We propose that prolonged CMV causes diaphragm disuse, which, in turn, leads to activation of the ALP through oxidative stress and the induction of the FOXO1 transcription factor.

BackgroundMitochondrial injury develops in skeletal muscles during the course of severe sepsis. Autophagy is a protein and organelle recycling pathway which functions to degrade or recycle unnecessary, redundant, or inefficient cellular components. No information is available regarding the degree of sepsis-induced mitochondrial injury and autophagy in the ventilatory and locomotor muscles. This study tests the hypotheses that the locomotor muscles are more prone to sepsis-induced mitochondrial injury, depressed biogenesis and autophagy induction compared with the ventilatory muscles.Methodology/Principal FindingsAdult male C57/Bl6 mice were injected with i.p. phosphate buffered saline (PBS) or E. coli lipopolysaccharide (LPS, 20 mg/kg) and sacrificed 24 h later. The tibialis anterior (TA), soleus (SOLD) and diaphragm (DIA) muscles were quickly excised and examined for mitochondrial morphological injury, Ca++ retention capacity and biogenesis. Autophagy was detected with electron microscopy, lipidation of Lc3b proteins and by measuring gene expression of several autophagy-related genes. Electron microscopy revealed ultrastructural injuries in the mitochondria of each muscle, however, injuries were more severe in the TA and SOL muscles than they were in the DIA. Gene expressions of nuclear and mitochondrial DNA transcription factors and co-activators (indicators of biogenesis) were significantly depressed in all treated muscles, although to a greater extent in the TA and SOL muscles. Significant autophagosome formation, Lc3b protein lipidation and upregulation of autophagy-related proteins were detected to a greater extent in the TA and SOL muscles and less so in the DIA. Lipidation of Lc3b and the degree of induction of autophagy-related proteins were significantly blunted in mice expressing a muscle-specific IκBα superrepresor.Conclusion/SignificanceWe conclude that locomotor muscles are more prone to sepsis-induced mitochondrial injury, decreased biogenesis and increased autophagy compared with the ventilatory muscles and that autophagy in skeletal muscles during sepsis is regulated in part through the NFκB transcription factor.

The coronavirus disease 2019 (COVID-19) outbreak affects not just populations but also global and local economies and supply chains. The outbreak itself has impacted on production lines and manufacturing capacities. In response to the outbreak, policies have been put in place that blocks the movement of people and materials, causing supply chain disruptions. Mainstream supply chain management has been at a loss in responding to these disruptions, mostly due to a dominant focus on minimizing costs for stable operations, while following lean, just-in-time, and zero-inventory approaches. On the other hand, pandemic response supply chains, and their related supply chain disruptions, share many characteristics with disaster response and thereby with humanitarian supply chains. Much can thus be learned from humanitarian supply chains for managing pandemic-related supply chain disruptions. What is more, facing, and managing, supply chain disruptions can be considered the new norm also in light of other disruptive forces such as climate change, or financial or political crises. This article therefore presents lessons learned from humanitarian supply chains that help mitigate and overcome supply chain disruptions. These lessons not only relate to preparedness and mobilization, but also relate to standardization, innovation, and collaboration. Together, they brace organizations, supply chains, and societies, to manage current and future disruptions.

Resistive breathing induces acute lung injury and inflammation.