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Polymeric surfactants are amphiphilic molecules with two or more different types of monomers. If one type of monomer interacts favorably with a liquid, and another type of monomer interacts favorably with another, immiscible liquid, then polymeric surfactants adsorb at the interface between the two liquids and reduce the interfacial tension. The effects of polymer architecture on the structural and thermodynamic properties of the liquid–liquid interface are studied using molecular simulations. The interface is modeled with a non-additive binary Lennard-Jones fluid in the two-phase region of the phase diagram. Block and gradient copolymer surfactants are represented with coarse-grained, bead-spring models, where each component of the polymer favors one or the other liquid. Gradient copolymers have a greater concentration at the interface than do block copolymers because the gradient copolymers adopt conformations partially aligned with the interface. The interfacial tension is determined as a function of the surface excess of polymeric surfactant. Gradient copolymers are more potent surfactants than block copolymers because the gradient copolymers cross the dividing surface multiple times, effectively acting as multiple individual surfactants. For a given surface excess, the interfacial tension decreases monotonically when changing from a block to a gradient architecture. The coarse-grained simulations are complemented by all-atom simulations of acrylic-acid/styrene copolymers at the chloroform-water interface, which have been studied in experiments. The agreement between the simulations (both coarse-grained and atomistic) and experiments is shown to be excellent, and the molecular-scale structures identified in the simulations help explain the variation of surfactancy with copolymer architecture. [ABSTRACT FROM AUTHOR]

Background: Acute stroke patients are usually transported to the nearest hospital regardless of their required level of care. This can lead to increased pressure on emergency departments and treatment delay. Objective: The aim of the study was to explore the benefit of a mobile stroke unit (MSU) in the UK National Health Service (NHS) for reduction of hospital admissions. Methods: Prospective cohort audit observation with dispatch of the MSU in the East of England Ambulance Service area in Southend-on-Sea was conducted. Emergency patients categorized as code stroke and headache were included from June 5, 2018, to December 18, 2018. Rate of avoided admission to the accident and emergency (A&E) department, rate of admission directly to target ward, and stroke management metrics were assessed. Results: In 116 MSU-treated patients, the following diagnoses were made: acute stroke, n = 33 (28.4%); transient ischaemic attacks, n = 13 (11.2%); stroke mimics, n = 32 (27.6%); and other conditions, n = 38 (32.8%). Pre-hospital thrombolysis was administered to 8 of 28 (28.6%) ischaemic stroke patients. Pre-hospital diagnosis avoided hospital admission for 29 (25.0%) patients. As hospital treatment was indicated, 35 (30.2%) patients were directly triaged to the stroke unit, 1 patient (0.9%) even directly to the catheter laboratory. Thus, only 50 (43.1%) patients required transfer to the A&E department. Moreover, the MSU enabled thrombolysis with a median dispatch-to-needle time of 42 min (interquartile range, 40–60). Conclusion: This first deployment of an MSU in the UK NHS demonstrated improved triage decision-making for or against hospital admission and admission to the appropriate target ward, thereby reducing pressure on strained A&E departments. [ABSTRACT FROM AUTHOR]

The aim was to investigate the biomechanical, physiological, and perceptual responses to different motor learning strategies derived to elicit a flatter foot contact. Twenty‐eight rearfoot‐striking recreational runners (age 24.9 ± 2.8 years; body mass 78.8 ± 13.6 kg; height 1.79 ± 0.09 m) were matched by age, mass, and height and assigned to one verbal cue group: internal focus of attention (IF), external focus of attention (EF), and a clinically derived condition (CLIN) incorporating an IF followed by an EF statement. Participants completed two treadmill runs at 10 km h−1 for 6 minutes each: normal running (control) followed by the experimental condition (IF, EF, or CLIN). Lower limb kinematics, oxygen consumption (V˙O2), and central and peripheral ratings of perceived exertion (RPE) were recorded for each run. Compared to the control condition, foot angle was reduced in the IF (difference = 5.86°, d = 2.58) and CLIN (difference = 3.00°, d = 1.31) conditions, but unchanged in the EF condition (difference = 0.33°, d = 0.14), while greater knee flexion at initial contact in the EF and CLIN conditions was observed (difference = −5.19°, d = 1.97; difference = −3.66°, d = 1.39, respectively). A higher V˙O2 was observed in the CLIN condition (difference = −4.56 mL kg−1 min−1, d = 2.29), but unchanged in the IF (difference = −1.87 mL kg−1 min−1, d = 0.94) and EF conditions (difference = −0.37 mL kg−1 min−1, d = 0.19). All experimental conditions increased central and peripheral RPE (difference = −1.08, d = 0.54 and difference = −2.39, d = 1.33, respectively). Providing gait retraining instructions using an internally directed focus of attention was the most effective way to target specific changes in running kinematics, with no detrimental effect on physiological responses. Yet, perceptual effort responses increased regardless of the type of cue provided. [ABSTRACT FROM AUTHOR]

Background: Crestal bone thickness is a critical determinant of peri-implant tissue stability. This retrospective observational study sought to quantify the buccal bone thickness achieved adjacent to virtual dental implants following guided bone regeneration (GBR) surgery and evaluate the influence of patient- and procedure-related variables on buccal bone thickness.Methods: Cone-beam computed tomography (CBCT) images acquired from patients who had undergone GBR surgery between July 1, 2012, and November 7, 2016, were used for this analysis. In all cases, the GBR procedure involved a dense polytetrafluoroethylene (dPTFE) barrier membrane and a mineralized cortical particulate freeze-dried bone allograft (FDBA). Eighty-four virtual dental implants were placed at planned locations using CBCT images from 84 patients, and the adjacent buccal bone thickness was measured at each site. The effects of sex, age, estimated baseline ridge width, number of missing teeth in site, site type (tooth-bounded versus terminal position in arch), dental arch (mandibular or maxillary), arch location (anterior or posterior), smoking status, titanium reinforcement in the membrane, membrane fixation, and tenting screw use were assessed.Results: The mean post-GBR buccal bone thickness adjacent to virtual dental implants was 2.24 ± 1.01 mm. Fifty-nine of 84 virtual implants (70%) exhibited buccal bone thickness > 1.9 mm. GBR sites using membrane fixation produced significantly greater virtual implant buccal bone thickness than those without membrane fixation (2.31 ± 0.96 versus 1.15 ± 1.25 mm, P = 0.012). Virtual implant buccal bone thickness also exhibited moderate correlation with estimated initial ridge width (r = 0.43, P < 0.0001). The alveolar ridge at 81 virtual implant sites (96%) was classified as good or satisfactory, meaning dental implants were actually placed at these sites, with or without additional grafting at implant placement.Conclusions: Observations in this study suggest GBR procedures using dPTFE membranes and FDBA result in favorable ridge dimensions for dental implant placement in most cases. However, additional augmentation at implant surgery may be necessary at ≈ 30% of sites, if buccal bone thickness > 1.9 mm is intended. [ABSTRACT FROM AUTHOR]

Background and Purpose: Tuberculosis (TB) remains a major global health threat and is now the leading cause of death from a single infectious agent worldwide. The current TB drug regimen is inadequate, and new anti-tubercular agents are urgently required to be able to successfully combat the increasing prevalence of drug-resistant TB. The purpose of this study was to investigate a piperidinol compound derivative that is highly active against the Mycobacterium tuberculosis bacillus.Experimental Approach: The antibacterial properties of the piperidinol compound and its corresponding bis-Mannich base analogue were evaluated against M. smegmatis and Gram-negative organisms. Cytotoxicity studies were undertaken in order to determine the selectivity index for these compounds. Spontaneous resistant mutants of M. smegmatis were generated against the piperidinol and corresponding bis-Mannich base lead derivatives and whole genome sequencing employed to determine the genetic modifications that lead to selection pressure in the presence of these compounds.Key Results: The piperidinol and the bis-Mannich base analogue were found to be selective for mycobacteria and rapidly kill this organism with a cytotoxicity selectivity index for mycobacteria of >30-fold. Whole genome sequencing of M. smegmatis strains resistant to the lead compounds led to the identification of a number of single nucleotide polymorphisms indicating multiple targets.Conclusion and Implications: Our results indicate that the piperidinol moiety represents an attractive compound class in the pursuit of novel anti-tubercular agents.Linked Articles: This article is part of a themed section on Drug Metabolism and Antibiotic Resistance in Micro-organisms. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.14/issuetoc. [ABSTRACT FROM AUTHOR]

Responsive polymers and polymer-coated nanoparticles have many potential bio-applications with the crucial parameter being the exact temperature where the transition occurs. Chemical modification of hydrophobic/hydrophilic or ligand binding sites has been widely explored as a tool for controlling this transition, but requires the synthesis of many different components to achieve precise control. This study reports an extensive investigation into the use of blending (i.e. mixing) as a powerful tool to modulate the transition temperature of poly(N-isopropylacrylamide) (PNIPAM) coated gold nanoparticles. By simply mixing two nanoparticles of different compositions, precise control over the transition temperature can be imposed. This was shown to be flexible to all possible mixing parameters (different polymers on different particles, different polymers on same particles and different sized particles with identical/different polymers). Evidence of the co-operative aggregation of differently sized nanoparticles (with different cloud points) is shown using transmission electron microscopy; particles with higher cloud points aggregate with those with lower cloud points with homo-aggregates not seen, demonstrating the co-operative behaviour. These interactions, and the opportunities for transition tuning will have implications in the rational design of responsive biomaterials. [ABSTRACT FROM AUTHOR]

Inspired by nature's exploitation of the 1,2-dihydroxybenzene unit (or catechol) in mammalian and bacterial siderophores, we report the first example of a nanoparticle sensing system that utilises the strong catechol- Fe3+ binding motif to trigger nanoparticle aggregation, promoting a powerful optical response. Gold nanoparticles are functionalised with RAFT polymerisation-prepared water-soluble poly(N-hydroxyethyl acrylamide) containing a catechol moiety at the a-chain-end. A strong red-to-purple colorimetric response occurs in the presence of Fe3+ at serum concentrations (8-25 μM) in saline solution. Sodium chloride is critical in generating a strong optical output, as is the length of polymer used to coat the AuNPs. This behaviour is also demonstrated to be selective for Fe3+ over a host of other biologically relevant ions. [ABSTRACT FROM AUTHOR]

Tethering polymers to surfaces represents the cornerstone of a wide range of applications, including the stabilization of colloids/biomolecules and the preparation of functional coatings. Unfortunately, despite the prevalence of protein-tethered polymers in the pharmaceutical sector, the analysis of such polymer monolayers on a molecular level is difficult. In this work, simple 1H NMR spectroscopy and the catalytic properties of α-chymotrypsin are used to analyze the conformational/permeability properties of protein-bound monolayers of poly(oligoethyleneglycol monomethylether methacrylate) (pOEGMA), a biocompatible comb-polymer of interest in the biomedical field. By analyzing >100 distinct conjugates of α-chymotrypsin and pOEGMA, a detailed picture of the behavior of pOEGMA on the surface of a protein was obtained. Remarkably, control of polymer conformation and inter-penetration produced a thus far overlooked molecular sieving effect. The application of this effect for the 'smart' PEGylation of proteins is portrayed, from which insight is provided for the design of other therapeutic bioconjugates and functional coatings with selective permeability properties. [ABSTRACT FROM AUTHOR]

Objectives The conventional dissolution test, particularly the USP apparatus I and II, remains an important tool in the armory of the pharmaceutical development scientist. For realistic dissolution characterization, sink conditions, where saturation solubility of a drug in the dissolution medium is at least three times more than the drug concentration, are critical. These conditions can be problematic to maintain with formulations containing poorly-soluble actives. This review summarizes the role of the dissolution test in the pharmaceutical industry, together with some traditional techniques/additives used to enhance solubility and facilitate the achievement of sink conditions. The biphasic dissolution system, an innovative model for the treatment of poorly-soluble species, will also be discussed. Key findings The biphasic dissolution model utilizes media comprising immiscible aqueous and organic layers whereby the drug, following initial aqueous dissolution, partitions into the organic layer. This step, which acts to remove all dissolved species from the aqueous layer, enables further aqueous dissolution to occur and hence the dissolution-partition cycle continues. Crucially, the aqueous layer does not saturate allowing sink conditions to be maintained and hence the experiment will, in theory, yield complete dissolution. Summary This review highlights important concepts regarding solubility/sink limitation and intends to provoke debate among analytical and formulation scientists as to the potential advantages, long-term development and widespread implementation of a biphasic dissolution system in drug development. [ABSTRACT FROM AUTHOR]

The transport mechanism for the evaporation of dispersing liquid during the solidification of an epoxy dispersion that had been stabilized to prevent crack formation with a latex dispersion was studied. Aqueous dispersions consisting of an experimentally determined ratio of epoxy resin and nitrile latex were evaporated at 35°C. When the dispersion was orated under controlled conditions without forced air flow, a flexible and adherent polymer material formed. The mechanism for coalescence was related to the loss in weight of dispersing liquid during an initial zero order kinetics stage. This was followed by a rate-controlled Fick's law diffusion through the developing coating with subsequent evaporation to the atmosphere. Experimental measurements are compared with theoretical predictions. The rate constant for the zero order time frame is 0.086 ± 0.02 hr-1. In the second time frame, Ficks's law evaporation rate constant is 0.046 ± 0.017 cm.hr-1 with a diffusion coefficient of 0.00092 ± 0.00051 cm².hr-1 at 35 ± 1°C and RH 35 ± 7%. Applications for evaporation kinetics are discussed. [ABSTRACT FROM AUTHOR]

The α-termini of RAFT-derived thermoresponsive polymers were functionalised via thiol exchange with pyridyl disulfide. Addition of hydrophilic end-groups dramatically increased the observed cloud point of the polymers, without changing the composition of the main chain. Selective cleavage of the disulfide-linked end-groups was observed under conditions intended to mimic intracellular glutathione concentration. This allowed the thermoresponsive behaviour to be ‘switched on’ without the need for a temperature stimulus – an ‘isothermal’ switch. [ABSTRACT FROM AUTHOR]