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Background: Preoperative fasting is performed to reduce aspiration risk during general anesthesia. Recommendations are that patients should fast for 6 hours from solids and nonhuman milk, 4 hours from breast milk, and 2 hours from clear fluids. However, previous studies have shown that children fast far in excess of these times, which can result in perioperative complications and unnecessary discomfort for the child. Aims: This prospective, mixed‐methods study aims to explore the experiences of pediatric patients undergoing preoperative fasting in Leeds General Infirmary. It also aims to investigate fasting durations of these patients and factors which influence these. Methods: Over 2 weeks, surveys were distributed to all parents of elective pediatric patients and completed prior to their child being called to theater. Children over the age of six were offered a child survey, which had been specifically developed for the study, with visual Likert scales and an area for free text. The gathering of children's comments about their experience of preoperative fasting is unique to this study. Results: Seventy‐one parent surveys and 48 child surveys were completed, with a mean patient age of 8.3 years (SD 4.1). The mean preoperative fasting time for food was 11.7 hours (SD 4.4) and 6.9 hours (SD 5.0) for fluids. Fasting times were far in excess of the minimums recommended, negatively impacting patient experience with 34% reporting being hungry/very hungry and 19% thirsty/very thirsty. Most children's comments suggested that they coped well with the fasting; however, several children reported feelings of sadness and anxiety. Conclusion: Preoperative fasting times in pediatric patients far exceed the durations set by international guidelines. Given that many children reported extreme feelings of hunger and thirst or emotional effects from the fast, these durations need to be optimized in order to improve patient experience. [ABSTRACT FROM AUTHOR]

Selection methods are used to identify Affimers that recognise α-helix mimicking N-alkylated aromatic oligoamides thus demonstrating foldamer and natural α-amino acid codes are compatible. [ABSTRACT FROM AUTHOR]

Inhibition of protein-protein interactions (PPIs) represents a major challenge in chemical biology and drug discovery. α-Helix mediated PPIs may be amenable to modulation using generic chemotypes, termed 'proteomimetics', which can be assembled in a modular manner to reproduce the vectoral presentation of key side chains found on a helical motif from one partner within the PPI. In this work, it is demonstrated that by using a library of N-alkylated aromatic oligoamide helix mimetics, potent helix mimetics which reproduce their biophysical binding selectivity in a cellular context can be identified. [ABSTRACT FROM AUTHOR]

Inhibition of protein-protein interactions (PPIs) represents a major challenge in chemical biology and drug discovery. α-Helix mediated PPIs may be amenable to modulation using generic chemotypes, termed 'proteomimetics', which can be assembled in a modular manner to reproduce the vectoral presentation of key side chains found on a helical motif from one partner within the PPI. In this work, it is demonstrated that by using a library of N-alkylated aromatic oligoamide helix mimetics, potent helix mimetics which reproduce their biophysical binding selectivity in a cellular context can be identified. [ABSTRACT FROM AUTHOR]

This paper describes the design, synthesis and structural analysis of a 3- O-alkylated aromatic oligoamide that incorporates an additional hydrophilic 6- O-alkyl substituent in the central monomer. This oligomer exhibits low μ M inhibitory potency against the p53- hDM2 interaction compared with its unfunctionalised counterpart and significantly improved solubility. [ABSTRACT FROM AUTHOR]

We report the simple synthesis and full investigation of a novel heparin binding dye, mallard blue, an arginine-functionalized thionine. This dye binds heparin in highly competitive media, including water with high levels of competitive electrolyte, buffered aqueous solution and human serum. The dye reports on heparin levels by a significant change in its UV-vis spectroscopic profile. Molecular dynamics modeling provides detailed insight into the binding mode. Heparin binding is shown to be selective over other glycosaminoglycans, such as hyaluronic acid and chondroitin sulfate. Importantly, we demonstrate that, in the most competitive conditions, mallard blue outperforms standard dyes used for heparin sensing such as azure A. [ABSTRACT FROM AUTHOR]

Multivalency is a powerful strategy for achieving high-affinity molecular recognition in biological systems. Recently, attention has begun to focus on using self-assembly rather than covalent scaffold synthesis to organize multiple ligands. This approach has a number of advantages, including ease of synthesis/assembly, tunability of nanostructure morphology and ligands, potential to incorporate multiple active units, and the responsive nature of self-assembly. We suggest that self-assembled multivalency is a strategy of fundamental importance in the design of synthetic nanosystems to intervene in biological pathways and has potential applications in nanomedicine. [ABSTRACT FROM AUTHOR]

Die Anwendung multivalenter Wechselwirkungen ist eine leistungsfähige Strategie biologischer Systeme, um eine hochaffine molekulare Erkennung zu erzielen. Seit kurzem richtet die Aufmerksamkeit der Synthesechemie vermehrt auf die selbstorganisierte anstelle einer kovalenten Synthese zur Anordnung von Liganden. Dieser Ansatz bietet mehrere Vorteile, z. B. eine einfache Synthese/Assemblierung, gezielt einstellbare Morphologien und Liganden, die Möglichkeit zum Einbau mehrerer aktiver Einheiten und die responsive Natur der Selbstorganisation. Wir zeigen, dass selbstorganisierte Multivalenz eine Strategie mit fundamentaler Bedeutung für den Entwurf synthetischer Nanosysteme ist, die in biologische Reaktionswege eingreifen können und potenzielle Anwendungen in der Nanomedizin finden. [ABSTRACT FROM AUTHOR]

This paper uses a combined experimental and theoretical approach to gain unique insight into gene delivery. We report the synthesis and investigation of a new family of second-generation dendrons with four triamine surface ligands capable of binding to DNA, degradable aliphatic-ester dendritic scaffolds, and hydrophobic units at their focal points. Dendron self-assembly significantly enhances DNA binding as monitored by a range of experimental methods and confirmed by multiscale modeling. Cellular uptake studies indicate that some of these dendrons are highly effective at transporting DNA into cells (ca. 10 times better than poly(ethyleneimine), PEI). However, levels of transgene expression are relatively low (ca. 10% of PEI). This indicates that these dendrons cannot navigate all of the intracellular barriers to gene delivery. The addition of chloroquine indicates that endosomal escape is not the limiting factor in this case, and it is shown, both experimentally and theoretically, that gene delivery can be correlated with the ability of the dendron assemblies to release DNA. Mass spectrometric assays demonstrate that the dendrons, as intended, do degrade under biologically relevant conditions over a period of hours. Multiscale modeling of degraded dendron structures suggests that complete dendron degradation would be required for DNA release. Importantly, in the presence of the lower pH associated with endosomes, or when bound to DNA, complete degradation of these dendrons becomes ineffective on the transfection time scale—we propose this explains the poor transfection performance of these dendrons. As such, this paper demonstrates that taking this kind of multidisciplinary approach can yield a fundamental insight into the way in which dendrons can navigate barriers to cellular uptake. Lessons learned from this work will inform future dendron design for enhanced gene delivery. [ABSTRACT FROM AUTHOR]

Review: ca. 80 refs. [ABSTRACT FROM AUTHOR]

[Display omitted] The design, synthesis, and conformational analysis of a novel aromatic oligoester helix mimetic scaffold is reported. A range of amino acid-type side-chain functionality can be readily incorporated into monomer building blocks over three facile synthetic steps. Analysis of representative dimers revealed a stable conformer capable of effective mimicry of a canonical α-helix and the scaffold was found to be surprisingly stable to degradation in aqueous solutions at acidic and neutral pH. [ABSTRACT FROM AUTHOR]

[Display omitted] The design, synthesis, and conformational analysis of a novel aromatic oligoester helix mimetic scaffold is reported. A range of amino acid-type side-chain functionality can be readily incorporated into monomer building blocks over three facile synthetic steps. Analysis of representative dimers revealed a stable conformer capable of effective mimicry of a canonical α-helix and the scaffold was found to be surprisingly stable to degradation in aqueous solutions at acidic and neutral pH. [ABSTRACT FROM AUTHOR]

Background: Early manipulation of nasal fractures can negate the need for formal rhinoplasty. However, residual nasal deformity is reported in up to 50 % of cases. The aim of this study was to evaluate the outcome following manipulation of nasal fractures in a regional plastic surgery department and quantify the subsequent rhinoplasty conversion rate. Methods: A retrospective review of all patients presenting with nasal fractures who had undergone manipulation under anaesthetic (MUA) in a single plastic surgery unit over a 7-year period was performed. Results: Three hundred fifty-three MUA procedures were performed, the majority of which were in young males (76 %). Common causes included assault (54 %), sporting injuries (24 %) and falls (12 %). MUA was performed for nasal bone fracture (69 %) or bony and septal fracture (31 %). Only 37 % (130 patients) attended outpatient follow-up. Functional problems were identified in 17 % (22 patients), whilst 24 % (31 patients) noted residual deformity. Of these, 10 patients (3 %) accepted and underwent formal rhinoplasty surgery. This accounted for 17 % of all rhinoplasties carried out within the time period. Conclusions: In our department, the outcome following manipulation of these injuries compares favourably with the literature, with the majority of patients having no major long-term sequelae. Our data suggest that many patients are happy to accept a degree of residual deformity and decline further surgery. Level of Evidence: Level IV, risk / prognostic study [ABSTRACT FROM AUTHOR]

The self-assembly of dendritic molecules is an effective way of generating functionalised nanoscale architectures. This study reports a computer-aided analysis of the EPR spectra of 5 doxyl-stearic acid (5DSA) and Cu(ii) probes interacting with self-assembling dendrons in water. The dendrons investigated have previously been reported as potential gene delivery vehicles, and possess amine surface groups, different dendritic architectures based on ether-amide or ester branching, and hydrophobic groups at the focal point which can encourage self-assembly in aqueous solution. The parameters extracted from computation provide information about both the structure and dynamics in solution and the interacting ability of the dendrons to be used in gene therapy. The hydrophobic 5DSA probe is able to effectively probe the hydrophobic core of self-assembled dendron nanostructures. It reports on the polarity of its local environment and is most affected by dendrons with two cholesterol units at the focal point, partly affected by dendrons with cholesterol groups at their focal point, but is unaffected by dendrons with a simple phenyl group at the focal point. This reflects the different modes of self-assembly observed for these dendrons. When Cu(ii) is used as an EPR probe of the branched environment, it was found that at pH7, much of the Cu(ii) was ‘external’ to the dendritic structure, presumably due to protonation of the peripheral amine groups. On gradually increasing the Cu(ii) loading, and using computer-aided analysis, it was possible to quantify the levels of ‘internal’ (dendron-bound) and ‘external’ Cu(ii) and it was found that this was strongly dependent on the structure of the dendritic branching and the ability of the dendron to self-assemble, with self-assembling ester dendrons being best able to bind the Cu(ii). It was also possible to propose the nature of the copper binding sites associated with the ‘internal’ signal as either Cu–NO3 and Cu–N2O2 distorted square-planar coordination sites. The self-assembling ester based dendrons which also contain 1,2,3-triazole units, had higher levels of ‘internal’ Cu(ii) and showed the latter form of coordination, while the other dendrons, with lower levels of Cu(ii) uptake showed the former. In summary, this paper demonstrates that two complementary EPR probes can be used to provide information about different regions of a self-assembled dendritic architecture. [ABSTRACT FROM AUTHOR]