Stereocontrolled Access to Quaternary Centers by Birch Reduction/Alkylation of Chiral Esters of Salicylic Acids.

8-Phenylmenthol esters of salicylic acid derivatives undergo efficient Birch reduction and in situ diastereoselective alkylations to afford methoxycyclohexadienes bearing new quaternary stereogenic centers. The use of an ester-based auxiliary is a designed improvement over the use of prolinol-derived amides, which are expensive and often very difficult to cleave.

Stress propagation in locally loaded packings of disks and pentagons.

The mechanical strength and flow of granular materials can depend strongly on the shapes of individual grains. We report quantitative results obtained from photoelasticimetry experiments on locally loaded, quasi-two-dimensional granular packings of either disks or pentagons exhibiting stick-slip dynamics. Packings of pentagons resist the intruder at significantly lower packing fractions than packings of disks, transmitting stresses from the intruder to the boundaries over a smaller spatial extent. Moreover, packings of pentagons feature significantly fewer back-bending force chains than packings of disks. Data obtained on the forward spatial extent of stresses and back-bending force chains collapse when the packing fraction is rescaled according to the packing fraction of steady state open channel formation, though data on intruder forces and dynamics do not collapse. We comment on the influence of system size on these findings and highlight connections with the dynamics of the disks and pentagons during slip events.

A Direct Synthesis of Highly Substituted π-Rich Aromatic Heterocycles from Oxetanes.

The ubiquitous use of π-rich five-membered heterocycles has driven the development of new methods for their synthesis for more than a century. Here, we disclose a general and reliable reaction manifold for the construction of highly substituted heterocycles through a facile Lewis-acid-catalyzed oxetane rearrangement. Notably, this methodology employs a keto-oxetane motif as a 1,4-dicarbonyl surrogate, which can be synthesized using robust alkylation or alkenylation reactions, and thus obviates the need to access 1,4-dicarbonyl compounds via umpoled starting materials. We harnessed this reactivity to generate a broad range of substituted furans and pyrroles, and extended this methodology to produce benzo-fused versions thereof.

Copper-Catalyzed Amidation of Primary and Secondary Alkyl Boronic Esters.

The oxidative copper-catalyzed cross-coupling of functionalized alkyl boronic esters with primary amides is reported. Through the identification of appropriate diketimine ligands, conditions for efficient coupling of both primary and secondary alkyl boronic esters with diverse primary amides, including acetamide, have been developed.

Evolution of force networks during stick-slip motion of an intruder in a granular material: Topological measures extracted from experimental data.

In quasi-two-dimensional experiments with photoelastic particles confined to an annular region, an intruder constrained to move in a circular path halfway between the annular walls experiences stick-slip dynamics. We discuss the response of the granular medium to the driven intruder, focusing on the evolution of the force network during sticking periods. Because the available experimental data do not include precise information about individual contact forces, we use an approach developed in our previous work [Basak et al., J. Eng. Mech. 147, 04021100 (2021)0733-939910.1061/(ASCE)EM.1943-7889.0002003] based on networks constructed from measurements of the integrated strain magnitude on each particle. These networks are analyzed using topological measures based on persistence diagrams, revealing that force networks evolve smoothly but in a nontrivial manner throughout each sticking period, even though the intruder and granular particles are stationary. Characteristic features of persistence diagrams show identifiable slip precursors. In particular, the number of generators describing the structure and complexity of force networks increases consistently before slips. Key features of the dynamics are similar for granular materials composed of disks or pentagons, but some details are consistently different. In particular, we find significantly larger fluctuations of the measures computed based on persistence diagrams and, therefore, of the underlying networks, for systems of pentagonal particles.

Effects of neonatal antiepileptic drug exposure on cognitive, emotional, and motor function in adult rats.

Despite the potent proapoptotic effect of several antiepileptic drugs (AEDs) in developmental rodent models, little is known about the long-term impact of exposure during brain development. Clinically, this is of growing concern. To determine the behavioral consequences of such exposure, we examined phenobarbital, phenytoin, and lamotrigine for their effects on adult behaviors after administration to neonatal rats throughout the second postnatal week. AED treatment from postnatal days 7 to 13 resulted in adult deficits in spatial learning in the Morris water maze and decreased social exploration for all drugs tested. Phenobarbital exposure led to deficits in cued fear conditioning, risk assessment in the elevated plus maze, and sensorimotor gating as measured by prepulse inhibition, but it did not affect motor coordination on the rotorod task. In contrast, phenytoin and lamotrigine exposure led to impaired rotorod performance, but no deficits in sensorimotor gating. Phenytoin, but not lamotrigine or phenobarbital, increased exploration in the open field. Phenytoin and phenobarbital, but not lamotrigine, disrupted cued fear conditioning. These results indicate that AED administration during a limited sensitive postnatal period is sufficient to cause a range of behavioral deficits later in life, and the specific profile of behavioral deficits varies across drugs. The differences in the long-term outcomes associated with the three AEDs examined are not predicted by either the mechanism of AED action or the proapoptotic effect of the drugs. Our findings suggest that a history of AED therapy during development must be considered as a variable when assessing later-life cognitive and psychiatric outcomes.

Universal features of the stick-slip dynamics of an intruder moving through a confined granular medium.

Experiments and simulations of an intruder dragged by a spring through a two-dimensional annulus of granular material exhibit robust force fluctuations. At low packing fractions (ϕ<ϕ_{0}), the intruder clears an open channel. Above ϕ_{0}, stick-slip dynamics develop, with an average energy release that is independent of the particle-particle and particle-base friction coefficients but does depend on the width W of the annulus and the diameter D of the intruder. A simple model predicts the dependence of ϕ_{0} on W and D, allowing for a data collapse for the average energy release as a function of ϕ/ϕ_{0}. These results pose challenges for theories of mechanical failure in amorphous materials.

A clinical evaluation of the intubating laryngeal airway as a conduit for tracheal intubation in children.

BACKGROUND: The air-Q Intubating Laryngeal Airway (ILA) (Cookgas LLC, Mercury Medical, Clearwater, FL) is a supraglottic airway device available in pediatric sizes, with design features to facilitate passage of cuffed tracheal tubes when used to guide tracheal intubation. We designed this prospective observational study of the ILA to assess the ease of its placement in paralyzed pediatric patients, determine its position and alignment to the larynx using a fiberoptic bronchoscope, gauge its efficacy as a conduit for fiberoptic intubation with cuffed tracheal tubes, and evaluate the ability to remove the ILA without dislodgement of the tracheal tube after successful tracheal intubation. METHODS: One hundred healthy children, aged 6 months to 8 years, ASA physical status I to II, and scheduled for elective surgery requiring general endotracheal anesthesia were enrolled in this prospective study. Based on the manufacturer's guidelines, each patient received either a size 1.5 or 2.0 ILA according to their weight. The number of attempts for successful insertion, leak pressures, fiberoptic grade of view, number of attempts and time for tracheal intubation, time for ILA removal, and complications were recorded. RESULTS: ILA placement, fiberoptic tracheal intubation, and ILA removal were successful in all patients. The size 1.5 ILA cohort had significantly higher rates of epiglottic downfolding compared with the size 2.0 ILA cohort (P < 0.001), despite adequate ventilation variables. When comparing fiberoptic grade of view to weight, a moderate negative correlation was found (r = -0.41, P < 0.001), indicating that larger patients tended to have better fiberoptic grades of view. The size 1.5 ILA cohort had a significantly longer time to intubation (P = 0.04) compared with the size 2.0 ILA cohort. However, this difference may not be clinically significant because there was a large overlap of confidence bounds in the average times of the size 1.5 ILA (27.0 ± 13.0 seconds) and size 2.0 ILA cohorts (22.7 ± 6.9 seconds). When comparing weight to time to tracheal intubation, a weak correlation that was not statistically significant was found (r = -0.17, P = 0.09), showing that time to intubation did not differ significantly according to weight, despite higher fiberoptic grades in smaller patients. CONCLUSIONS: The ILA was easy to place and provided an effective conduit for tracheal intubation with cuffed tracheal tubes in children with normal airways. Additionally, removal of the ILA after successful intubation could be achieved quickly and without dislodgement of the tracheal tube. Because of the higher incidence of epiglottic downfolding in smaller patients, the use of fiberoptic bronchoscopy is recommended to assist with tracheal intubation through this device.

Retrospective audit of the air-Q intubating laryngeal airway as a conduit for tracheal intubation in pediatric patients with a difficult airway.

OBJECTIVES: To assess the efficacy of the ILA as a conduit for tracheal intubation in pediatric patients with a difficult airway. AIM: The primary goals of this retrospective audit were to assess the clinical performance of the ILA in pediatric patients with a difficult airway, expand on our initial favorable experience with this device, and collect pilot data for future prospective and comparison studies. METHODS: The charts of patients with a difficult airway in whom the ILA was used during a period of 1 year in a freestanding pediatric institution were reviewed following a practice change in the authors' institution favoring the ILA over the laryngeal mask airway as a conduit for tracheal intubation. RESULTS: Thirty-four pediatric patients had an ILA placed during the course of their airway management. Eight of the 34 patients in this cohort required emergent airway management. The median age was 47.1 (0.3-202.2) months and the median weight was 16.3 (3.9-86.0) kilograms. Three of the cases were unanticipated difficult airways and the remaining were anticipated difficult airways as a result of craniofacial syndromes (n = 21), cervical spine instability or immobility (n = 7), or airway hemorrhage (n = 3). Thirty-three of the 34 patients (97%) were intubated on the first attempt through the ILA, with the aid of a fiberoptic bronchoscope (n = 25), a Shikani Optical Stylet (n = 7), or blindly (n = 2). In one patient, blind tracheal intubation required a second attempt for successful intubation, making the overall success rate 100%. Oxygen desaturation was noted in 6 of the 34 cases. CONCLUSIONS: In a series of pediatric patients with difficult airways, the ILA was successfully used as a conduit for tracheal intubation in all patients. Visualization techniques may offer a greater degree of success in intubations through the ILA due to the potential for epiglottic down-folding in children.

Modified Use of a Fibular Strut in the Reduction and Stabilization of 2-Part Osteoporotic Proximal Humerus Fractures.

PURPOSE: This study introduces a modified use of a fibular strut allograft as an adjunct to lateral locked plating in the treatment of osteoporotic two-part fractures of the proximal humerus. METHODS: A prospective series of 13 consecutive patients (mean age 68; range, 60 to 88) with displaced two-part fractures of the proximal humerus were included. The main outcome measures included radiographic healing, clinical and radiographic findings of complications, assessment of shoulder function measured with the Shoulder Function Index, and ultrasonography assessment of rotator cuff disruption. RESULTS: At postoperative month four, every fracture healed as evidenced on radiographic assessment. Clinically, patients achieved an average shoulder forward flexion of 141.5°, external rotation of 37°, and abduction of 98°. The mean Shoulder Function Index score was 73.2 (range, 64 to 77). No patients were included who required a major or a minor revision surgery. The average follow-up was 13.2 months (range, 12 to 15). Ultrasonography demonstrated no tears of the rotator cuff. DISCUSSION: In a series of 13 patients, our technique facilitated fracture reduction while avoiding additional soft-tissue dissection at the fracture site and enabled supplementary stabilization after application of a lateral locking plate. Using this technique, we had minimal complications, a high rate of osseous healing, and achieved favorable clinical outcomes in a challenging patient population.

Intruder in a two-dimensional granular system: Effects of dynamic and static basal friction on stick-slip and clogging dynamics.

We present simulation results for an intruder pulled through a two-dimensional granular system by a spring using a model designed to mimic the experiments described by Kozlowski et al. [Phys. Rev. E 100, 032905 (2019)2470-004510.1103/PhysRevE.100.032905]. In that previous study the presence of basal friction between the grains and the base was observed to change the intruder dynamics from clogging to stick-slip. Here we first show that our simulation results are in excellent agreement with the experimental data for a variety of experimentally accessible friction coefficients governing interactions of particles with each other and with boundaries. We then use simulations to explore a broader range of parameter space, focusing on the friction between the particles and the base. We consider both static and dynamic basal friction coefficients, which are difficult to vary smoothly in experiments. The simulations show that dynamic friction strongly affects the stick-slip behavior when the coefficient is decreased below 0.1, while static friction plays only a marginal role.

Dynamics of a grain-scale intruder in a two-dimensional granular medium with and without basal friction.

We report on a series of experiments in which a grain-sized intruder is pushed by a spring through a two-dimensional granular material composed of photoelastic disks in a Couette geometry. We study the intruder dynamics as a function of packing fraction for two types of supporting substrates: A frictional glass plate and a layer of water for which basal friction forces are negligible. We observe two dynamical regimes: Intermittent flow, in which the intruder moves freely most of the time but occasionally gets stuck, and stick-slip dynamics, in which the intruder advances via a sequence of distinct, rapid events. When basal friction is present, we observe a smooth crossover between the two regimes as a function of packing fraction, and we find that reducing the interparticle friction coefficient causes the stick-slip regime to shift to higher packing fractions. When basal friction is eliminated, we observe intermittent flow at all accessible packing fractions. For all cases, we present results for the statistics of stick events, the intruder velocity, and the force exerted on the intruder by the grains. Our results indicate the qualitative importance of basal friction at high packing fractions and suggest a possible connection between intruder dynamics in a static material and clogging dynamics in granular flows.

Bundle Payment for Musculoskeletal Care: Current Evidence (Part 1).

In the face of escalating costs and variations in quality of care, bundled payment models for total joint arthroplasty procedures are becoming increasingly common, both through the Centers for Medicare & Medicaid Services and private payer organizations. The effective implementation of these payment models requires cooperation between multiple service providers to ensure economic viability without deterioration in care quality. This article introduces a stepwise model for the financial analysis of bundled contracts for use in negotiations between hospitals and private payer organizations.

Bundle Payment for Musculoskeletal Care: Current Evidence (Part 2).

In an effort to rein in expenditures and improve quality of care, the Centers for Medicare and Medicaid Services (CMS) has initiated bundled reimbursement programs for total joint arthroplasty (TJA) procedures. The success of CMS's bundled payment models has prompted some private insurers to collaborate with provider organizations to institute similar bundled contracts for TJA. The authors review the experiences of orthopedic groups in the implementation of bundled payments for primary and revision TJA through both public and private payers. The authors also discuss the potential benefits, risks, and barriers groups may encounter under this novel payment model.

Pediatric pain management.

Regional anesthesia has become an integral part of adult anesthesia. Although not routinely used in children because of the need for general anesthesia that is necessary to keep the patients from moving and cooperating with the operator, regional anesthesia has been gaining immense popularity in the last decade. Although there is not much objective evidence, large prospective databases and expert opinion have favored administering regional anesthesia in the asleep child safely because major neural damage has not been reported in children. This review discusses a comprehensive approach to acute pain management in infants, children, and adolescents using regional anesthesia.

Cytotoxicity of Pseudomonas secreted exotoxins requires OxyR expression.

BACKGROUND: Nosocomial infections often lead to sepsis and multisystem organ failure in critically injured patients, including burn and trauma patients. A better understanding of the bacterial response to the host immune system is essential to develop better antimicrobials against pathogens. Pseudomonas aeruginosa combats host-initiated oxidant stress through expression of the transactivating factor, OxyR. Here we have tested the premise that OxyR regulates Pseudomonal cytotoxicity through secreted exotoxin production. MATERIALS AND METHODS: Wild-type P. aeruginosa (PAO1) and a deletion mutant lacking the oxyR gene (Delta oxyR) were grown for 18 h in Luria broth and the supernatant containing the secreted products was removed using centrifugation. Secreted proteins were isolated using ammonium sulfate precipitation. ER-MP20(+) myeloid progenitor cells were harvested from the bone marrow of C57Blk/6J mice. These cells were differentiated into dendritic cells and macrophages. Various concentrations (0-20 microg/100 microL) of the bacterial proteins were added to the medium and cells were allowed to differentiate for 7 days. Cellular viability was then assayed using a proliferation assay. These studies were repeated on two other macrophage cell lines, human U937 and murine P388D1. RESULTS: At a protein concentration of 5 microg/100 microL PAO1 supernatant protein, cellular proliferation was significantly reduced to 4.2 +/- 2.8% compared to untreated controls, while the DeltaoxyR supernatant protein remained at 103.3 +/- 4.0% of untreated controls (P < 0.05). Similar significant results were seen in the U937-, P388D1-, and ER-MP20(+)-derived macrophage cells. CONCLUSIONS: Taken together, our data indicate that OxyR regulates the secretion of potent cytotoxic factors by P. aeruginosa.