A further nutrigenomics model named multiple hit extends the second hit model, suggesting that multiple disease biomarkers and factors such as genes and nutrition influence NAFLD and NASH progression. This model attempts to use these factors to predict the impact of lifestyle changes and genetics for the evolution of the NAFLD pathology. Many researchers describe NAFLD as a multisystem disease, as it impacts and is influenced by organs and regulatory pathways other than the liver.The accumulation of senescent cells in the liver is seen in persons with NAFLD. In mice, liver senescent hepatocytes result in increased liver fat deposition. Treatment of NAFLD mice with senolytic agents has been shown to reduce hepatic steatosis.Based on gene knockout studies in murine models, it has been suggested that, among many other pathogenic factors, TGF beta signals may be crucially involved in promoting the progression of NASH. Fructose consumption
Non-alcoholic and alcoholic fatty liver disease share similar histological features, which suggests that they might share common pathogenic pathways. Fructose can cause liver inflammation and addiction similarly to ethanol by using similar metabolic pathways, unlike glucose. Therefore, some researchers argue that non-alcoholic and alcoholic fatty liver diseases are more alike than previously thought. Furthermore, high fructose consumption promotes fat accumulation in the liver by stimulating de novo lipogenesis in the liver and reducing the beta-oxidation of fat. Unlike the sugar glucose, the enzyme fructokinase rapidly metabolizes fructose. This leads to a decreased level of intracellular adenosine triphosphate (ATP).
The shelf-life of AVA is reported to be three years when stored between 2 °C and 8 °C (36 °F and 46 °F) and never frozen. History
Initial research and development (1954-1970)
The vaccine efficacy of AVA in humans was initially established by Philip S. Brachman of the United States Public Health Service (USPHS) in a controlled study undertaken between 1954 and 1959. The study field sites were four wool-sorting mills in the northeastern United States where employees were sometimes exposed to anthrax spores in the course of their work. Over the five years, 379 vaccinees were compared against 414 unvaccinated control subjects. There were 23 cases among controls (5 of them inhalation anthrax) compared with 3 cases among vaccinated (0 inhalation cases). The vaccine was judged to have a 92.5% vaccine efficacy against all types of anthrax experienced. Subsequently, there were no controlled clinical trials in humans of the efficacy of AVA due to the rarity of the condition (especially in the inhalational form) in humans and the ethical inadmissibility of conducting dangerous challenge studies in human subjects. Supportive animal challenge studies were done, however, showing that unvaccinated animals uniformly die whereas vaccinated animals are protected. About 95% of rhesus monkeys (62 of 65) survived challenge, as did 97% of rabbits (114 of 117). Guinea pigs (which are a poorer model for human anthrax than are monkeys or rabbits) showed a 22% protection (19 of 88).