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Frataxin (FXN) is a highly conserved mitochondrial protein whose deficiency causes Friedreich's ataxia, a neurodegenerative disease. The precise physiological function of FXN is still unclear; however, there is experimental evidence that the protein is involved in biosynthetic iron-sulfur cluster machinery, redox imbalance, and iron homeostasis. FXN is synthesized in the cytosol and imported into the mitochondria, where it is proteolytically cleaved to the mature form. Its involvement in the redox imbalance suggests that FXN could interact with mitochondrial superoxide dismutase (SOD2), a key enzyme in antioxidant cellular defense. In this work, we use site-directed spin labelling coupled to electron paramagnetic resonance spectroscopy (SDSL-EPR) and fluorescence quenching experiments to investigate the interaction between human FXN and SOD2 in vitro. Spectroscopic data are combined with rigid body protein-protein docking to assess the potential structure of the FXN-SOD2 complex, which leaves the metal binding region of FXN accessible to the solvent. We provide evidence that human FXN interacts with human SOD2 in vitro and that the complex is in fast exchange. This interaction could be relevant during the assembly of iron-sulfur (FeS) clusters and/or their incorporation in proteins when FeS clusters are potentially susceptible to attacks by reactive oxygen species.

Background: Verification of the central venous catheters (CVCs) position by chest X-ray (CXR) is usually performed in the postoperative period with the risk related to possible malposition. This prospective observational study aimed to assess the diagnostic accuracy and reproducibility of ultrasound (US) and "bubble test" to detect malpositions of CVC in the preoperative setting., Methods: The study included 105 patients undergoing preoperative CVC placement. A US protocol aimed at direct visualization of the CVC was completed by a single operator and two consecutive "bubble tests" were performed independently by different physicians. Two parameters were considered: complete right atrium (RA) opacization versus visualization of "no or few bubbles" and time from agitated saline injection to visualization of micro-bubbles in the RA ("push-to-bubbles" time)., Results: CXR identified 14 (13%) CVC malpositions. Vascular US showed a sensitivity of 64% and a specificity of 100% while visualization of "no or few bubbles" at bubble test yielded a sensitivity of 50% and a specificity of 100%. "Push-to-bubbles" times were ≈9 times longer in patients with compared to those without CVC malposition (1400 [702-2160] ms versus 167 [123-228] ms, P<0.001). A cut off value of 500 ms had a sensitivity of 100% and a specificity of 99% for CVC malposition with an inter-observer agreement of 99% (kappa 0.96, P<0.001)., Conclusion: CVC malposition was observed in a sizeable proportion of patients undergoing preoperative central venous cannulation. Measurement of "push-to-bubbles" time is a fast, accurate and highly reproducible tool for verifying the correct CVC position.

This work proposes a hybrid experimental-numerical technique with the aim to improve strain measurements at stress concentration regions. The novel technique is performed employing the computer vision scale invariant feature transform (SIFT) algorithm and meshless methods, here termed SIFT-meshless. The SIFT is applied to perform feature points matching in two images of the specimen surface at different stages of mechanical deformation. The output data are provided as a set of displacement measurements by tracking matched feature points. This information is then used to model displacement and strain field on the surface by means of a meshless formulation based on the moving least squares approximation. By applying the proposed SIFT-meshless method, the strain distribution around a semicircular notch in a plate under bending load was investigated. The experimental results were compared with those obtained by a digital image correlation technique based on a subset approach and to simulations from finite element analysis software. The experimental results demonstrated that the present method is capable of performing reliable strain measurements at distances close to the notch where the peak strain value is expected, even in the presence of high strain gradients.

Brugada syndrome is an electrical cardiac disease predisposing to ventricular arrhythmias in which typical electrocardiographic (ECG) features consist of nonischemic repolarization abnormalities in the right precordial leads V1-V3. The appearance of a Brugada-ECG pattern is increasingly observed in critically ill patients and is traditionally attributed to the effect of body temperature and/or drug modulation on cardiac ion channels ("acquired Brugada syndrome"). A patient with complicated malaria in whom Brugada-ECG abnormalities appeared in concomitance with fever and propofol administration is presented. The repolarization changes did not disappear until the patient's clinical course improved., (© 2013 Elsevier Inc. All rights reserved.)

Takotsubo cardiomyopathy (TTC) is a transient left ventricular (LV) dysfunction due to akinesia of the LV mid-apical segments ('apical ballooning') in the absence of critical coronary stenoses which can be complicated in the acute phase by heart failure, mitral regurgitation, life-threatening ventricular arrhythmias, or apical LV thrombosis. The syndrome is typically precipitated by intense emotional or physical stress; however, other causes of sympathetic overstimulation including administration of exogenous sympathomimetics or withdrawal of sympathetic antagonists can trigger TTC. We report the case of a patient who unexpectedly developed an 'apical ballooning' with severe reduction in the LV systolic function and heart failure after the withdrawal of methadone. The case supports the concept that increased sympathetic activity secondary to opioids withdrawal can trigger a stress-induced severe LV dysfunction. Physicians should be aware that the abrupt discontinuation of a long-term therapy with opioids may lead to serious cardiac complications. The administration of clonidine may be considered to prevent early clinical manifestations of addictive withdrawal, including TTC.

Central venous catheterization is of common practice in intensive care units; despite representing an essential device in various clinical circumstances, it represents a source of complications, sometimes even fatal, related to its management. We report the removal of a central venous catheter (CVC) that had been wrongly positioned through left internal jugular vein. The vein presented complete thrombosis at vascular ultrasonography. An echocardiogram performed 24 hours after CVC removal showed the presence, apparently unjustified, of microbubbles in right chambers of the heart. A neck-thorax CT scan showed the presence of air bubbles within the left internal jugular vein, left innominate vein, and left subclavian vein. A vascular ultrasonography, focused on venous catheter insertion site, disclosed the presence of a vein-to-dermis fistula, as portal of air entry. Only after air occlusive dressing, we documented echographic disappearance of air bubbles within the right cardiac cavity. This report emphasizes possible air entry even many hours after CVC removal, making it mandatory to perform 24-72-hour air occlusive dressing or, when inadequate, to perform a purse string.

The conduction of anaesthesia in a patient with a diagnosis of porphyria cutanea tarda is described. The aim of this paper is to provide further evidence for safety of TIVA (Total Intra Venous Anaesthesia) paying particular attention to propofol and atracurium (there are not sufficient data about it in the literature) in patients with porphyria cutanea tarda and high levels of uroporphyrin. The study of the anaesthetic management of a patient suffering from Porphyria Cutanea Tarda (PCT), the most common form of porphyria, can offer useful indications. Due to the fact that PCT is less severe than the acute forms, there is less risk for the patient under anaesthesia. In this particular case preoperative, intraoperative and postoperative urinary porphyrin are compared and furthermore, the liver function and the eventual development of skin lesions are monitored. A not significant increase of urinary porphyrin levels after surgery, no skin lesions and no modifications of liver function have been observed. TIVA proved to be safe in this case of PCT.