The explanation for these divergent findings is unclear. Importantly, our model combines effects of re-activation of the diaphragm, which ameliorates the activation proteolytic cascade and, in the same time leads to an uncontrolled loading of the diaphragm. Overloading of the diaphragm leads to injury itself and may be existent in our model. Regardless, it seems likely that the mechanism responsible for MV-induced Nutlin-3 reduction in diaphragmatic specific force production is likely due to several changes in diaphragm muscle fibers including oxidative damage to myofibrillar proteins and proteolytic cleavage of sarcomeric structural proteins resulting in a reduced ability for the sarcomere to generate force. In this regard, our data reveal that 24 hours of recovery from MV result in the disappearance of 4- HNE-conjugated proteins in the diaphragm and close correlation between the levels of 4-HNE conjugated proteins and diaphragmatic force in all frequencies. With this reduction in oxidized proteins, we do observe a significant increase in force production after 24 hours of recovery compared to CMV. Importantly, Thomas and colleagues could not detect a decrease in oxidative damage after 4–7 hours of spontaneous breathing although recovery of function occurs. Both studies suggest that oxidative modification of diaphragm proteins is a major, but not solely the explanation for the contractile deficit after MV. Type 1 diabetes is a chronic disease with a preclinical phase characterized by auto-immunity against pancreatic islet cells ultimately leading to absolute insulin deficiency. Interactions between polygenetic susceptibility and one or more triggering environmental factors are assumed to provide the essential components for this T cell mediated auto-immune disease. While the occurrence of childhood diabetes was stable in the first half of the 20th century, in the second half there was a continuous increase in the prevalence and incidence of type 1 diabetes worldwide, despite genetic stability of the genes related to this disease. This increase, therefore, is most likely related to changes in the occurrence of risk factors, both host related and environmental. There have been several studies that focused on the host and environmental risk factors of type 1 diabetes during the prenatal life and early childhood. These studies have shown associations between developing type 1 diabetes and caesarean sections, preeclamptic toxemia, maternal age, birth weight, gestational age, infections, short breast feeding, early exposure to dietary cow’s milk proteins and solid food, deficiency of vitamin D, exposure to toxins like N-nitroso compounds, and neonatal eczema. Although a substantial number of drugs are known to induce hyperglycemia and therefore increasing the risk of diabetes, the influence of medication on the manifestation of type 1 diabetes has not been systematically studied yet. Prior to the clinical presentation of type 1 diabetes there is a highly variable asymptomatic period of beta cell destruction, which can vary between a few months up to several years.