Climate change and healthy ageing: An assessment of the impact of climate hazards on older people

Copyright \ua9 2024 by the Journal of Global Health. All rights reserved. Background: Climate change not only directly impacts older people\u27s longevity but also healthy ageing, which is the process of maintaining physical and mental capacities while optimising functional abilities. The urgency to address both population ageing and climate change necessitates a rethink and assessment of the impact of climate change on older people. This includes identifying what can be done to anticipate, mitigate and adapt to climate change and engage older persons. Methods: A review of climate change and healthy ageing forms the basis of evidence in this report. We developed a comprehensive search to assess current literature, combining terms related to ageing and climate change across four major data sets and assessing articles published up to the end of 2021. Results: We summarised the current and future impact of climate change on older people and developed a framework identifying climate change impacts on older persons, recognising social and environmental determinants of healthy ageing. Major hazards and some key exposure pathways include extreme temperatures, wildfire, drought, flooding, storm and sea level rise, air quality, climate-sensitive infectious diseases, food and water insecurities, health and social care system displacement, migration, and relocation. Strategies to address climate change require interventions to improve systems and infrastructure to reduce vulnerability and increase resilience. As a heterogeneous group, older people\u27s perceptions of climate change should be integrated into climate activism. Increasing climate change literacy among older people and enabling them to promote intergenerational dialogue will drive the development and implementation of equitable solutions. Pathways may operate via direct or indirect exposures, requiring longitudinal studies that enable assessment of exposures and outcomes at multiple time points, and analyses of cumulative impacts of hazards across the life course. Conclusions: The lack of systematic reviews and primary research on the impact of most climate hazards, except for heat, on older people is apparent. Future research should include outcomes beyond mortality and morbidity and assess how older people interact with their environment by focusing on their capacities and optimising abilities for being and doing what they value

Electroporation increases antitumoral efficacy of the bcl-2 antisense G3139 and chemotherapy in a human melanoma xenograft

<p>Abstract</p> <p>Background</p> <p>Nucleic acids designed to modulate the expression of target proteins remain a promising therapeutic strategy in several diseases, including cancer. However, clinical success is limited by the lack of efficient intracellular delivery. In this study we evaluated whether electroporation could increase the delivery of antisense oligodeoxynucleotides against bcl-2 (G3139) as well as the efficacy of combination chemotherapy in human melanoma xenografts.</p> <p>Methods</p> <p>Melanoma-bearing nude mice were treated i.v. with G3139 and/or cisplatin (DDP) followed by the application of trains of electric pulses to tumors. Western blot, immunohistochemistry and real-time PCR were performed to analyze protein and mRNA expression. The effect of electroporation on muscles was determined by histology, while tumor apoptosis and the proliferation index were analyzed by immunohistochemistry. Antisense oligodeoxynucleotides tumor accumulation was measured by FACS and confocal microscopy.</p> <p>Results</p> <p>The G3139/Electroporation combined therapy produced a significant inhibition of tumor growth (TWI, more than 50%) accompanied by a marked tumor re-growth delay (TRD, about 20 days). The efficacy of this treatment was due to the higher G3139 uptake in tumor cells which led to a marked down-regulation of bcl-2 protein expression. Moreover, the G3139/EP combination treatment resulted in an enhanced apoptotic index and a decreased proliferation rate of tumors. Finally, an increased tumor response was observed after treatment with the triple combination G3139/DDP/EP, showing a TWI of about 75% and TRD of 30 days.</p> <p>Conclusions</p> <p>These results demonstrate that electroporation is an effective strategy to improve the delivery of antisense oligodeoxynucleotides within tumor cells <it>in vivo </it>and it may be instrumental in optimizing the response of melanoma to chemotherapy. The high response rate observed in this study suggest to apply this strategy for the treatment of melanoma patients.</p

Prediction in the face of uncertainty: a Monte Carlo-based approach for systems biology of cancer treatment

Cancer is known to be a complex disease and its therapy is difficult. Much information is available on molecules and pathways involved in cancer onset and progression and this data provides a valuable resource for the development of predictive computer models that can help to identify new potential drug targets or to improve therapies. Modeling cancer treatment has to take into account many cellular pathways usually leading to the construction of large mathematical models. The development of such models is complicated by the fact that relevant parameters are either completely unknown, or can at best be measured under highly artificial conditions. Here we propose an approach for constructing predictive models of such complex biological networks in the absence of accurate knowledge on parameter values, and apply this strategy to predict the effects of perturbations induced by anti-cancer drug target inhibitions on an epidermal growth factor (EGF) signaling network. The strategy is based on a Monte Carlo approach, in which the kinetic parameters are repeatedly sampled from specific probability distributions and used for multiple parallel simulations. Simulation results from different forms of the model (e.g., a model that expresses a certain mutation or mutation pattern or the treatment by a certain drug or drug combination) can be compared with the unperturbed control model and used for the prediction of the perturbation effects. This framework opens the way to experiment with complex biological networks in the computer, likely to save costs in drug development and to improve patient therapy