Innate immune responses are tightly regulated by various pathways to control infections and maintain homeostasis. One of these pathways, the inflammasome pathway, activates a family of cysteine proteases called inflammatory caspases. They orchestrate an immune response by cleaving specific cellular substrates. Canonical inflammasomes activate caspase-1, whereas non-canonical inflammasomes activate caspase-4 and -5 in humans and caspase-11 in mice. Caspases are highly specific enzymes that select their substrates through diverse mechanisms. During inflammation, caspase activity is responsible for the secretion of inflammatory cytokines and the execution of a form of lytic and inflammatory cell death called pyroptosis. This review aims to bring together our current knowledge of the biochemical processes behind inflammatory caspase activation, substrate specificity, and substrate signalling.

PurposeDecontamination following chemical, biological, radiological and nuclear (CBRN)/Hazmat incidents is a critical activity carried out in order to mitigate and contain the risk posed by any hazardous materials involved. Human behaviour plays a crucial role in such incidents, as casualties will have little understanding of the situation they find themselves in, leading to uncertainty in what actions to take. This will result in very difficult circumstances within which first responders must operate. However, the importance of human behaviour appears to be a fundamental element being missed in the preparation, training and planning assumptions being made by emergency services and planners in preparation for these events.Design/methodology/approachThis paper looks to understand the scope of this omission by reviewing relevant literature on the subject and engaging with Fire and Rescue Service personnel and managers in the UK. This study utilised semi-structured interviews with 10 Fire and Rescue Service Mass Decontamination Operatives, four Fire and Rescue Service Hazardous Material Advisers and three Fire and Rescue Service Strategic Officers participating. These interviews were then analysed using a thematic framework to identified key themes from the research which were then validated using two independent researchers to provide an inter-rater reliability measure. Finally, a follow-up validation questionnaire was also developed to test the validity of the themes identified and this was completed by another with 36 Fire and Rescue Service Mass Decontamination Operatives.FindingsBoth the literature review and interviews undertaken with emergency responders and mangers demonstrated the crucial importance of accounting for behavioural aspects in these situations especially in regards to the likely levels of compliance to be expected by responders and the potential problem of casualties not remaining at the scene of an incident to undergo decontamination.Originality/valueThis research identifies a number of key themes so far not recognized through any other research and in doing so offers insights into potential flaws in the UK Fire and Rescue Service response planning for CBRN/Hazmat incidents requiring mass decontamination. It is intended that this research will inform further study into the areas identified in order to ensure gaps in planning, training and strategies for mass decontamination operations can be more fully informed and if required allow for a more effective response.

Cellular senescence is a state of permanent cell cycle arrest triggered by various intrinsic and extrinsic stressors. Cellular senescence results in impaired tissue repair and remodeling, loss of physiological integrity, organ dysfunction, and changes in the secretome. The systemic accumulation of senescence cells has been observed in many age-related diseases. Likewise, cellular senescence has been implicated as a risk factor and driving mechanism in chronic obstructive pulmonary disease (COPD) pathogenesis. Airway epithelium exhibits hallmark features of senescence in COPD including activation of the p53/p21WAF1/CIP1 and p16INK4A/RB pathways, leading to cell cycle arrest. Airway epithelial senescent cells secrete an array of inflammatory mediators, the so-called senescence-associated secretory phenotype (SASP), leading to a persistent low-grade chronic inflammation in COPD. SASP further promotes senescence in an autocrine and paracrine manner, potentially contributing to the onset and progression of COPD. In addition, cellular senescence in COPD airway epithelium is associated with telomere dysfunction, DNA damage, and oxidative stress. This review discusses the potential mechanisms of airway epithelial cell senescence in COPD, the impact of cellular senescence on the development and severity of the disease, and highlights potential targets for modulating cellular senescence in airway epithelium as a potential therapeutic approach in COPD.

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