internet]. Journal of Community Medicine & Public Health. Gavin Publishers; 2023 [cited 2025 May 5]. Available from: https://www.gavinpublishers.com/article/view/trends-in-the-magnitude-of-ncds-among-schedule-tribe-population-of-kashmir-with-special-reference-to-health-and-nutritional Jong K de, Ford N, van, Kamalini Lokuge, Fromm S, Galen R van, et al. Conflict in the Indian Kashmir Valley I: exposure to violence. Conflict and Health [Internet]. 2008 Oct 14 [cited 2025 May 5];2(1). Available from: https://conflictandhealth.biomedcentral.com/articles/10.1186/1752-1505-2-10 Authorities must end repression of dissent in Jammu and Kashmir [Internet]. Amnesty International. 2024 [cited 2025 Jun 11]. Available from: https://www.amnesty.org/en/latest/news/2024/09/india-authorities-must-end-repression-of-dissent-in-jammu-and-kashmir/ Project Gallery

Looking at caspase-8’s inability to trigger cell death Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link CEDS: a break in cell death Last updated: 12/09/25, 11:08 Published: 11/09/25, 07:00 Looking at caspase-8’s inability to trigger cell death This is article no. 11 in a series on rare diseases. Next article coming soon. Previous article: Ehlers-Danlos syndrome . Cell death, as we know it, is a crucial phenomenon by which our bodies remove unnecessary or damaged cells to maintain internal stability, a process known as homeostasis. Cell death can occur in many ways, but the mechanisms by which cells die follow two main paths. It may occur as naturally programmed, as in apoptosis, or as a result of toxic trauma or physical damage, like necrosis. While cell death due to trauma can often be more noticeable and dramatic, programmed cell death happens continually, not only because of cell damage but also because it is a normal part of development, and inducing it is a core function of immune system cells. In essence, cell death comes naturally, removing cells that are possibly damaged or infected to maintain the body as a whole. But what if cell death stops? As many fiction stories will tell you, immortality is never a good thing, and this is accurate for our cells, too. Although excessive cell death is also destructive, cell death in its natural controlled manner not only stops the spread of infection but also prevents the survival of cancer cells and auto-reactive immune cells, which can damage the body by forming cancerous tumours and triggering autoimmune diseases, respectively. This demonstrates that a careful balance of life and death must always be in place to maintain homeostatic conditions and allow our unimpeded survival. However, as cell death is a multi-step mechanism, it can go wrong in several ways. Furthermore, diseases causing faults in the cell death process can be challenging to diagnose. Not only can there be numerous reasons for patients to exhibit symptoms associated with the loss of cell death, but some of these reasons may also be rare disorders and, therefore, difficult for healthcare professionals to identify. One rare disease that researchers recently recognised is Caspase-8 Deficiency Syndrome (CEDS). This disease, stemming from a genetic mutation in the gene coding for caspase-8, results in extensive issues related to immunodeficiency, and they are all caused by caspase-8’s inability to trigger cell death. So what is Caspase-8? Caspase-8 is a pivotal regulator of the apoptotic pathway. Essentially, apoptosis can happen through two key pathways: the extrinsic pathway, when triggers originate outside the cell; and the intrinsic pathway, when the cell itself activates the cell death pathway. Whilst there are several key players in apoptosis, caspase-8 is a central mediator of the extrinsic apoptotic pathway. Caspase-8 can be activated through numerous ways, but it is often through so-called death receptors, which are typically members of the Tumour Necrosis Factor Receptor (TNFR) family of transmembrane proteins. Upon their activation, a chain reaction occurs, involving the recruitment of caspase-8 into a complex, known as the death-inducing signalling complex (DISC). This complex then cleaves further downstream caspases or the BH3 Bcl2-interacting protein. This cascade leads to DNA fragmentation, degradation of the cytoskeleton, formation of apoptotic bodies, expression of ligands for phagocytic cell receptors, and finally, uptake by phagocytes, thus completing the death of the cell and its cleanup ( Figure 2. ). Caspase-8 therefore plays a crucial role in completing the death inducing pathway. While there are other methods of cell death, the loss of Caspase-8 undoubtedly leads to significant consequences. Caspase-8 deficiency syndrome (CEDS) Scientists first discovered CEDs in the early 2000s. By this time, there had already been extensive research into a similar disease known as Autoimmune Lymphoproliferative Syndrome (ALPS), which results from defective apoptosis leading to abnormal immune cell survival. However, at the time of ALPS discovery, there was no identified link to a loss of Caspase-8. Furthermore, there was a lack of available mouse models to study, as inducing homozygous caspase-8 deficiency caused embryonic lethality in mice, significantly limiting research. Therefore, a loss of caspase-8 was also considered to have the same effect in humans. This train of thought continued until 2002, when Chun et al. conducted major studies into apoptosis-related diseases. During one of their many trials, two siblings—a 12-year-old girl and an 11-year-old boy—were found to exhibit symptoms similar to those of ALPS (lymphadenopathy, splenomegaly, and defective CD95-induced apoptosis of peripheral blood lymphocytes). However, unlike ALPS, the siblings were also immunodeficient and suffered from recurrent sinopulmonary and herpes simplex virus (HSV) infections, as well as a poor response to immunisation. Following the discovery of these additional symptoms in the siblings, researchers examined their other family members but were surprised to find that neither the parents nor another sibling suffered in a similar fashion. The only symptom they had was a partial defect in apoptosis mediated by CD95. It was determined that the mother, father, sibling, and several other extended family members were potentially heterozygous carriers of the mutation found in the affected siblings. Subsequently, a DNA analysis was conducted, and a mutation was found in the CASP8 gene. This mutation was a homozygous deletion, which ultimately led to a loss of function of the caspase-8 protein. This loss of function in caspase-8 resulted in defective interleukin 2 production and diminished T-cell proliferation, explaining the immunodeficiency associated with CEDS and highlighting the important role caspase-8 plays in regulating cell death and immune responses. Since CEDS was first identified in the 2002 study, very few cases have been reported in medical literature. However, despite this, research continues, and it has allowed further insights into caspase-8’s pathophysiology and, in many studies, new genetic variants have been identified. One such variant is a homozygous missense mutation resulting in significant immune dysregulation in an affected individual, which results in immune responses and inflammatory conditions associated with the disease. Alongside research into the causes of this disease, focus has also shifted to how we might best diagnose and treat the disease and provide patients with the good quality of life they deserve. Diagnosis As with all rare diseases, one of the main issues stopping correct diagnosis of CEDS and delaying treatment is the fact healthcare providers are not familiar with disease symptoms, let alone the genetic basis of the disease. To make matters worse, the presentation of disease varies depending on the age of onset, which makes it even more difficult to recognise CEDS as the common underlying cause. For instance, early-onset often results in symptoms, such as severe infections and organomegaly, while adult-onset patients may present with neurological issues, multi-organ failure and chronic inflammatory conditions. Further adding to these diagnostic difficulties is the fact CEDS overlaps with other conditions, such as the previously mentioned ALPs. As a result, a patient could receive multiple different diagnoses before CEDS is identified as the cause of their suffering. For effective CEDS diagnosis, expertise in immunology, genetics and infectious diseases is required. However, this specialised knowledge is hard to come by, and as with all diseases, the familiarity the healthcare provider has with it contributes greatly to whether you will get diagnoses, and this familiarity does not exist for rare diseases. Furthermore, diagnostic methods in general are tricky for this disease, with multiple tests often being required including an analysis of patient history alongside genetic testing through methods like whole exome sequencing and immunological tests analysing the types and states of immune cells and abnormal levels of immunoglobulins. Each of these diagnostic methods takes time, in an often-strained healthcare system, which can lead to a sense of helplessness in disease sufferers who only suffer more the longer they do not know what is wrong. Treatments Unfortunately for patients, a difficult diagnosis is not the only challenge they face, as there is currently no cure for CEDS, and no specific treatments. However, there are more general treatments available that could potentially alleviate symptoms and help individuals achieve some level of normality in their lives. The best possible way to approach treatment of CEDS, as with most immunodeficiency related diseases, would be to treat both the immune dysfunction and prevent recurrent infections. This could involve a multifaceted treatment plan tailored to the individual, aiming to avoid complications from immune dysfunction and improve quality of life. Potential treatment plans could include the use of antibiotic and antiviral medications for recurrent infections, and also more complex treatments such as Immunoglobulin replacement therapy (IVIG). IVIG provides necessary antibodies to bolster patients’ immune system, when they are not able to themselves, which both helps avoid overuse of antibiotic and antiviral treatments and prevents infections in the first place before treatment is required. Alongside these treatment methods, due to it being a relatively unknown disease, CEDS patients will also require a great deal of supportive and hands on care. As part of this care patients could potentially be provided with a specialised diet plan with all the correct nutrition to help them combat any gastrointestinal issues (GI’s) associated with CEDS, as primary immunodeficiency patients have found this method to help with control of GIs. In addition to current therapies several innovative approaches to treatment of genetic diseases are in development which could be used in CEDS treatment. Recent advances in gene therapy research offer new hope for treating immune deficiencies resulting from genetic defects, which means these therapies could potentially benefit CEDS patients. One promising method for gene therapy utilises CRISPR-Cas9 to correct the genetic mutations, such as those in CASP8 leading to CEDS. Another approach uses viral vectors to deliver functional genes into patients’ cells, and this could potentially deliver a functional CASP8 gene. Additionally, another very promising therapy, previously used for ALPS patients, involves genetically modifying stem cells to correct a faulty gene (such as the faulty CASP8 gene) before re-infusing them into the patient to produce healthy immune cells. These treatments could revolutionise the management of rare genetic diseases like CEDS. The future for CEDS as a rare disease Rare diseases like CEDS are often chronic and, in many cases, life threatening. Due to the scarcity of information on these conditions, few if any treatments exist. Furthermore, due to their rarity, patients of rare diseases are not only small in number but also dispersed worldwide, leading to a feeling of isolation as they rarely meet someone who shares in their experiences. However, as scientific research progresses, treatments and therapies become more effective and accessible, and with 72% of rare diseases, including CEDS, having a genetic basis, gene therapies appear incredibly promising. Yet, there is still a long way to go to fully realize their potential, and even more that can be done to help and support those who continue to suffer alone with rare diseases. Written by Faye Boswell REFERENCES Telford WG. Multiparametric analysis of apoptosis by flow cytometry. Methods Mol Biol. 2018;1678:167–202. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC8063493/ Smith C. Monitoring apoptosis by flow cytometry. Biocompare. 2017 Jan 17. Available from: https://www.biocompare.com/Editorial-Articles/332620-Monitoring-Apoptosiby-Flow-Cytometry/ Tummers B, Green DR. Caspase-8; regulating life and death. Immunol Rev. 2017 May;277(1):76–89. doi: 10.1111/imr.12541. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC5417704/ Leeies M, Flynn E, Turgeon AF, Paunovic B, Loewen H, Rabbani R, Abou-Setta AM, Ferguson ND, Zarychanski R. High-flow oxygen via nasal cannulae in patients with acute hypoxemic respiratory failure: a systematic review and meta-analysis. Syst Rev. 2017 Oct 18;6(1):202. doi: 10.1186/s13643-017-0607-1. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439260/ Goyal A, Moitra D, Goldstein DB, Savage H, Lisco A, Rosenzweig SD, et al. Caspase-8 deficiency presenting as a novel immune dysregulation syndrome: case report and literature review. Allergy Asthma Clin Immunol. 2023;19(1):57. doi:10.1186/s13223-023-00778-3. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10084589/ Chun HJ, Zheng L, Ahmad M, Wang J, Speirs CK, Siegel RM, et al. Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency. Nature. 2002 Sep 26;419(6905):395–9. doi:10.1038/nature01063. Available from: https://pubmed.ncbi.nlm.nih.gov/12353035/ Khan S, Saha S, Saha S, et al. Early and frequent exposure to antibiotics in early childhood and risk of overweight: a systematic review and dose-response meta-analysis. Obes Rev. 2021;22(3):e13113. doi:10.1111/obr.13113. 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Impact of war and geopolitics on health in Palestine Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Life under occupation: the health and well-being of Palestinians Last updated: 08/01/26, 18:56 Published: 13/03/25, 08:00 Impact of war and geopolitics on health in Palestine This is article no. 1 in a series about global health injustices. Next article: Civil war in Sudan . Introduction Welcome to the Global Health Injustices Series, which will focus on critically examining the health inequalities and inequities faced by vulnerable populations within different countries and regions worldwide and even put forward actionable steps to improve their health and wellbeing. This series will begin with Palestine, as it has been an enduring crisis that should be addressed to include long-lasting benefits and outcomes for the Palestinians. Palestine: from a rich history to current occupation Palestine is a country in the Middle East (West Asia) mainly bordered by Israel. Palestine is unique in its various cultures and knowledge, moulded by multifaceted events and geopolitical shifts over centuries. The multidimensional cultural landscape of Palestine illustrates the impact of civilisations, such as the Romans, Byzantines, and Ottomans, who each had their religions, languages, and cultures, which still exist in various forms today. The resilience of the Palestinians is evident through their distinct traditions, art, food and environment, which are essential to their identity. With these testaments in mind, Palestinians are facing consistent strife because they are under constant occupation, blockade and cutting off of needed supplies carried out by Israel, as noted by several humanitarian and human rights non-governmental organisations (NGOs) like Amnesty International and Save the Children. These actions are facilitated by nations, notably the United States and the United Kingdom, through arms and weapons trade. Hence, the struggle for the Palestinians to have autonomy and freedom, among other human rights within their own homeland, is a consistent fight that requires ongoing international cooperation and solidarity. Geopolitics: its detrimental impacts on the Palestinians Given the currently divisive geopolitical landscape, it is essential to bring attention to the health outcomes of the Palestinian population, especially since at least half of them are children. A report from the Global Nutrition Cluster called “Nutrition Vulnerability and Situation Analysis / Gaza” had several key findings and tables (see Tables 1 and 2 ). Firstly, more than 90% of children less than a year old, along with pregnant and breastfeeding women, encounter high under-nutrition due to poverty. Another finding was that approximately 90% of children under five are impacted by at least one infectious disease, and 81% of households in Gaza lack clean and safe water. However, the authors noted limitations in their analysis, such as limited data sources because collecting it is difficult within the context of Gaza, and this was true for screening. Another report from the organisation Medical Aid For Palestinians (MAP), titled “Health Under Occupation” from 2017, discussed healthcare access and outcomes more broadly. For example, they noted that in 2016, up to one-third of patients’ permits to exit Gaza for healthcare access were either denied or delayed. Moreover, they stated that 40% of people in Gaza live below the poverty line. Given the recent geopolitical shifts in power, these findings from both reports will likely be higher now. This brings forthcoming uncertainty about whether the health outcomes of Palestinians will improve. In a recent qualitative study involving the views of Palestinian physicians in the West Bank, they shared their experiences of violence, threats of violence, issues with healthcare access for themselves and patients, financial difficulties to support their families, struggle to help their patients and limited access to education due to harsher life under occupation. Thinking more largely about emergency care in Palestine, one scoping review reported the depletion of healthcare resources such as medical equipment and medications. The authors even related how human rights violations and the destruction of the Palestinian healthcare system, including emergencies, have exacerbated outcomes; the most notable were stroke, myocardial infarction and traumatic injury, among other non-infectious diseases. Although the authors included this information from a human rights standpoint, they called for additional interventions and research to fill in and learn gaps within emergency care to enhance health outcomes for Palestinians. This review was published in 2022, and again, many geopolitical shifts in power have taken place within a few years. Therefore, it can be deduced that emergency care is drastically needed for the Palestinians; this is primarily compelled by the blockade in Gaza and occupation in the West Bank. Focusing on the mental health outcomes among Palestinians, they have become worse. In another scoping review, researchers focused on trauma among young Palestinian people in Gaza; the authors noted that events, such as exposure to devastation and violence, as well as the death or loss of friends and family, have contributed to mental health outcomes ranging from post-traumatic stress disorder (PTSD) to depression. Nevertheless, the authors stated that further qualitative research is vital to addressing gaps in knowledge and enhancing mental health outcomes among the Palestinian youth and the wider population. Connecting back to how the modern geopolitical landscape is very dynamic, the poorer mental health outcomes among Palestinians have conceivably increased. Urgent calls to action: recommendations from NGOs to upholding human rights Given all of these detrimental impacts on the health and wellbeing of Palestinians, there are recommendations from organisations, notably the United Nations (UN), for ways forward towards upholding the human rights of Palestinians: Immediately end all practices of collective punishment, including lifting its blockade and closures – and the “complete siege”- of Gaza, and urgently ensure immediate access to humanitarian and commercial goods throughout Gaza, commensurate with the immense humanitarian needs. Ensure that all Palestinians forcibly displaced from Gaza are allowed to return to their homes creating safe conditions and fulfil its responsibilities as an occupying Power in this regard. End the 56-year occupation of the Occupied Palestinian Territory, including East Jerusalem as part of a broader process towards achieving equality, justice, democracy, non-discrimination, and the fulfilment of all human rights for all Palestinians. These recommendations, among others mentioned in the report from the United Nations (UN) High Commissioner for Human Rights, were divulged in 2024; the year had been a challenging time, particularly in Gaza, due to the complete blockade of food, water and essentials like medical supplies; in addition to this, many explosives were dropped on Gaza, killing thousands of men, women and children. Finally, buildings, such as hospitals and homes, were destroyed. Conclusion: moving forward towards a equitable and equal future for Palestinians Reflecting on everything discussed in this article, the numerous injustices happening to Palestinians must not go on; they have been suppressed for nearly 75 years by governments and the mainstream media before receiving closer attention, examination and debate within Western society recently. Therefore, we need to take actionable steps by initiating more open discussions of justice and advocacy involving the voices of Palestinians, such as myself and others. Furthermore, 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. Both of these actions uphold the health and wellbeing of Palestinians living in Gaza and the West Bank, especially as enabling the recommendations from the UN and other NGOs. As for the wider international community, we must continue upholding human rights to maintain our health and wellbeing. In my next article, I will discuss Sudan because this population has also encountered many injustices, primarily the civil war that has been occurring since 2023. This has impacted the health and wellbeing of the Sudanese population, which requires thorough attention and discussion. Written by Sam Jarada Related articles: Gentrification and well-being / Health Inequalities / Impacts of global warming on NTDs / Global health injustices- Bangladesh , Sri Lankan Tamils REFERENCES Human rights in Israel and the Occupied Palestinian Territory. Amnesty International. 2022. Available from: https://www.amnesty.org/en/location/middle-east-and-north-africa/middle-east/israel-and-the-occupied-palestinian-territory/report-israel-and-the-occupied-palestinian-territory/ Occupied Palestinian Territory. Save the Children International. 2024. Available from: https://www.savethechildren.net/occupied-palestinian-territory Nutrition Vulnerability and Situation Analysis / Gaza. 2024. Available from: https://www.nutritioncluster.net/sites/nutritioncluster.com/files/2024-02/GAZA-Nutrition-vulnerability-and-SitAn-v7.pdf HEALTH UNDER OCCUPATION. Medical Aid For Palestinians. 2017. Available from: https://www.map.org.uk/downloads/health-under-occupation---map-report-2017.pdf Husam Dweik, Hadwan AA, Beesan Maraqa, Taher A, Zink T. Perspectives of Palestinian physicians on the impact of the Gaza War in the West Bank. SSM - Qualitative Research in Health. 2024 Nov 14;6:100504–4. Available from: https://www.sciencedirect.com/science/article/pii/S2667321524001136 Rosenbloom R, Leff R. Emergency Care in the Occupied Palestinian Territory: A Scoping Review. Health and Human Rights. 2022 Dec;24(2):255. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9790939/ Abdallah Abudayya, Fugleberg T, Nyhus HB, Radwan Aburukba, Tofthagen R. Consequences of war-related traumatic stress among Palestinian young people in the Gaza Strip: A scoping review. Mental Health & Prevention. 2023 Nov 25;32:200305–5. Available from: https://www.sciencedirect.com/science/article/pii/S2212657023000478 M.I. Human rights situation in the Occupied Palestinian Territory, including East Jerusalem, and the obligation to ensure accountability and justice - Report of the United Nations High Commissioner for Human Rights - Advance unedited version (A/HRC/55/28) - Question of Palestine. United Nations. Available from: https://www.un.org/unispal/document/human-rights-situation-in-opt-unohchr-23feb-2024/ Project Gallery