Methadone-induced mortality in the treatment of chronic pain: Role of QT prolongation

Methadone is increasingly prescribed for chronic pain, yet the associated mortality appears to be rising disproportionately relative to other opioid analgesics. We review the available evidence on methadone-associated mortality, and explore potential pharmacokinetic and pharmacodynamic explanations for its greater apparent lethality. While methadone shares properties of central nervous system and respiratory depression with other opioids, methadone is unique as a potent blocker of the delayed rectifier potassium ion channel (IKr). This results in QT-prolongation and torsade de pointes (TdP) in susceptible individuals. In some individuals with low serum protein binding of methadone, the extent of blockade is roughly comparable to that of sotalol, a potent QT-prolonging drug. Predicting an individual’s propensity for methadone-induced TdP is difficult at present given the inherent limitations of the QT interval as a risk-stratifier combined with the multifactorial nature of the arrhythmia. Consensus recommendations have recently been published to mitigate the risk of TdP until further studies better define the arrhythmia risk factors for methadone. Studies are needed to provide insights into the clinical covariates most likely to result in methadone-associated arrhythmia and to assess the feasibility of current risk mitigation strategies

A digital shadow cloud-based application to enhance quality control in manufacturing

In Industry 4.0 era, rapid changes to the global landscape of manufacturing are transforming industrial plants in increasingly more complex digital systems. One of the most impactful innovations generated in this context is the "Digital Twin", a digital copy of a physical asset, which is used to perform simulations, health predictions and life cycle management through the use of a synchronized data flow in the manufacturing plant. In this paper, an innovative approach is proposed in order to contribute to the current collection of applications of Digital Twin in manufacturing: a Digital Shadow cloud-based application to enhance quality control in the manufacturing process. In particular, the proposal comprises a Digital Shadow updated on high performance computing cloud infrastructure in order to recompute the performance prediction adopting a variation of the computer-aided engineering model shaped like the actual manufactured part. Thus, this methodology could make possible the qualification of even not compliant parts, and so shift the focus from the compliance to tolerance requirements to the compliance to usage requirements. The process is demonstrated adopting two examples: the structural assessment of the geometry of a shaft and the one of a simplified turbine blade. Moreover, the paper presents a discussion about the implications of the use of such a technology in the manufacturing context in terms of real-time implementation in a manufacturing line and lifecycle management. Copyright (C) 2020 The Authors

Исследование кристаллизации NaCl из водного раствора, находящегося в магнитном поле

In the context of developing single-site stereoselective post-metallocene catalysts, the case for isospecific styrene polymerization catalysts based on methylaluminoxane-activated group 4 metal bis(phenolato) complexes is summarized. In the context of developing single-site stereoselective post-metallocene catalysts, the case for isospecific styrene polymerization catalysts based on methylaluminoxane-activated group 4 metal bis(phenolato) complexes is summarized. Ligands derived from the 1,4-dithiabutanediyl-linked bis(phenol)s have been found to induce stereochemical rigidity by the presence of the hemi-labile sulfide donor functions. Isospecific styrene polymerization was achieved using easily accessible catalyst precursors of the type [MX 2(OC6H2-tBu2-4,6) 2S(CH2)2S] (M = Ti, Zr, Hf; X = Cl, O iPr, CH2Ph). Activating the dibenzyl titanium complex [Ti(CH2Ph)2(OC6H2- tBu2-4,6)2S(CH2)2S] with B(C6F5)3 and AliBu3, controlled isotactic polymerization became possible at lower temperatures. A remarkable dependence of both the activity and stereoselectivity on the ligand substitution pattern was observed. Analogous precursors with the 1,5-dithiapentanediyl-linked bis(phenolato) ligand gave syndiotactic polystyrene with lower activity. © 2004 Elsevier B.V. All rights reserved

Therapeutic Strategies in HCC: Radiation Modalities

Patients with hepatocellular carcinoma (HCC) comply with an advanced disease and are not eligible for radical therapy. In this distressed scenario new treatment options hold great promise; among them transarterial chemoembolization (TACE) and transarterial metabolic radiotherapy (TAMR) have shown efficacy in terms of both tumor shrinking and survival. External radiation therapy (RTx) by using novel three-dimensional conformal radiotherapy has also been used for HCC patients with encouraging results while its role had been limited in the past for the low tolerance of surrounding healthy liver. The rationale of TAMR derives from the idea of delivering exceptional radiation dose locally to the tumor, with cell killing intent, while preserving normal liver from undue exposition and minimizing systemic irradiation. Since the therapeutic efficacy of TACE is being continuously disputed, the TAMR with 131I Lipiodol or 90Y microspheres has gained consideration providing adequate therapeutic responses regardless of few toxicities. The implementation of novel radioisotopes and technological innovations in the field of RTx constitutes an intriguing field of research with important translational aspects. Moreover, the combination of different therapeutic approaches including chemotherapy offers captivating perspectives. We present the role of the radiation-based therapies in hepatocellular carcinoma patients who are not entitled for radical treatment

The stereoselective polymerization of linear conjugated dienes

Polydienes are amongst the largest worldwide produced and manufactured classes of polymers. This is because of their elastomeric properties, which make them suitable for many applications as synthetic rubbers.1

Recent Advancements in Metal-catalysts Design for CO2/Epoxide Reactions

Carbon dioxide utilization is considered an effective strategy to mitigate the carbon footprint of chemical industry. Among other uses, the incorporation of carbon dioxide into cyclic organic carbonates (COCs) and aliphatic polycarbonates (APCs) has received great attention in the field of homogeneous catalysis. After few decades of research activity, a wide range of metal-based catalytic systems has been reported to promote this reaction. Nonetheless, a better comprehension of the apparently simple reaction mechanism of such transformations has been reached only in recent years. This, in turn, allowed for the design of new catalytic systems guided by a clearer mechanistic picture. In this review, we present the most recent advancements in this field, distinguishing between catalysts for COCs and APCs production classified on the bases of their ligand structures

Terpolymerization of co2 with epoxides and cyclic organic anhydrides or cyclic esters

The synthesis of polymeric materials starting from CO2 as a feedstock is an active task of research. In particular, the copolymerization of CO2 with epoxides via ring-opening copolymerization (ROCOP) offers a simple, efficient route to synthesize aliphatic polycarbonates (APC). In many cases, APC display poor physical and chemical properties, limiting their range of application. The terpolymerization of CO2 with epoxides and organic anhydrides or cyclic esters offers the possibility, combining the ROCOP with ring-opening polymerization (ROP), to access a wide range of materials containing polycarbonate and polyester segments along the polymer chain, showing enhanced properties with respect to the simple APC. This review will cover the last advancements in the field, evidencing the crucial role of the catalytic system in determining the microstructural features of the final polymer

Role of the metal center in the ethylene polymerization promoted by group 4 complexes supported by a tetradentate [OSSO]-type Bis(phenolato) ligand

The mechanism responsible for the production of branched polyethylene from ethylene feed during its polymerization promoted by dichloro{1,4-dithiabutanediyl-2,2\u2032-bis(4,6-di-tert-butyl-phenoxy)}titanium complex 1 activated by methylalumoxane (MAO) was investigated by using a density functional theory (DFT) approach. The following processes, chain propagation (CP) reaction, beta hydrogen elimination (\u3b2HE, hydrogen elimination from an alkyl chain to the metal in the absence of a coordinated alkene) and transfer (\u3b2HT, hydrogen transfer from the alkyl chain to a coordinated alkene) were considered to individuate the possible competing reactions responsible for the production of ethylene oligomers. The latter two processes are generally ascribed as termination reactions for the chain propagation. We found that \u3b2HT is the more plausible termination pathway leading to the formation of oligomers that can be reinserted in the growing chain, and thus giving the branched polyethylene. Furthermore, by comparing the energetic profile of CP and \u3b2HT for the analogue zirconium compound 2 we found that \u3b2HT is 50 times more competitive with CP than for the Ti-based compound. As a matter of fact, the MAO activated zirconium complex exclusively produces oligomers with even number of carbon atoms, thus confirming fairly well the calculations that indicated the possibility of tuning the catalytic activity and selectivity of this class of compounds simply by changing the nature of the metal center

Stereoregular Polymerization of Acyclic Terpenes

The growing environmental pollution and the expected depleting of fossil resources have sparked interest in recent years for polymers obtained from monomers originating from renewable sources. Furthermore, nature can provide a variety of building blocks with special structural features (e. g. side groups or stereo-elements) that cannot be obtained so easily via fossil-based pathways. In this context, terpenes are widespread natural compounds coming from non-food crops, present in a large variety of structures, and ready to use as monomers with or without further modifications. The present review aims to provide an overview of how chemists can stereospecifically polymerize terpenes, particularly the acyclic ones like myrcene, ocimene, and farnesene, using different metal catalyst systems in coordination-insertion polymerization. Attention is also paid to their copolymers, which have recently been disclosed, and to the possible applications of these bio-based materials in various industrial sectors such as in the field of elastomers. © 2021 The Authors. ChemPlusChem published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes