Generation and Trapping of Ketenes in Flow.

Ketenes were generated by the thermolysis of alkoxyalkynes under flow conditions, and then trapped with amines and alcohols to cleanly give amides and esters. For a 10 min reaction time, temperatures of 180, 160, and 140 °C were required for >95 % conversion of EtO, iPrO, and tBuO alkoxyalkynes, respectively. Variation of the temperature and flow rate with inline monitoring of the output by IR spectroscopy allowed the kinetic parameters for the conversion of 1-ethoxy-1-octyne to be easily estimated (Ea = 105.4 kJ/mol). Trapping of the in-situ-generated ketenes by alcohols to give esters required the addition of a tertiary amine catalyst to prevent competitive [2+2] addition of the ketene to the alkoxyalkyne precursor.

Pilot study to determine the utility of point-of-care ultrasound in the assessment of difficult laryngoscopy.

OBJECTIVES: Prediction of difficult laryngoscopy in emergency care settings is challenging. The preintubation clinical screening tests may not be applied in a large number of emergency intubations due to the patient's clinical condition. The objectives of this study were 1) to determine the utility of sonographic measurements of thickness of the tongue, anterior neck soft tissue at the level of the hyoid bone, and thyrohyoid membrane in distinguishing difficult and easy laryngoscopies and 2) to examine the association between sonographic measurements (thickness of tongue and anterior neck soft tissue) and difficult airway clinical screening tests (modified Mallampati score, thyromental distance, and interincisor gap). METHODS: This was a prospective observational study at an academic medical center. Adult patients undergoing endotracheal intubation for an elective surgical procedure were included. The investigators involved in data collection were blinded to each other's assessments. Demographic variables were collected preoperatively. The clinical screening tests to predict a difficult airway were performed. The ultrasound (US) measurements of tongue and anterior neck soft tissue were obtained. The laryngoscopic view was graded using Cormack and Lehane classification by anesthesia providers on the day of surgery. To allow for comparisons between difficult airway and easy airway groups, a two-sided Student's t-test and Fisher's exact test were employed as appropriate. Spearman's rank correlation coefficients were used to examine the association between screening tests and sonographic measurements. RESULTS: The mean (±standard deviation [SD]) age of 51 eligible patients (32 female, 19 male) was 53.1 (±13.2) years. Six of the 51 patients (12%, 95% confidence interval [CI] = 3% to 20%) were classified as having difficult laryngoscopy by anesthesia providers. The distribution of laryngoscopy grades for all subjects was 63, 25, 4, and 8% for grades 1, 2, 3, and 4, respectively. In this study, 83% of subjects with difficult airways were males. No other significant differences were noted in the demographic variables and difficult airway clinical screening tests between the two groups. The sonographic measurements of anterior neck soft tissue were greater in the difficult laryngoscopy group compared to the easy laryngoscopy group at the level of the hyoid bone (1.69, 95% CI = 1.19 to 2.19 vs. 1.37, 95% CI = 1.27 to 1.46) and thyrohyoid membrane (3.47, 95% CI = 2.88 to 4.07 vs. 2.37, 95% CI = 2.29 to 2.44). No significant correlation was found between sonographic measurements and clinical screening tests. CONCLUSIONS: This pilot study demonstrated that sonographic measurements of anterior neck soft tissue thickness at the level of hyoid bone and thyrohyoid membrane can be used to distinguish difficult and easy laryngoscopies. Clinical screening tests did not correlate with US measurements, and US was able to detect difficult laryngoscopy, indicating the limitations of the conventional screening tests for predicting difficult laryngoscopy.

Discovery of a potent series of non-steroidal non α-trifluoromethyl carbinol glucocorticoid receptor agonists with reduced lipophilicity.

A novel series of indazole non-steroidal glucocorticoid receptor agonist has been discovered. This series features a sulfonamide central core and meta amides which interact with the extended ligand binding domain. This series has produced some of the most potent and least lipophilic agonists of which we are aware such as 20a (NFκB pIC(50) 8.3 (100%), clogP 1.9). Certain analogues in this series also display evidence for modulated pharmacology.

Moderate alcohol intake and motor vehicle crashes: the conflict between health advantage and at-risk use.

AIMS: To review the evidence on moderate alcohol intake and motor vehicle crash (MVC) risk, and discuss the possible public health tension in balancing risk reduction and increment with respect to moderate alcohol intake. METHOD: A Medline review was conducted on moderate alcohol intake, MVC, and cardiovascular disease (CVD) risks. RESULT: Moderate alcohol intake (24 g ethanol, two US standard drinks, or less a day) is associated with 20% reduction in risk of CVD. Public awareness of this may contribute to why rates of driving with blood alcohol content (BAC) <0.08 g/dl in the United States are static. Studies show 3- to 17-fold increased risk of a fatal MVC with BAC < 0.08 g/dl compared to sober drivers. The United States has 0.08 g/dl BAC laws, higher than that reached by a driver drinking two drinks per day or less. CONCLUSION: The public should be educated that although moderate alcohol drinking may not violate BAC laws, it still carries significant risk of MVC. Current BAC laws in some countries needs re-evaluation.