Echocardiography practice, training and accreditation in the intensive care: document for the World Interactive Network Focused on Critical Ultrasound (WINFOCUS)

Echocardiography is increasingly used in the management of the critically ill patient as a non-invasive diagnostic and monitoring tool. Whilst in few countries specialized national training schemes for intensive care unit (ICU) echocardiography have been developed, specific guidelines for ICU physicians wishing to incorporate echocardiography into their clinical practice are lacking. Further, existing echocardiography accreditation does not reflect the requirements of the ICU practitioner. The WINFOCUS (World Interactive Network Focused On Critical UltraSound) ECHO-ICU Group drew up a document aimed at providing guidance to individual physicians, trainers and the relevant societies of the requirements for the development of skills in echocardiography in the ICU setting. The document is based on recommendations published by the Royal College of Radiologists, British Society of Echocardiography, European Association of Echocardiography and American Society of Echocardiography, together with international input from established practitioners of ICU echocardiography. The recommendations contained in this document are concerned with theoretical basis of ultrasonography, the practical aspects of building an ICU-based echocardiography service as well as the key components of standard adult TTE and TEE studies to be performed on the ICU. Specific issues regarding echocardiography in different ICU clinical scenarios are then described

The Milky Way's Supermassive Black Hole: How Good a Case Is It?

The compact and, with 4.3+-0.3 million solar masses, very massive object located at the center of the Milky Way is currently the very best candidate for a supermassive black hole (SMBH) in our immediate vicinity. The strongest evidence for this is provided by measurements of stellar orbits, variable X-ray emission, and strongly variable polarized near-infrared emission from the location of the radio source Sagittarius~A* (SgrA*) in the middle of the central stellar cluster. If SgrA* is indeed a SMBH it will, in projection onto the sky, have the largest event horizon and will certainly be the first and most important target of the Event Horizon Telescope (EHT) Very Long Baseline Interferometry (VLBI) observations currently being prepared. These observations in combination with the infrared interferometry experiment GRAVITY at the Very Large Telescope Interferometer (VLTI) and other experiments across the electromagnetic spectrum might yield proof for the presence of a black hole at the center of the Milky Way. It is, however, unclear when the ever mounting evidence for SgrA* being associated with a SMBH will suffice as a convincing proof. Additional compelling evidence may come from future gravitational wave observatories. This manuscript reviews the observational facts, theoretical grounds and conceptual aspects for the case of SgrA* being a black hole. We treat theory and observations in the framework of the philosophical discussions about "(Anti)Realism and Underdetermination", as this line of arguments allows us to describe the situation in observational astrophysics with respect to supermassive black holes. Questions concerning the existence of supermassive black holes and in particular SgrA* are discussed using causation as an indispensable element. We show that the results of our investigation are convincingly mapped out by this combination of concepts.Comment: 64 pages; 13 pages of references; 13 figures; 3 tables; 4 appendices; With minor differences published in -Foundations of Physics- Published by Springer in March 2017 in Foundations of Physics, 47(5), 553-624, here resubmitted with extended abstrac

Corrigendum to "Cardiolipin-deficient cells depend on anaplerotic pathways to ameliorate defective TCA cycle function" [Biochim. Biophys. Acta, Mol. Cell Biol. Lipids 1864/5(2019) 654-661]

The authors regret to report an error in Table 1 of this publication. The mating type of yeast strain BY4741 should have been listed as MATa rather than MATα as printed. All additional information in this table is correct. The authors would like to apologise for any inconvenience caused

Cardiolipin-deficient cells depend on anaplerotic pathways to ameliorate defective TCA cycle function

Previous studies have shown that the cardiolipin (CL)-deficient yeast mutant, crd1Δ has decreased levels of acetyl-CoA and decreased activities of the TCA cycle enzymes aconitase and succinate dehydrogenase. These biochemical phenotypes are expected to lead to defective TCA cycle function. In this study, we report that signaling and anaplerotic metabolic pathways that supplement defects in the TCA cycle are essential in crd1Δ mutant cells. The crd1Δ mutant is synthetically lethal with mutants in the TCA cycle, retrograde (RTG) pathway, glyoxylate cycle, and pyruvate carboxylase 1. Glutamate levels were decreased, and the mutant exhibited glutamate auxotrophy. Glyoxylate cycle genes were up-regulated, and the levels of glyoxylate metabolites succinate and citrate were increased in crd1Δ. Import of acetyl-CoA from the cytosol into mitochondria is essential in crd1Δ as deletion of the carnitine-acetylcarnitine translocase led to lethality in the CL mutant. β-oxidation was functional in the mutant, and oleate supplementation rescued growth defects. These findings suggest that TCA cycle deficiency caused by the absence of CL necessitates activation of anaplerotic pathways to replenish acetyl-CoA and TCA cycle intermediates. Implications for Barth syndrome, a genetic disorder of CL metabolism, are discussed