Assessing Physical Activity Using Accelerometers in Youth with Duchenne Muscular Dystrophy.

BACKGROUND: Physical activity, assessed by accelerometers, has been proposed as a quantitative outcome measure for patients with DMD, but research is limitedObjective:To assess the total amount and patterns of physical activity in patients with DMD using accelerometers. METHODS: Physical activity was assessed in patients with DMD (n = 49, 13.6±4.0-year-old) and age- and sex-matched healthy controls (n = 15, 14.0±2.3-year-old) using wrist- and ankle-worn accelerometers. To assess the amount of activity, accelerometer recordings were converted into acceleration estimates (counts/min). Patterns of activity were assessed as the time that participants spent in sedentary, low-intensity, and moderate-to-vigorous physical activity categories. The sedentary category was divided into three (sedentary -1, -2, and -3) and the low-intensity into two (low-intensity-1, and -2) subcategories. RESULTS: Physical activity across intensity categories differed between study groups (p < 0.001). Patients with DMD spent on average 98.8% of their daytime in the sedentary and low-intensity categories. Compared to non-ambulatory, ambulatory patients spent more time in sedentary-3 and low-intensity-2 subcategories (p < 0.001). Amount of activity was lower in all patients than controls (p < 0.05) and in non-ambulatory than ambulatory patients and controls (p < 0.001), but similar between ambulatory patients and controls. Activity measures in patients were significantly affected by age and ambulation status (p < 0.05) but not corticosteroid use. CONCLUSION: Patients with DMD spent most of their daytime in sedentary and low-intensity activities. Dividing these intensities into three and two subcategories, respectively, allows better characterization of activity patterns in DMD. Ambulation status and age but not corticosteroid use affected activity measures in patients with DMD.

Effector Protein Cig2 Decreases Host Tolerance of Infection by Directing Constitutive Fusion of Autophagosomes with the Coxiella-Containing Vacuole.

UNLABELLED: Coxiella burnetii replicates in an acidified lysosome-derived vacuole. Biogenesis of the Coxiella-containing vacuole (CCV) requires bacterial effector proteins delivered into host cells by the Dot/Icm secretion system. Genetic and cell biological analysis revealed that an effector protein called Cig2 promotes constitutive fusion of autophagosomes with the CCV to maintain this compartment in an autolysosomal stage of maturation. This distinguishes the CCV from other pathogen-containing vacuoles that are targeted by the host autophagy pathway, which typically confers host resistance to infection by delivering the pathogen to a toxic lysosomal environment. By maintaining the CCV in an autolysosomal stage of maturation, Cig2 enabled CCV homotypic fusion and enhanced bacterial virulence in the Galleria mellonella (wax moth) model of infection by a mechanism that decreases host tolerance. Thus, C. burnetii residence in an autolysosomal organelle alters host tolerance of infection, which indicates that Cig2-dependent manipulation of a lysosome-derived vacuole influences the host response to infection. IMPORTANCE: Coxiella burnetii is an obligate, intracellular bacterial pathogen that replicates inside a unique, lysosome-like compartment called the Coxiella-containing vacuole (CCV). Over 130 bacterial effector proteins are delivered into the host cell cytosol by the C. burnetii Dot/Icm type IV secretion system. Although the Dot/Icm system is essential for pathogenesis, the functions of most effectors remain unknown. Here we show that the effector protein Cig2 is essential for converting the CCV to an organelle that is similar to the autolysosome. Cig2 function promotes constitutive fusion between the CCV and autophagosomes generated by selective autophagy. Cig2-directed biogenesis of an autolysosomal vacuole is essential for the unique fusogenic properties of the CCV and for virulence in an animal model of disease. This work highlights how bacterial subversion of the host autophagy pathway can influence the cell biological properties of the CCV and influence the host response to infection.