Dynamic transcriptomic analysis reveals suppression of PGC1α/ERRα drives perturbed myogenesis in facioscapulohumeral muscular dystrophy

Facioscapulohumeral muscular dystrophy (FSHD) is a prevalent, incurable myopathy, linked to epigenetic de-repression of D4Z4 repeats on chromosome 4q, leading to ectopic DUX4 expression. FSHD patient myoblasts have defective myogenic differentiation, forming smaller myotubes with reduced myosin content. However, molecular mechanisms driving such disrupted myogenesis in FSHD are poorly understood. We performed high-throughput morphological analysis describing FSHD and control myogenesis, revealing altered myogenic differentiation results in hypotrophic myotubes. Employing polynomial models and an empirical Bayes approach, we established eight critical time-points during which human healthy and FSHD myogenesis differ. RNA-sequencing at these eight nodal time-points in triplicate, provided temporal depth for a multivariate regression analysis, allowing assessment of interaction between progression of differentiation and FSHD disease status. Importantly, the unique size and structure of our data permitted identification of many novel FSHD pathomechanisms undetectable by previous approaches. Selected for further analysis here, were pathways that control mitochondria: of interest considering known alterations in mitochondrial structure and function in FSHD muscle, and sensitivity of FSHD cells to oxidative stress. Notably, we identified suppression of mitochondrial biogenesis, in particular via PGC1α, the co-factor and activator of ERRα. PGC1α knock-down caused hypotrophic myotubes to form from healthy myoblasts. Known ERRα agonists and safe food supplements Biochanin A, Genistein or Daidzein, each rescued the hypotrophic FSHD myotube phenotype. Together our work describes transcriptomic changes in high resolution that occur during myogenesis in FSHD ex-vivo, identifying suppression of the PGC1α-ERRα axis leading to perturbed myogenic differentiation, which can effectively be rescued by readily-available food supplements

Author Correction: Scalable and robust SARS-CoV-2 testing in an academic center.

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Comparison of patient doses in interventional radiology procedures performed in two large hospitals in Greece

Purpose of the study was to determine patient doses in the most common interventional radiology (IR) procedures performed in two large Greek hospitals. A total of 164 patients who underwent 4 types of IR procedures were studied. Fluoroscopy time, total exposure time, number of frames, number of runs, radiation field size, and cumulative dose-area product (DAP) were recorded. The median DAP values for carotid arteriography and lower limb arteriography were 66 and 123 Gy cm2 for hospital 'A' and 21 and 49 Gy cm2 for hospital 'B'. For the cerebral arteriographies performed in hospital 'A', the median DAP was 116 Gy cm2 while for the hepatic embolizations performed in hospital 'B', it was 104 Gy cm2. The DAP values observed in hospital 'A' for carotid arteriography and lower limb arteriography were almost three times than those of hospital 'B'. From the data analysis, it is evident that dose optimization in hospital 'A' should be pursued through revision of the techniques used. © The Author 2007. Published by Oxford University Press