Increased expression of GDF-15 may mediate ICU-acquired weakness by down-regulating muscle microRNAs.

RATIONALE: The molecular mechanisms underlying the muscle atrophy of intensive care unit-acquired weakness (ICUAW) are poorly understood. We hypothesised that increased circulating and muscle growth and differentiation factor-15 (GDF-15) causes atrophy in ICUAW by changing expression of key microRNAs. OBJECTIVES: To investigate GDF-15 and microRNA expression in patients with ICUAW and to elucidate possible mechanisms by which they cause muscle atrophy in vivo and in vitro. METHODS: In an observational study, 20 patients with ICUAW and seven elective surgical patients (controls) underwent rectus femoris muscle biopsy and blood sampling. mRNA and microRNA expression of target genes were examined in muscle specimens and GDF-15 protein concentration quantified in plasma. The effects of GDF-15 on C2C12 myotubes in vitro were examined. MEASUREMENTS AND MAIN RESULTS: Compared with controls, GDF-15 protein was elevated in plasma (median 7239 vs 2454 pg/mL, p=0.001) and GDF-15 mRNA in the muscle (median twofold increase p=0.006) of patients with ICUAW. The expression of microRNAs involved in muscle homeostasis was significantly lower in the muscle of patients with ICUAW. GDF-15 treatment of C2C12 myotubes significantly elevated expression of muscle atrophy-related genes and down-regulated the expression of muscle microRNAs. miR-181a suppressed transforming growth factor-ß (TGF-ß) responses in C2C12 cells, suggesting increased sensitivity to TGF-ß in ICUAW muscle. Consistent with this suggestion, nuclear phospho-small mothers against decapentaplegic (SMAD) 2/3 was increased in ICUAW muscle. CONCLUSIONS: GDF-15 may increase sensitivity to TGF-ß signalling by suppressing the expression of muscle microRNAs, thereby promoting muscle atrophy in ICUAW. This study identifies both GDF-15 and associated microRNA as potential therapeutic targets.

[Telemedicine: Who, what, with what aids, where, why, how, when?]. / Télémédecine: quis, quid, ubi, quibus auxiliis, cur, quomodo, quando?

Telemedicine can be defined as the practice of medicine or surgery via telecommunication interposition using technologies which permit the exchange of medical information and the application of medical care at a distance. Geographic separation, logistical problems which impede the delivery of care, extreme climactic conditions, artificial environments, or a combination of these parameters may all influence the health of patients and the ability of healthcare professionals to do their work effectively. This article reviews the standards of current telemedical and telesurgical systems, defines target groups who may benefit from such care, and details the technologic requirements of telemetry; it uses selected cases and a review the medical literature. The conclusion focuses on future developments and the potential for further improvements through ongoing research.

[Use of telemedicine in Switzerland]. / Applications de la télémédecine en Suisse.

In the 21st century, telemedicine has become daily business. Nevertheless, they are still a lack of precise definitions of telemedicine. Legal and financial implications of telemedical applications are complex, with lots of local restrictions, far beyond global technological aspects. In the United States, telemedicine is a reality since decades, and is basically defined as the provision of health care when distance separates the participants. Technology and networks for telemedicine are universally globalized, but the legal and financial implications are diametrically more local based. Any CT-scan made at midnight in Switzerland can be accurately assessed within minutes by any Australian radiologist, for whom it will be the morning, and so far around the globe at any time of the day or the night. But how will the billing work intercontinentally? And what about legal implications of this telemedical service? In this paper, we review the actual definitions of telemedicine, check our local legal responsibilities, and present the Tarmed financial positions for billing.