BASHY Dyes Are Highly Efficient Lipid Droplet-Targeting Photosensitizers that Induce Ferroptosis through Lipid Peroxidation

Ferroptosis is an iron-dependent lipid-peroxidation-driven mechanism of cell death and a promising therapeutic target to eradicate cancer cells. In this study, we discovered that boronic acid-derived salicylidenehydrazone (BASHY) dyes are highly efficient singlet-oxygen photosensitizers (PSs; Φ up to 0.8) that induce ferroptosis triggered by photodynamic therapy. The best-performing BASHY dye displayed a high phototoxicity against the human glioblastoma multiform U87 cell line, with an IC value in the low nanomolar range (4.40 nM) and a remarkable phototoxicity index (PI > 22,700). Importantly, BASHY dyes were shown to accumulate in lipid droplets (LDs) and this intracellular partition was found to be essential for the enhanced phototoxicity and the induction of ferroptosis through lipid peroxidation. The safety and phototoxicity of this platform were validated using an in vivo zebrafish model (Danio rerio

A Compact Multiphoton 3D Imaging System for Recording Fast Neuronal Activity

We constructed a simple and compact imaging system designed specifically for the recording of fast neuronal activity in a 3D volume. The system uses an Yb:KYW femtosecond laser we designed for use with acousto-optic deflection. An integrated two-axis acousto-optic deflector, driven by digitally synthesized signals, can target locations in three dimensions. Data acquisition and the control of scanning are performed by a LeCroy digital oscilloscope. The total cost of construction was one order of magnitude lower than that of a typical Ti:sapphire system. The entire imaging apparatus, including the laser, fits comfortably onto a small rig for electrophysiology. Despite the low cost and simplicity, the convergence of several new technologies allowed us to achieve the following capabilities: i) full-frame acquisition at video rates suitable for patch clamping; ii) random access in under ten microseconds with dwelling ability in the nominal focal plane; iii) three-dimensional random access with the ability to perform fast volume sweeps at kilohertz rates; and iv) fluorescence lifetime imaging. We demonstrate the ability to record action potentials with high temporal resolution using intracellularly loaded potentiometric dye di-2-ANEPEQ. Our design proffers easy integration with electrophysiology and promises a more widespread adoption of functional two-photon imaging as a tool for the study of neuronal activity. The software and firmware we developed is available for download at http://neurospy.org/ under an open source license

J Cardiothorac Vasc Anesth

DESPITE THE AGING POPULATION and new lung cancer cases being on the rise, clinicians are forced to be more efficient and more productive without additional resources. Fast-track pathways have been described showing outstanding results, such as a faster recovery process and shorter length of hospital stay,but mainly for abdominal and orthopedic surgeries. Although enhanced recovery paths might seem to be an excellent option to solve this problem, there is a scarcity of trials in thoracic surgery in general on this subject. Therefore, it is essential to implement recovery pathway programs for patients undergoing thoracic surgery. Thoracic epidural analgesia (TEA) is the gold standard to relieve pain after thoracotomy because of its association with severe pain. Thus, a crucial point to implement a fast-track pathway in thoracic surgery is to offer TEA. It reduces significantly the incidence of postoperative morbidity compared with other types of analgesia. In contrast, TEA encompasses important side effects. Postoperative urinary retention (POUR) is one of the most frequent, with an average incidence of 26%. To avoid this complication, it is a common practice to place a transurethral catheter, as long as the epidural is in situ and functioning well. Nevertheless, a urinary bladder catheter impedes early ambulation and can lead to urinary tract infection (UTI), which increases patients’ hospital length of stay and governmental costs. Recent studies have reported that transurethral catheters can be removed earlier safely in thoracic surgery patients. Hence, the goal of the present review was to determine when is the most appropriate timing to remove the bladder catheter in patients undergoing thoracic surgery receiving TEA. This paper reviews the literature to provide recommendations from experts’ opinions for both the appropriate removal period of the indwelling bladder catheter and the management of POUR for patients scheduled for thoracotomy receiving working TEA. This review aims to contribute to the building of a fast-track pathway for patients undergoing thoracotomy

Transcontinental anaesthesia: A pilot study

BackgroundAlthough telemedicine is one of the key initiatives of the World Health Organization, no study has explored the feasibility and efficacy of teleanaesthesia. This bi-centre pilot study investigates the feasibility of transcontinental anaesthesia.MethodsTwenty patients aged ≥18 yr undergoing elective thyroid surgery for ≥30 min were enrolled in this study. The remote and local set-up was composed of a master-computer (Montreal) and a slave-computer (Pisa). Standard Internet connection, remote desktop control, and video conference software were used. All patients received total i.v. anaesthesia controlled remotely (Montreal). The main outcomes were feasibility, clinical performance, and controller performance of transcontinental anaesthesia. The clinical performance of hypnosis control was the efficacy to maintain bispectral index (BIS) at 45: 'excellent', 'good', 'poor', and 'inadequate' control represented BIS values within 10, from 11 to 20, from 21 to 30, or >30% from target. The clinical performance of analgesia was the efficacy to maintain Analgoscore values at 0 (-9 to 9); -3 to +3 representing 'excellent' pain control, -3 to -6 and +3 to +6 representing 'good' pain control, and -6 to -9 and +6 to +9 representing 'insufficient' pain control. The controller performance was evaluated using Varvel parameters. ResultsTranscontinental anaesthesia was successful in all 20 consecutive patients. The clinical performance of hypnosis showed an 'excellent and good' control for 69% of maintenance time, and the controller performance showed an average global performance index of 57. The clinical performance of analgesia was 'excellent and good' for 92% of maintenance time, and the controller performance showed a global performance index of 1118. ConclusionsTranscontinental anaesthesia is feasible; control of anaesthesia shows good performance indexes.Clinical registration numberNCT01331096. © 2013 Author

Numerical and experimental analysis of nonlinear regenerative amplifiers overcoming the gain bandwidth limitation

International audience—We present a numerical and experimental analysis of a nonlinear architecture to overcome the gain bandwidth limitation in regenerative amplifiers. This technique is based on the optimization of dispersion and nonlinear effects during the amplification process to obtain broad-bandwidth pulses that can be compressed to short durations with high temporal quality. We demonstrate the advantage of this method to maintain an excellent temporal quality of pulses even at high levels of optical nonlinearity. The technique has been applied to regenerative amplifiers using Yb:YAG, Yb:KYW, and Yb:CALGO crystals as gain media. In all cases we achieved the shortest pulse duration ever obtained from regenerative amplifiers using the respective laser crystals. These results underline the benefits of this amplification technique with respect to current state of the art