Fluorogenic In Situ Thioacetalization: Expanding the Chemical Space of Fluorescent Probes, Including Unorthodox, Bifurcated, and Mechanosensitive Chalcogen Bonds.

Progress with fluorescent flippers, small-molecule probes to image membrane tension in living systems, has been limited by the effort needed to synthesize the twisted push-pull mechanophore. Here, we move to a higher oxidation level to introduce a new design paradigm that allows the screening of flipper probes rapidly, at best in situ. Late-stage clicking of thioacetals and acetals allows simultaneous attachment of targeting units and interfacers and exploration of the critical chalcogen-bonding donor at the same time. Initial studies focus on plasma membrane targeting and develop the chemical space of acetals and thioacetals, from acyclic amino acids to cyclic 1,3-heterocycles covering dioxanes as well as dithiolanes, dithianes, and dithiepanes, derived also from classics in biology like cysteine, lipoic acid, asparagusic acid, DTT, and epidithiodiketopiperazines. From the functional point of view, the sensitivity of membrane tension imaging in living cells could be doubled, with lifetime differences in FLIM images increasing from 0.55 to 1.11 ns. From a theoretical point of view, the complexity of mechanically coupled chalcogen bonding is explored, revealing, among others, intriguing bifurcated chalcogen bonds.

Fluorescent Flippers: Small-Molecule Probes to Image Membrane Tension in Living Systems.

Flipper probes have been introduced as small molecule fluorophores to image physical forces, that is, membrane tension in living systems. Their emergence over one decade is described, from evolution in design and synthesis to spectroscopic properties. Responsiveness to physical compression in equilibrium at the ground state is identified as the ideal origin of mechanosensitivity to image membrane tension in living cells. A rich collection of flippers is described to deliver and release in any subcellular membrane of interest in a leaflet-specific manner. Chalcogen-bonding cascade switching and dynamic covalent flippers are developed for super-resolution imaging and dual-sensing of membrane compression and hydration. Availability and broad use in the community validate flipper probes as a fine example of the power of translational supramolecular chemistry, moving from fundamental principles to success on the market.

Airway Management of Patients with Suspected or Confirmed COVID-19: Survey Results from Physicians from 19 Countries in Latin America.

Airway management during the COVID-19 pandemic has been one of the most challenging aspects of care that anesthesiologists and intensivists face. This study was conducted to evaluate the management of tracheal intubation in patients with suspected or confirmed COVID-19 infection. This is a cross-sectional and international multicenter study based on a 37-item questionnaire. The survey was available to physicians who had performed intubations and tracheostomies in patients with suspected or confirmed COVID-19 and had provided informed consent to participate. The primary outcome is the preference to use a specific device for tracheal intubation. Secondary outcomes are clinical practice variables, use of video laryngoscopes, difficult airway management, and safety features to prevent cross-infection. This study included 2411 physicians who performed an average of 11.90 and 20.67 tracheal intubations in patients diagnosed or suspected of having COVID-19 disease, respectively. Physicians were mainly from the specialties of Anesthesiology (61.2%) and Intensive Care (7.4%). COVID-19 infection diagnosed by positive PCR or serology in physicians participating in intubation in this study was 15.1%. Respondents considered preoxygenation for more than three minutes very useful (75.7%). The preferred device for tracheal intubation was the video laryngoscope (64.8%). However, the direct laryngoscope (57.9%) was the most commonly used, followed by the video laryngoscope (37.5%). The preferred device to facilitate intubation was the Eschmann guide (34.2%). Percutaneous tracheostomy was the preferred technique (39.5%) over the open tracheostomy (22%). The predicted or unpredicted difficult airway management in these patients was preferably performed with a video laryngoscope (61.7% or 63.7, respectively). Intubation was mostly performed by two or more expert airway physicians (61.6%). The use of personal protective equipment increased the practitioners' discomfort during intubation maneuvers. The video laryngoscope is the preferred device for intubating patients with COVID-19, combined with the Eschmann guide, flexible stylet within the endotracheal tube, or Frova guide to facilitate intubation. The sub-analysis of the two groups of physicians by the level of intubation experience showed a higher use of the video laryngoscope (63.4%) in the experts group and no significant differences between the two groups in terms of cross-infection rates in physicians, in their preference for the use of the video laryngoscope or in the number of intubations performed in confirmed or suspected COVID-19 patients.