In healthy humans, ventilation is propelled by the rhythmic contraction of the diaphragm, the main muscle of inspiration. In contrast, in patients admitted to the intensive care unit, ventilation is carried out by a machine - to facilitate oxygen uptake in the lungs - and the diaphragm is inactive. However, mechanical ventilation is clearly a two-edged sword: recent studies suggest that during mechanical ventilation the diaphragm rapidly weakens. Thus, prolonged mechanical ventilation may be required because of diaphragm weakness caused by the mechanical ventilation itself. This so-called weaning failure is frequently encountered in ICU patients and contributes to mortality. Diaphragm muscle fiber weakness and ubiquitin-proteasome activation in critically ill patients. Hooijman PE, Beishuizen A, Witt CC, de Waard MC, Girbes AR, Spoelstra-de Man AM, Niessen HW, Manders E, van Hees HW, van den Brom CE, Silderhuis V, Lawlor MW, Labeit S, Stienen GJ, Hartemink KJ, Paul MA, Heunks LM, Ottenheijm CAC. Am J Respir Crit Care Med. 2015 15;191(10):1126-38. Hooijman PE, Paul MA, Stienen GJ, Beishuizen A, Van Hees HW, Singhal S, Bashir M, Budak MT, Morgen J, Barsotti RJ, Levine S, Ottenheijm CAC. Unaffected contractility of diaphragm muscle fibers in humans on mechanical ventilation. Am J Physiol Lung Cell Mol Physiol. 2014 Sep 15;307(6):L460-70. Manders E, Bogaard HJ, M. Handoko, M van de Veerdonk, A Keogh, N Westerhof, G. Stienen, C dos Remedios, M Humbert, P Dorfmüller, E Fadel, C Guignabert, van der Velden J, Noordegraaf A, de Man F, and Ottenheijm CAC. Contractile dysfunction of left ventricular cardiomyocytes in patients with pulmonary arterial hypertension. J Am Coll Cardiol. 2014 Jul 8; 64 (1): 28-37 Hooijman PE, Beishuizen A, de Waard MC, de Man FS, Vermeijden JW, Steenvoorde P, Bouwman RA, Lommen W, van Hees HW, Heunks LM, Dickhoff C, van der Peet DL, Girbes AR, Jasper JR, Malik FI, Stienen GJ, Hartemink KJ, Paul MA, and Ottenheijm CAC. Diaphragm fiber strength is reduced in critically ill patients and restored by a troponin activator. Am J Respir Crit Care Med. 2014 Apr 1;189(7):863-5. doi: 10.1164/rccm.201312-2260LE FS de Man, H van Hees, ML Handoko, H Niessen, I Schalij, P Postmus, N Westerhof, G Stienen, W van der Laarse, A Vonk-Noordegraaf, and Ottenheijm CAC. Diaphragm muscle weakness in Pulmonary Arterial Hypertension. Am J Respir Crit Care Med; 2011. 183(10):1411-8.