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Determining the full five-parameter grain boundary characteristics from experiments is essential for understanding grain boundaries impact on material properties, improving related models, and designing advanced alloys. However, achieving this is generally challenging, in particular at nanoscale, due to their 3D nature. In our study, we successfully determined the grain boundary characteristics of an annealed nickel-tungsten alloy (NiW) nanocrystalline needle-shaped specimen (tip) containing twins using Scanning Precession Electron Diffraction (SPED) Tomography. The presence of annealing twins in this face-centered cubic (fcc) material gives rise to common reflections in the SPED diffraction patterns, which challenges the reconstruction of orientation-specific virtual dark field (VDF) images required for tomographic reconstruction of the 3D grain shapes. To address this, an automated post-processing step identifies and deselects these shared reflections prior to the reconstruction of the VDF images. Combined with appropriate intensity normalization and projection alignment procedures, this approach enables high-fidelity 3D reconstruction of the individual grains contained in the needle-shaped sample volume. To probe the accuracy of the resulting boundary characteristics, the twin boundary surface normal directions were extracted from the 3D voxelated grain boundary map using a 3D Hough transform. For the sub-set of coherent Σ3 boundaries, the expected {111} grain boundary plane normals were obtained with an angular error of <3° for boundary sizes down to 400 nm². This work advances our ability to precisely characterize and understand the complex grain boundaries that govern material properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Biomarkers like white blood cells, C-reactive protein, procalcitonin, and interleukin-1 are used in patients with sepsis for early diagnosis, differentiating various infections, making decisions to start antibiotics and evaluate their response, and to prognosticate morbidity and mortality. Despite the availability of these biomarkers, the prognosis of patients with sepsis in the ICU remains poor. Hence, this study was carried out to test the efficacy of procalcitonin and neutrophil-to-lymphocyte ratio (NLR) to prognosticate mortality and morbidity in terms of incidence of organ dysfunction and length of ICU stay in sepsis patients., Methods: In this prospective observational study, we measured NLR and procalcitonin at days one, three, and seven of sepsis patients and divided them into four groups: low NLR and high procalcitonin (LNHP), high NLR and high procalcitonin (HNHP), high NLR and low procalcitonin (HNLP), and low NLR and low procalcitonin (LNLP). Mortality at 28 days was noted as the primary outcome., Results: Out of 85 patients included in the study, five were lost to follow-up. Although no statistically significant difference was found in the primary outcome between all four groups, regression analysis showed that rising NLR and procalcitonin values were associated with a significant increase in mortality., Conclusion: Serial values of NLR and procalcitonin are more important in predicting severity in comparison to a single value at presentation and can be used as a prognostic marker in sepsis patients., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Artemis Health Sciences Institutional Ethics Committee (AHS-IEC) issued approval 504256. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Singhal et al.)

Morphing materials are typically either very compliant to achieve large shape changes or very stiff but with small shape changes that require large actuation forces. Interestingly, fish fins overcome these limitations: fish fins do not contain muscles, yet they can change the shape of their fins with high precision and speed while producing large hydrodynamic forces without collapsing. Here, we present a 'stiff' morphing beam inspired from the individual rays in natural fish fins. These synthetic rays are made of acrylic (PMMA) outer beams ('hemitrichs') connected with rubber ligaments which are 3-4 orders of magnitude more compliant. Combinations of experiments and models of these synthetic rays show strong nonlinear geometrical effects: the ligaments are 'mechanically invisible' at small deformations, but they delay buckling and improve the stability of the ray at large deformations. We use the models and experiments to explore designs with variable ligament densities, and we generate design guidelines for optimum morphing shape (captured using the first moment of curvature), that capture the trade-offs between morphing compliance (ease of morphing the structure) and flexural stiffness. The design guidelines proposed here can help the development of stiff morphing bioinspired structures for a variety of applications in aerospace, biomedicine or robotics., Competing Interests: We declare we have no competing interests., (© 2024 The Authors.)

State-of-the-art morphing materials are either very compliant to achieve large shape changes (flexible metamaterials, compliant mechanisms, hydrogels), or very stiff but with infinitesimal changes in shape that require large actuation forces (metallic or composite panels with piezoelectric actuation). Morphing efficiency and structural stiffness are therefore mutually exclusive properties in current engineering morphing materials, which limits the range of their applicability. Interestingly, natural fish fins do not contain muscles, yet they can morph to large amplitudes with minimal muscular actuation forces from the base while producing large hydrodynamic forces without collapsing. This sophisticated mechanical response has already inspired several synthetic fin rays with various applications. However, most 'synthetic' fin rays have only considered uniform properties and structures along the rays while in natural fin rays, gradients of properties are prominent. In this study, we designed, modeled, fabricated and tested synthetic fin rays with bioinspired gradients of properties. The rays were composed of two hemitrichs made of a stiff polymer, joined by a much softer core region made of elastomeric ligaments. Using combinations of experiments and nonlinear mechanical models, we found that gradients in both the core region and hemitrichs can increase the morphing and stiffening response of individual rays. Introducing a positive gradient of ligament density in the core region (the density of ligament increases towards the tip of the ray) decreased the actuation force required for morphing and increased overall flexural stiffness. Introducing a gradient of property in the hemitrichs, by tapering them, produced morphing deformations that were distributed over long distances along the length of the ray. These new insights on the interplay between material architecture and properties in nonlinear regimes of deformation can improve the designs of morphing structures that combine high morphing efficiency and high stiffness from external forces, with potential applications in aerospace or robotics., (© 2024 IOP Publishing Ltd.)

Quinalizarin, an analogue of anthracycline anticancer agents, is an anticancer agent itself. A Cu II complex was prepared and characterized by elemental analysis, UV-Vis & IR spectroscopy, mass spectrometry, EPR and DFT. The intention behind the preparation of the complex was to increase cellular uptake, compare its binding with DNA against that of quinalizarin, modulation of semiquinone formation, realization of human DNA topoisomerase I & human DNA topoisomerase II inhibition and observation of anticancer activity. While the first two attributes of complex formation lead to increased efficacy, decrease in semiquinone generation could results in a compromise with efficacy. Inhibition of human DNA topoisomerase makes up this envisaged compromise in free radical activity since the complex shows remarkable ability to disrupt activities of human DNA topoisomerase I and II. The complex unlike quinalizarin, does not catalyze flow of electrons from NADH to O 2 to the extent known for quinalizarin. Hence, decrease in semiquinone or superoxide radical anion could make modified quinalizarin [as Cu II complex] less efficient in free radical pathway. However, it would be less cardiotoxic and that would be advantageous to qualify it as a better anticancer agent. Although binding to calf thymus DNA was comparable to quinalizarin, it was weaker than anthracyclines. Low cost of quinalizarin could justify consideration as a substitute for anthracyclines but the study revealed IC 50 of quinalizarin/Cu II -quinalizarin was much higher than anthracyclines or their complexes. Even then, there is a possibility that Cu II -quinalizarin could be an improved and less costly form of quinalizarin as anticancer agent., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Fins from ray-finned fishes do not contain muscles, yet fish can change the shape of their fins with high precision and speed, while producing large hydrodynamic forces without collapsing. This remarkable performance has been intriguing researchers for decades, but experiments have so far focused on homogenized properties, and models were developed only for small deformations and small rotations. Here we present fully instrumented micromechanical tests on individual rays from Rainbow trout in both morphing and flexural deflection mode and at large deflections. We then present a nonlinear mechanical model of the ray that captures the key structural elements controlling the mechanical behavior of rays under large deformations, which we successfully fit onto the experiments for property identification. We found that the flexural stiffness of the mineralized layers in the rays (hemitrichs) is 5-6 times lower than their axial stiffness, an advantageous combination to produce stiff morphing. In addition, the collagenous core region can be modeled with spring elements which are 3-4 orders of magnitude more compliant than the hemitrichs. This fibrillar structure provides negligible resistance to shearing from the initial position, but it prevents buckling and collapse of the structure at large deformations. These insights from the experiments and nonlinear models can serve as new guidelines for the design of efficient bioinspired stiff morphing materials and structures at large deformations. STATEMENT OF SIGNIFICANCE: Fins from ray-finned fishes do not contain muscles, yet fish can change the shape of their fins with high precision and speed, while producing large hydrodynamic forces without collapsing. Experiments have so far focused on homogenized properties, and models were developed only for small deformations and small rotations providing limited insight into the rich nonlinear mechanics of natural rays. We present micromechanical tests in both morphing and flexural deflection mode on individual rays, a nonlinear model of the ray that captures the mechanical behavior of rays under large deformations and combine microCT measurements to generate new insights into the nonlinear mechanics of rays. These insights can serve as new guidelines for the design of efficient bioinspired stiff morphing materials and structures at large deformations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

An important aspect of research pertaining to Curcumin (HCur) is the need to arrest its degradation in aqueous solution and in biological milieu. This may be achieved through complex formation with metal ions. For this reason, a complex of HCur was prepared with Zn II , that is not likely to be active in redox pathways, minimizing further complications. The complex is monomeric, tetrahedral, with one HCur, an acetate and a molecule of water bound to Zn II . It arrests degradation of HCur to a considerable extent that was realized by taking it in phosphate buffer and in biological milieu. The structure was obtained by DFT calculations. Stable adduct formation was identified between optimized structures of HCur and [Zn(Cur)] with DNA (PDB ID: 1BNA) through experiments validated with multiscale modeling approach. Molecular docking studies provide 2D and 3D representations of binding of HCur and [Zn(Cur)] through different non-covalent interactions with the nucleotides of the chosen DNA. Through molecular dynamics simulation, a detailed understanding of binding pattern and key structural characteristics of the generated DNA-complex was obtained following analysis by RMSD, RMSF, radius of gyration, SASA and aspects like formation of hydrogen bonds. Experimental studies provide binding constants for [Zn(Cur)] with calf thymus DNA at 25 °C that effectively helps one to realize its high affinity towards DNA. In the absence of an experimental binding study of HCur with DNA, owing to its tendency to degrade in solution, a theoretical analysis of the binding of HCur to DNA is extremely helpful. Besides, both experimental and simulated binding of [Zn(Cur)] to DNA may be considered as a case of pseudo-binding of HCur to DNA. In a way, such studies on interaction with DNA helps one to identify HCur's affinity for cellular target DNA, not realized through experiments. The entire investigation is an understanding of experimental and theoretical approaches that has been compared continuously, being particularly useful when a molecule's interaction with a biological target cannot be realized experimentally., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The properties of polycrystalline materials are related to their microstructures and hence a complete description, including size, shape, and orientation of the grains, is necessary to understand the behavior of materials. Here, we use Scanning Precession Electron Diffraction (SPED) in the Transmission Electron Microscope (TEM) combined with a tilt series to reconstruct individual grains in 3D within a polycrystalline dual-phase cold wire-drawn pearlitic steel sample. Nanoscale ferrite grains and intragranular cementite particles were indexed using an Automated Crystallographic Orientation Mapping (ACOM) tool for each tilt dataset. The grain orientations were tracked through the tilt datasets and projections of the individual grains were reconstructed from the diffraction data using an orientation-specific Virtual Dark Field (VDF) approach for tomographic reconstruction. The algorithms used to process and reconstruct such datasets are presented. These algorithms represent an extension to the ACOM approach that may be straightforwardly applied to other multi-phase polycrystalline materials to enable 3D spatial and orientation reconstructions., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Formation of nitro radical anion (-NO 2 •- ) and other reduction products of 5-nitroimidazoles, although important for antimicrobial activity, makes the drugs neurotoxic. Hence, an appropriate generation and their role in the free radical pathway needs proper realization. This was attempted by studying the action of tinidazole and its Cu II complexes on model targets (nucleic acid bases and calf thymus DNA). Results obtained were correlated with studies on biological species where prevention of biofilm formation on Staphylococcus aureus and Pseudomonas aeruginosa was followed. Tinidazole and its Cu II complexes subjected to electrochemical reduction in aqueous solution, under de-aerated conditions, interact with model nucleic acid bases and calf thymus DNA. These model targets were followed to realize what happens when such compounds undergo enzymatic reduction within cells of microorganisms that they eventually kill. Studies reveal that Cu II complexes were better in modifying nucleic acid bases and calf thymus DNA than tinidazole; damage caused to nucleic acid bases was correlated with that caused to DNA, indicating that compounds affect DNA rich in thymine and adenine. Minimum bactericidal concentrations on sessile S. aureus and P. aeruginosa for the monomeric Cu II complex were 12.5 and 20.25 μM respectively, while those for the dimeric complex were 40.0 and 45.0 μM, respectively. Biofilm formation by P. aeruginosa and S. aureus and viability count of sessile cells were also determined. Cu II complexes of tinidazole brought about substantial reduction in carbohydrate and protein content in S. aureus and P. aeruginosa . Downregulation of quorum sensing signaling mechanism viz. reduced production of pyocyanin and elastase during biofilm formation was also detected. Cu II complexes showed much higher tendency to prevent biofilm formation than tinidazole, almost comparable to amoxicillin, an established drug in this regard., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

A Co(III) complex of 1-amino-4-hydroxy-9,10-anthraquinone (QH) (Scheme-1) having the molecular formula CoQ 3 (Scheme-2) was prepared and characterized by elemental analysis, FTIR spectroscopy, UV-vis spectroscopy, fluorescence spectroscopy, and mass spectrometry. In the absence of a single crystal, the energy-optimized molecular structure of CoQ 3 was determined by employing computational methods that was validated using spectroscopic evidences, elemental analysis, and mass spectrometry data. The electrochemical properties of the complex were analyzed using cyclic voltammetry and indicate a substantial modification of the electrochemical properties of the parent amino-hydroxy-9,10-anthraquinone. CoQ 3 was thereafter tested on MCF-7 human breast cancer cells. The IC 50 value for a 24 h incubation was found to be (95 ± 0.05) μg/mL. The study showed that such cancer cells underwent both early and late apoptosis following the interaction with CoQ 3 ., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Curcumin is a tantalizing molecule with multifaceted therapeutic potentials. However, its therapeutic applications are severely hampered because of poor bioavailability, attributed to its instability and aqueous insolubility. In an attempt to overcome this inherent limitation and develop curcumin-based antibacterials, we had earlier synthesized and characterized a metal complex of Cu(II) with curcumin, having the formula [Cu(Curcumin)(OCOCH 3 )(H 2 O)], hereafter referred to as Cu(Cur). In this study, the complex, i.e., Cu(Cur), was investigated for its stability and antibacterial activity along with its possible mechanism of action in comparison to the parent molecule, curcumin. Complex formation resulted in improved stability as Cu(Cur) was found to be highly stable under different physiological conditions. Such improved stability was verified with the help of UV-Vis spectroscopy and HPLC. With improved stability, Cu(Cur) exhibited potent and significantly enhanced activity over curcumin against both E. coli and S. aureus. Calcein leakage assay revealed that the complex triggered immediate membrane permeabilization in S. aureus. This membrane disruptive mode of action was further corroborated by microscopic visualization. The excellent potency of the complex was augmented by its safe toxicological profile as it was non-hemolytic and non-cytotoxic towards mammalian cells, making it a suitable candidate for in vivo investigations. Altogether, this investigation is a critical appraisal that advocates the antibacterial potential of this stable, membrane-targeting and non-toxic complex, thereby presenting new perspectives for its therapeutic application against bacterial infections., (Copyright © 2021. Published by Elsevier Inc.)

Cytotoxicity by anthracycline antibiotics is attributed to several pathways. Important among them are formation of free-radical intermediates. However, their generation makes anthracyclines cardiotoxic which is a concern on their use as anticancer agents. Hence, any change in redox behavior that address cardiotoxicity is welcome. Modulation of redox behavior raises the fear that cytotoxicity could be compromised. Regarding the generation of free radical intermediates on anthracyclines, a lot depends on the surrounding environment (oxic or anoxic), polarity and pH of the medium. In case of anthracyclines, one-electron reduction to semiquinone or two-electron reduction to quinone-dianion are crucial both for cytotoxicity and for cardiotoxic side effects. The disproportion-comproportionation equilibria at play between quinone-dianion, free quinone and semiquinone control biological activity. Whatever is the form of reduction, semiquinones are generated as a consequence of the presence of anthracyclines and these interact with a biological target. Alizarin, a simpler anthracycline analogue and its Mn II complex were subjected to electrochemical reduction to realize what happens when anthracyclines are reduced by compounds present in cells as members of the electron transport chain. Glassy carbon electrode maintained at the pre-determined reduction potential of a compound was used for reduction of the compounds. Nucleobases and calf thymus DNA that were maintained in immediate vicinity of such radical generation were used as biological targets. Changes due to the generated species under aerated/de-aerated conditions on nucleobases and on DNA helps one to realize the process by which alizarin and its Mn II complex might affect DNA. The study reveals alizarin was more effective on nucleobases than the complex in the free radical pathway. Difference in damage caused by alizarin and the Mn II complex on DNA is comparatively less than that observed on nucleobases; the complex makes up for any inefficacy in the free radical pathway by its other attributes., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s).)

Objectives: "Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016" provides guidelines in regard to prompt management and resuscitation of sepsis or septic shock. The study is aimed to assess the robustness of randomized controlled trials (RCTs) that formulate these guidelines in terms of fragility index and reverse fragility index., Method: RCTs that contributed to these guidelines having parallel two-group design, 1:1 allocation ratio, and at least one dichotomous outcome were included in the study. The median fragility index was calculated for RCTs with significant statistical outcomes, whereas the median reverse fragility index was calculated for RCTs with nonsignificant statistical results., Results: Hundred RCTs that met the inclusion criteria were analyzed. The median fragility index was 5.5 [95% confidence interval (CI) 1-30] and median reverse fragility index was 13 (95% CI 12.07-16.8) at a p value of 0.05. The median reverse fragility index was 16 (95% CI 10-26) at a p value of 0.01. Most of the RCTs included in this analysis were of good quality, having a median Jadad score of 6., Conclusion: This analysis found that the surviving sepsis guidelines were based on highly robust RCTs with statistically insignificant results and on some moderately robust RCTs with statistically significant results. RCTs with statistically insignificant results were more robust than RCTs with statistically significant results in regard to these guidelines., Highlights: The study assessed the robustness of randomized controlled trials (RCTs) that were used to formulate surviving sepsis guidelines. Most RCTs showed statistically nonsignificant results. RCTs with statistically significant results were moderately fragile whereas RCTs with nonsignificant results were more robust., How to Cite This Article: Choupoo NS, Das SK, Saikia P, Dey S, Ray S. How Robust are the Evidences that Formulate Surviving Sepsis Guidelines? An Analysis of Fragility and Reverse Fragility of Randomized Controlled Trials that were Referred in these Guidelines. Indian J Crit Care Med 2021;25(7):773-779., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2021; Jaypee Brothers Medical Publishers (P) Ltd.)

A family of three water-soluble half-sandwich arene-ruthenium complexes, depicted as C 1 - C 3 , having the general formula [Ru( p -cymene)(L)Cl]Cl has been synthesized, where L represents (1 H -benzo[ d ]imidazol-2-yl)guanidine ( L 1 ) or (benzo[ d ]oxazol-2-yl)guanidine ( L 2 ) or (benzo[ d ]thiazol-2-yl)guanidine ( L 3 ). The crystal structure of complex C 3 has been determined. The complexes show several absorption bands in the visible and ultraviolet regions, and they also show prominent emission in the visible region while excited near 400 nm. Studies on the interaction of ligands L 1 - L 3 and complexes C 1 - C 3 with calf thymus DNA reveal that the complexes are better DNA binders than the ligands, which is attributable to the imposed planarity of the ruthenium-bound guanidine-based ligand, enabling it to serve as a better intercalator. Molecular docking studies show that the complexes effectively bind with DNA through electrostatic and H-bonding interactions and partial intercalation of the guanidine-based ligands. Cytotoxicity studies carried out on two carcinoma cell lines (PC3 and A549) and on two non-cancer cell lines (BPH1 and WI-38) show a marked improvement in antitumor activity owing to complex formation, which is attributed to improvement in cellular uptake on complex formation. The C 1 complex is found to exhibit the most prominent activity against the PC3 cell line. Inclusion of the guanidine-based ligands in the half-sandwich ruthenium-arene complexes is found to be effective for displaying selective cytotoxicity to cancer cells and also for convenient tracing of the complexes in cells due to their prominent emissive nature., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Purpose: The present study systematically searched important medical databases, assessed the quality of available pieces of evidence, and performed a meta-analysis to test the efficacy of different therapeutic options currently available for treating COVID-19., Materials and Methods: PubMed, CNKI, LILACS, Koreamed, WHO clinical trial registry, and medRxiv were searched since December 2019. Any observational or controlled study that tested the efficacy of any pharmacological intervention in COVID-19 patients either prospectively or retrospectively was included in the qualitative analysis. We assessed outcomes as dichotomous variables, i.e., a patient having a positive clinical outcome. Relative risks/risk ratios (RR) having a 95% confidence interval (CI) were derived. Studies conforming to inclusion criteria were pooled using the random-effect model., Results: Nine trials on hydroxychloroquine (HCQ), six studies on antiviral, four studies on monoclonal antibodies, two on corticosteroids, two on convalescent plasma (CP), and one on interferon-α2b were included in the systematic review. Meta-analysis containing six scientific trials and analyzing 522 patients revealed that the relative risk of positive clinical outcomes with HCQ treatment was 1.042 (95% CI, 0.884 to 1.874) with a number needed to treat (NNT) of 12.6. A meta-analysis of two studies analyzing 285 patients showed that the relative risk of clinical resolution with lopinavir and ritonavir combination was 1.152 (95% CI 0.709 to 1.87). Out of various antiviral used, the only remdesivir showed a positive result in a case series. Monoclonal antibodies showed decreased C-reactive protein, decreased oxygen, and ventilator requirements. A corticosteroid may increase mortality with increased dose. Two small case series on CP showed some promising results., Conclusion: The study showed slightly favorable results with HCQ, monoclonal antibodies, remdesivir, and CP in treating COVID-19 patients. Further research is warranted in establishing the efficacy of studied interventions., Prospero Identifier: CRD42020180979., How to Cite This Article: Choupoo NS, Das SK, Haldar R, Sarkar H, Tewari R, Ray S. Evaluating the Efficacy and Safety of the Existing Repurposed Pharmacological Agents for Treating COVID-19: A Meta-analysis and Systematic Review of Clinical Trials. Indian J Crit Care Med 2020;24(11):1106-1113., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2020; Jaypee Brothers Medical Publishers (P) Ltd.)

The treatment of malignant cells that are deficient in oxygen due to the insufficient flow of blood is often seen as a major hindrance in radiotherapy. Such cells become radio-resistant because molecular oxygen, the natural and best radio-sensitizer, is depleted. Hence, to compensate this deficiency in oxygen, there is a need for agents that enhance radiation-induced damage of cells (radio-sensitizers) in a manner that normal cells are least affected. Simultaneously, agents capable of showing activity under hypoxic conditions are known as hypoxic cytotoxins that selectively and preferably destroy cells under hypoxic environments. 5-Nitroimidazoles fit both definitions. Their efficiency is based on their ability to generate the nitro radical anion that interacts with the strands of DNA within cells, either damaging or modifying them, leading to cell death. 5-Nitroimidazoles are important radio-pharmaceuticals (radio-sensitizers) in cancer-related treatments where the nitro radical anion has an important role. Since its generation leads to neurotoxic side effects that may be controlled through metal complex formation, this study looks at the possibility of two monomeric complexes of Ornidazole [1-chloro-3-(2-methyl-5-nitro-1 H -imidazole-1-yl)propan-2-ol] with Cu II and Zn II to be better radio-sensitizers and/or hypoxic cytotoxins than Ornidazole. The study reveals that although there is a decrease in nitro radical anion formation by complexes, such a decrease does not hamper their radio-sensitizing ability. Nucleic acid bases (thymine, cytosine, and adenine) or calf thymus DNA used as targets were irradiated with 60 Co γ rays either in the absence or presence of Ornidazole and its monomeric complexes. Radiation-induced damage of nucleic acid bases was followed by high-performance liquid chromatography (HPLC), and modification of calf thymus DNA was followed by ethidium bromide fluorescence. Studies indicate that the complexes were better in performance than Ornidazole. Cu II -ornidazole was significantly better than either Ornidazole or Zn II -ornidazole, which is attributed to certain special features of the Cu II complex; aspects like having a stable lower oxidation state enable it to participate in Fenton reactions that actively influence radio-sensitization and the ability of the complex to bind effectively to DNA., Competing Interests: The authors declare no competing financial interest.

Curcumin is an important molecule with a plethora of pharmacological activities and therapeutic potentials. Despite its efficacy, it remained a potential drug candidate owing to hydrolytic instability and poor aqueous solubility. To overcome the limitations related to low solubility, low bioavailability, and the fact that curcumin is never present in solution as a "single unit", its complex was prepared with Mn II with the idea that binding to a metal ion might help to resolve these issues. The complex was characterized by elemental and spectral analysis. The structure of the complex was determined by density functional theory calculations. The complex was stable at physiological buffer conditions, unlike curcumin. It did not have any detrimental effect on mammalian cells. There was a significant enhancement in the antibacterial activity of the complex compared to curcumin against both Gram-positive ( Staphylococcus aureus ) and Gram-negative ( Escherichia coli ) bacteria. It showed a strong affinity for deoxyribonucleic acid (DNA) evident from a high binding constant value with calf thymus DNA and also from the retarded electrophoretic mobility of bacterial plasmid DNA. The complex showed "superoxide dismutase-like" activity leading to the generation of reactive oxygen species (ROS). The complex caused bacterial membrane perturbation evident from calcein leakage assay, which was further corroborated by scanning and transmission electron microscopic experiments. Overall, the present study shows improved stability and antibacterial potency of a nontoxic complex over curcumin. Its multitargeting mode of action such as ROS-production, effective binding with DNA, and permeabilization of bacterial membrane together allows it to be an effective antibacterial agent that could be taken further for therapeutic use against bacterial infections., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

A monomeric complex of Zn II with ornidazole [Zn(Onz) 2 Cl 2 ] decreases formation of the nitro-radical anion (R-NO 2 ˙ - ), and this is realized by recording it in an enzyme assay using xanthine oxidase, which is a model nitro-reductase. Although the formation of R-NO 2 ˙ - is essential for drug action, as it is also associated with neurotoxic side effects, it is imperative to control its generation in order to avoid excess presence. With a decrease in R-NO 2 ˙ - , while the neurotoxic side effects should decrease, it can be expected that a compromise with regard to therapeutic efficacy will be seen since the complex will be less active in the free radical pathway. Since R-NO 2 ˙ - is crucial for the functioning of 5-nitroimidazoles, we attempted to find out if its biological activity is affected in any way in our effort to control its formation. For this purpose, Entamoeba histolytica (HM1:IMS Strain) was chosen as a biological target to realize the performance of the complex with respect to ornidazole (R-NO 2 ). The experiments revealed that the complex not only compares well with ornidazole, but in fact, under longer exposure times, it also performs better than it. This efficacy of the complex was seen despite a decrease in R-NO 2 ˙ - , as identified by an enzyme assay, and this was probably due to certain attributes of the complex formation that are not known for ornidazole. These attributes outweigh any loss in efficacy in the free radical pathway following complex formation. This is certainly an advantage of complex formation and helps to improve the therapeutic index. This study has attempted to look at some of the possible reasons why the complex performs better than ornidazole. One reason is its ability to bind to DNA better than ornidazole does, and this can be understood by following the interaction of ornidazole and its Zn(ii) complex with calf-thymus DNA using cyclic voltammetry. Therefore, this study showed that despite a decrease in R-NO 2 ˙ - , the complex does not compromise its efficacy, and this was examined using a biological target. In addition, the complex is likely to have less toxic side effects on the host of the disease-causing microbes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Purpose: To explain the observed radio-protection properties of an azo compound, 2-(2-hydroxyphenylazo)-indole-3 ∕ -acetic acid (HPIA)., Materials and Methods: Mechanism of radioprotection by HPIA was attempted using the stable free radical 2, 2-diphenyl-1-picrylhydrazyl (DPPH) using UV-Vis and electron paramagnetic resonance (EPR) spectroscopy. The radical destroying ability of HPIA was studied by depletion of reactive oxygen species (ROS) in WI 38 lung fibroblast cells., Results & Discussion: Studies indicate HPIA interacts with radical intermediates formed in solution following irradiation by 60 Co γ-rays. As a result, reactive radical intermediates do not cause any damage on chosen substrates like thymine or calf thymus DNA when irradiated in presence of HPIA. The study showed that reactive intermediates not only react with HPIA but that the kinetics of their reaction is definitely faster than their interaction either with thymine or with DNA. Had this not been the case, much more damage would have been observed on chosen substrates following irradiation with 60 Co γ-rays, in the presence of HPIA than actually observed in experiments, particularly those that were performed in a relatively high dose. Experiments reveal radiation induced-damage caused to thymine in presence of HPIA was ~ 1 36 to ~ 1 32 times that caused in its absence under different conditions indicating the radio-protection properties of HPIA. In case of calf thymus DNA, damage in presence of HPIA was much lower than in its absence. A fluorometric microplate assay for depletion of ROS by detecting the oxidation of 2',7'-dichlorofluorescin-diacetate (DCF-DA) into the highly fluorescent compound 2',7' dichlorofluorescein (DCF) indicated HPIA brought about a considerable check on ROS-mediated damage to cells by scavenging them right away., Conclusion: The study indicates HPIA may be an antioxidant supplement during radiotherapy., (© 2020 The Author(s).)

Background and Aim: The leaves of Annonareticulata Linn (niú x ınguǒ; Bullock's heart), a member of Annonaceae family, have been used extensively in folk medicine; however, its wound healing potential is yet to be explored. Our aim was to investigate the wound healing ability of A. reticulata leaf extract in vitro and in streptozotocin induced diabetic mice model., Material and Methods: We observed the plant extract induced proliferation and migration of primary human dermal fibroblast (HDF), human skin fibroblast cell line (GM00637) and human keratinocyte cell line (HACAT). The expression of transforming growth factor beta (TGF-β), connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF), alpha smooth muscle actin (α-SMA), matrix metalloproteinases (MMP-2, MMP-9), collagen-1, collagen-3, focal adhesion kinase (FAK) were evaluated by Western blot and gelatin zymography. Excisional diabetic wound model was used for in vivo wound healing assay. Furthermore, we processed wound tissue for histological and immunohistochemical study., Result: A. reticulata L. leaf extract stimulates proliferation and migration of HDF, skin fibroblast and keratinocyte significantly in a dose dependent manner; expression of TGF-β, CTGF, VEGF, α-SMA, MMP-2, MMP-9, collagen-1, collagen-3, FAK increased. Additionally, an enhanced expression of phospho-SMAD2, phospho-SMAD3 in the treated cells indicated the activation of TGF-β signal transduction pathway, similarly increased expression of phospho-AkT suggested activation of PI3/AkT pathway. Expression of CTGF and α-SMA was also increased significantly in wound tissue. Mass spectrometric analysis revealed that mainly two compounds to be present in the extract: quercetin and β-sitosterol., Conclusion: Collective data suggest that A.reticulata leaf extract may have a stimulatory effect in diabetic wound healing., Competing Interests: Authors have none to declare., (© 2019 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.)

How to cite this article: Das SK, Reddy MM, Ray S. Hemostatic Agents in Critically Ill Patients. Indian J Crit Care Med 2019;23(Suppl 3):S226-S229., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2019; Jaypee Brothers Medical Publishers (P) Ltd.)

There is enough proof to believe that free-radical intermediates of anthracycline based anticancer agents are involved in different stages of drug action. Subtle therapeutic differences observed in the actions of different anthracyclines largely influence the mechanism of action of the drugs that distinguish one member from another. Redox properties control biological responses related either to the one-electron quinone/semiquinone couple or the two-electron quinone/quinone-dianion couple. Comproportionation also leads to generation of semiquinone. Hence, whatever the form of reduction of the quinone moiety, a substantial amount of semiquinone is eventually formed in the system. Immediately after formation, there is competition between natural radical-decay pathways and one-electron transfer reactions that generate the superoxide-radical anion. Prototropic properties control rate of radical decay while redox properties control rate of electron transfer to molecular oxygen. In aerated medium, semiquinone-radical anion and superoxide-radical anion co-exist while in de-aerated medium semiquinone-radical anion predominates. All the radicals are damaging to the biological system. Through this study, attempt was made to detect changes induced by the radicals on pyrimidine based nucleic acid bases and calf thymus DNA in aerated and de-aerated (Ar saturated) medium to know the mechanism by which Emodin, its Cu II /Mn II complexes might affect DNA. Semiquinone-radical anion was generated electrochemically maintaining a glassy carbon electrode at the first reduction potential of each compound. Since the chosen compound (Emodin), its complexes are analogues of anthracyclines, findings on them can be extrapolated to understand the differences in anticancer activity or of adverse drug reactions reported in an innumerable number of clinical studies related to anthracyclines where the difference in structure of different members is due to differences in the relative positioning of hydroxy groups on the hydroxy-9, 10-anthraquinone moiety of anthracyclines. The study helps to realize action of compounds of this class as anticancer agents., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The accuracy of respiratory variation of the inferior vena cava (rvIVC) in predicting fluid responsiveness, particularly in spontaneously breathing patients is unclear., Objectives: To consider the evidence to support the accuracy of rvIVC in identifying patients who are unlikely to benefit from fluid administration., Design: Systematic review and meta-analysis., Data Source: We searched MEDLINE, EMBASE, Cochrane Library, KoreaMed, LILCAS and WHO Clinical Trial Registry from inception to June 2017., Eligibility Criteria: Case-control or cohort studies that evaluated the accuracy of rvIVC in living adult humans were included. A study was included in the meta-analysis if data enabling construction of 2 × 2 tables were reported, calculated or could be obtained from authors and met the above cited criteria., Result: A total of 23 studies including 1574 patients were included in qualitative analysis. The meta-analysis involved 20 studies and 761 patients. Pooled sensitivity and specificity of rvIVC in 330 spontaneously breathing patients were 0.80 [95% confidence interval (CI) 0.68 to 0.89] and 0.79 (95% CI 0.60 to 0.90). Pooled sensitivity and specificity of rvIVC in 431 mechanically ventilated patients were 0.79 (95% CI 0.67 to 0.86) and 0.70 (95% CI 0.63 to 0.76)., Conclusion: Decreased inferior vena caval respiratory variation is moderately accurate in predicting fluid unresponsiveness both in spontaneous and mechanically ventilated patients. The findings of this review should be used in the appropriate clinical context and in conjunction with other clinical assessments of fluid status., Identifier: CRD 42017068028.

Quinalizarin (THAQ), a hydroxy-9,10-anthraquinone analogue of the family of anthracycline anticancer drugs and an inhibitor of protein kinase, was observed for its anticancer activity. Because apart from showing anticancer activity, anthracyclines and their analogues also show cardiotoxic side effects, believed to be addressed through metal complex formation; an effort was made to realize this by preparing a Co II complex of THAQ. The aim of this study was to find out if complex formation leads to a decrease in the generation of intermediates that are responsible for toxic side effects. However, because this also meant that efficacy on cancer cells would be compromised, studies were undertaken on two cancer cell lines, namely, acute lymphoblastic leukemia (ALL) MOLT-4 and HCT116 cells. The complex decreases the flow of electrons from NADH to molecular oxygen (O 2 ) in the presence of NADH dehydrogenase forming less semiquinone than THAQ. It showed increased affinity toward DNA with binding constant values remaining constant over the physiological pH range unlike THAQ (for which decrease in binding constant values with increase in pH was observed). The complex is probably a human DNA topoisomerase I and human DNA topoisomerase II poison acting by stabilizing the covalent topoisomerase-cleaved DNA adduct, a phenomenon not observed for THAQ. Activity of the compounds on cancer cells suggests that THAQ was more effective on ALL MOLT-4 cells, whereas the complex performed better on HCT116 cells. Results suggest that the formation of semiquinone probably dominates the action because of THAQ, whereas the performance of the complex is attributed to increased DNA binding, inhibition of topoisomerase, and so forth. Inspite of a decrease in the generation of superoxide by the complex, it did not hamper efficacy on either cell line, probably compensated by improved DNA binding and inhibition of topoisomerase enzymes which are positive attributes of complex formation. A decrease in superoxide formation suggests that the complex could be less cardiotoxic, thus increasing its therapeutic index., Competing Interests: The authors declare no competing financial interest.

pK a of a compound is crucial for determining the contributions of different forms of it towards overall binding with DNA. Hence it is important to use correct pK a values in DNA interaction studies. This study takes a look at the importance of pK a values to realize binding of compounds with DNA. Since pK a of a compound determined in the presence of DNA is quite different from that determined in its absence hence, presence of different forms of a compound during interaction with DNA is different from that realized if the determination of pK a is done in normal aqueous solution in absence of DNA. Hence, calculations determining contributions of different forms of a compound interacting with DNA are affected accordingly. Two simple analogues of anthracyclines, alizarin and purpurin, were used to investigate the influence DNA has on pK a values. Indeed, they were different in presence of DNA than when determined in normal aqueous solution. pK a1 for alizarin and purpurin determined in the absence and presence of calf thymus DNA were used in equations that determine contributions of two forms (neutral and anionic) towards overall binding with DNA. The study concludes that correct pK a values, determined correctly i.e. under appropriate conditions, must be used for DNA binding experiments to evaluate contributions of individual forms., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Access to adequate water, sanitation and hygiene (WASH) is essential for the health, well-being and dignity of all people. The World Health Organization South-East Asia Region has made considerable progress in WASH provision during the past two decades. However, compared with increases in coverage of improved drinking water, in some parts of the region, access to adequate sanitation remains low, with continued prevalence of open defecation. The Sustainable Development Goals (SDGs) have set ambitious targets for WASH services to be achieved by 2030. Examples of major health outcomes that would benefit from meeting these targets are diarrhoea and nutrition status. Although the total number of deaths attributable to diarrhoea declined substantially between 1990 and 2012, inadequate WASH still accounts for more than 1000 child deaths each day worldwide. And, despite the reductions in mortality, diarrhoea morbidity attributable to diarrhoea remains unchanged at around 1.7 billion cases per year. It has been known for decades that repeated episodes of diarrhoea increase a child's risk of long-term undernutrition, reduced growth and impaired cognitive development. Nutritional effects of inadequate WASH also include environmental enteropathy, leading to chronic intestinal inflammation, malnutrition and developmental deficits in young children. Inadequate WASH also contributes to iron deficiency anaemia resulting from infestation with soil-transmitted helminths. The cross-sectoral emphasis of the SDGs should act as a stimulus for intersectoral collaboration on research and interventions to reduce all inequities that result from inadequate WASH.

Introduction: Reported incidence of acute cor pulmonale (ACP) in patients with acute respiratory distress syndrome (ARDS) varies from 10% to 84%, despite being subjected to lung protective ventilation according to the current guidelines. The objective of this review is to find pooled cumulative incidence of ACP in patients with ARDS undergoing lung protective ventilation., Materials and Methods: We searched MEDLINE, EMBASE, Cochrane Library, KoreaMed, LILACS, and WHO Clinical Trial Registry. Cross-sectional or cohort studies were included if they reported or provided data that could be used to calculate the incidence proportion of ACP. Inverse variance heterogeneity (IVhet) and random effect model were used for the main outcome and measures., Results: We included 16 studies encompassing 1661 patients. The cumulative incidence of ACP using IVhet analysis was 23% (95% confidence interval [CI] = 18%-28%) over 3 days of lung protective ventilation. Random effect analysis of 7 studies (1250 patients) revealed pooled odd ratio of mortality of 1.16 (95% CI = 0.80-1.67, P = 0.44) due to ACP., Conclusion: Patients with ARDS have a 23% risk of developing ACP with lung protective ventilation. Findings of this review indicate the need of updating existing guidelines for ventilating ARDS patients to incorporate right ventricle protective strategy., Competing Interests: There are no conflicts of interest.

Despite the need for molecularly smooth self-assembled monolayers (SAMs) on silicon dioxide surfaces (the most common dielectric surface), current techniques are limited to nonideal silane grafting. Here, we show unique bioinspired zwitterionic molecules forming a molecularly smooth and uniformly thin SAM in "water" in <1 min on various dielectric surfaces, which enables a dip-coating process that is essential for organic electronics to become reality. This monomolecular layer leads to high mobility of organic field-effect transistors (OFETs) based on various organic semiconductors and source/drain electrodes. A combination of experimental and computational techniques confirms strong adsorption (W ad > 20 mJ m -2 ), uniform thickness (∼0.5 or ∼1 nm) and orientation (all catechol head groups facing the oxide surface) of the "monomolecular" layers. This robust (strong adsorption), rapid, and green SAM represents a promising advancement toward the next generation of nanofabrication compared to the current nonuniform and inconsistent polysiloxane-based SAM involving toxic chemicals, long processing time (>10 h), or heat (>80 °C).

The active fraction and/or compounds of Calendula officinalis responsible for wound healing are not known yet. In this work we studied the molecular target of C. officinalis hydroethanol extract (CEE) and its active fraction (water fraction of hydroethanol extract, WCEE) on primary human dermal fibroblasts (HDF). In vivo, CEE or WCEE were topically applied on excisional wounds of BALB/c mice and the rate of wound contraction and immunohistological studies were carried out. We found that CEE and only its WCEE significantly stimulated the proliferation as well as the migration of HDF cells. Also they up-regulate the expression of connective tissue growth factor (CTGF) and α-smooth muscle actin (α-SMA) in vitro. In vivo, CEE or WCEE treated mice groups showed faster wound healing and increased expression of CTGF and α-SMA compared to placebo control group. The increased expression of both the proteins during granulation phase of wound repair demonstrated the potential role of C. officinalis in wound healing. In addition, HPLC-ESI MS analysis of the active water fraction revealed the presence of two major compounds, rutin and quercetin-3-O-glucoside. Thus, our results showed that C. officinalis potentiated wound healing by stimulating the expression of CTGF and α-SMA and further we identified active compounds. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Wetting of rough surfaces involves time-dependent effects, such as surface deformations, nonuniform filling of surface pores within or outside the contact area, and surface chemistries, but the detailed impact of these phenomena on wetting is not entirely clear. Understanding these effects is crucial for designing coatings for a wide range of applications, such as membrane-based oil-water separation and desalination, waterproof linings/windows for automobiles, aircrafts, and naval vessels, and antibiofouling. Herein, we report on time-dependent contact angles of water droplets on a rough polydimethylsiloxane (PDMS) surface that cannot be completely described by the conventional Cassie-Baxter or Wenzel models or the recently proposed Cassie-impregnated model. Shells of sand dollars (Dendraster excentricus) were used as lithography-free, robust templates to produce rough PDMS surfaces with hierarchical, periodic features ranging from 1 × 10(-7) to 1 × 10(-4) m. Under saturated vapor conditions, we found that in the short term (<1 min), the contact angle of a sessile water droplet on the templated PDMS, θ(SDT) = 140 ± 3°, was accurately described by the Cassie-Baxter model (predicted θ(SDT) = 137°); however, after 90 min, θ(SDT) fell to 110°. Fluorescent confocal microscopy confirmed that the initial reduction in θ(SDT) to 110° (the Wenzel limit) was primarily a Cassie-Baxter to Wenzel transition during which pores within the contact area filled gradually, and more rapidly for ethanol-water mixtures. After 90 min, the contact line of the water droplet became pinned, perhaps caused by viscoelastic deformation of the PDMS around the contact line, and a significant volume of water began to flow from the droplet to pores outside the contact region, causing θ(SDT) to decrease to 65° over 48 h on the rough surface. The system we present here to explore the concept of contact angle time dependence (dynamics) and modeling of natural surfaces provides insights into the design and development of long- and short-lived coatings.

The role of friction in the functional performance of biomaterial interfaces is widely reckoned to be critical and complicated but poorly understood. To better understand friction forces, we investigated the natural adaptation of the holdfast or byssus of mussels that live in high-energy surf habitats. As the outermost covering of the byssus, the cuticle deserves particular attention for its adaptations to frictional wear under shear. In this study, we coacervated one of three variants of a key cuticular component, mussel foot protein 1, mfp-1 [(1) Mytilus californianus mcfp-1, (2) rmfp-1, and (3) rmfp-1-Dopa], with hyaluronic acid (HA) and investigated the wear protection capabilities of these coacervates to surfaces (mica) during shear. Native mcfp-1/HA coacervates had an intermediate coefficient of friction (μ ∼0.3) but conferred excellent wear protection to mica with no damage from applied loads, F ⊥ , as high as 300 mN (pressure, P , > 2 MPa). Recombinant rmfp-1/HA coacervates exhibited a comparable coefficient of friction (μ ∼0.3); however, wear protection was significantly inferior (damage at F ⊥ > 60 mN) compared with that of native protein coacervates. Wear protection of rmfp-1/HA coacervates increased 5-fold upon addition of the surface adhesive group 3,4-dihydroxyphenylalanine, (Dopa). We propose a Dopa-dependent wear protection mechanism to explain the differences in wear protection between coacervates. Our results reveal a significant untapped potential for coacervates in applications that require adhesion, lubrication, and wear protection. These applications include artificial joints, contact lenses, dental sealants, and hair and skin conditioners.

Despite the recent progress in and demand for wet adhesives, practical underwater adhesion remains limited or non-existent for diverse applications. Translation of mussel-inspired wet adhesion typically entails catechol functionalization of polymers and/or polyelectrolytes, and solution processing of many complex components and steps that require optimization and stabilization. Here we reduced the complexity of a wet adhesive primer to synthetic low-molecular-weight catecholic zwitterionic surfactants that show very strong adhesion (∼50 mJ m(-2)) and retain the ability to coacervate. This catecholic zwitterion adheres to diverse surfaces and self-assembles into a molecularly smooth, thin (<4 nm) and strong glue layer. The catecholic zwitterion holds particular promise as an adhesive for nanofabrication. This study significantly simplifies bio-inspired themes for wet adhesion by combining catechol with hydrophobic and electrostatic functional groups in a small molecule.

Mussel adhesion to mineral surfaces is widely attributed to 3,4-dihydroxyphenylalanine (Dopa) functionalities in the mussel foot proteins (mfps). Several mfps, however, show a broad range (30-100%) of Tyrosine (Tyr) to Dopa conversion suggesting that Dopa is not the only desirable outcome for adhesion. Here, we used a partial recombinant construct of mussel foot protein-1 (rmfp-1) and short decapeptide dimers with and without Dopa and assessed both their cohesive and adhesive properties on mica using a surface forces apparatus (SFA). Our results demonstrate that at low pH, both the unmodified and Dopa-containing rmfp-1s show similar energies for adhesion to mica and self-self interaction. Cohesion between two Dopa-containing rmfp-1 surfaces can be doubled by Fe 3+ chelation, but remains unchanged with unmodified rmfp-1. At the same low pH, the Dopa modified short decapeptide dimer did not show any change in cohesive interactions even with Fe 3+ . Our results suggest that the most probable intermolecular interactions are those arising from electrostatic (i.e., cation-π) and hydrophobic interactions. We also show that Dopa in a peptide sequence does not by itself mediate Fe 3+ bridging interactions between peptide films: peptide length is a crucial enabling factor., Competing Interests: The authors declare no conflict of interest.

Numerous attempts have been made to translate mussel adhesion to diverse synthetic platforms. However, the translation remains largely limited to the Dopa (3,4-dihydroxyphenylalanine) or catechol functionality, which continues to raise concerns about Dopa's inherent susceptibility to oxidation. Mussels have evolved adaptations to stabilize Dopa against oxidation. For example, in mussel foot protein 3 slow (mfp-3s, one of two electrophoretically distinct interfacial adhesive proteins in mussel plaques), the high proportion of hydrophobic amino acid residues in the flanking sequence around Dopa increases Dopa's oxidation potential. In this study, copolyampholytes, which combine the catechol functionality with amphiphilic and ionic features of mfp-3s, were synthesized and formulated as coacervates for adhesive deposition on surfaces. The ratio of hydrophilic/hydrophobic as well as cationic/anionic units was varied in order to enhance coacervate formation and wet adhesion properties. Aqueous solutions of two of the four mfp-3s-inspired copolymers showed coacervate-like spherical microdroplets (ϕ ≈ 1-5 μm at pH ∼4 (salt concentration ∼15 mM). The mfp-3s-mimetic copolymer was stable to oxidation, formed coacervates that spread evenly over mica, and strongly bonded to mica surfaces (pull-off strength: ∼17.0 mJ/m(2)). Increasing pH to 7 after coacervate deposition at pH 4 doubled the bonding strength to ∼32.9 mJ/m(2) without oxidative cross-linking and is about 9 times higher than native mfp-3s cohesion. This study expands the scope of translating mussel adhesion from simple Dopa-functionalization to mimicking the context of the local environment around Dopa.

Surfactant self-assembly on surfaces is an effective way to tailor the complex forces at and between hydrophobic-water interfaces. Here, the range of structures and forces that are possible at surfactant-adsorbed hydrophobic surfaces are demonstrated: certain long-chain bolaform surfactants-containing a polydimethylsiloxane (PDMS) mid-block domain and two cationic α, ω-quarternary ammonium end-groups-readily adsorb onto thin PDMS films and form dynamically fluctuating nanostructures. Through measurements with the surface forces apparatus (SFA), it is found that these soft protruding nanostructures display polymer-like exploration behavior at the PDMS surface and give rise to a long-ranged, temperature- and rate-dependent attractive bridging force (not due to viscous forces) on approach to a hydrophilic bare mica surface. Coulombic interactions between the cationic surfactant end-groups and negatively-charged mica result in a rate-dependent polymer bridging force during separation as the hydrophobic surfactant mid-blocks are pulled out from the PDMS interface, yielding strong adhesion energies. Thus, (i) the versatile array of surfactant structures that may form at hydrophobic surfaces is highlighted, (ii) the need to consider the interaction dynamics of such self-assembled polymer layers is emphasized, and (iii) it is shown that long-chain surfactants can promote robust adhesion in aqueous solutions., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Understanding the interactions between collagen and adhesive mussel foot proteins (mfps) can lead to improved medical and dental adhesives, particularly for collagen-rich tissues. Here we investigated interactions between collagen type-1, the most abundant load-bearing animal protein, and mussel foot protein-3 (mfp-3) using a quartz crystal microbalance and surface forces apparatus (SFA). Both hydrophilic and hydrophobic variants of mfp-3 were exploited to probe the nature of the interaction between the protein and collagen. Our chief findings are: 1) mfp-3 is an effective chaperone for tropocollagen adsorption to TiO2 and mica surfaces; 2) at pH 3, collagen addition between two mfp-3 films (Wc = 5.4 ± 0.2 mJ/m(2)) increased their cohesion by nearly 35%; 3) oxidation of Dopa in mfp-3 by periodate did not abolish the adhesion between collagen and mfp-3 films, and 4) collagen bridging between both hydrophilic and hydrophobic mfp-3 variant films is equally robust, suggesting that hydrophobic interactions play a minor role. Extensive H-bonding, π-cation and electrostatic interactions are more plausible to explain the reversible bridging of mfp-3 films by collagen., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: Early confirmation of endotracheal tube placement is of paramount importance to prevent hypoxia and its catastrophic consequences. Despite certain limitations, capnography is considered the gold standard to evaluate the proper placement of an endotracheal tube. Ultrasound is a novel tool with some definitive advantages over capnography. It enables a real-time view and can be performed quickly; furthermore, it is independent of pulmonary blood flow and does not require lung ventilation. In this review, we aimed to evaluate the diagnostic accuracy of transtracheal ultrasound in detecting endotracheal intubation., Source: We completed an extensive search of MEDLINE®, EMBASE™, The Cochrane Library, KoreaMed, LILACS, OpenGrey, and the World Health Organization International Clinical Trials Registry from their inception to September 4, 2014. The studies that met the inclusion criteria were pooled and a meta-analysis was conducted., Principal Findings: Eleven studies and 969 intubations were included in the final analysis. Eight studies and 713 intubations were performed in emergency situations and the others were carried out in elective situations. Transtracheal ultrasonography's pooled sensitivity and specificity with 95% confidence intervals (CIs) were 0.98 (95% CI 0.97 to 0.99) and 0.98 (95% CI 0.95 to 0.99), respectively. In emergency scenarios, transtracheal ultrasonography showed an aggregate sensitivity and specificity of 0.98 (95% CI 0.97 to 0.99) and 0.94 (95% CI 0.86 to 0.98), respectively., Conclusion: Transtracheal ultrasound is a useful tool to confirm endotracheal intubation with an acceptable degree of sensitivity and specificity. It can be used in emergency situations as a preliminary test before final confirmation by capnography.

Background and Aims: Postsurgical pain is the leading complaint after laparoscopic cholecystectomy that may delay the postoperative recovery and hence we undertook a prospective randomized trial to analyze the role of flupirtine as a preemptive analgesic for postoperative pain relief in patients undergoing above surgery., Material and Methods: A total of 66 cases were randomly assigned to two groups to receive capsule flupirtine (200 mg) or capsule vitamin B complex administered orally, 2 h before the laparoscopic cholecystectomy surgery. Time to first analgesic requirement, assessment of postoperative pain in terms of visual analog score, and analgesic requirement postoperatively were measured as a primary outcome., Results: Time to first analgesic requirement was significantly prolonged in the flupirtine group as compared with the placebo group. There was significant pain reduction in early postoperative period (up to 4 h), but no changes occurred thereafter. Total analgesic requirement (including rescue analgesia) and side-effects were comparable between the groups except for higher sedation in flupirtine group., Conclusions: Flupirtine is effective as a preemptive analgesic in providing adequate pain relief during the immediate postoperative period after laparoscopic cholecystectomy surgery. However, continuation of drug therapy postoperatively could possibly delineate its optimal analgesic profile more profoundly.

A 1 : 2 copper(II) complex of 1-amino-4-hydroxy-9,10-anthraquinone (QH) having the molecular formula CuQ2 was prepared and characterized by elemental analysis, NMR, FTIR, UV-vis and mass spectroscopy. The powder diffraction of the solid complex, magnetic susceptibility and ESR spectra were also recorded. The presence of the planar anthraquinone moiety in the complex makes it extremely difficult to obtain a single crystal suitable for X-ray diffraction studies. To overcome this problem, density functional theory (DFT) was used to evaluate an optimized structure of CuQ2. In the optimized structure, it was found that there is a tilt of the two planar aromatic anthraquinone rings of the complex with respect to each other in the two planes containing the O-Cu(II)-O plane. The present study is an important addition to the understanding of the structural aspects of metal-anthracyclines because there are only a few reports on the actual structures of metal-anthracyclines. The theoretical vibrational spectrum of the complex was assigned with the help of vibrational energy distribution analysis (VEDA) using potential energy distribution (PED) and compared with experimental results. Being important in producing the biochemical action of this class of molecules, the electrochemical behavior of the complex was studied in aqueous and non-aqueous solvents to find certain electrochemical parameters. In aqueous media, reduction involves a kinetic effect during electron transfer at an electrode surface, which was characterized very carefully using cyclic voltammetry. Electrochemical studies showed a significant modification in the electrochemical properties of 1-amino-4-hydroxy-9,10-anthraquinone (QH) when bound to Cu(II) in the complex compared to those observed for free QH. This suggests that the copper complex might be a good choice as a biologically active molecule, which was reflected in the lack of stimulated superoxide generation by the complex.

Mussel foot protein-1 (mfp-1) is an essential constituent of the protective cuticle covering all exposed portions of the byssus (plaque and the thread) that marine mussels use to attach to intertidal rocks. The reversible complexation of Fe(3+) by the 3,4-dihydroxyphenylalanine (Dopa) side chains in mfp-1 in Mytilus californianus cuticle is responsible for its high extensibility (120%) as well as its stiffness (2 GPa) due to the formation of sacrificial bonds that help to dissipate energy and avoid accumulation of stresses in the material. We have investigated the interactions between Fe(3+) and mfp-1 from two mussel species, M. californianus (Mc) and M. edulis (Me), using both surface sensitive and solution phase techniques. Our results show that although mfp-1 homologues from both species bind Fe(3+), mfp-1 (Mc) contains Dopa with two distinct Fe(3+)-binding tendencies and prefers to form intramolecular complexes with Fe(3+). In contrast, mfp-1 (Me) is better adapted to intermolecular Fe(3+) binding by Dopa. Addition of Fe(3+) did not significantly increase the cohesion energy between the mfp-1 (Mc) films at pH 5.5. However, iron appears to stabilize the cohesive bridging of mfp-1 (Mc) films at the physiologically relevant pH of 7.5, where most other mfps lose their ability to adhere reversibly. Understanding the molecular mechanisms underpinning the capacity of M. californianus cuticle to withstand twice the strain of M. edulis cuticle is important for engineering of tunable strain tolerant composite coatings for biomedical applications.

The discovery and understanding of gecko 'frictional-adhesion' adhering and climbing mechanism has allowed researchers to mimic and create gecko-inspired adhesives. A few experimental and theoretical approaches have been taken to understand the effect of surface roughness on synthetic adhesive performance, and the implications of stick-slip friction during shearing. This work extends previous studies by using a modified surface forces apparatus to quantitatively measure and model frictional forces between arrays of polydimethylsiloxane gecko footpad-mimetic tilted microflaps against smooth and rough glass surfaces. Constant attachments and detachments occur between the surfaces during shearing, as described by an avalanche model. These detachments ultimately result in failure of the adhesion interface and have been characterized in this study. Stick-slip friction disappears with increasing velocity when the flaps are sheared against a smooth silica surface; however, stick-slip was always present at all velocities and loads tested when shearing the flaps against rough glass surfaces. These results demonstrate the significance of pre-load, shearing velocity, shearing distances, commensurability and shearing direction of gecko-mimetic adhesives and provide us a simple model for analysing and/or designing such systems., (© 2015 The Author(s) Published by the Royal Society. All rights reserved.)

We review direct force measurements on a broad class of hydrophobic and hydrophilic surfaces. These measurements have enabled the development of a general interaction potential per unit area, W(D) = -2γ(i)Hy exp(-D/D(H)) in terms of a nondimensional Hydra parameter, Hy, that applies to both hydrophobic and hydrophilic interactions between extended surfaces. This potential allows one to quantitatively account for additional attractions and repulsions not included in the well-known combination of electrostatic double layer and van der Waals theories, the so-called Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. The interaction energy is exponentially decaying with decay length D(H) ≈ 0.3-2 nm for both hydrophobic and hydrophilic interactions, with the exact value of D(H) depending on the precise system and conditions. The pre-exponential factor depends on the interfacial tension, γ(i), of the interacting surfaces and Hy. For Hy > 0, the interaction potential describes interactions between partially hydrophobic surfaces, with the maximum hydrophobic interaction (i.e., two fully hydrophobic surfaces) corresponding to Hy = 1. Hydrophobic interactions between hydrophobic monolayer surfaces measured with the surface forces apparatus (SFA) are shown to be well described by the proposed interaction potential. The potential becomes repulsive for Hy < 0, corresponding to partially hydrophilic (hydrated) interfaces. Hydrated surfaces such as mica, silica, and lipid bilayers are discussed and reviewed in the context of the values of Hy appropriate for each system.