Simulation of Adult Surgical Cricothyrotomy for Anesthesiology and Emergency Medicine Residents: Adapted for COVID-19.

Introduction: In a CICO (cannot intubate, cannot oxygenate) situation, anesthesiologists and acute care physicians must be able to perform an emergency surgical cricothyrotomy (front-of-neck airway procedure). CICOs are high-acuity situations with rare opportunities for safe practice. In COVID-19 airway management guidelines, bougie-assisted surgical cricothyrotomy is the recommended emergency strategy for CICO situations. Methods: We designed a 4-hour procedural simulation workshop on surgical cricothyrotomy to train 16 medical residents. We provided prerequisite readings, a lecture, and a videotaped demonstration. Two clinical scenarios introduced deliberate practice on partial-task neck simulators and fresh human cadavers. We segmented an evidence-based procedure and asked participants to verbalize the five steps of the procedure on multiple occasions. Results: Thirty-two residents who participated in the workshops were surveyed, with a 97% response rate (16 of 16 from anesthesiology, 15 of 16 from emergency medicine). Participants commented positively on the workshop's authenticity, its structure, the quality of the feedback provided, and its perceived impact on improving skills in surgical cricothyrotomy. We analyzed narrative comments related to three domains: preparation for the procedure, performing the procedure, and maintaining the skills. Participants highlighted the importance of performing the procedure many times and mentioned the representativeness of fresh cadavers. Discussion: We developed a surgical cricothyrotomy simulation workshop for anesthesiology and emergency medicine residents. Residents in the two specialities uniformly appreciated its format and content. We identified common pitfalls when executing the procedure and provided practical tips and material to facilitate implementation, in particular to face the COVID-19 pandemic.

Structural Diversity in 2,2'-[Naphthalene-1,8:4,5-bis(dicarboximide)-N,N'-diyl]-bis(ethylammonium) Iodoplumbates.

Crystallization from solutions containing 2,2'-[naphthalene-1,8:4,5-bis(dicarboximide)-N,N'-diyl]-bis(ethylammonium) diiodide ((NDIC2)I2) and PbI2 has been investigated. Eight different materials are obtained, either by variation of crystallization conditions or by subsequent thermal or solvent-induced transformations. Crystal structures have been determined for five materials. [(NDIC2)2Pb5I14(DMF)2]·4DMF (DMF = N,N-dimethylformamide) (1), [(NDIC2)Pb4I10]·4DMF (3), [(NDIC2)Pb2I6]·4NMP (NMP = N-methyl-2-pyrrolidone) (4), and [(NDIC2)Pb2I6]·2H2O (5) form 1-dimensional (1D) chains consisting of PbI6 (and, in the case of 1, PbI5(DMF)) octahedra, either solely face-sharing or a mixture of face-sharing and vertex-sharing. The structure of [(NDIC2)3Pb5I16]·6NMP (2) contains 0D clusters; these consist of three PbI6 octahedra and two unusually coordinated lead centers that exhibit three relatively short Pb-I bonds, two very long Pb-I contacts, and η2-coordination of an aromatic ring of NDIC2 to the lead. Close contacts between iodide ions and the imide rings of NDIC2 in four of the structures suggest that an iodide-to-NDIC2 charge-transfer interaction may be responsible for the observed red coloration of the materials. The optical and electrical properties of 1 have been studied; its onset of absorption is at 2.0 eV, and its conductivity was measured as 5.4 × 10-5 ± 1.1 × 10-5 S m-1.

Understanding Color Tuning and Reversible Oxidation of Conjugated Azomethines.

With the aim of achieving reversible oxidation and color tuning, the effect of the central aromatic on the spectroscopic, electrochemical, and spectrochemical properties of a series of electrochromic azomethine triads was investigated. The absorption of the alkylated thiophene derivatives was blue-shifted relative to their unalkylated counterparts when the central aromatic was either a bi- or terthiophene. It was further found that the alkylated thiophene derivatives had larger Stokes shifts than their unsubstituted counterparts. Theoretical calculations demonstrated that the torsion angles of these alkylated cores with respect to the flanking azomethines were responsible for the spectroscopic effects. While the electrochemical oxidation potential of the triads varied by only 100 mV, the reversibility of their anodic process was contingent on the central aromatic. The absorption of the electrochemically produced state red-shifted between 165 and 280 nm from its corresponding neutral state, leading to perceived color changes between orange and blue. Reversible color changes were chemically mediated with ferric chloride/hydrazine. The absorption of the chemically oxidized state shifted between 155 and 220 nm from the corresponding neutral state, contingent on the central aromatic. The palette of perceived colors that was possible with oxidation included orange, yellow, blue, and gray.

(4NPEA)2PbI4 (4NPEA = 4-Nitrophenylethylammonium): Structural, NMR, and Optical Properties of a 3 × 3 Corrugated 2D Hybrid Perovskite.

(4NPEA)2PbI4 (4NPEA = 4-nitrophenylethylammonium) is the first 3 × 3 corrugated 2D organic-Pb/I perovskite. The nitro groups are involved in cation-cation and cation-iodide interactions. The structure contains both highly distorted and near-ideal PbI6 octahedra, consistent with the observation of two 207Pb NMR resonances, while the optical properties resemble those of other 2D perovskites with distorted PbI6 octahedra.

Simulation-based assessment of anesthesiology residents' competence: development and implementation of the Canadian National Anesthesiology Simulation Curriculum (CanNASC).

The specialty of anesthesiology will soon adopt the Competence By Design (CBD) approach to residency education developed by the Royal College of Physicians and Surgeons of Canada (RCPSC). A foundational component of CBD is frequent and contextualized assessment of trainees. In 2013, the RCPSC Anesthesiology Specialty Committee assembled a group of simulation educators, representing each of the 17 Canadian anesthesiology residency programs, to form the Canadian National Anesthesiology Simulation Curriculum (CanNASC) Task Force. The goals were to develop, implement, and evaluate a set of consensus-driven standardized mannequin-based simulation scenarios that every trainee must complete satisfactorily prior to completion of anesthesiology residency and certification. Curriculum development followed Kern's principles and was accomplished via monthly teleconferences and annual face-to-face meetings. The development and implementation processes included the following key elements: 1) Curriculum needs assessment: 368 of 958 invitees (38.4%) responded to a national survey resulting in 64 suggested scenario topics. Use of a modified Delphi technique resulted in seven important and technically feasible scenarios. 2) Scenario development: All scenarios have learning objectives from the National Curriculum for Canadian Anesthesiology Residency. Standardized scenario templates were created, and the content was refined and piloted. 3) Assessment: A validated Global Rating Scale (GRS) is the primary assessment tool, informed by using scenario-specific checklists (created via a modified Delphi technique) and the Anesthesia Non-Technical Skills GRS. 4) Implementation: Standardized implementation guidelines, pre-brief/debrief documents, and rater training videos, guide, and commentary were generated. National implementation of the scenarios and program evaluation is currently underway. It is highly feasible to achieve specialty-based consensus on the elements of a national simulation-based curriculum. Our process could be adapted by any specialty interested in implementing a simulation-based curriculum incorporating competency-based assessment on a national scale.

Regio- and Stereoselective Hydrosilylation of Unsymmetrical Alkynes Catalyzed by a Well-Defined, Low-Valent Cobalt Catalyst.

Herein, the use of a well-defined low-valent cobalt(I) catalyst [HCo(PMe3)4] capable of performing the highly regio- and stereoselective hydrosilylation of internal alkynes is reported. The reaction can be applied to a variety of hydrosilanes, symmetrical and unsymmetrical alkynes, giving in many cases a single hydrosilylation isomer. Experimental and theoretical studies suggest the key step to be a hydro-cobaltation and that the reaction proceeds through a classical Chalk-Harrod mechanism.

Hydrogen-Bond and Supramolecular-Contact Mediated Fluorescence Enhancement of Electrochromic Azomethines.

An electronic push-pull fluorophore consisting of an intrinsically fluorescent central fluorene capped with two diaminophenyl groups was prepared. An aminothiophene was conjugated to the two flanking diphenylamines through a fluorescent quenching azomethine bond. X-ray crystallographic analysis confirmed that the fluorophore formed multiple intermolecular supramolecular bonds. It formed two hydrogen bonds involving a terminal amine, resulting in an antiparallel supramolecular dimer. Hydrogen bonding was also confirmed by FTIR and NMR spectroscopic analyses, and further validated theoretically by DFT calculations. Intrinsic fluorescence quenching modes could be reduced by intermolecular supramolecular contacts. These contacts could be engaged at high concentrations and in thin films, resulting in fluorescence enhancement. The fluorescence of the fluorophore could also be restored to an intensity similar to its azomethine-free counterpart with the addition of water in >50 % v/v in tetrahydrofuran (THF), dimethyl sulfoxide (DMSO), and acetonitrile. The fluorophore also exhibited reversible oxidation and its color could be switched between yellow and blue when oxidized. Reversible electrochemically mediated fluorescence turn-off on turn-on was also possible.

Moderately strong phenols dissociate by forming an ion-pair kinetic intermediate.

We show computational evidence that ground-state moderately strong hydroxyarenes (Ar-OH, pKa ∼ 0) dissociate by forming an ion-pair intermediate that lives for 3-5 ps. The concentration of this intermediate is approximately 2 times smaller than that of the un-ionized acid at pH ∼ 0.6 and is characterized by average C-O bond lengths (1.30 Å) that are intermediate between those of un-ionized (1.29 Å) and fully dissociated (1.34 Å) species. During the lifetime of the ion-pair intermediate the excess proton fluctuates between the oxygen atom of the phenolic moiety and those of water molecules in the first and second solvation shells on a subpicosecond time scale (∼100-300 fs).

Hemoglobin levels and transfusions in neurocritically ill patients: a systematic review of comparative studies.

INTRODUCTION: Accumulating evidence suggests that, in critically ill patients, a lower hemoglobin transfusion threshold is safe. However, the optimal hemoglobin level and associated transfusion threshold remain unknown in neurocritically ill patients. METHODS: We conducted a systematic review of comparative studies (randomized and nonrandomized) to evaluate the effect of hemoglobin levels on mortality, neurologic function, intensive care unit (ICU) and hospital length of stay, duration of mechanical ventilation, and multiple organ failure in adult and pediatric neurocritically ill patients. We searched MEDLINE, The Cochrane Central Register of Controlled Trials, Embase, Web of Knowledge, and Google Scholar. Studies focusing on any neurocritical care conditions were included. Data are presented by using odds ratios for dichotomous outcomes and mean differences for continuous outcomes. RESULTS: Among 4,310 retrieved records, six studies met inclusion criteria (n = 537). Four studies were conducted in traumatic brain injury (TBI), one in subarachnoid hemorrhage (SAH), and one in a mixed population of neurocritically ill patients. The minimal hemoglobin levels or transfusion thresholds ranged from 7 to 10 g/dl in the lower-Hb groups and from 9.3 to 11.5 g/dl in the higher-Hb groups. Three studies had a low risk of bias, and three had a high risk of bias. No effect was observed on mortality, duration of mechanical ventilation, or multiple organ failure. In studies reporting on length of stay (n = 4), one reported a significant shorter ICU stay (mean, -11.4 days (95% confidence interval, -16.1 to -6.7)), and one, a shorter hospital stay (mean, -5.7 days (-10.3 to -1.1)) in the lower-Hb groups, whereas the other two found no significant association. CONCLUSIONS: We found insufficient evidence to confirm or refute a difference in effect between lower- and higher-Hb groups in neurocritically ill patients. Considering the lack of evidence regarding long-term neurologic functional outcomes and the high risk of bias of half the studies, no recommendation can be made regarding which hemoglobin level to target and which associated transfusion strategy (restrictive or liberal) to favor in neurocritically ill patients.

Mast cell tryptase stimulates myoblast proliferation; a mechanism relying on protease-activated receptor-2 and cyclooxygenase-2.

BACKGROUND: Mast cells contribute to tissue repair in fibrous tissues by stimulating proliferation of fibroblasts through the release of tryptase which activates protease-activated receptor-2 (PAR-2). The possibility that a tryptase/PAR-2 signaling pathway exists in skeletal muscle cell has never been investigated. The aim of this study was to evaluate whether tryptase can stimulate myoblast proliferation and determine the downstream cascade. METHODS: Proliferation of L6 rat skeletal myoblasts stimulated with PAR-2 agonists (tryptase, trypsin and SLIGKV) was assessed. The specificity of the tryptase effect was evaluated with a specific inhibitor, APC-366. Western blot analyses were used to evaluate the expression and functionality of PAR-2 receptor and to assess the expression of COX-2. COX-2 activity was evaluated with a commercial activity assay kit and by measurement of PGF2α production. Proliferation assays were also performed in presence of different prostaglandins (PGs). RESULTS: Tryptase increased L6 myoblast proliferation by 35% above control group and this effect was completely inhibited by APC-366. We confirmed the expression of PAR-2 receptor in vivo in skeletal muscle cells and in satellite cells and in vitro in L6 cells, where PAR-2 was found to be functional. Trypsin and SLIGKV increased L6 cells proliferation by 76% and 26% above control, respectively. COX-2 activity was increased following stimulation with PAR-2 agonist but its expression remained unchanged. Inhibition of COX-2 activity by NS-398 abolished the stimulation of cell proliferation induced by tryptase and trypsin. Finally, 15-deoxy-Δ-12,14-prostaglandin J2 (15Δ-PGJ2), a product of COX-2-derived prostaglandin D2, stimulated myoblast proliferation, but not PGE2 and PGF2α. CONCLUSIONS: Taken together, our data show that tryptase can stimulate myoblast proliferation and this effect is part of a signaling cascade dependent on PAR-2 activation and on the downstream activation of COX-2.

Sequential bilateral upper extremity intravenous regional anesthesia with chloroprocaine.

PURPOSE: This case report describes the novel use of sequential bilateral upper extremity intravenous regional anesthesia with 2-chloroprocaine for bilateral endoscopic carpal tunnel decompression. CLINICAL FEATURES: A 49-yr-old female, American Society of Anesthesiologists physical status I, presented for outpatient bilateral carpal tunnel release. Sequential bilateral intravenous regional anesthesia was performed with 0.5% 2-chloroprocaine 30 mL per arm using a double upper arm tourniquet. Intraoperative sedation consisted of midazolam and fentanyl. Tourniquet times for the right and left arms were 28 and 19 min, respectively. After deflation of each tourniquet, mild limb twitching occurred but resolved immediately after administration of intravenous midazolam. The patient made a rapid recovery, and she was discharged home uneventfully. CONCLUSIONS: Bilateral sequential intravenous regional anesthesia with 2-chloroprocaine is effective for upper extremity surgery of short duration. Recommendations to minimize the risk of local anesthetic toxicity are reviewed.

Identification of chaulmoogric acid as a small molecule activator of protein phosphatase 5.

Protein phosphatase 5 (PP5) is an important protein phosphatase that is abundantly expressed in the central nervous system. Recent studies showed that PP5 activity in the neocortex from patients with Alzheimer's disease (AD) is decreased significantly, suggesting that small molecule PP5 activator may have therapeutic potential for AD. We performed a biochemical screening for PP5 activators with the microsource compound library. Chaulmoogric acid was identified to be an effective activator with EC(50) value of 134.5 microM. Importantly, results from circular dichroism (CD) and limited proteolysis study showed that chaulmoogric acid binds to a region of tetratricopeptide repeat (TPR) domain of PP5 resulting in complete loss of helical contents. These results demonstrate a different mechanism of action from that of arachidonic acid, a known activator for PP5 dephosphorylation activity. Synergistic activation of PP5 enzymatic activity was also observed with combined application of both compounds at relatively low concentrations. Therefore, further structure activity relationship study of chaulmoogric acid may facilitate the discovery of small molecules that can synergize with endogenous arachidonic acid for PP5 activation.

Identification of small-molecule HSF1 amplifiers by high content screening in protection of cells from stress induced injury.

Small molecule amplifiers of heat shock response have shown promising results in rescuing stress related injury through chaperone amplification. Herein, we report the results of a high content target-based primary screening of several known bioactive libraries. Screening resulted in the identification of three potent gedunin derivatives and a sappanone A derivative. Western blot results confirmed compound-induced activation of HSF1 and increased expression level of HSP70. These compounds rescued cells from cell death caused by proteasome inhibitor MG-132 and RNAi knockdown of HSF1 significantly reversed the cytoprotective effects, confirming an HSF1-dependent mechanism of action. These HSF1 amplifiers were tested in two mammalian cell based models of Huntington's disease (HD) and found to improve survival. Therefore, these screening hits may have therapeutic potential for HD and possibly other protein conformational disorders.

Glucose control and mortality in patients with severe traumatic brain injury.

INTRODUCTION: The optimal glucose range in patients with severe traumatic brain injury (TBI) remains unclear. The goal of this study was to examine the association of serum glucose levels on mortality in patients with severe TBI. As a secondary endpoint, we determined the risk of hyperglycemic and hypoglycemic events, and their association with mortality. METHODS: We conducted a retrospective cohort study of patients admitted to the ICU between May 2000 and March 2006 with severe TBI (Glasgow Coma Scale ≤ 8) who survived at least 12 h. Average daily morning glucose levels for the first 10 days of admission were calculated and divided into quintiles. RESULTS: A total of 170 patients were included in the analysis. We found no association between quintiles of mean daily morning glucose and hospital mortality. Episodes of hyperglycemia ( ≥ 11.1 mmol/l or 200 mg/dl) during the first 10 days occurred in 65% of patients (5.4% of all glucose measurements). Using multivariable regression, a single episode of hyperglycemia was associated with 3.6-fold increased risk of hospital mortality (95%CI: 1.2-11.2, P = 0.02). Hypoglycemia ( ≤ 4.4 mmol/l or 80 mg/dl) was present in 48% of patients (4.3% of all glucose measurements), and was not associated with mortality. CONCLUSION: Any episode of hyperglycemia ( ≥ 11.1 mmol/l or 200 mg/dl) was associated with 3.6-fold increased risk of hospital mortality in patients with severe TBI and thus, should be avoided. Maintaining serum glucose ≤ 10 mmol/l appears to be a reasonable balance to avoid extremes of glucose control, but further studies are needed to determine the optimal glucose range.

Chloro-oxime derivatives as novel small molecule chaperone amplifiers.

Chloro-oxime derivatives were investigated as novel small molecule chaperone amplifiers. Lead optimization led to the discovery of compounds that displayed potent HSF1 activation activity, significant cytoprotection in MG-132 stress, ER stress and PolyQ stress cell models (EC(50)<10 microM).

Inflammation-induced leukocyte accumulation in injured skeletal muscle: role of mast cells.

Inflammation consequent to muscle damage is characterized by an accumulation of leukocytes. Our aim in this study was to determine whether mast cells can modulate inflammation-induced leukocyte trafficking. One approach consisted of giving rats a mast cell-degranulating agent, CMP 48/80, prior to a protocol of lengthening contractions inducing inflammation without neutrophil accumulation; in parallel, other rats were given the mast cell-stabilizing agent, cromolyn, prior to injecting muscle with bupivacaine, which induces neutrophil accumulation. Damage was evaluated through measurement of contractile force and inflammation using histochemical and immunohistochemical methods. Stimulation with CMP 48/80 increased the proportion of degranulated mast cells significantly and neutrophil accumulation occurred with lengthening contractions. With bupivacaine, accumulation of neutrophils decreased by 70% when degranulation was inhibited. These results indicate that mast cells are important in the process governing leukocyte trafficking in skeletal muscle trauma and that targeting their inhibition could be an attractive alternative for control of inflammation.

Poor visualization during direct laryngoscopy and high upper lip bite test score are predictors of difficult intubation with the GlideScope videolaryngoscope.

BACKGROUND: The GlideScope videolaryngoscope allows equal or superior glottic visualization compared with direct laryngoscopy, but predictive features for difficult GlideScope intubation have not been identified. We undertook this prospective study to identify patient characteristics associated with difficult GlideScope intubation. METHODS: Demographic and morphometric factors were recorded preoperatively for 400 patients undergoing anesthesia with endotracheal intubation. After induction, direct laryngoscopy was performed in all patients to assess the Cormack and Lehane grade of glottic visualization followed by GlideScope intubation. The number of attempts and time needed for intubation were recorded. Univariate and multivariate analyses were performed to identify the characteristics associated with difficult GlideScope intubation. RESULTS: Intubation required 1, 2, and 3 attempts in 342, 48, and 9 participants, respectively, with one failure. Mean time for intubation was 21 +/- 14 s. After univariate analysis, the following characteristics were significantly correlated (P < 0.05) with longer time to intubate and/or multiple attempts: older age, male sex, history of snoring, high Mallampati class, small mouth opening, short sternothyroid and manubriomental distances, large neck circumference, high upper lip bite test score, and high Cormack and Lehane grade during direct laryngoscopy. However, after introducing these variables in nominal logistic and proportional hazard multiple regression models, only high Cormack and Lehane grade during direct laryngoscopy, high upper lip bite test score, and short sternothyroid distance were significantly associated with multiple attempts or lengthier intubations. CONCLUSION: Despite a high success rate, intubation with the GlideScope is likely to be more challenging in patients with high Cormack and Lehane grade during direct laryngoscopy, high upper lip bite test score, or short sternothyroid distance.

Cervical spine motion during tracheal intubation with manual in-line stabilization: direct laryngoscopy versus GlideScope videolaryngoscopy.

BACKGROUND: The optimal tracheal intubation technique for patients with potential cervical (C) spine injury remains controversial. Using continuous cinefluoroscopy, we conducted a prospective study comparing C-spine movement during intubation using direct laryngoscopy (DL) or GlideScope videolaryngoscopy (GVL), with uninterrupted manual in-line stabilization of the head by an assistant. METHODS: Twenty patients without C-spine pathology were studied. After induction of general anesthesia with neuromuscular blockade, both DL and GVL were performed on every patient in random order. Cinefluoroscopic images of C-spine movement during GVL and DL were acquired and divided into four stages: a baseline image before airway manipulation, glottic visualization, insertion of the endotracheal tube into the glottis, and tracheal intubation. Peak segmental motion from the occiput to C5 was measured offline for each patient and each stage, averages were calculated, and movements induced by each instrument were compared using a two-way ANOVA. Also studied were the proportion of patients with occiput-C1 rotation exceeding 10, 15, or 20 degrees, and the quality of glottic visualization. RESULTS: No significant difference was found between DL and GVL regarding average segmental spine movement at any level (P values between 0.22 and 0.70). During both techniques, motion was mainly an extension concentrated in the rostral C-spine and occurred predominantly during glottic visualization. The proportion of patients with occiput-C1 extension of more than 10, 15, or 20 degrees was not significantly different. Glottic visualization was significantly better with GVL compared with DL. CONCLUSION: During intubation under general anesthesia with neuromuscular blockade and manual in-line stabilization, the use of GVL produced better glottic visualization, but did not significantly decrease movement of the nonpathologic C-spine when compared with DL.

High avidity binding of engineered papaya mosaic virus virus-like particles to resting spores of Plasmodiophora brassicae.

Papaya mosaic virus (PapMV) like particles (VLPs) were used as a platform for fusion of affinity peptides binding to resting spores of Plasmodiophora brassicae-a major pathogen of crucifers. Three peptides with specific affinity to the target were isolated and cloned at the C-terminus of the PapMV coat protein (CP), generating three different high avidity VLPs. The peptides were exposed at the surface of the VLPs and their avidity to resting spores of P. brassicae was measured by flow cytometry. NLP-A, with the peptide DPAPRPR, showed the highest avidity. The binding avidity of NLP-A to P. brassicae spores was comparable to that of a polyclonal antibody. NLP-A was also shown to be more specific than the antibody. Fusion of the affinity peptide to a monomeric form (mCP) of the CP [Lecours, K., Tremblay, M.-H., Laliberté Gagné, M.-E., Gagné, S.M., Leclerc, D., 2006. Purification and biochemical characterization of a monomeric form of papaya mosaic potexvirus coat protein. Protein Express. Purific. 47, 273-280] generated a fusion protein that was unable to assemble into VLPs, and mCP-A fusions failed to bind resting spores. The avidity of VLP-A was increased by adding a glycine spacer between the C-terminus of the PapMV CP and the peptide, and improved even further by using a duplicated A peptide in the fusion protein. The use of high avidity VLPs has advantages over polyclonal antibodies because of target specificity. VLPs offers the specificity of monoclonal antibodies but can be more easily generated using the powerful selection of phage display.