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Background and Aims: Videolaryngoscopes have an undisputed role in difficult airway management, but their role in routine intubation scenarios remains underappreciated. McGrath MAC is a lightweight laryngoscope with a disposable blade. It remains to be proven if it performs as efficiently as the reusable videolaryngoscopes like C-MAC and whether it has an advantage over standard Macintosh laryngoscope in predicted normal airways. Material and Methods: We recruited 180 adult patients and randomly divided them into three groups for intubation with either Macintosh laryngoscope (Group-A), C-MAC (Group-B), and McGrath (Group-C). The primary objective was to compare the first attempt success rate. Secondary objectives included Cormack-Lehane (CL) grades, laryngoscopy time, intubation time, ease of intubation, need for optimization manoeuver, and the number of passes to place the endotracheal tube. Results: The two videolaryngoscopes provided a superior first attempt success rate as compared to Macintosh laryngoscope (P = 0.027). The CL grade-I was 100% in group B, 41.7% in group-A and 90% in group-C (B vs C; P = 0.037). Laryngoscopy time was 9.9 ± 2.5 s, 12.6 ± 0.8 s, and 13.1 ± 0.8 s for groups A, B, and C, respectively (B vs C; P = 0.001). Intubation time was 24.4 ± 12 s, 28.3 ± 1.9 s, and 37.3 ± 5.8 s for groups A, B, and C, respectively (P < 0.0001). The number of tube passes was highest in group C. Conclusion: Videolaryngoscopes provided a superior glottic view and resulted in a superior first attempt success rate as compared to Macintosh laryngoscope. When comparing the two videolaryngoscopes, C-MAC resulted in better intubation characteristics (shorter intubation time, better glottic views, and higher first-attempt success rates) and should be preferred over McGrath for intubation in adult patients with normal airways.

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Computational quantum chemistry can be more than just numerical experiments when methods are specifically adapted to investigate chemical concepts. One important example is the development of energy decomposition analysis (EDA) to reveal the physical driving forces behind intermolecular interactions. In EDA, typically the interaction energy from a good-quality density functional theory (DFT) calculation is decomposed into multiple additive components that unveil permanent and induced electrostatics, Pauli repulsion, dispersion, and charge-transfer contributions to noncovalent interactions. Herein, we formulate, implement, and investigate decomposing the forces associated with intermolecular interactions into the same components. The resulting force decomposition analysis (FDA) is potentially useful as a complement to the EDA to understand chemistry, while also providing far more information than an EDA for data analysis purposes such as training physics-based force fields. We apply the FDA based on absolutely localized molecular orbitals (ALMOs) to analyze interactions of water with sodium and chloride ions as well as in the water dimer. We also analyze the forces responsible for geometric changes in carbon dioxide upon adsorption onto (and activation by) gold and silver anions. We also investigate how the force components of an EDA-based force field for water clusters, namely MB-UCB, compare to those from force decomposition analysis.

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How to cite this article: Das AK, Sharma A, Kothari N, Goyal S. Opium Addiction: Practical Issues in ICU. Indian J Crit Care Med 2021;25(9):1082-1083.

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The dynamics and spectroscopy of N-methyl-acetamide (NMA) and trialanine in solution are characterized from molecular dynamics simulations using different energy functions, including a conventional point charge (PC)-based force field, one based on a multipolar (MTP) representation of the electrostatics, and a semiempirical DFT method. For the 1D infrared spectra, the frequency splitting between the two amide-I groups is 10 cm-1 from the PC, 13 cm-1 from the MTP, and 47 cm-1 from self-consistent charge density functional tight-binding (SCC-DFTB) simulations, compared with 25 cm-1 from experiment. The frequency trajectory required for the frequency fluctuation correlation function (FFCF) is determined from individual normal mode (INM) and full normal mode (FNM) analyses of the amide-I vibrations. The spectroscopy, time-zero magnitude of the FFCF C(t = 0), and the static component Δ02 from simulations using MTP and analysis based on FNM are all consistent with experiments for (Ala)3. Contrary to this, for the analysis excluding mode-mode coupling (INM), the FFCF decays to zero too rapidly and for simulations with a PC-based force field, the Δ02 is too small by a factor of two compared with experiments. Simulations with SCC-DFTB agree better with experiment for these observables than those from PC-based simulations. The conformational ensemble sampled from simulations using PCs is consistent with the literature (including PII, ß, αR, and αL), whereas that covered by the MTP-based simulations is dominated by PII with some contributions from ß and αR. This agrees with and confirms recently reported Bayesian-refined populations based on 1D infrared experiments. FNM analysis together with a MTP representation provides a meaningful model to correctly describe the dynamics of hydrated trialanine.

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Many pairwise additive force fields are in active use for intrinsically disordered proteins (IDPs) and regions (IDRs), some of which modify energetic terms to improve the description of IDPs/IDRs but are largely in disagreement with solution experiments for the disordered states. This work considers a new direction-the connection to configurational entropy-and how it might change the nature of our understanding of protein force field development to equally well encompass globular proteins, IDRs/IDPs, and disorder-to-order transitions. We have evaluated representative pairwise and many-body protein and water force fields against experimental data on representative IDPs and IDRs, a peptide that undergoes a disorder-to-order transition, for seven globular proteins ranging in size from 130 to 266 amino acids. We find that force fields with the largest statistical fluctuations consistent with the radius of gyration and universal Lindemann values for folded states simultaneously better describe IDPs and IDRs and disorder-to-order transitions. Hence, the crux of what a force field should exhibit to well describe IDRs/IDPs is not just the balance between protein and water energetics but the balance between energetic effects and configurational entropy of folded states of globular proteins.

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To study intermolecular interactions involving radicals at the correlated level, the energy decomposition analysis scheme for second-order MoÌ·ller-Plesset perturbation theory based on absolutely localized molecular orbitals (ALMO-MP2-EDA) is generalized to unrestricted and restricted open-shell MP2. The benefit of restricted open-shell MP2 is that it can provide accurate binding energies for radical complexes where density functional theory can be error-prone due to delocalization errors. As a model application, the open-shell ALMO-MP2-EDA is applied to study the first solvation step of halogenated benzene radical cations, where both halogen- and hydrogen-bonded isomers are possible. We determine that the lighter halogens favor the hydrogen-bonded form, while the iodine-substituted species prefers halogen bonding due to larger polarizability and charge transfer at the halogen. As a second application, relevant to the activation of CO2 in photoelectrocatalysis, complexes of CO2-· interacting with both pyridine and imidazole are analyzed with ALMO-MP2-EDA. The results reveal the importance of charge transfer into the π* orbital of the heterocycle in controlling the stability of the carbamate binding mode, which is favored for pyridine but not for imidazole.

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Given the piecewise approach to modeling intermolecular interactions for force fields, they can be difficult to parametrize since they are fit to data like total energies that only indirectly connect to their separable functional forms. Furthermore, by neglecting certain types of molecular interactions such as charge penetration and charge transfer, most classical force fields must rely on, but do not always demonstrate, how cancellation of errors occurs among the remaining molecular interactions accounted for such as exchange repulsion, electrostatics, and polarization. In this work we present the first generation of the (many-body) MB-UCB force field that explicitly accounts for the decomposed molecular interactions commensurate with a variational energy decomposition analysis, including charge transfer, with force field design choices that reduce the computational expense of the MB-UCB potential while remaining accurate. We optimize parameters using only a single water molecule and water cluster data up through pentamers, with no fitting to condensed phase data, and we demonstrate that high accuracy is maintained when the force field is subsequently validated against conformational energies of larger water cluster data sets, radial distribution functions of the liquid phase, and the temperature dependence of thermodynamic and transport water properties. We conclude that MB-UCB is comparable in performance to MB-Pol but is less expensive and more transferable by eliminating the need to represent short-ranged interactions through large parameter fits to high order polynomials.

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In this work, we have developed an anisotropic polarizable model for the AMOEBA force field that is derived from electrostatic fitting on a gas phase water molecule as the primary approach to improve the many-body polarization model. We validate our approach using small to large water cluster benchmark data sets and ambient liquid water properties and through comparisons to a variational energy decomposition analysis breakdown of molecular interactions for water and water-ion trimer systems. We find that the accounting of anisotropy polarization for a single water molecule demonstrably improves the description of the many-body polarization energy in all cases. This study provides a proof of principle for extending our protocol for developing a general purpose anisotropic polarizable force field for other biological and material functional groups to better describe complex and asymmetric environments for which accurate polarization models are most needed.

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Structural characterization of the copper-coordination shell is important in catalysis and biology. Cu-containing domains are prevalent in biological systems and play important roles in oxidation and electron transport process. Here, the solution structure, solvent organization, and dynamics around aqueous [Cu(II)(Imidazole)4] were characterized using atomistic simulations. Asymmetric axial water coordination around the metal atom was found which agrees with results from Minuit X-ray absorption near-edge structure (MXAN) experiments. The simulations reveal that exchange of the axial water occurs on the 25 to 50 ps time scale and is facilitated by and coupled to the flexibility of the copper-out of plane motion relative to the nitrogen atoms. Both concerted and stepwise water exchange of the two axially coordinated water molecules with first-shell water molecules are observed. The results suggest that axial access of a copper center can be fine-tuned by the degree of flexibility of its first coordination sphere.

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The transfer of charge at the molecular level plays a fundamental role in many areas of chemistry, physics, biology and materials science. Today, more than 60 years after the seminal work of R. A. Marcus, charge transfer is still a very active field of research. An important recent impetus comes from the ability to resolve ever faster temporal events, down to the attosecond time scale. Such a high temporal resolution now offers the possibility to unravel the most elementary quantum dynamics of both electrons and nuclei that participate in the complex process of charge transfer. This review covers recent research that addresses the following questions. Can we reconstruct the migration of charge across a molecule on the atomic length and electronic time scales? Can we use strong laser fields to control charge migration? Can we temporally resolve and understand intramolecular charge transfer in dissociative ionization of small molecules, in transition-metal complexes and in conjugated polymers? Can we tailor molecular systems towards specific charge-transfer processes? What are the time scales of the elementary steps of charge transfer in liquids and nanoparticles? Important new insights into each of these topics, obtained from state-of-the-art ultrafast spectroscopy and/or theoretical methods, are summarized in this review.

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Nitric oxide binding and unbinding from myoglobin (Mb) is central to the function of the protein. By using reactive molecular dynamics (MD) simulations, the dynamics following NO dissociation were characterized in both time and space. Ligand rebinding can be described by two processes on the 10 ps and 100 ps timescale, which agrees with recent optical and X-ray absorption experiments. Explicitly including the iron out-of-plane (Fe-oop) coordinate is essential for a meaningful interpretation of the data. The proposed existence of an "Fe-oop/NO-bound" state is confirmed and assigned to NO at a distance of approximately 3 Šaway from the iron atom. However, calculated XANES spectra suggest that it is diffcult to distinguish between NO close to the heme-Fe and positions further away in the primary site. Another elusive state, with Fe-ON coordination, was not observed experimentally because it is masked by the energetically more favorable but dissociative (4) A state in this region, which makes the Fe-ON local minimum unobservable in wild-type Mb. However, suitable active-site mutations may stabilize this state.

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The solvent dynamics in Fe-tris-bipyridine [Fe(bpy)3](2+) upon electronic excitation (oxidation) and subsequent relaxation is followed on the picosecond time scale by using atomistic simulations. Starting from the low spin (LS) Fe(II)LS state the transition to the excited Fe(III) (1,3)MLCT (metal-to-ligand charge transfer) state decreases the water coordination in immediate proximity of the central iron atom. This readjustment of the solvent shell occurs on the subpicosecond time scale. Full relaxation of the water environment would occur on the 10 ps time scale which is, however, never reached as the lifetime of the (1,3)MLCT state is only 200 fs. Further relaxation toward the long-lived (665 ps) [Fe(II)HS(bpy)3] high spin (HS) state does not change the degree of solvation. The results support a model in which the change in the degree of solvation is driven by electronic effects (charge redistribution) and not by structural changes (change in bond lengths). Furthermore, the results are consistent with recent combined X-ray emission (XES) and X-ray diffusion (XDS) scattering experiments which provided evidence for a reduced solvent density upon excitation of the [Fe(II)LS(bpy)3] initial state. However, the time scale for water exchange dynamics is faster than that found in the experiments.

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The solvent dynamics around fluorinated acetonitrile is characterized by 2-dimensional infrared spectroscopy and atomistic simulations. The lineshape of the linear infrared spectrum is better captured by semiempirical (density functional tight binding) mixed quantum mechanical/molecular mechanics simulations, whereas force field simulations with multipolar interactions yield lineshapes that are significantly too narrow. For the solvent dynamics, a relatively slow time scale of 2 ps is found from the experiments and supported by the mixed quantum mechanical/molecular mechanics simulations. With multipolar force fields fitted to the available thermodynamical data, the time scale is considerably faster--on the 0.5 ps time scale. The simulations provide evidence for a well established CF-HOH hydrogen bond (population of 25%) which is found from the radial distribution function g(r) from both, force field and quantum mechanics/molecular mechanics simulations.

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