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1.
Angew Chem Int Ed Engl ; 63(20): e202402795, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38465783

RESUMO

While the nucleophilic addition of ammonia to ketones is an archetypal reaction in classical organic chemistry, the reactivity of heavier group 14 carbonyl analogues (R2E=O; E=Si, Ge, Sn, or Pb) with NH3 remains sparsely investigated, primarily due to the synthetic difficulties in accessing heavier ketone congeners. Herein, we present a room-temperature stable boryl-substituted amidinato-silanone {(HCDippN)2B}{PhC(tBuN)2}Si=O (Dipp=2,6-iPr2C6H3) (together with its germanone analogue), formed from the corresponding silylene under a N2O atmosphere. This system reacts cleanly with ammonia in 1,2-fashion to give an isolable sila-hemiaminal complex {(HCDippN)2B}{PhC(tBuN)2}Si(OH)(NH2). Quantum chemical calculations reveal that the formation of this sila-hemiaminal is crucially dependent on the nature of the ancillary ligand scaffold. It is facilitated thermodynamically by the hemi-lability of the amidinate ligand (which allows for the formation of an energetically critical intramolecular N⋅⋅⋅HO hydrogen bond within the product) and is enabled mech-anistically by a process in which the silanone initially acts in umpolung fashion as a base (rather than an acid), due to the strongly electron-releasing and sterically bulky nature of the ancillary boryl ligand.

2.
Angew Chem Int Ed Engl ; 63(22): e202405053, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38536728

RESUMO

The homoleptic magnesium bis(aluminyl) compound Mg[Al(NON)]2 (NON=4,5-bis(2,6-diisopropylanilido)-2,7-di-tert-butyl-9,9-dimethylxanthene) can be accessed from K2[Al(NON)]2 and MgI2 and shown to possess a non-linear geometry (∠Al-Mg-Al=164.8(1)°) primarily due to the influence of dispersion interactions. This compound acts a four-electron reservoir in the reductive de-fluorination of SF6, and reacts thermally with polar substrates such as MeI via nucleophilic attack through aluminium, consistent with the QT-AIM charges calculated for the metal centres, and a formal description as a Al(I)-Mg(II)-Al(I) trimetallic. On the other hand, under photolytic activation, the reaction with 1,5-cyclooctadiene leads to the stereo-selective generation of transannular cycloaddition products consistent with radical based chemistry, emphasizing the covalent nature of the Mg-Al bonds and a description as a Al(II)-Mg(0)-Al(II) synthon. Consistently, photolysis of Mg[Al(NON)]2 in hexane in the absence of COD generates [Al(NON)]2 together with magnesium metal.

3.
Angew Chem Int Ed Engl ; 63(23): e202404527, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38545953

RESUMO

Bimetallic compounds containing direct metal-group 13 element bonds have been shown to display unprecedented patterns of cooperative reactivity towards small molecules, which can be influenced by the identity of the group 13 element. In this context, we present here a systematic appraisal of group 13 metallo-ligands of the type [(NON)E]- (NON=4,5-bis(2,6-diisopropylanilido)-2,7-di-tert-butyl-9,9-dimethylxanthene) for E=Al, Ga and In, through a comparison of structural and spectroscopic parameters associated with the trans L or X ligands in linear d10 complexes of the types LM{E(NON)} and XM'{E(NON)}. These studies are facilitated by convenient syntheses (from the In(I) precursor, InCp) of the potassium indyl species [{K(NON)In}⋅KCp]n (1) and [(18-crown-6)2K2Cp] [(NON)In] (1'), and lead to the first structural characterisation of Ag-In and Hg-E (E=Al, In) covalent bonds. The resulting structural, spectroscopic and quantum chemical probes of Ag/Hg complexes are consistent with markedly stronger σ-donor capabilities of the aluminyl ligand, [(NON)Al]-, over its gallium and indium counterparts.

4.
J Am Chem Soc ; 145(8): 4408-4413, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36786728

RESUMO

The reactions of anionic aluminium or gallium nucleophiles {K[E(NON)]}2 (E = Al, 1; Ga, 2; NON = 4,5-bis(2,6-diisopropylanilido)-2,7-ditert-butyl-9,9-dimethylxanthene) with beryllocene (BeCp2) led to the displacement of one cyclopentadienyl ligand at beryllium and the formation of compounds containing Be-Al or Be-Ga bonds (NON)EBeCp (E = Al, 3; Ga, 4). The Be-Al bond in the beryllium-aluminyl complex [2.310(4) Å] is much shorter than that found in the small number of previous examples [2.368(2) to 2.432(6) Å], and quantum chemical calculations suggest the existence of a non-nuclear attractor (NNA) for the Be-Al interaction. This represents the first example of a NNA for a heteroatomic interaction in an isolated molecular complex. As a result of this unusual electronic structure and the similarity in the Pauling electronegativities of beryllium and aluminium, the charge at the beryllium center (+1.39) in 3 is calculated to be less positive than that of the aluminium center (+1.88). This calculated charge distribution suggests the possibility for nucleophilic behavior at beryllium and correlates with the observed reactivity of the beryllium-aluminyl complex with N,N'-diisopropylcarbodiimide─the electrophilic carbon center of the carbodiimide undergoes nucleophilic attack by beryllium, thereby yielding a beryllium-diaminocarbene complex.

5.
Chemistry ; 29(20): e202203634, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-36598847

RESUMO

A new synthetic access to the Lewis acid [Au(OTeF5 )3 ] and the preparation of the related, unprecedented anion [Au(OTeF5 )4 ]- with inorganic or organic cations starting from commercially available and easy-to-handle gold chlorides are presented. In this first extensive study of the Lewis acidity of a transition-metal teflate complex by using different experimental and quantum chemical methods, [Au(OTeF5 )3 ] was classified as a Lewis superacid. The solid-state structure of the triphenylphosphine oxide adduct [Au(OPPh3 )(OTeF5 )3 ] was determined, representing the first structural characterization of an adduct of this highly reactive [Au(OTeF5 )3 ]. Therein, the coordination environment around the gold center slightly deviates from the typical square planar geometry. The [Au(OTeF5 )4 ]- anion shows a similar coordination motif.

6.
Chemistry ; 29(20): e202300006, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-36594576

RESUMO

The reduction of the boryl-substituted SnII bromide {(HCDippN)2 B}Sn(IPrMe)Br with 1.5 equivalents of potassium graphite leads to the generation of the cyclic tetratin tetraboryl system K2 [Sn4 {B(NDippCH)2 }4 ], a homo-metallic heavier analogue of the cyclobutadiene dianion. This system is non-aromatic as determined by Nucleus Independent Chemical Shift Calculations (NICS(0)=-0.28, NICS(1)=-3.17), with the primary contributing resonance structures shown by Natural Resonance Theory (NRT) to involve a Sn=Sn double bond and 1,2-localized negative charges. Abstraction of the K+ cations or oxidation leads to contraction or cleavage of the Sn4 unit, respectively, while protonation generates the neutral dihydride 1,2-Sn4 {B(NDippCH)2 }4 H2 (a heavier homologue of cyclobutene) in a manner consistent with the predicted charge distribution in the [Sn4 {B(NDippCH)2 }4 ]2- dianion.

7.
Chemistry ; 29(10): e202203395, 2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36399407

RESUMO

Boryltin compounds featuring the metal in the+1 or 0 oxidation states can be synthesized from the carbene-stabilized tin(II) bromide (boryl)Sn(NHC)Br (boryl={B(NDippCH)2 }; NHC=C{(Ni PrCMe)2 }) by the use of strong reducing agents. The formation of the mono-carbene stabilized distannyne and donor-free distannide systems (boryl)SnSn(IPrMe)(boryl) (2) and K2 [Sn2 (boryl)2 ] (3), using Mg(I) and K reducing agents mirrors related germanium chemistry. In contrast to their lighter congeners, however, systems of the type [Sn(boryl)]n are unstable with respect to disproportionation. Carbene abstraction from 2 using BPh3 , and two-electron oxidation of 3 both result in the formation of a 2 : 1 mixture of the Sn(II) compound Sn(boryl)2 , and the hexatin cluster, Sn6 (boryl)4 (4). A viable mechanism for this rearrangement is shown by quantum chemical studies to involve a vinylidene intermediate (analogous to the isolable germanium compound, (boryl)2 Ge=Ge), which undergoes facile atom transfer to generate Sn(boryl)2 and trinuclear [Sn3 (boryl)2 ]. The latter then dimerizes to give the observed hexametallic product 4, with independent studies showing that similar trigermanium species aggregate in analogous fashion.

8.
Chemistry ; 29(51): e202301684, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37340637

RESUMO

We report on a comprehensive reactivity study starting from [AuF3 (SIMes)] to synthesize different motifs of monomeric gold(III) fluorides. A plethora of different ligands has been introduced in a mono-substitution yielding trans-[AuF2 X(SIMes)] including alkynido, cyanido, azido, and a set of perfluoroalkoxido complexes. The latter were better accomplished via use of perfluorinated carbonyl-bearing molecules, which is unprecedented in gold chemistry. In case of the cyanide and azide, triple substitution gave rise to the corresponding [AuX3 (SIMes)] complexes. Comparison of the chemical shift of the carbene carbon atom in the 13 C{1 H} NMR spectrum, the calculated SIMes affinity and the Au-C bond length in the solid state with related literature-known complexes yields a classification of trans-influences for a variety of ligands attached to the gold center. Therein, the mixed fluorido perfluoroalkoxido complexes have a similar SIMes affinity to AuF3 with a very low Gibbs energy of formation when using the perfluoro carbonyl route.

9.
Environ Sci Technol ; 57(29): 10708-10720, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-37437161

RESUMO

Particulate matter air pollution is a leading cause of global mortality, particularly in Asia and Africa. Addressing the high and wide-ranging air pollution levels requires ambient monitoring, but many low- and middle-income countries (LMICs) remain scarcely monitored. To address these data gaps, recent studies have utilized low-cost sensors. These sensors have varied performance, and little literature exists about sensor intercomparison in Africa. By colocating 2 QuantAQ Modulair-PM, 2 PurpleAir PA-II SD, and 16 Clarity Node-S Generation II monitors with a reference-grade Teledyne monitor in Accra, Ghana, we present the first intercomparisons of different brands of low-cost sensors in Africa, demonstrating that each type of low-cost sensor PM2.5 is strongly correlated with reference PM2.5, but biased high for ambient mixture of sources found in Accra. When compared to a reference monitor, the QuantAQ Modulair-PM has the lowest mean absolute error at 3.04 µg/m3, followed by PurpleAir PA-II (4.54 µg/m3) and Clarity Node-S (13.68 µg/m3). We also compare the usage of 4 statistical or machine learning models (Multiple Linear Regression, Random Forest, Gaussian Mixture Regression, and XGBoost) to correct low-cost sensors data, and find that XGBoost performs the best in testing (R2: 0.97, 0.94, 0.96; mean absolute error: 0.56, 0.80, and 0.68 µg/m3 for PurpleAir PA-II, Clarity Node-S, and Modulair-PM, respectively), but tree-based models do not perform well when correcting data outside the range of the colocation training. Therefore, we used Gaussian Mixture Regression to correct data from the network of 17 Clarity Node-S monitors deployed around Accra, Ghana, from 2018 to 2021. We find that the network daily average PM2.5 concentration in Accra is 23.4 µg/m3, which is 1.6 times the World Health Organization Daily PM2.5 guideline of 15 µg/m3. While this level is lower than those seen in some larger African cities (such as Kinshasa, Democratic Republic of the Congo), mitigation strategies should be developed soon to prevent further impairment to air quality as Accra, and Ghana as a whole, rapidly grow.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Gana , Monitoramento Ambiental , República Democrática do Congo , Material Particulado/análise , Poluição do Ar/análise
10.
Philos Trans A Math Phys Eng Sci ; 381(2248): 20220009, 2023 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-37031698

RESUMO

Perception of the relationship of the discipline of logic to other exact sciences changes with the years. No twentieth-century proposal for a single logical system that would support the whole of mathematics satisfied everyone, so weaker formal systems with applications in many different contexts are now sought, in mathematics, philosophy, computer science or elsewhere. As always, logicians help by asking such questions as 'Is this theory correct for the given context?' and 'Can it be used in other contexts?' The Introduction of this paper surveys the history of logic and its links to other scientific disciplines such as biology, economics, engineering and physics, and some details of current and future research projects are given. Then the very weak set theory PROVI is introduced and its support for the techniques of constructibility (Gödel 1935) and forcing (Cohen PJ 1963 The independence of the continuum hypothesis, I. Proc. Natl Acad. Sci. USA 50, 1143-1148. (doi:10.1073/pnas.50.6.1143)) is given in outline, full details being already in print. Relations with other known techniques are explored and developed. New results coming from the study of illfounded [Formula: see text]-models of PROVI and other systems are given; and new formal systems in the style of Quine (1937 Quine WV. 1936 Set-theoretic foundations for logic. J. Symb. Log. 1, 45-57. (doi:10.2307/2268548)) are described. This article is part of the theme issue 'Modern perspectives in Proof Theory'.

11.
Anaesthesia ; 78(10): 1215-1224, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37402349

RESUMO

The purpose of this study was to understand the views and experiences of patients enrolled and staff involved in the prehabilitation of elective patients undergoing cardiac surgery trial. This sub-study was informed by normalisation process theory, a framework for evaluating complex interventions, and used consecutive sampling to recruit patients assigned to both the intervention and control groups. Patients and all staff involved in delivering the trial were invited to participate in focus groups, which were recorded, transcribed verbatim and subjected to reflexive thematic analysis. Five focus groups were held comprising 24 participants in total (nine patients assigned to the prehabilitation; seven assigned to control; and eight staff). Five themes were identified. First, preparedness for surgery reduced fear, where participants described that knowing what to expect from surgery and preparing the body physically increased feelings of control and subsequently reduced apprehension regarding surgery. Second, staff were concerned but trusted in a safe environment, describing how, despite staff's concerns regarding the risks of exercise in this population, the patients felt safe in their care whilst participating in an exercise programme in hospital. Third, rushing for recovery and the curious carer, where patients from both groups wanted to mobilise quickly postoperatively whilst staff visited patients on the ward to observe their recovery progress. Fourth, to survive and thrive postoperatively, reflecting staff and patients' expectations from the trial and what motivated them to participate. Fifth, benefits are diluted by lengthy waiting periods, reflecting the frustration felt by patients waiting for their surgery after completing the intervention and the fear about continuing exercise at home before they had been 'fixed'. To conclude, functional exercise capacity may not have improved following prehabilitation in people before elective cardiac surgery due to concerns regarding the safety of exercise that may have hindered delivery and receipt of the intervention. Instead, numerous non-physical benefits were elicited. The information from this qualitative study offers valuable recommendations regarding refining a prehabilitation intervention and conducting a subsequent trial.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Exercício Pré-Operatório , Humanos , Exercício Físico , Modalidades de Fisioterapia , Cuidados Pré-Operatórios
12.
Anaesthesia ; 78(9): 1120-1128, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37402352

RESUMO

The feasibility, safety and efficacy of prehabilitation in adult patients awaiting elective cardiac surgery are unknown. A total of 180 participants undergoing elective cardiac surgery were allocated randomly to receive either standard pre-operative care or prehabilitation, consisting of pre-operative exercise and inspiratory muscle training. The primary outcome was change in six-minute walk test distance from baseline to pre-operative assessment. Secondary outcomes included change in inspiratory muscle strength (maximal inspiratory pressure); sarcopenia (handgrip strength); quality of life and compliance. Safety outcomes were pre-specified surgical and pulmonary complications and adverse events. All outcomes were assessed at baseline; at pre-operative assessment; and 6 and 12 weeks following surgery. Mean (SD) age was 64.7 (10.2) years; 33/180 (18%) were women. In total, 65/91 (71.4%) participants who were allocated to prehabilitation attended at least four of eight supervised in-hospital exercise classes; participants aged > 50 years were more likely than younger participants to attend (odds ratio (95%CI) of 4.6 (1.0-25.1)). Six-minute walk test was not significantly different between groups (mean difference (95%CI) -7.8 m (-30.6-15.0), p = 0.503) in the intention-to-treat analysis. Subgroup analyses based on tests for interaction indicated improvements in six-minute walk test distance were larger amongst sarcopenic patients in the prehabilitation group (p = 0.004). Change in maximal inspiratory pressure from baseline to all time-points was significantly greater in the prehabilitation group, with the greatest mean difference (95%CI) observed 12 weeks after surgery (10.6 cmH2 O (4.6-16.6) cmH2 O, p < 0.001). There were no differences in handgrip strength or quality of life up to 12 weeks after surgery. There was no significant difference in postoperative mortality (one death in each group), surgical or pulmonary complications. Of 71 pre-operative adverse events, six (8.5%) were related to prehabilitation. The combination of exercise and inspiratory muscle training in a prehabilitation intervention before cardiac surgery was not superior to standard care in improving functional exercise capacity measured by six-minute walk test distance pre-operatively. Future trials should target patients living with sarcopenia and include inspiratory muscle strength training.


Assuntos
Exercício Pré-Operatório , Sarcopenia , Adulto , Humanos , Feminino , Masculino , Qualidade de Vida , Sarcopenia/complicações , Força da Mão , Exercício Físico/fisiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia
13.
Chaos ; 33(8)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38060771

RESUMO

The E×B drift motion of particles in tokamaks provides valuable information on the turbulence-driven anomalous transport. One of the characteristic features of the drift motion dynamics is the presence of chaotic orbits for which the guiding center can experience large-scale drifts. If one or more exits are placed so that they intercept chaotic orbits, the corresponding escape basins structure is complicated and, indeed, exhibits fractal structures. We investigate those structures through a number of numerical diagnostics, tailored to quantify the final-state uncertainty related to the fractal escape basins. We estimate the escape basin boundary dimension through the uncertainty exponent method and quantify final-state uncertainty by the basin entropy and the basin boundary entropy. Finally, we recall the Wada property for the case of three or more escape basins. This property is verified both qualitatively and quantitatively using a grid approach.

14.
J Am Chem Soc ; 144(20): 8908-8913, 2022 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-35536684

RESUMO

The reaction of amido-substituted stannylenes with phospha-Wittig reagents (Me3PPR) results in release of hexamethyldisilazane and tethering of the resulting -CH2PMe2PR fragment to the tin center to give P-donor stabilized stannylenes featuring four-membered Sn,C,P,P heterocycles. Through systematic increases in steric loading, the structures of these systems in the solid state can be tuned, leading to successive P-P bond lengthening and Sn-P contraction and, in the most encumbered case, to complete P-to-Sn transfer of the phosphinidene fragment. The resulting stannaphosphene features a polar Sn═P double bond as determined by structural and computational studies. The reversibility of phosphinidene transfer can be established by solution phase measurements and reactivity studies.

15.
J Surg Res ; 269: 94-102, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34537533

RESUMO

BACKGROUND: Balanced blood product transfusion improves the outcomes of trauma patients with exsanguinating hemorrhage, but it remains unclear whether administering cryoprecipitate improves mortality. We aimed to examine the impact of early cryoprecipitate transfusion on the outcomes of the trauma patients needing massive transfusion (MT). METHODS: All MT patients 18 years or older in the 2017 Trauma Quality Improvement Program (TQIP) were retrospectively reviewed. MT was defined as the transfusion of ≥10 units of blood within 24 hours. Propensity score analysis (PSA) was used to 1:1 match then compare patients who received and those who did not receive cryoprecipitate in the first 4 hours after injury. Outcomes included in-hospital mortality, 1-day mortality, in-hospital complications and transfusion needs at 24 hours. RESULTS: Of 1,004,440 trauma patients, 1,454 MT patients received cryoprecipitate and 2,920 did not. After PSA, 877 patients receiving cryoprecipitate were matched to 877 patients who did not. In-hospital mortality was lower among patients who received cryoprecipitate (49.4% v. 54.9%, P = 0.022), as was 1-day mortality. Sub-analyses showed that mortality was lower with cryoprecipitate in patients with penetrating (37.5% versus. 48%, adjusted P = 0.008), but not blunt trauma (58.5% versus. 59.8%, adjusted P = 1.000). In penetrating trauma, the cryoprecipitate group also had lower 1-day mortality (21.8% versus. 38.6%, P <0.001) and a higher rate of hemorrhage control surgeries performed within 24 hours (71.4% versus. 63.3%, P = 0.018). CONCLUSIONS: Cryoprecipitate in MT is associated with improved survival in penetrating, but not blunt, trauma. Randomized trials are needed to better define the role of cryoprecipitate in MT.


Assuntos
Ferimentos e Lesões , Ferimentos não Penetrantes , Ferimentos Penetrantes , Transfusão de Sangue , Hemorragia/complicações , Hemorragia/terapia , Mortalidade Hospitalar , Humanos , Estudos Retrospectivos , Centros de Traumatologia , Ferimentos e Lesões/complicações , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/terapia , Ferimentos Penetrantes/complicações , Ferimentos Penetrantes/terapia
16.
Eur Spine J ; 31(6): 1508-1514, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35488132

RESUMO

AIMS: Flucloxacillin is a frequently used antibiotic in the treatment of spondylodiscitis. We assessed steady-state concentrations and time above minimal inhibitory concentration (fT > MIC) of flucloxacillin in the intervertebral disc, vertebral cancellous bone, subcutaneous tissue and plasma, after intravenous and oral administration. METHODS: Sixteen pigs were randomized into two groups; Group Peroral (Group PO) and Group Intravenous (Group IV) received 1 g flucloxacillin every 6 h for 24 h orally or intravenously. Microdialysis was used for sampling in the compartments of interest. A flucloxacillin target of 50% fT > MIC was applied for three MIC targets: 0.125, 0.5 and 2.0 µg/mL. RESULTS: Intravenous administration resulted in significantly longer fT > MIC for all targets. Target attainment was only reached for the low target of 0.125 µg/mL in Group IV in vertebral cancellous bone, subcutaneous tissue, and plasma (intervertebral disc 47%). In Group IV, mean fT > MIC values in the investigated compartments were in the range of 47-67% of the dosing interval for 0.125 µg/mL, 20-35% for 0.5 µg/mL, and 0-15% for 2.0 µg/mL. In Group PO, mean fT > MIC values for 0.125 µg/mL were in the range of 1-33%. No pigs reached a concentration of 0.5 µg/mL in any of the investigated compartments in Group PO. CONCLUSION: Administration of 1 g flucloxacillin every 6 h resulted in surprisingly low steady-state fT > MIC after intravenous and oral administration. However, intravenous administration resulted in significantly higher concentrations across compartments compared to oral administration. Sufficient target tissue concentrations for treatment of spondylodiscitis may require a dose increase or alternative dosing regimens.


Assuntos
Discite , Disco Intervertebral , Administração Intravenosa , Animais , Antibacterianos/farmacologia , Osso Esponjoso , Discite/tratamento farmacológico , Floxacilina , Humanos , Testes de Sensibilidade Microbiana , Microdiálise/métodos , Suínos
17.
Angew Chem Int Ed Engl ; 61(48): e202211616, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36161749

RESUMO

A systematic study to access stable stannaimines is reported, by combining different heteroleptic stannylenes with a range of organic azides. The reactions of terphenyl-/hypersilyl-substituted stannylenes yield the putative tin nitrogen double bond, but is directly followed by 1,2-silyl migration to give SnII systems featuring bulky silylamido ligands. By contrast, the transition from a two σ donor ligand set to a mixed σ-donor/π-donor scaffold allows access to three new stannaimines which can be handled at room temperature. The reactivity profile of these Sn=N bonded species is crucially dependent on the substituent at the nitrogen atom. As such, the Sn=NMes (Mes=2,4,6-Me3 C6 H2 ) system is capable of activating a broad range of substrates under ambient conditions via 1,2-addition reactions, [2+2] and [4+2] cycloaddition reactions. Most interestingly, very rare examples of main group multiple bond metathesis reactions are also found to be viable.

18.
Glia ; 69(8): 1897-1915, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33811396

RESUMO

Peripheral nerves contain sensory and motor neuron axons coated by glial cells whose interplay ensures function, but molecular details are lacking. SNARE-proteins mediate the exchange and secretion of cargo by fusing vesicles with target organelles, but how glial SNAREs contribute to peripheral nerve function is largely unknown. We, here, identify non-neuronal Synaptobrevin (Syb) as the essential vesicular SNARE in Drosophila peripheral glia to insulate and metabolically supply neurons. We show that tetanus neurotoxin light chain (TeNT-LC), which potently inhibits SNARE-mediated exocytosis from neurons, also impairs peripheral nerve function when selectively expressed in glia, causing nerve disintegration, defective axonal transport, tetanic muscle hyperactivity, impaired locomotion, and lethality. While TeNT-LC disrupts neural function by cleaving neuronal Synaptobrevin (nSyb), it targets non-neuronal Synaptobrevin (Syb) in glia, which it cleaves at low rates: Glial knockdown of Syb (but not nSyb) phenocopied glial TeNT-LC expression whose effects were reverted by a TeNT-LC-insensitive Syb mutant. We link Syb-necessity to two distinct glial subtypes: Impairing Syb function in subperineurial glia disrupted nerve morphology, axonal transport, and locomotion, likely, because nerve-isolating septate junctions (SJs) could not form as essential SJ components (like the cell adhesion protein Neurexin-IV) were mistargeted. Interference with Syb in axon-encircling wrapping glia left nerve morphology and locomotion intact but impaired axonal transport, likely because neural metabolic supply was disrupted due to the mistargeting of metabolite shuffling monocarboxylate transporters. Our study identifies crucial roles of Syb in various glial subtypes to ensure glial-glial and glial-neural interplay needed for proper nerve function, animal motility, and survival.


Assuntos
Proteínas de Drosophila , Animais , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Neuroglia/metabolismo , Nervos Periféricos , Proteínas R-SNARE/metabolismo
19.
J Surg Res ; 268: 432-439, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34416415

RESUMO

BACKGROUND: Several studies have demonstrated that low-molecular weight heparin (LMWH) is superior to unfractionated heparin (UFH) in trauma patients. The superiority of either one has not been established for the elderly. In this study, we compared LMWH to UFH in elderly trauma patients. METHODS: A retrospective analysis of the American College of Surgeons' Trauma Quality Improvement Program database was performed for patients aged ≥65 y. Propensity score matching was performed to minimize confounders between the two groups. Outcomes included venous thromboembolic (VTE) and bleeding events. RESULTS: Overall, 93,987 patients were identified (mean age 77.1 ± 7.3 y, females 55,035 [58.6%]), of which 67,738 (72.1%) patients received LMWH and 26,249 (27.9%) received UFH. After Propensity score matching, LMWH was associated with a lower incidence of deep venous thrombosis (1.7% versus 2.1%, P = 0.007) and pulmonary embolisms (0.6% versus 1%, P< 0.001). LMWH was also associated with fewer bleeding complications (transfusions: 2.8% versus 3.5%, P< 0.001, procedures: 0.7% versus 0.9%, P = 0.007). Sub-analyses showed that differences in VTE rates were identified in patients with mild injuries (Injury Severity Score [ISS] <16, 0.6% versus 1.9%, P< 0.001). Differences in bleeding complications were identified in patients with injuries of mild (ISS <16, transfusions: 3% versus 3.8%, P< 0.001, surgeries: 0.3% versus 0.4%, P= 0.015) and moderate severity (ISS 16-24, transfusions: 1.9% versus 2.7%, P= 0.038, surgeries: 1% versus 1.7%, P= 0.013). CONCLUSION: LMWH prophylaxis is superior to UFH for VTE prevention among elderly trauma patients. LMWH prophylaxis is associated with fewer bleeding complications compared to UFH in patients with injuries of mild or moderate severity.


Assuntos
Heparina de Baixo Peso Molecular , Tromboembolia Venosa , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Feminino , Heparina/efeitos adversos , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Peso Molecular , Estudos Retrospectivos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
20.
J Surg Res ; 266: 35-43, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33975028

RESUMO

BACKGROUND: Bedside experience and studies of critically ill patients with coronavirus disease 2019 (COVID-19) indicate COVID-19 to be a devastating multisystem disease. We aim to describe the incidence, associated variables, and outcomes of rhabdomyolysis in critically ill COVID-19 patients. MATERIALS AND METHODS: Data for all critically ill adult patients (≥18 years old) admitted to the ICU at a large academic medical center with confirmed COVID-19 between March 13, 2020 and April 18, 2020 were prospectively collected. Patients with serum creatine kinase (CK) concentrations greater than 1000 U/L were diagnosed with rhabdomyolysis. Patients were further stratified as having moderate (serum CK concentration 1000-4999 U/L) or severe (serum CK concentration ≥5000 U/L) rhabdomyolysis. Univariate and multivariate analyses were performed to identify outcomes and variables associated with the development of rhabdomyolysis. RESULTS: Of 235 critically ill COVID-19 patients, 114 (48.5%) met diagnostic criteria for rhabdomyolysis. Patients with rhabdomyolysis more often required mechanical ventilation (P < 0.001), prone positioning (P < 0.001), pharmacological paralysis (P < 0.001), renal replacement therapy (P = 0.010), and extracorporeal membrane oxygenation (ECMO) (P = 0.025). They also had longer median ICU length of stay (LOS) (P < 0.001) and hospital LOS (P < 0.001). No difference in mortality was observed. Male sex, patients with morbid obesity, SOFA score, and prone positioning were independently associated with rhabdomyolysis. CONCLUSIONS: Nearly half of critically ill COVID-19 patients in our cohort met diagnostic criteria for rhabdomyolysis. Male sex, morbid obesity, SOFA score, and prone position were independently associated with rhabdomyolysis.


Assuntos
COVID-19/complicações , Obesidade Mórbida/epidemiologia , Rabdomiólise/epidemiologia , Idoso , Índice de Massa Corporal , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/virologia , Comorbidade , Creatina Quinase/sangue , Estado Terminal , Feminino , Mortalidade Hospitalar , Humanos , Incidência , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Obesidade Mórbida/diagnóstico , Escores de Disfunção Orgânica , Decúbito Ventral , Estudos Prospectivos , Rabdomiólise/sangue , Rabdomiólise/diagnóstico , Rabdomiólise/etiologia , Medição de Risco/estatística & dados numéricos , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Fatores Sexuais
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