Acyl Azolium-Photoredox-Enabled Synthesis of ß-Keto Sulfides.

α-Heteroatom functionalization is a key strategy for C-C bond formation in organic synthesis, as exemplified by the addition of a nucleophile to electrophilic functional groups, such as iminium ions; oxocarbenium ions; and their sulfur analogues, sulfenium ions. We envisioned a photoredox-enabled radical Pummerer-type reaction realized through the single-electron oxidation of a sulfide. Following this oxidative event, α-deprotonation would afford α-thio radicals that participate in radical-radical coupling reactions with azolium-bound ketyl radicals, thereby accessing a commonly proposed mechanistic intermediate of the radical-radical coupling en route to functionalized additive Pummerer products. This system provides a complementary synthetic approach to highly functionalized sulfurous products, including modification of methionine residues in peptides, and beckons further exploration in C-C bond formations previously limited in the standard two-electron process.

The Effects of an E-learning Module on Medical Trainees Rotating on a Perioperative Medicine Clinical Service.

Introduction: Dedicated perioperative care can be cost-effective and improve patient outcomes. Training future physicians to practice perioperative medicine is an important responsibility of medical educators. An e-learning module delivered asynchronously during clinical rotations in perioperative medicine may help to better satisfy this responsibility. Method: Articulate software was used to create an interactive, 1-hour e-module based on six educational objectives. The e-module was offered as an elective self-directed learning experience to trainees on perioperative medicine clinical rotations, including third- and fourth-year medical students as well as residents from internal medicine, anesthesiology, neurology, and physical medicine and rehabilitation training programs. We assessed the effectiveness of this learning strategy as a complement to real-time clinical experiences by measuring the knowledge, confidence, and satisfaction of trainees before and after completion of the e-module. Results: Of 113 trainees invited to participate, 75 completed the module and were included in our analysis. Knowledge scores improved for student (p < .001), intern (p < .001), and resident (p < .001) subgroups. Confidence ratings also improved for student (p < .001), intern (p < .001), and resident (p < .001) subgroups. Trainees reported high satisfaction with the e-module, and 60 (87%) reported that it would alter their practice. Discussion: An e-module presenting evidence-based, interactive education to trainees during clinical rotations in perioperative medicine was an effective learning strategy. Sharing e-learning tools across institutions may help to deliver standardized education on core clinical topics, including perioperative medicine.

Photoredox-Catalyzed Radical-Radical Coupling of Potassium Trifluoroborates with Acyl Azoliums.

Potassium trifluoroborates have gained significant utility as coupling partners in organic synthesis, particularly in the Suzuki-Miyaura coupling reaction. Recently, they have also been used as radical precursors under oxidative conditions to generate carbon-centered radicals. These versatile reagents have found new applications in photoredox catalysis, including radical substitution, conjugate addition reactions, and transition metal dual catalysis. In addition, this photomediated redox neutral process has enabled radical-radical coupling with persistent radicals in the absence of a metal, and this process remains to be fully explored. In this study, we report the radical-radical coupling of benzylic potassium trifluoroborate salts with isolated acyl azolium triflates, which are persistent radical precursors. The reaction is catalyzed by an organic photocatalyst and forms isolable tertiary alcohol species. These compounds can be transformed into a range of substituted ketone products by simple treatment with a mild base.

The Use of Pectoralis Blocks in Breast Surgery: A Practice Advisory and Narrative Review from the Society for Ambulatory Anesthesia (SAMBA).

Although pectoralis (PECS) blocks are commonly used for breast surgery, recommendations regarding the efficacy of these blocks have thus far not been developed by any professional anesthesia society. Given the potential impact of PECS blocks on analgesia after outpatient breast surgery, The Society for Ambulatory Anesthesia (SAMBA) convened a task force to develop a practice advisory on the use of this analgesic technique. In this practice advisory, we compare the efficacy of PECS blocks with systemic analgesia, local infiltration anesthesia, and paravertebral blockade. Our objectives were to advise on two clinical questions. (1) Does PECS-1 and/or -2 blockade provide more effective analgesia for breast-conserving surgery than either systemic analgesics or surgeon-provided local infiltration anesthesia? (2) Does PECS-1 and/or -2 blockade provide equivalent analgesia for mastectomy compared with a paravertebral block (PVB)? Among patients undergoing breast-conserving surgery, PECS blocks moderately reduce postoperative opioid use, prolong time to analgesic rescue, and decrease postoperative pain scores when compared with systemic analgesics. SAMBA recommends the use of a PECS-1 or -2 blockade in the absence of systemic analgesia (Strength of Recommendation A). No evidence currently exists that strongly favors the use of PECS blocks over surgeon-performed local infiltration in this surgical population. SAMBA cannot recommend PECS blocks over surgical infiltration (Strength of Recommendation C). For patients undergoing a mastectomy, a PECS block may provide an opioid-sparing effect similar to that achieved with PVB; SAMBA recommends the use of a PECS block if a patient is unable to receive a PVB (Strength of Recommendation A).

Non-Fellowship regional anesthesia training and assessment: an international Delphi study on a consensus curriculum.

BACKGROUND AND OBJECTIVES: While there are several published recommendations and guidelines for trainees undertaking subspecialty Fellowships in regional anesthesia, a similar document describing a core regional anesthesia curriculum for non-fellowship trainees is less well defined. We aimed to produce an international consensus for the training and teaching of regional anesthesia that is applicable for the majority of worldwide anesthesiologists. METHODS: This anonymous, electronic Delphi study was conducted over two rounds and distributed to current and immediate past (within 5 years) directors of regional anesthesia training worldwide. The steering committee formulated an initial list of items covering nerve block techniques, learning objectives and skills assessment and volume of practice, relevant to a non-fellowship regional anesthesia curriculum. Participants scored these items in order of importance using a 10-point Likert scale, with free-text feedback. Strong consensus items were defined as highest importance (score ≥8) by ≥70% of all participants. RESULTS: 469 participants/586 invitations (80.0% response) scored in round 1, and 402/469 participants (85.7% response) scored in round 2. Participants represented 66 countries. Strong consensus was reached for 8 core peripheral and neuraxial blocks and 17 items describing learning objectives and skills assessment. Volume of practice for peripheral blocks was uniformly 16-20 blocks per anatomical region, while ≥50 neuraxial blocks were considered minimum. CONCLUSIONS: This international consensus study provides specific information for designing a non-fellowship regional anesthesia curriculum. Implementation of a standardized curriculum has benefits for patient care through improving quality of training and quality of nerve blocks.

Preoperative Management of Opioid and Nonopioid Analgesics: Society for Perioperative Assessment and Quality Improvement (SPAQI) Consensus Statement.

There is a lack of guidelines for preoperative dosing of opioid and nonopioid pain medications for surgical patients, which can lead to suboptimal preoperative pain control. The Society for Perioperative Assessment and Quality Improvement identified preoperative dosing of opioid and nonopioid analgesics as an area in which consensus could improve patient care. The aim of this guideline is to provide consensus that will allow perioperative physicians to make optimal recommendations regarding preoperative pain medication dosing. Six categories of pain medications were identified: opioid agonists, opioid antagonists, opioid agonist-antagonists, acetaminophen, muscle relaxants, and triptans/headache medications. We then used a Delphi survey technique to develop consensus recommendations for preoperative dosing of individual medications in each of these groups.

Radical coupling of ß-ketoesters and amides promoted by Brønsted/Lewis acids.

Recent advances in photocatalysis have enabled radical methods with complementary chemoselectivity to established two electron bond forming approaches. While this radical strategy has previously been limited to substrates with favorable redox potentials, Brønsted/Lewis acid activation has emerged as a means of facilitating otherwise difficult reductions. We report herein our investigations into the Lewis acid-promoted redox activation of ß-ketocarbonyls in a model photocatalytic radical alkylation reaction. Rapid evaluation of substrates and reactions conditions was achieved by high throughput experimentation using 96-well plate photoreactors.

Glycosyl Cross-Coupling of Anomeric Nucleophiles: Scope, Mechanism, and Applications in the Synthesis of Aryl C-Glycosides.

Stereoselective manipulations at the C1 anomeric position of saccharides are one of the central goals of preparative carbohydrate chemistry. Historically, the majority of reactions forming a bond with anomeric carbon has focused on reactions of nucleophiles with saccharide donors equipped with a leaving group. Here, we describe a novel approach to stereoselective synthesis of C-aryl glycosides capitalizing on the highly stereospecific reaction of anomeric nucleophiles. First, methods for the preparation of anomeric stannanes have been developed and optimized to afford both anomers of common saccharides in high anomeric selectivities. We established that oligosaccharide stannanes could be prepared from monosaccharide stannanes via O-glycosylation with Schmidt-type donors, glycal epoxides, or under dehydrative conditions with C1 alcohols. Second, we identified a general set of catalytic conditions with Pd2(dba)3 (2.5 mol%) and a bulky ligand (JackiePhos, 10 mol%) controlling the ß-elimination pathway. We demonstrated that the glycosyl cross-coupling resulted in consistently high anomeric selectivities for both anomers with mono- and oligosaccharides, deoxysugars, saccharides with free hydroxyl groups, pyranose, and furanose substrates. The versatility of the glycosyl cross-coupling reaction was probed in the total synthesis of salmochelins (siderophores) and commercial anti-diabetic drugs (gliflozins). Combined experimental and computational studies revealed that the ß-elimination pathway is suppressed for biphenyl-type ligands due to the shielding of Pd(II) by sterically demanding JackiePhos, whereas smaller ligands, which allow for the formation of a Pd-F complex, predominantly result in a glycal product. Similar steric effects account for the diminished rates of cross-couplings of 1,2-cis C1-stannanes with aryl halides. DFT calculations also revealed that the transmetalation occurs via a cyclic transition state with retention of configuration at the anomeric position. Taken together, facile access to both anomers of various glycoside nucleophiles, a broad reaction scope, and uniformly high transfer of anomeric configuration make the glycosyl cross-coupling reaction a practical tool for the synthesis of bioactive natural products, drug candidates, allowing for late-stage glycodiversification studies with small molecules and biologics.

Highly Stereospecific Cross-Coupling Reactions of Anomeric Stannanes for the Synthesis of C-Aryl Glycosides.

We demonstrate that configurationally stable anomeric stannanes undergo a stereospecific cross-coupling reaction with aromatic halides in the presence of a palladium catalyst with exceptionally high levels of stereocontrol. In addition to a broad substrate scope (>40 examples), this reaction eliminates critical problems inherent to nucleophilic displacement methods and is applicable to (hetero)aromatics, peptides, pharmaceuticals, common monosaccharides, and saccharides containing free hydroxyl groups.

Continuous pipeline subject to transverse PGD: A comparison of solutions

The response of buried continuos pipeline to transverse Permanent Ground Deformation (PGD)has been studied by a number of investigators over the past few years. In this paper the numerical results by O'Rourke (1988) and Suzuki et al (1988) as well as analytical results by O'Rourke (1989) are compared. It is shown that the numerical results for moderate to large widths of the PGD zone (with >/ 30 m) agree reasonably well, and compare favorably with simplified analytical results. However, for small widths of the PGD zone (with = 10 m) the numerical results differ among investigators. New numerical and analytical results are presented which clarify these differences and suggest appropriate approaches for the "small width" case. Finally, information from PGD case histories, primarily form Japan, is used to establish the range of likely values of the width of the PGD zone.(AU)

Failure criterion for buried pipe subject to longitudinal PGD : Benchmark case history

The effects of longitudinal Permanent Ground Deformation (PGD) on a buried continuous steel pipeline is considered. Longitudinal PGD, (ground movement parallel to the pipe's axis) is characterized by the amount of movement, & and its spatial extent, L. Local compressional buckling of the pipe wall and tensile failure of pipeline are taken as the failure modes of interest. Critical values for the amount of ground movement and the spatial extent, which lead to compressive failure, &cr and Lcr, are determined for five grades od steel, various R/t ratios and burial conditions. Three buried pipelines which were subject to longitudinal PGD during the 1994 Northridge California event are used to benchmark the proposed failure criterion. The proposed analytical procedure suggest that two of the three pipes, the Los Angeles Dept of Water and Power Granada Trunk Line and the So. Cal. Gas (SCG) Line 120; both located along Balboa Blvd. at the Northern and of the San Fernando Valley would suffer damage. The observed behavior matches the predicted behavior. The third line, the newer SCG line along McLennan Ave., is also considered. For the third line, we postulate as to why it was not damaged. There are two other lines along Balboa which were undamaged by the PGD. These two lines are excluded from consideration because of a lack of information on certain parameters. Finally the effects of an expansion joint which was installed in the LADWP line after the 1971 San Fernando earthquake are discussed in detail.(AU)

Seismic effects on underground pipelines due to permanent longitudinal ground deformations

The bahavior of buried, welded steel pipelines subjected to longitudinal permanent deformations (PGD) is considered. Longitudinal PGD refers to soil movements which are parallel to the pipelines axis. The induced axial strain in the pipe is shown to theoretically be a function of the length of the PGD zone, the spatial distribution of the ground movement and the pipes embedment length. The embedment length for the pipe is similar to a development length for a reinforcing bar in concrete design. Analytical expressions and graphs are developed for evaluating pipe strain due to five idealized patterns of longitudinal PGD. These expressions are then used to determine axial atrain in three hypothetical pipeline due to 27 PGD patterns observed by Japanese investigators.(AU)