Synthesis of Known and Previously Inaccessible Poly(pyrazolyl)Borates under Mild Conditions.

Poly(pyrazolyl)borate ligands have been obtained through the reaction of highly reactive haloboranes with in situ formed pyrazolides under very mild conditions. This versatile synthetic method allows the selective synthesis of bis-, tris-, or tetrakis(pyrazolyl)borates. Furthermore, the method is compatible with the use of functional groups on the heterocyclic moieties of the poly(pyrazolyl)borates that were not accessible to date. Strongly encumbered sodium and thallium(I) poly(pyrazolyl)borates with a reduced donating ability have been obtained for the first time.

Reducing Volatile Anesthetic Waste Using a Commercial Electronic Health Record Clinical Decision Support Tool to Lower Fresh Gas Flows.

BACKGROUND: Volatile anesthetic consumption can be reduced by minimizing excessive fresh gas flows (FGFs). Currently, it is unknown whether decision support tools embedded within commercial electronic health record systems can be successfully adopted to achieve long-term reductions in FGF rates. The authors describe the implementation of an electronic health record-based clinical decision support tool aimed at reducing FGF and evaluate the effectiveness of this intervention in achieving sustained reductions in FGF rates and volatile anesthetic consumption. METHODS: On August 29, 2018, we implemented a decision support tool within the Epic Anesthesia Information Management System (AIMS) to alert providers of high FGF (>0.7 L/min for desflurane and >1 L/min for sevoflurane) during maintenance of anesthesia. July 22, 2015, to July 10, 2018, served as our baseline period before the intervention. The intervention period spanned from August 29, 2018, to December 31, 2019. Our primary outcomes were mean FGF (L/min) and volatile agent consumption (mL/MAC-h). Because a simple comparison of 2 time periods may result in false conclusions due to underlying trends independent of the intervention, we performed segmented regression of the interrupted time series to assess the change in level at the start of the intervention and the differences in slopes before and after the intervention. The analysis was also adjusted for potential confounding variables. Data included 44,899 cases using sevoflurane preintervention with 26,911 cases postintervention, and 17,472 cases using desflurane with 1185 cases postintervention. RESULTS: Segmented regression of the interrupted times series demonstrated a decrease in mean FGF by 0.6 L/min (95% CI, 0.6-0.6 L/min; P < .0001) for sevoflurane and 0.2 L/min (95% CI, 0.2-0.3 L/min; P < .0001) for desflurane immediately after implementation of the intervention. For sevoflurane, mL/MAC-h decreased by 3.8 mL/MAC-h (95% CI, 3.6-4.1 mL/MAC-h; P < .0001) after implementation of the intervention and decreased by 4.1 mL/MAC-h (95% CI, 2.6-5.6 mL/MAC-h; P < .0001) for desflurane. Slopes for both FGF and mL/MAC-h in the postintervention period were statistically less negative than the preintervention slopes (P < .0001 for sevoflurane and P < .01 for desflurane). CONCLUSIONS: A commercial AIMS-based decision support tool can be adopted to change provider FGF management patterns and reduce volatile anesthetic consumption in a sustainable fashion.

When is the optimal time to discharge patients after liver transplantation with respect to short-term outcomes? A systematic review of the literature and expert panel recommendations.

BACKGROUND: Several factors associated with prolonged hospital stay have been described. A recent study demonstrated that hospital length of stay (LOS) is directly associated with an increased cost for liver transplantation (LT) and may be associated with greater mortality; however, the factors associated with post-LT mortality are also related to a prolonged hospital stay, that is, those factors are confounders. Thus, the actual impact of the length of post-LT hospital stay on both short-term and long-term patient and graft survival remains uncertain. OBJECTIVES: To identify the optimal time to discharge patients after LT with respect to short-term outcomes; readmission rate, 30-90-mortality and morbidity. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Initial search keywords for screening were as follows; ((discharge AND (time OR "time point" OR "time-point")) OR "length of hospital stay" OR "length of stay") AND ((liver OR hepatic) AND (transplant OR transplantation)). PROSPERO ID: CRD42021245598 RESULTS: The strength of recommendation was rated as Weak, and we did not identify the direction of recommendations regarding the optimal timing after LT concerning short-term outcomes, including "Readmission rate," six studies on 30- and/or 90-day mortality, and five studies on "30- and/or 90-day morbidity rate." CONCLUSIONS: Evidence is scarce to judge the optimal timing to discharge patients after LT with respect to short-term outcomes. In centers with robust outpatient follow-up, discharge can occur safely as early as post-transplant 6-8 days (Quality of Evidence [QOE]; Low | Grade of Recommendation; Weak).

Straightforward Synthesis of α-Chloromethylketimines Catalyzed by Gold(I). A Clean Way to Building Blocks.

α-Chloromethylketimines have been obtained through a gold-catalyzed hydroamination of aromatic and aliphatic 1-chloroalkynes with aromatic amines by using equimolar amounts of both reagents. This procedure has allowed the preparation and spectroscopic characterization of α-chloromethylketimines for the first time with a high degree of purity, complete conversion, and atom economy. The synthetic usefulness of the methodology has been demonstrated with the preparation of ß-chloroamines and indoles.

Empirical assumptions behind the violation of expectation experiments in human and non-human animals.

One of the most widely used procedures applied to non-human animals or pre-linguistic humans is the "violation of expectation paradigm". Curiously there is almost no discussion in the philosophical literature about it. Our objective will be to provide a first approach to the meta-theoretical nature of the assumptions behind the procedure that appeals to the violation of expectation and to extract some consequences. We show that behind them exists an empirical principle that affirms that the violation of the expectation of certain mental rules generates surprise. We then proceeded to discuss the nature of these "mental rules". We show that, as is often the case with theoretical concepts proposed by theories, they do not have a fixed interpretation. This will allow us to show that the usual relationship found in the developmental psychology literature between this experimental paradigm and cognitive approaches (which interpret experimental results in terms of higher-level mental activities) is not necessary. Finally, we relate this experimental design with the mark test and the inequity aversion test and discuss the possible ampliation of the application of the empirical principle of violation of expectation.

A Quantitative Model for Alkane Nucleophilicity Based on C-H Bond Structural/Topological Descriptors.

A first quantitative model for calculating the nucleophilicity of alkanes is described. A statistical treatment was applied to the analysis of the reactivity of 29 different alkane C-H bonds towards in situ generated metal carbene electrophiles. The correlation of the recently reported experimental reactivity with two different sets of descriptors comprising a total of 86 parameters was studied, resulting in the quantitative descriptor-based alkane nucleophilicity (QDEAN) model. This model consists of an equation with only six structural/topological descriptors, and reproduces the relative reactivity of the alkane C-H bonds. This reactivity can be calculated from parameters emerging from the schematic drawing of the alkane and a simple set of sums.

Gold-catalyzed ethylene cyclopropanation.

Ethylene can be directly converted into ethyl 1-cyclopropylcarboxylate upon reaction with ethyl diazoacetate (N2CHCO2Et, EDA) in the presence of catalytic amounts of IPrAuCl/NaBArF 4 (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene; BArF 4 = tetrakis(3,5-bis(trifluoromethyl)phenyl)borate).

Measuring the Relative Reactivity of the Carbon-Hydrogen Bonds of Alkanes as Nucleophiles.

We report quantitative measurements of the relative reactivities of a series of C-H bonds of gaseous or liquid Cn H2n+2 alkanes (n=1-8, 29 different C-H bonds) towards in situ generated electrophiles (copper, silver, and rhodium carbenes), with methane as the reference. This strategy surpasses the drawback of previous model reactions of alkanes with strong electrophiles suffering from C-C cleavage processes, which precluded direct comparison of the relative reactivities of alkane C-H bonds.

Impact of a quality improvement project on deceased organ donor management.

CONTEXT: Donors showed poor glucose control in the period between declaration of brain death and organ recovery. The level of hyperglycemia in the donors was associated with a decline in terminal renal function. OBJECTIVE: To determine whether implementation of a quality improvement project improved glucose control and preserved renal function in deceased organ donors. METHODS: Data collected retrospectively included demographics, medical history, mechanism of death, laboratory values, and data from the United Network for Organ Sharing. RESULTS: After implementation of the quality improvement project, deceased donors had significantly lower mean glucose concentrations (mean [SD], 162 [44] vs 212 [42] mg/dL; P<.001) and prerecovery glucose concentration (143 [66] vs 241 [69] mg/dL; P<.001). When the donor cohorts from before and after the quality improvement project were analyzed together, mean glucose concentration remained a significant predictor of terminal creatinine level (P<.001). Multivariate analysis of delayed graft function in kidney recipients matched to donors indicated that higher terminal creatinine level was associated with delayed graft function in recipients (P<.001). CONCLUSION: The quality improvement project improved donor glucose homeostasis, and the data confirm that poor glucose homeostasis is associated with worsening terminal renal function.

Catalytic functionalization of methane and light alkanes in supercritical carbon dioxide.

The development of catalytic methods for the effective functionalization of methane yet remains a challenge. The best system known to date is the so-called Catalytica Process based on the use of platinum catalysts to convert methane into methyl bisulfate with a TOF rate of 10(-3) s. In this contribution, we report a series of silver complexes containing perfluorinated tris(indazolyl)borate ligands that catalyze the functionalization of methane into ethyl propionate upon reaction with ethyl diazoacetate (EDA) by using supercritical carbon dioxide (scCO2) as the reaction medium. The employment of this reaction medium has also allowed the functionalization of ethane, propane, butane, and isobutane.

FeCl3·6H2O-catalyzed Mukaiyama-aldol type reactions of enolizable aldehydes and acetals.

Mukaiyama-aldol type reactions of acetals derived from enolizable aldehydes with FeCl3·6H2O, an eco-friendly, low-cost, and stable catalyst, lead to ß-methoxycarbonyl compounds with nearly quantitative yields. The methodology is extended to the parent aldehydes as starting materials, leading to the corresponding aldols with lower yields, but efficiently. Different alkyl and aryl substituted acetals and aldehydes have been tested in the reaction with linear and cyclic silyl enol ethers. Reactions are carried out in an open air atmosphere, and additives are not required. Acetals can be considered activating groups of the carbonyl moiety rather than a protecting group in this type of FeCl3·6H2O-catalyzed condensation.

The Influence of Hydroxyapatite Crystals on the Viscoelastic Behavior of Poly(vinyl alcohol) Braid Systems.

Composites of poly(vinyl alcohol) (PVA) in the shape of braids, in combination with crystals of hydroxyapatite (HAp), were analyzed to perceive the influence of this bioceramic on both the quasi-static and viscoelastic behavior under tensile loading. Analyses involving energy-dispersive X-ray spectroscopy (EDS) and scanning electron microscopy (SEM) allowed us to conclude that the production of a homogeneous layer of HAp on the braiding surface and the calcium/phosphate atomic ratio were comparable to those of natural bone. The maximum degradation temperature established by thermogravimetric analysis (TGA) showed a modest decrease with the addition of HAp. By adding HAp to PVA braids, an increase in the glass transition temperature (Tg) is noticed, as demonstrated by dynamic mechanical analysis (DMA) and differential thermal analysis (DTA). The PVA/HAp composite braids' peaks were validated by Fourier transform infrared (FTIR) spectroscopy to be in good agreement with common PVA and HAp patterns. PVA/HAp braids, a solution often used in the textile industry, showed superior overall mechanical characteristics in monotonic tensile tests. Creep and relaxation testing showed that adding HAp to the eight and six-braided yarn architectures was beneficial. By exhibiting good mechanical performance and most likely increased biological qualities that accompany conventional care for bone applications in the fracture healing field, particularly multifragmentary ones, these arrangements can be applied as a fibrous fixation system.

Associations between insulin-like growth factor I, vascular endothelial growth factor and its soluble receptor 1 in umbilical serum and endothelial cells obtained from normotensive and preeclamptic pregnancies.

The aim of this study was to investigate the associations between insulin-like growth factor I (IGF-I) with vascular endothelial growth factor (VEGF) and its soluble receptor 1 (sFlt-1) in umbilical serum and to study the effects of IGF-I upon sFlt-1 synthesis in human umbilical vein endothelial cells (HUVEC) in normotensive (NT) and preeclamptic (PE) pregnancies. As compared with the NT group, umbilical serum IGF-I and VEGF levels were lower in the PE group, while sFlt-1 concentrations were higher. Levels of sFlt-1 correlated with IGF-I in the NT group and with VEGF in the PE group. Basal concentration of sFlt-1 in HUVEC culture media was higher in the PE group. IGF-I stimulated sFlt-1 synthesis only in the NT group. In summary, umbilical serum sFlt-1 is associated with IGF-I in normotensive pregnancy and with VEGF in preeclampsia. IGF-I stimulates sFlt-1 synthesis in endothelial cells in normotensive but not in PE pregnancies.

Scandium(III)-zeolites as new heterogeneous catalysts for imino-Diels-Alder reactions.

This study demonstrates the first zeolite-catalyzed synthesis of piperidine derivatives, including peptidomimetics and indoloquinolizidine alkaloids. The approach developed utilizes a highly effective one-pot reaction cascade, through imine formation and imino-Diels-Alder reactions, promoted by scandium-loaded zeolites as a heterogeneous catalyst. The methodology described benefits from very low catalyst loadings (≤5 mol % of Sc(III) ), commercially and readily available starting materials, and mild reaction conditions. Furthermore, the Sc(III) -zeolite catalyst can be readily reused more than 10 times without any loss in efficiency.

Epoxidation of olefins with a silica-supported peracid in supercritical carbon dioxide under flow conditions.

Anhydrous 2-percarboxyethyl-functionalized silica (2b), a recyclable supported peracid, is a suitable reagent to perform the epoxidation of alkenes 1 in supercritical carbon dioxide at 250 bar and 40 °C under flow conditions. This procedure simplifies the isolation of the reaction products and uses only carbon dioxide as a solvent under mild conditions. The solid reagent 2b can be easily recycled by a reaction with 30% hydrogen peroxide in an acid medium.

Osteosynthesis Metal Plate System for Bone Fixation Using Bicortical Screws: Numerical-Experimental Characterization.

This study reports the numerical and experimental characterization of a standard immobilization system currently being used to treat simple oblique bone fractures of femoral diaphyses. The procedure focuses on the assessment of the mechanical behavior of a bone stabilized with a dynamic compression plate (DCP) in a neutralization function, associated to a lag screw, fastened with surgical screws. The non-linear behavior of cortical bone tissue was revealed through four-point bending tests, from which damage initiation and propagation occurred. Since screw loosening was visible during the loading process, damage parameters were measured experimentally in independent pull-out tests. A realistic numerical model of the DCP-femur setup was constructed, combining the evaluated damage parameters and contact pairs. A mixed-mode (I+II) trapezoidal damage law was employed to mimic the mechanical behavior of both the screw-bone interface and bone fractures. The numerical model replicated the global behavior observed experimentally, which was visible by the initial stiffness and the ability to preview the first loading peak, and bone crack satisfactorily.

Scandium(III) zeolites as new heterogeneous catalysts: [4+2]cyclocondensation of in situ generated aryl imines with alkenes.

Scandium(III)-exchanged zeolite was used as heterogeneous ligand-free catalysts for the [4+2]cyclocondensation of amines and aldehydes with alkenes through the in situ formation of imines. Such catalysts offered a versatile, efficient, and highly regio- and stereoselective synthesis of tetrahydroquinoline derivatives. These catalysts exhibited a wide scope and compatibility with functional groups. They are very simple to use, easy to remove (by simple filtration), and they are recyclable (up to three times without loss of activity).

Increasing the use of multimodal analgesia during adult surgery in a tertiary academic anaesthesia department.

OBJECTIVE: Multimodal analgesia pathways have been shown to reduce opioid use and side effects in surgical patients. A quality improvement initiative was implemented to increase the use of multimodal analgesia in adult patients presenting for general anaesthesia at an academic tertiary care centre. The aim of this study was to increase adoption of a perioperative multimodal analgesia protocol across a broad population of surgical patients. The use of multimodal analgesia was tracked as a process metric. Our primary outcome was opioid use normalised to oral morphine equivalents (OME) intraoperatively, in the postanaesthesia care unit (PACU), and 48 hours postoperatively. Pain scores and use of antiemetics were measured as balancing metrics. METHODS: We conducted a quality improvement study of a multimodal analgesia protocol implemented for adult (≥18 and≤70) non-transplant patients undergoing general anaesthesia (≥180 min). Components of multimodal analgesia were defined as (1) preoperative analgesic medication (acetaminophen, celecoxib, diclofenac, gabapentin), (2) regional anaesthesia (peripheral nerve block or catheter, epidural catheter or spinal) or (3) intraoperative analgesic medication (ketamine, ketorolac, lidocaine infusion, magnesium, acetaminophen, dexamethasone ≥8 mg, dexmedetomidine). We compared opioid use, pain scores and antiemetic use for patients 1 year before (baseline group-1 July 2018 to 30 June 2019) and 1 year after (implementation group-1 July 2019 to 30 June 2020) project implementation. RESULTS: Use of multimodal analgesia improved from 53.9% in the baseline group to 67.5% in the implementation group (p<0.001). There was no significant difference in intraoperative OME use before and after implementation (ß0=44.0, ß2=0.52, p=0.875). OME decreased after the project implementation in the PACU (ß0=34.4, ß2=-3.88, p<0.001) and 48 hours postoperatively (ß0=184.9, ß2=-22.59, p<0.001), while pain scores during those time points were similar. CONCLUSION: A perioperative pragmatic multimodal analgesic intervention was associated with reduced OME use in the PACU and 48 hours postoperatively.

Sc(III)-doped zeolites as new heterogeneous catalysts: mukaiyama aldol reaction.

Sc(III)-doped solids based on zeolite materials have been investigated for the first time as catalysts in organic synthesis. Sc(III)-USY zeolite proved to be a novel and very efficient heterogeneous catalyst for the Mukaiyama aldol reaction. This easy-to-prepare catalyst exhibited wide scope and compatibility with functional groups and is very simple to use, easy to remove (by simple filtration), and is recyclable (up to three times without loss of activity).

Application of MEMS technology and engineering in medicine: a new paradigm for facial muscle reanimation.

Translational research may lead to development of micro-electromechanical system-based devices to treat muscle and nerve dysfunctions whose current treatments are inadequate and, at best, palliative. This paper discusses the development of engineered microsystems as a treatment option for palsies of the seventh cranial nerve and the potential application of these devices as a platform technology for treatment of other nervous dysfunctions. The engineering techniques for electrical and chemical stimulation of denervated muscle are discussed along with current caveats from clinical and engineering standpoints. As opposed to current treatments, miniaturized implants offer the possibility of the reduced toxicity and increased specificity of direct drug delivery. As with the increased miniaturization of other technologies, engineering of these increasingly small implantable microsystems holds great promise for the future development of yet smaller, even nanoscale, implantable devices.