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Based on the ideas of Aristippus and Aristotle Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link A perspective on well-being: hedonic VS eudaimonic well-being 28/03/25, 11:40 Last updated: Published: 02/07/24, 10:51 Based on the ideas of Aristippus and Aristotle Since ancient times well-being has been discussed in two broad domains: hedonic and eudaimonic. Hedonic well-being is based on the ideas of Aristippus, who proposed that the ultimate aim of all human endeavours and pursuits is pleasure (hedonism). Therefore, hedonic well-being (aka subjective well-being) is a shorter-term evaluation of well-being that balances between positive and negative emotions and between pleasure attainment and pain avoidance. A real-life example of behaviour that leads to hedonic happiness is spending a large amount of money on a designer item to satisfy the need to stay current with fashion trends. According to Keyes et al. (2002), the three aspects of subjective well-being are positive affect (mood), negative affect (mood) and life satisfaction. The most common tools used to measure subjective well-being are the Positive and Negative Affect Schedule (PANAS) by Watson, Clark & Tellegen (1988) and the Satisfaction with Life Scale (SWLS) by Diener et al. (1985). Subjective well-being has been associated with having a present temporal focus and higher income levels, suggesting it is grounded in physical aspects of life and not the greater goals of self-actualisation. On the other hand, eudaimonic well-being is based on the philosophy of Aristotle, who argued that humans can only achieve true happiness and flourish by finding meaning and purpose in life (eudaimonia). Thus, eudaimonic well-being (aka psychological well-being) is a longer-term evaluation of well-being that results from engagement with development and challenges in life posed during the search for meaning and self-reflection. An example of an action that leads to eudaimonic happiness is reading philosophical books and learning more about life holistically. According to Keyes et al. (2002), the six aspects of psychological well-being are autonomy, environmental mastery, personal growth, purpose in life, positive relations with others and self-acceptance. The Scales of Psychological Well-being by Riff (1989) are often used to measure eudaimonic well-being. Recent research shows that psychological well-being is associated with higher levels of self-compassion, mindfulness practices and exposure to natural environments. Therefore, hedonic and eudaimonic well-being represent distinct perspectives on life. Hedonic well-being is more focused on a person's present emotional state and evaluation of their current life circumstances, whereas eudaimonic well-being takes a longer-term view, considering how well a person is functioning and developing their potential over time. The two different types of well-being also are related to separate life outcomes. Higher subjective well-being is associated with better physical health, longevity and relationship quality; while greater psychological well-being is linked to resilience, continued personal growth and self-actualisation. Whilst perhaps it is impossible to determine which well-being is more beneficial, it is definite that hedonic and eudaimonic well-being are intertwined into our daily lives. Written by Aleksandra Lib Related articles: Motivating the mind / Environmental factors and exercise / Physical and mental health / Life under occupation REFERENCES Diener, E., & Chan, M. Y. (2011). Happy people live longer: Subjective well-being contributes to health and longevity. Applied Psychology: Health and Well-Being, 3 (1), 1-43. Diener, E. D., Emmons, R. A., Larsen, R. J., & Griffin, S. (1985). The satisfaction with life scale. Journal of personality assessment , 49 (1), 71-75. Howell, A. J., Passmore, H.-A., & Holder, M. D. (2023). Savoring the here and now: The role of temporal focus for well-being. Journal of Positive Psychology, 18 (2), 221-236. Keyes, C. L., Shmotkin, D., & Ryff, C. D. (2002). Optimizing well-being: the empirical encounter of two traditions. Journal of personality and social psychology , 82 (6), 1007. Koo, J., & Park, K. (2022). Does money buy happiness after all? Revisiting the income-wellbeing link. Journal of Happiness Studies, 23 (3), 1133-1154. Mair, C., Jarrett, M., Watson, M., & Jones, P. B. (2022). The impact of nature exposure on psychological well-being: A systematic review. Environmental Research, 208 , 112677. Krieger, T., Hermann, H., Zimmermann, J., & grosse Holtforth, M. (2022). The role of self-compassion in promoting psychological well-being during the COVID-19 pandemic. Journal of Counseling Psychology, 69 (4), 380–396. Ryff, C.D. (1989). Happiness is everything, or is it? Explorations on the meaning of psychological well-being. Journal of Personality and Social Psychology 57 , 1069–1081. Ryff, C. D. (2014). Psychological well-being revisited: Advances in the science and practice of eudaimonia. Psychotherapy and Psychosomatics, 83 (1), 10-28. Watson, D., Clark, L. A., & Tellegen, A. (1988). Development and validation of brief measures of positive and negative affect: the PANAS scales. Journal of personality and social psychology , 54 (6), 1063. Project Gallery

Non-cell-autonomous cancer progression from chromosomal instability Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Immune signals initiated by chromosomal instability lead to metastasis 27/02/25, 11:34 Last updated: Published: 14/09/24, 21:17 Non-cell-autonomous cancer progression from chromosomal instability Unravelling the intricate relationship between immune cells and cancer cells through STING pathway rewiring. Introduction Chromosomal instability ( CIN ) has long been recognised as a prominent feature of advanced cancers. However, recent research has shed light on the intricate connection between CIN and the STING (Stimulator of Interferon Genes) pathway. Researchers at Memorial Sloan Kettering Cancer Center (MSK) and Weill Cornell Medicine conducted this ground-breaking study, which has provided fascinating insights into the function of the immune system and its interactions with cancer cells. In this article, we will delve into the findings of this study and explore the implications for future cancer treatments. STING pathway The STING pathway plays a crucial role in the response to cellular stress and the innate immunity response to DNA damage and chromosomal instability. Chromosomal instability refers to the increased rate of chromosomal aberrations, such as mutations, rearrangements, and aneuploidy, within a cell population. This instability can lead to genomic alterations that contribute to the initiation and evolution of cancer. This pathway is activated when the presence of cytosolic DNA is detected, which can be indicative of cellular damage or infection, triggering a cascade of signalling events leading to the production of type I interferons and other inflammatory cytokines. Many recent studies have revealed an intriguing relationship between chromosomal instability and the STING pathway, including the STING pathway’s ability to be activated by the accumulation of micronuclei resulting from chromosomal instability in cancer cells. This activation can lead to the promotion of anti-tumour immunity and the suppression of tumourigenesis. The Promise and Limitations of STING Agonist Drugs STING-agonist drugs have shown great potential in preclinical studies, arousing optimism for their use in cancer therapy. However, clinical trials have yielded disappointing results, with low response rates observed in patients. Dr. Samuel Bakhoum, an assistant member at MSK, highlights the discrepancy between lab findings and clinical outcomes. Only a small fraction of patients demonstrated a partial response, leading researchers to question the underlying reasons for this disparity. The Sinister Cooperation: CIN and Immune Cells Chromosomal instability acts as a driver for cancer metastasis, enabling cancer cells to spread throughout the body. The STING pathway, specifically, is where Dr. Bakhoum's team discovered that the immune system has a significant impact on this process. The cooperation between cancer cells with CIN and immune cells is orchestrated by STING, resulting in a pro-metastatic tumour microenvironment. This finding provides a crucial understanding of why STING-agonist drugs have not been effective in clinical trials. Introducing Contact Tracing: Unravelling Cell-to-Cell Interactions Researchers utilised a newly developed tool called ContactTracing to examine cell-to-cell interactions and cellular responses within growing tumours. By analysing single-cell transcriptomic data, they gained valuable insights into the effects of CIN and STING activation. The tool's capabilities allowed them to identify patients who could still mount a robust response to STING activation, enabling the selection of better candidates for STING agonist therapy. STING Inhibition: A Potential Solution Interestingly, the study suggests that patients with high levels of CIN may actually benefit from STING inhibition rather than activation. Treatment of study mice with STING inhibitors successfully reduced metastasis in models of melanoma, breast, and colorectal cancer. These findings open up new possibilities for personalised medicine, where patients can be stratified based on their tumour's response. By identifying the subset of patients whose tumours can still mount a strong response to STING activation, doctors could select better candidates for STING agonists. This biomarker-based approach could help figure out which patients would benefit from turning on STING and which would benefit from turning it off. This could lead to more targeted and effective treatments for people with advanced cancer that is caused by chromosomal instability. Conclusion Based on the research findings, it can be concluded that chronic activation of the STING pathway, induced by CIN, promotes changes in cellular signalling that hinder anti-tumour immunity and facilitate cancer metastasis. This rewiring of downstream signalling ultimately renders STING-agonist drugs ineffective in advanced cancer patients. However, the study also suggests that STING inhibitors may benefit these patients by reducing chromosomal instability-driven metastasis. The research highlights the importance of identifying biomarkers to determine which patients would benefit from STING activation or inhibition. Overall, these findings provide valuable insights into the underlying mechanisms of cancer progression and offer potential opportunities for improved treatment strategies for patients with advanced cancer. The study shown in figure 1, analysed 39,234 single cells within the tumour microenvironment (TME), categorised by cell subtype assignment. It showed that tumour cell rates of CIN were genetically dialled-up or dialled-down. The study also showed CIN-dependent effects on differential abundance at the neighbourhood level, grouped by cell subtype and ranked by mean log2 (FC) within each cell subtype. Node opacity was scaled by the p-value. Written by Sara Maria Majernikova Related articles: Cancer immunologist Polly Matzinger / The Hippo signalling pathway / Cancer metastasis / Arginine and tumour growth Reference: Li, J., Hubisz, M.J., Earlie, E.M. et al. Non-cell-autonomous cancer progression from chromosomal instability. Nature 620 , 1080–1088 (2023). https://doi.org/10.1038/s41586-023-06464-z Project Gallery

Completing the human genome puzzle with the missing piece Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The Y chromosome unveiled 14/02/25, 13:48 Last updated: Published: 07/10/23, 13:23 Completing the human genome puzzle with the missing piece A brief history of the Human Genome Project The Human Genome Project is one of the most important biomedical research projects of the 20th Century. It aimed to sequence all the human genome and DNA, and by 2003, the Human Genome Project had generated the first sequence of the human genome, accounting for over 90% of the information. By 2022, the sequence was finalised, but it only contained information about the female genome, with two X chromosomes. The Y chromosome was missing as it contains many repetitive sequences that are not transcribed to messenger RNA, making it difficult to assemble it fully. However, due to advancements in sequencing technology, a new study in 2023 published in Nature aimed to, for the first time, assemble complete sequences of multiple human Y chromosomes from 43 unrelated males around the world. Sanger DNA sequencing method DNA sequencing is a method used to determine the exact order of DNA bases (adenine, thymine, cytosine, and guanine) within a DNA molecule. Due to the aim of the Human Genome Project (to sequence all of the DNA), many methods were experimented with, leading to scientists ultimately refining, improving and using the Sanger DNA sequencing method. This method is the most accurate method for sequencing small fragments of DNA. It involves using patient DNA in a polymerase chain reaction (PCR). A mix of normal bases and chain-terminating bases is added. Chain-terminating bases stop DNA growth, creating fragments of different lengths, each ending in a terminator. The DNA fragments are separated by size through capillary gel electrophoresis. Each terminator base (adenine, thymine, cytosine, and guanine) has a different fluorescent tag. The fragments appear in order of length, and their fluorescent tags are recorded. This information is used to create a chromatograph, which is compared to a reference to identify variants, allowing DNA analysis. Analysis of the Y chromosome In 2023, a study published in Nature assembled complete sequences of multiple human Y chromosomes from 43 unrelated males around the world. The study discovered a high level of structural variation across the Y chromosomes, which was unexpected. The analysis showed a high level of diversity of the Y chromosome, and it is the beginning of the exploration of male genetic diversity. The study highlights that the information gained can be used in various fields of biomedicine, such as to gain more insight into the function and evolution of the human genome and to understand more about Y chromosome variants. This discovery can also lead to improved genetic testing accuracy and targeted treatments for personalised medicine. Written by Naoshin Haque Project Gallery

Captive breeding has grown the California condor population over 18-fold Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Conserving the California condors 24/04/25, 11:46 Last updated: Published: 04/11/24, 14:56 Captive breeding has grown the California condor population over 18-fold This is article no. 2 in a series on animal conservation. Next article: Beavers are back in Britain . Previous article: The cost of coats: celebrating 55 years of vicuna conservation . California condors are critically endangered birds living on the west coast of North America. Their population decline was first reported in 1953, and they were nearly extinct by 1987. Since then, a captive breeding and reintroduction program has saved the species in the face of multiple human threats. This article will describe some of those threats and available measures to mitigate them. Why California condors became endangered Lead poisoning was the main cause of California condor mortality in the late 20th century. Like vultures, California condors eat dead mammals. When these mammals were shot dead with lead bullets, condors ingested fragments of the bullets, and the lead poisoned their bloodstream. Multiple condors feeding on the same carcass got poisoned, which could be why the population crashed so badly. Today, lead poisoning is the biggest, but not the only, threat to California condor survival ( Figure 1 ). The birds used to be hunted for museums and private collections in the early 20th century, but nowadays, any shootings are accidental. A bigger concern, and the second-most common human-related cause of mortality, is condors colliding with utility poles and power lines. The third-most common is fires: a 2015 study found that every recent wildfire in California has coincided with at least one condor death. Climate change will make these fires more frequent and severe. These threats mainly apply to inland California condors - halogenated organic compound (HOC) pollution is an issue for coastal birds. When coastal condors eat marine mammals contaminated with HOCs, the compounds disrupt their reproductive system and thin their eggshells. In short, humans have created a hostile environment for California condors. Successful captive breeding and population recovery Despite these threats, captive breeding has grown the California condor population over 18-fold ( Figure 2 ). In 1987, all remaining wild condors were captured and bred, with juveniles released to the wild from 1992 onwards. Reintroduced birds are monitored regularly, and poisoned birds are treated with chelation therapy - where a drug binds to lead in the bloodstream and takes it to the kidneys to be filtered out. Since 1995, power line collisions have been avoided by giving juveniles behavioural training before reintroduction. Because of these measures, the California condor mortality rate in the wild decreased from 37.2% in 1992-1994 to 5.4% in 2001-2011. Challenges of conserving California condors Although captive breeding has saved the California condor population, it has also altered behaviours. The original condors stay with one mate longer than reintroduced condors, which may form polygamous relationships. Scientists think that spending so much time with non-family members in captivity has made juveniles promiscuous when reintroduced. Captive bred condors have also gotten used to being fed by people - so they approach people more often, spend longer in areas of human activity, and forage over a smaller area than the original condors. Moreover, condors in southern California were spotted feeding their chicks human litter. These behavioural changes mean the wild California condor population is not self-sustaining. The wild population is also not self-sustaining because condors are still being poisoned ( Figure 3 ). Banning lead bullets is the most effective way to guarantee population growth, but enforcing it has been challenging. Non-toxic alternative bullets like copper cannot find popularity. For population growth, every adult California condor killed is estimated to be worth 2-3 reintroduced juveniles. This is because released juveniles are more vulnerable and take years to reach breeding age. Therefore, American conservationists must keep pressuring authorities to reduce threats to adult California condors. Conclusion Pollution, urbanisation, and climate change have made it hard for the California condor population to recover from decades of lead poisoning. Long generation times and behavioural changes mean captive breeding is the species’ only hope of survival. Perhaps humans are the ones who need to change their behaviour - not feeding California condors and switching to copper bullets would allow these majestic birds to keep roaming the skies. Written by Simran Patel Related articles: Marine iguana conservation / Deception by African birds / Emperor penguins REFERENCES Bakker, V.J. et al. (2024) Practical models to guide the transition of California condors from a conservation-reliant to a self-sustaining species. Biological Conservation . 291: 110447. Available from: https://www.sciencedirect.com/science/article/pii/S0006320724000089 (Accessed 19th September 2024). D’Elia, J., Haig, S.M., Mullins, T.D. & Miller, M.P. (2016) Ancient DNA reveals substantial genetic diversity in the California Condor (Gymnogyps californianus) prior to a population bottleneck. The Condor . 118 (4): 703–714. Available from: https://doi.org/10.1650/CONDOR-16-35.1 (Accessed 28th September 2024). Finkelstein, M.E. et al. (2023) California condor poisoned by lead, not copper, when both are ingested: A case study. Wildlife Society Bulletin . 47 (3): e1485. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/wsb.1485 (Accessed 28th September 2024). Kelly, T.R. et al. (2015) Two decades of cumulative impacts to survivorship of endangered California condors in California. Biological Conservation . 191: 391–399. Available from: https://www.sciencedirect.com/science/article/pii/S0006320715300173 (Accessed 28th September 2024). Mee, A. & Snyder, N. (2007) California Condors in the 21st Century - conservation problems and solutions. In: 243–279. Meretsky, V.J., Snyder, N.F.R., Beissinger, S.R., Clendenen, D.A. & Wiley, J.W. (2000) Demography of the California Condor: Implications for Reestablishment. Conservation Biology . 14 (4): 957–967. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1523-1739.2000.99113.x (Accessed 29th September 2024). Stack, M.E. et al. (2022) Assessing Marine Endocrine-Disrupting Chemicals in the Critically Endangered California Condor: Implications for Reintroduction to Coastal Environments. Environmental Science & Technology . 56 (12): 7800–7809. Available from: https://doi.org/10.1021/acs.est.1c07302 (Accessed 19th September 2024). U.S. Fish and Wildlife Service (2023) California Condor Population Graph, 1980-2022 | FWS.gov . 18 April 2023. Available from: https://www.fws.gov/media/california-condor-population-graph-1980-2022 (Accessed 28th September 2024). U.S. Fish and Wildlife Service (2020) California Condor Recovery Program 2020 Annual Population Status . Available from: https://www.fws.gov/sites/default/files/documents/2020-California-Condor-Population-Status.pdf (Accessed 28th September 2024). Project Gallery

Evaluating the advantages and disadvantages of gentrification in the context of health Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link How does moving houses impact your health and well-being? 13/03/25, 11:41 Last updated: Published: 13/07/24, 11:02 Evaluating the advantages and disadvantages of gentrification in the context of health Introduction According to the World Health Organization (WHO), health is “a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity". Another way to define health is an individual being in a condition of equilibrium within themselves and the surrounding environment, which includes their social interactions and other factors. Reflecting on historical views of health, ancient Indian and Chinese medicine and society in Ancient Greece thought of health as harmony between a person and their environment, which underlines the cohesion between the soul and body; this is similar to the WHO’s definition of health. Considering these ideas, one key determinant of health is gentrification (see Figure 1 ). It was first defined in 1964 by British sociologist Ruth Glass, who witnessed the dilapidated houses in the London Borough of Islington being taken over and renovated by middle-class proprietors. The broader consequences of gentrification include enhanced living conditions for the residents, differences in ownership prerequisites, increased prices of land and houses, and transformations in the social class structure. Also, these changes cause lower-income inhabitants to be pushed out or go to poorer neighbourhoods, and the conditions in these neighbourhoods, which can include racial separation, lead to inequities and discrepancies in health. For example, a systematic review discovered that elderly and Black residents were affected more by gentrification compared to younger and White citizens; this highlights the importance of support and interventions for specific populations during urban renewal. Given the knowledge provided above, this article will delve further into the advantages and disadvantages of gentrification in the context of health outcomes. Advantages of gentrification Gentrification does have its benefits. Firstly, it is positively linked with collective efficacy, which is about enhancing social cohesion within neighbourhoods and maintaining etiquette; this has health benefits for residents, like decreased rates of obesity, sexually transmitted diseases, and all-cause mortality. Another advantage of gentrification is the possibility of economic growth because as more affluent tenants move into specific neighbourhoods, they can bring companies, assets, and an increased demand for local goods and services, creating more jobs in the area for residents. Additionally, gentrification can be attributed to decreased crime rates in newly developed areas because the inflow of wealthier citizens often conveys a more substantial sense of community and investment in regional security standards. Therefore, this revitalised feeling of safety can make these neighbourhoods more appealing to existing and new inhabitants, which leads to further economic development. Moreover, reducing crime can improve health outcomes by reducing stress and anxiety levels among residents, for example. As a result, the community's general well-being can develop, leading to healthier lifestyle choices and more lively neighbourhoods. Furthermore, the longer a person lives in a gentrifying neighbourhood, the better their self-reported health, which does not differ by race or ethnicity, as observed in Los Angeles. Disadvantages of gentrification However, it is also essential to mention the drawbacks of gentrification, which are more numerous. In a qualitative study involving elderly participants, for example, one of them stated that, “The cost of living increases, but the money that people get by the end of the month is the same, this concerning those … even retired people, and people receiving the minimum wage, the minimum wage increases x every year, isn’t it? But it is not enough”. Elderly residents in Barcelona faced comparable challenges of residential displacement between 2011 and 2017 due to younger adults with higher incomes and those pursuing university education moving into the city. These cases spotlight how gentrification can raise the cost of living without an associated boost in earnings, making it problematic for people with lower incomes or vulnerable individuals to live in these areas. Likewise, a census from gentrified neighbourhoods in Pittsburgh showed that participants more typically conveyed negative health changes and reduced resources. Additionally, one study examined qualitative data from 14 cities in Europe and North America and commonly noticed that gentrification negatively affects the health of historically marginalised communities. These include threats to housing and monetary protection, socio-cultural expulsion, loss of services and conveniences, and raised chances of criminal behaviour and compromised public security. This can be equally observed during green gentrification, where longtime historically marginalised inhabitants feel excluded from green or natural spaces, and are less likely to use them compared to newer residents. To mitigate these negative impacts of gentrification, inclusive urban renewal guidelines should be drafted that consider vulnerable populations to boost health benefits through physical and social improvements. The first step would be to provide residents with enough information and establish trust between them and the local authorities because any inequality in providing social options dramatically affects people’s health-related behaviours. Intriguingly, gentrification has been shown to increase the opportunity for exposure to tick-borne pathogens by populations staying in place, displacement within urban areas, and suburban removal. This increases tick-borne disease risk, which poses a health hazard to impacted residents ( Figure 2 ). As for mental health, research has indicated that residing in gentrified areas is linked to greater levels of anxiety and depression in older adults and children. Additionally, one study found young people encountered spatial disconnection and affective exclusion due to gentrification and felt disoriented by the quickness of transition. Therefore, all of these problems associated with gentrification reveal that it can harm public health and well-being, aggravating disparities and creating feelings of isolation and aloneness in impacted communities. Conclusion Gentrification is a complicated and controversial approach that has noteworthy consequences for the health of neighbourhoods. Its advantages include enhanced infrastructure and boosted economic prospects, potentially leading to fairer access to healthcare services and improved health outcomes for residents. However, gentrification often leads to removal and the loss of affordable housing, which can harm the health of vulnerable populations. Therefore, it is vital for policymakers and stakeholders to carefully evaluate the likely health effects of gentrification and enforce alleviation strategies to safeguard the well-being of all citizens (see Table 1 ). Written by Sam Jarada Related articles: A perspective on well-being / Life under occupation REFERENCES WHO. Health and Well-Being. Who.int . 2015. Available from: https://www.who.int/data/gho/data/major-themes/health-and-well-being Sartorius N. The meanings of health and its promotion. Croatian Medical Journal. 2006;47(4):662–4. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2080455/ Krahn GL, Robinson A, Murray AJ, Havercamp SM, Havercamp S, Andridge R, et al. It’s time to Reconsider How We Define Health: Perspective from disability and chronic condition. Disability and Health Journal. 2021 Jun;14(4):101129. Available from: https://www.sciencedirect.com/science/article/pii/S1936657421000753 Svalastog AL, Donev D, Jahren Kristoffersen N, Gajović S. Concepts and Definitions of Health and health-related Values in the Knowledge Landscapes of the Digital Society. Croatian Medical Journal. 2017 Dec;58(6):431–5. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778676/ Foryś I. Gentrification on the Example of Suburban Parts of the Szczecin Urban Agglomeration. remav. 2013 Sep 1;21(3):5–14. Uribe-Toril J, Ruiz-Real J, de Pablo Valenciano J. Gentrification as an Emerging Source of Environmental Research. Sustainability. 2018 Dec 19;10(12):4847. Schnake-Mahl AS, Jahn JL, Subramanian SV, Waters MC, Arcaya M. Gentrification, Neighborhood Change, and Population Health: a Systematic Review. Journal of Urban Health. 2020 Jan 14;97(1):1–25. 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 21/02/25, 12:17 Last updated: Published: 30/04/23, 10:55 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

Revolutionising drug discovery Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link A breakthrough procedure for efficient and effective development 27/02/25, 11:33 Last updated: Published: 07/01/24, 14:05 Revolutionising drug discovery Discover how researchers have transformed the early stages of drug development with a ground-breaking test that identifies the most promising compounds. "Saving time and resources by focusing on the most potential compounds". Researchers at the Centre for Cancer Drug Discovery at The Institute of Cancer Research (ICR), London have made a significant breakthrough in the field of drug discovery. Their new investigative procedure promises to revolutionize the early stages of drug development by making it more efficient and effective. This ground-breaking test allows scientists to identify new biologically active compounds with the highest potential, saving valuable time and resources. Thanks to this procedure, researchers worldwide can now select only the most promising compounds to develop into effective medications. The study, funded by Cancer Research UK, has been published in the prestigious Journal of Medicinal Chemistry, highlighting its importance and impact on the field. A new approach to fragment-based drug discovery Fragment-based drug discovery has become the standard method for identifying the starting point of a drug discovery program. Scientists screen libraries of compounds, known as fragments, to determine their interaction with a potential anti-cancer target. Previously, scientists could only qualify the interactions between fragments and target proteins as a simple "yes" or "no". However, weak, or nonspecific interactions were challenging to evaluate accurately. Now, thanks to this latest research, researchers have developed a quantitative approach to measure the strength of these interactions. By ranking the fragments based on their interaction strength, research teams can confidently identify the most active compounds to move forward in the drug development process. This additional information allows scientists to refine the selected fragments by optimizing their shape, combining them with other fragments, or both. The result is a more streamlined and efficient drug discovery workflow. Realising the potential of the new procedure Dr. Maggie Liu, the first author of the study and a Senior Scientific Officer at the ICR, expressed confidence that this new procedure will become an integral part of the standard drug discovery workflow. The method is accessible to any team with the right equipment, providing a valuable tool for the wider drug discovery community. The ICR has already started follow-up work on one of the identified fragments using this new test. They plan to utilize this procedure for all future projects, recognizing its potential to accelerate the development of life-saving drugs. Compounds discovered from fragment-based drug discovery (FBDD) and their potential effects FBDD has emerged as an effective strategy in drug discovery, leading to the identification of several compounds with promising potential, including: 1. Vemurafenib: FDA approved in 2011, Vemurafenib has shown efficacy against specific targets, potentially offering treatment options for certain conditions. 2. Venetoclax: Another FBDD-derived drug, Venetoclax, received FDA approval in 2016. It has demonstrated positive outcomes in clinical trials, indicating its potential as a therapeutic agent. 3. Pexidartinib: Approved in 2019, Pexidartinib is a fragment-derived drug that has exhibited promising effects against its intended targets. 4. Erdafitinib: Similarly, Erdafitinib, developed through FBDD, obtained FDA approval in 2019. It has shown potential in clinical trials, highlighting its significance as a therapeutic option. 5. Sotorasib: This compound, approved in 2021, is another example of a fragment-derived drug with potential therapeutic benefits against specific targets. 6. Asciminib: Lastly, Asciminib, also approved in 2021, is a fragment-based drug that has demonstrated efficacy in clinical trials, showcasing its potential as a therapeutic intervention. These compounds represent a fraction of the molecules discovered through FBDD, and their effects vary depending on the specific targets they interact with. Further research and clinical trials are necessary to fully understand the therapeutic potential of these compounds and their broader impact on various diseases and conditions. Testing the R2KD tool Dr. Liu and her team successfully used the R2KD tool to identify new biologically active compounds. This tool utilizes a ligand-observed nuclear magnetic resonance (LONMR) approach, similar to an MRI scanner, to observe fragment interactions. By measuring the transverse relaxation rate (R2) of the fragments, which indicates their speed in the solution, the researchers could determine the fragments' interaction with the target protein. They then applied a new mathematical formulation to calculate a binding affinity value (Kd) for each fragment and compare their Kd values. This allowed them to identify the fragments with the strongest interactions. The researchers named their test 'R2KD'; based on these steps. By using this method, scientists can now quantitatively determine the binding affinity of fragments, which helps in selecting compounds with the most potential for further development. This new procedure makes the early stages of drug discovery more efficient, saving time and resources by focusing on the most promising compounds. Written by Sara Maria Majernikova Related articles: AI in drug discovery / AI in medicinal chemistry / A breakthrough in prostate cancer treatment / Arginine and tumour growth Project Gallery

Pathology and promising therapeutics Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Secondary bone cancer 24/09/24, 13:05 Last updated: Published: 13/12/23, 17:27 Pathology and promising therapeutics Introduction: what is secondary bone cancer? Secondary bone cancer occurs when cancer cells spread to the bones from a tumour that started somewhere else in the body. The site where the tumour first develops is called primary cancer. Cancer cells can break away from the primary cancer, travel through the bloodstream or lymphatic system, and establish secondary cancers, known as metastasis. Bones are among the most common sites to which cancer can spread. Most type of cancer has the potential to metastasise to the bones, with the most frequent occurrences seen in prostate, breast, lung, thyroid, kidney, and myeloma cancers. Throughout the literature, secondary cancer in the bones is referred to as bone secondaries or bone metastases. The most common areas of secondary bone cancer are the spine, ribs, pelvis, humerus (upper bone of the arm), femur (upper bone of the leg) and skull. There are two main types of bone cancer referred to as osteolytic and osteoblastic metastases. In osteolytic metastases, cancer cells break down the bone, leading to significant weakening. This type of metastasis is more common than osteoblastic metastases and often occurs when breast cancer spreads to the bone. In osteoblastic metastases, cancer cells invade the bone and stimulate excessive bone cell formation. This process results in the bone becoming very dense (sclerotic). Osteoblastic metastases frequently occur when prostate cancer spreads to the bone. Although new bone forms, it grows abnormally, which weakens the overall bone structure. Hormone therapy Like primary bone cancer, treatment for secondary bone cancer includes surgical excision, chemotherapy, and radiation therapy. Treatment for secondary bone cancer aims to control the cancer growth and symptoms. Treatment depends on several factors, including the type of primary cancer, previous treatment, the number of bones affected by cancer, whether cancer has spread to other body parts, overall health, and symptoms. Breast and prostate cancers rely on hormones for their growth. Reducing hormone levels in the body can be effective in managing the proliferation of secondary cancer. Hormone therapy, also known as endocrine therapy, uses synthetic hormones to inhibit the impact of the body’s innate hormones. Typical side effects include hot flashes, mood fluctuations, changes in weight, and sweating. Bisphosphonates Bone is a dynamic tissue with a continuous process of bone formation and resorption. Osteoclasts are cells responsible for breaking down bone tissue. In secondary bone cancer, cancer cells often produce substances that stimulate the activity of osteoclasts. This leads to elevated levels of calcium in the blood (hypercalcemia), resulting in feelings of nausea and excessive thirst. Treating secondary bone cancer involves strengthening bones, alleviating bone pain and managing hypercalcaemia). One option for bone-strengthening is bisphosphonates. Bisphosphonates can be administered orally or intravenously. They have been in clinical practice for over 50 years and are used to treat metabolic bone diseases, osteoporosis, osteolytic metastases, and hypercalcaemia. These compounds selectively target osteoclasts to inhibit their function. Bisphosphonates can be classified into two pharmacologic categories based on their mechanism of action. Nitrogen-containing bisphosphonates, the most potent class, function by suppressing the activity of farnesyl pyrophosphate synthase, a key factor in facilitating the binding of osteoclasts to bone. Consequently, this interference causes the detachment of osteoclasts from the bone surface, effectively impeding the process of bone resorption. Examples of these bisphosphonates include alendronate and zoledronate. Bisphosphonates without nitrogen in their chemical structure are metabolised intracellularly to form an analogue of adenosine triphosphate (ATP), known as 5'-triphosphate pyrophosphate (ApppI). ApppI is a non-functional molecule that disrupts cellular energy metabolism, leading to osteoclast cell death (apoptosis) and, consequently, reduced bone resorption. Examples of these bisphosphonates include etidronate and clodronate. Non-nitrogen-containing bisphosphonates can inhibit bone mineralisation and cause osteomalacia, a condition characterised by bones becoming soft and weak. Due to these considerations, they are not widely utilised. Denosumab Denosumab is another option for bone strengthening. It is administered as an injection under the skin (subcutaneously). Denosumab is a human monoclonal antibody that inhibits RANKL to prevent osteoclast-mediated bone resorption. Denosumab-mediated RANKL inhibition hinders osteoclast maturation, function, and survival in contrast to bisphosphonates, which bind to bone minerals and are absorbed by mature osteoclasts. In some studies, Denosumab demonstrated equal or superior efficacy compared to bisphosphonates in preventing skeletal-related events (SREs) associated with bone metastasis. Denosumab’s mechanism of action provides a targeted approach that may offer benefits for specific populations, such as patients with renal impairment. Bisphosphonates are excreted from the human body by the kidneys. A study by Robinson and colleagues demonstrated that bisphosphonate users had a 14% higher risk of chronic kidney disease (CKD) stage progression (including dialysis and transplant) than non-users. On the other hand, denosumab is independent of renal function and less likely to promote deteriorations in kidney function. Take-home message Secondary bone cancer, resulting from the spread of cancer cells to the bones, poses challenges across various cancers. Two main types, osteolytic and osteoblastic metastases, impact bone structure differently. Hormone therapy, bisphosphonates, and Denosumab have shown promising results and offer effective management of secondary bone cancers. Ultimately, the decision between treatments should be made in consultation with a healthcare professional who can evaluate the specific clinical situation and individual patient factors. The choice should be tailored to meet the patient’s needs and treatment goals. Written by Favour Felix-Ilemhenbhio Related article: Bone cancer Project Gallery

Preserving trust and exposing betrayal Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Uncovering the Disturbing World of Healthcare Serial Killers 17/02/25, 14:53 Last updated: Published: 25/02/24, 15:08 Preserving trust and exposing betrayal Background We depend heavily on medical professionals during our most defenceless and vulnerable moments, trusting them with our well-being. However, what would happen if this trust was broken? What if the medical professionals were to pose harm rather than fulfil their intended function as protectors? Healthcare serial killers are one of the most disturbing subsets of serial killers - the name itself suggests that individuals within the healthcare industry exploit their position to murder patients. True crime and media often go hand in hand in the modern era. There are many web series, TV dramas, and movies that delve into real-life narratives. Accumulating over 68.31 million hours watched, Netflix's film "The Good Nurse" in 2022, depicts the story of Charles Cullen, a figure recognised as one of the most prolific serial killers in American history. The film quickly rose to prominence and became the best-performing English-language film production on the platform. This phenomenon in media underscores a broader pattern wherein the portrayal of serial killers becomes increasingly prevalent within popular culture. Motives Criminologists and true crime filmmakers engaged in extensive efforts to figure out what motivates serial killers to carry out such horrific crimes for decades. The motives behind killings are diverse, complex and sometimes unknown. Some perpetrators may attempt to justify their actions by claiming to ease the patient's suffering under the guise of “mercy killing”. Others can be driven by the desire to be praised, to exert power or control over the patient, or to gain financial benefits. For example, Dr. Harold Shipman, a British doctor killed over 200 patients, primarily driven by sadistic motives. His misdeeds were ultimately exposed when he attempted to forge the will of one of his victims. Key Traits and Methods Although it might be tempting to create a list of characteristics typical of healthcare serial killers, no universally applicable formula defines their personalities. However, according to research by Yardley, E., and Wilson, D. (2016), attention-seeking, strange behaviour when a patient dies, and frequent changes in hospital working locations are characteristics that healthcare serial killers frequently exhibit. Furthermore, the study conducted by Birmingham City University criminologists shows that the most popular technique employed by healthcare serial killers is poisoning, specifically through insulin overdose. Notably, insulin overdose was the principal method employed by 25% of healthcare serial killers. For instance, in the case of British nurse Lucy Letby, who was given a life sentence for killing seven infants and attempting to murder six others, the use of an insulin overdose was a notable method employed. Ethics Examining the ethical implications of healthcare serial killing is essential, as it involves the breach of trust and violation of core principles of the healthcare profession. The relationship between a medical professional and a patient is based solely on trust, which healthcare serial killers have exploited. What's worse is that medical professionals frequently target elderly, chronically ill, or vulnerable patients, highlighting significant ethical issues. Challenges Detecting healthcare serial killers is difficult, primarily because their victims are frequently elderly or suffering from chronic illnesses. Investigations typically stem from an unusually high number of deaths rather than patient or family complaints. Even if the police initiate an investigation, it may be too late to collect physical evidence, as bodies may have been cremated or significantly decomposed, leaving no trace of substances in the patients' systems. Furthermore, in rare cases where a medical professional faces charges, they may use defences such as assisted suicides or attribute deaths to unintentional medical errors, potentially resulting in reduced sentences or lesser degrees of homicide . Conclusion Healthcare serial killers are a deeply disturbing phenomenon within the medical profession. The idea that people upon whom we rely on to take care of us can occasionally exhibit malevolence is extremely unsettling. By employing research to understand the existence of serial killers in the healthcare industry, we can address the many questions that surround their behaviour. Studying the motive behind such crimes, looking at the key traits and methods, and addressing the challenges associated with identifying such perpetrators provide insights crucial for safeguarding the community of patients who are at risk and preserving the core moral principles of the medical field. Let’s conclude by saying that the way that healthcare serial killings are portrayed in popular media is a clear reminder of the moral and professional obligations inherent in the provision of healthcare. Written by Prabha Rana Related articles: Neurology of serial killers / Intern Blues References ‘The True Story Behind Netflix’s The Good Nurse’. TIME, 27 Oct. 2022, https://time.com/6225730/the-good-nurse-true-story-netflix/ . Menshawey, Rahma, and Esraa Menshawey. ‘Brave Clarice-Healthcare Serial Killers, Patterns, Motives, and Solutions’. Forensic Science, Medicine, and Pathology, vol. 19, no. 3, Sept. 2023, pp. 452–63. PubMed, https://doi.org/10.1007/s12024-022-00556-4 . Tinning, Danielle. ‘Meet The British Physician Who Killed Hundreds Of His Patients — On Purpose’. All That’s Interesting, 21 Apr. 2023, https://allthatsinteresting.com/haroldshipman . Guy, Fiona. ‘Medical Serial Killers: The So-Called Angels of Mercy’. Crime Traveller, 27 June 2018, https://www.crimetraveller.org/2018/06/healthcare-medical-serial-killers/ . Townsend, Mark. ‘Study Identifies Key Traits and Methods of Serial Killer Nurses’. The Guardian, 22 Nov. 2014. The Guardian, https://www.theguardian.com/uknews/2014/nov/22/study-identified-key-traits-serial-killer-nurses . Project Gallery

From the eyes of a chemist Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Polypharmacy: the complex landscape of multiple medications 21/10/24, 14:40 Last updated: Published: 21/09/24, 15:48 From the eyes of a chemist The concurrent use of many medications by a patient, known as polypharmacy, poses a complex challenge to modern healthcare, especially for the elderly and those with chronic diseases. Polypharmacy raises the risk of adverse drug responses, drug interactions, and medication non-adherence, even though it is essential for managing complicated health concerns. To maximise patient outcomes and guarantee safe treatment regimens, it is crucial to recognise the chemical interactions and effects of different medications. The Chemistry Behind Polypharmacy Polypharmacy stems from the intricate interactions between several chemicals in the human body. Every drug has unique chemical components intended to interact with biological targets in order to provide therapeutic benefits. Nevertheless, when several medications are taken at once, their combinations may have unexpected effects. Understanding polypharmacy requires a thorough understanding of pharmacokinetics—the way the body absorbs, distributes, metabolises, and excretes medications—and pharmacodynamics—the effects of pharmaceuticals on the body. For example, some pharmaceuticals may cause or inhibit the enzymes that metabolise other drugs, changing the levels of the drug and possibly increasing its toxicity or decreasing its effectiveness. Analytical Methods in Polypharmacy Management Chemistry offers a number of analytical and instrumental techniques for efficient polypharmacy management. Drug levels in the blood are tracked using methods like mass spectrometry (MS) and high-performance liquid chromatography (HPLC) to make sure they stay within therapeutic ranges. These techniques support dose modifications by identifying possible medication interactions. Furthermore, it is impossible to exaggerate the importance of chemistry in the creation of drug interaction databases and predictive modelling instruments. By helping medical professionals foresee and minimise harmful medication interactions, these materials help to ensure patient safety. The Role of Healthcare Professionals To successfully manage the complexity of polypharmacy, healthcare professionals—including physicians, chemists, and nurses—need to have a solid understanding of chemistry. Their expertise is essential for assessing each drug's requirement, taking possible interactions into account, and coming up with methods to make drug regimens easier to follow. Managing polypharmacy is especially important for chemists. They assess patients' prescriptions, look for any interactions, and suggest changes or substitutes using their knowledge of medicinal chemistry. Pharmacists who participate in collaborative care can greatly lower the hazards related to polypharmacy. Innovations in Medication Management Chemistry-driven advances in medical technology are improving polypharmacy management. Real-time alerts regarding potential drug interactions can be provided to prescribers through computerised physician order entry (CPOE) systems that are coupled with clinical decision support systems (CDSS). Optimising polypharmacy may also be possible with the emergence of personalised medicine, which adjusts drug regimens according to a patient's genetic profile. Conclusion Polypharmacy remains a significant challenge in healthcare, demanding a comprehensive understanding of chemistry and pharmacology to manage effectively. Healthcare practitioners can minimise the hazards associated with several medications and provide safer and enhanced patient care by utilising modern analytical methods, prediction technologies, and multidisciplinary teamwork. Written by Laura K Project Gallery