Epidemiology
In 2019 alone, roughly 236,000 people died from drowning, thereby causing it to be the third leading cause of unintentional death globally trailing only traffic injuries and falls.In many countries, drowning is one of the main causes of preventable death for children under 12 years old. In the United States in 2006, 1100 people under 20 years of age died from drowning. The United Kingdom has 450 drownings per year, or 1 per 150,000, whereas in the United States, there are about 6,500 drownings yearly, around 1 per 50,000. In Asia suffocation and drowning were the leading causes of preventable death for children under five years of age; a 2008 report by UNICEF found that in Bangladesh, for instance, 46 children drown each day.Due to a generally increased likelihood for risk-taking, males are four times more likely to have submersion injuries.In the fishing industry, the largest group of drownings is associated with vessel disasters in bad weather, followed by man-overboard incidents and boarding accidents at night, either in foreign ports or under the influence of alcohol. Scuba diving deaths are estimated at 700 to 800 per year, associated with inadequate training and experience, exhaustion, panic, carelessness and barotrauma. South Asia
Deaths due to drowning is high in the South Asian region with India, China, Pakistan and Bangladesh accounting for up to 52% of the global deaths.
Function, mechanism, signalling pathway
Members of interleukin-1 receptor (Il-1R) and the Toll-like receptor superfamily share an intracytoplasmic Toll-IL-1 receptor (TIR) domain, which mediates recruitment of the interleukin-1 receptor-associated kinase (IRAK) complex via TIR-containing adapter molecules. The TIR-IRAK signaling pathway appears to be crucial for protective immunity against specific bacteria but is redundant against most other microorganisms. IRAK4 is considered the “master IRAK” in the mammalian IRAK family because it is the only component in the IL-1/TLR signalling pathway that is absolutely crucial to its functioning. When one of these pathways is stimulated, the cell is triggered to release proinflammatory signals and to trigger innate immune actions. The loss of IRAK4, or its intrinsic kinase activity, can entirely stop signalling through these pathways.IRAK4 is involved in signal transduction pathways stimulated by the cellular receptors belonging to the Toll/Interleukin-1 receptor superfamily. The Toll-Like Receptors (TLRs) are stimulated by recognition of pathogen-associated molecular patterns (PAMPS), whereas members of the IL-1R family are stimulated by cytokines. Both play an essential role in the immune response. The ligand binding causes conformational changes to the intracellular domain which allows for the recruitment of scaffolding proteins. One of these proteins, MyD88, uses its death domains to recruit, orient, and activate IRAK4. IRAK2 can then be phosphorylated and joins with IRAK4 and MyD88 to form the myddosome complex, which further phosphorylates and recruits IRAK1. The myddosome complex and IRAK1 recruit and activate TNF receptor-associated factor 6 (TRAF6), a ubiquitin protein ligase.