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

Donepezil-Loaded Nanocarriers for the Treatment of Alzheimer’s Disease: Superior Efficacy of Extracellular Vesicles Over Polymeric Nanoparticles

Rummenigge Oliveira Silva,1 Hermine Counil,1 Jean-Michel Rabanel,2 Mohamed Haddad,1 Charlotte Zaouter,1 Mohamed Raâfet Ben Khedher,1,3 Shunmoogum A Patten,1 Charles Ramassamy1 1Centre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique, Laval, Québec, Canada; 2Faculté de Pharmacie, Université de Montréal, Montréal, Québec, Canada; 3Higher Institute of Biotechnology of Beja, University of Jendouba, Beja, TunisiaCorrespondence: Charles Ramassamy, INRS, Centre Armand-Frappier Santé Biotechnologie, 531 Boul des Prairies, Laval, QC, H7V 1B7, Canada, Tel +450-687 50 10, Email [email protected]: Drug delivery across the blood-brain barrier (BBB) is challenging and therefore severely restricts neurodegenerative diseases therapy such as Alzheimer’s disease (AD). Donepezil (DNZ) is an acetylcholinesterase (AChE) inhibitor largely prescribed to AD patients, but its use is limited due to peripheral adverse events. Nanodelivery strategies with the polymer Poly (lactic acid)-poly(ethylene glycol)-based nanoparticles (NPs-PLA-PEG) and the extracellular vesicles (EVs) were developed with the aim to improve the ability of DNZ to cross the BBB, its brain targeting and efficacy.Methods: EVs were isolated from human plasma and PLA-PEG NPs were synthesized by nanoprecipitation. The toxicity, brain targeting capacity and cholinergic activities of the formulations were evaluated both in vitro and in vivo.Results: EVs and NPs-PLA-PEG were designed to be similar in size and charge, efficiently encapsulated DNZ and allowed sustained drug release. In vitro study showed that both formulations EVs-DNZ and NPs-PLA-PEG-DNZ were highly internalized by the endothelial cells bEnd.3. These cells cultured on the Transwell® model were used to analyze the transcytosis of both formulations after validation of the presence of tight junctions, the transendothelial electrical resistance (TEER) values and the permeability of the Dextran-FITC. In vivo study showed that both formulations were not toxic to zebrafish larvae (Danio rerio). However, hyperactivity was evidenced in the NPs-PLA-PEG-DNZ and free DNZ groups but not the EVs-DNZ formulations. Biodistribution analysis in zebrafish larvae showed that EVs were present in the brain parenchyma, while NPs-PLA-PEG remained mainly in the bloodstream.Conclusion: The EVs-DNZ formulation was more efficient to inhibit the AChE enzyme activity in the zebrafish larvae head. Thus, the bioinspired delivery system (EVs) is a promising alternative strategy for brain-targeted delivery by substantially improving the activity of DNZ for the treatment of AD. Keywords: Alzheimer’s disease, donepezil, extracellular vesicular, PLA-PEG, bEnd.3 cells, zebrafis