Unraveling the effect of intra- and intercellular processes on acetaminophen-induced liver injury.

In high dosages, acetaminophen (APAP) can cause severe liver damage, but susceptibility to liver failure varies across individuals and is influenced by factors such as health status. Because APAP-induced liver injury and recovery is regulated by an intricate system of intra- and extracellular molecular signaling, we here aim to quantify the importance of specific modules in determining the outcome after an APAP insult and of potential targets for therapies that mitigate adversity. For this purpose, we integrated hepatocellular acetaminophen metabolism, DNA damage response induction and cell fate into a multiscale mechanistic liver lobule model which involves various cell types, such as hepatocytes, residential Kupffer cells and macrophages. Our model simulations show that zonal differences in metabolism and detoxification efficiency are essential determinants of necrotic damage. Moreover, the extent of senescence, which is regulated by intracellular processes and triggered by extracellular signaling, influences the potential to recover. In silico therapies at early and late time points after APAP insult indicated that prevention of necrotic damage is most beneficial for recovery, whereas interference with regulation of senescence promotes regeneration in a less pronounced way.

The use of digital implants for the correction of hammer toe deformity and their potential complications and management.

This manuscript deals with use of silicone implants as part of the correction for hammer toe deformity. A brief description of the historical correction of hammer toe is presented, with emphasis placed on the development and use of silicone prostheses. The surgical procedure is discussed and an overview of the authors' long-term results are included. Analysis of an informal survey taken of several practitioners known to utilize digital implants is also presented. This manuscript primarily focuses on potential complications that may accompany the procedure. Management and prevention of these complications is also discussed.