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The objectives of this survey were to examine the effectiveness of a static magnet device--4UlcerCare--in preventing recurrence of leg ulcers after healing. Two hundred and eighty-nine randomly selected purchasers of 4UlcerCare were telephoned and asked to complete a short questionnaire. Our focus was on the 211 respondents who had ulcers that had already healed. The average age of subjects, was 70.6 years and sex distribution was 55% female to 45% male. Mean duration of leg ulcers before using 4UlcerCare was 4.4 years. Sixty-five per cent of those surveyed had had ulcer recurrence before using 4UlcerCare, with a mean of 2.41 episodes of ulceration. This was close to the expected recurrence rate in the population of 67%. Using 4UlcerCare daily, these respondents' ulcers had healed within an average of 3.57 months. The survey took place an average of 19.94 months after healing. The manufacturers advise wearing 4UlcerCare daily post-healing, and of those respondents that had, none had suffered any recurrence.Extrapolating these results across the health economy, an estimate has been made of a potential pounds 153.7 million per year saving on leg ulcer care to the NHS. [ABSTRACT FROM AUTHOR]

Autistic adults are inadequately supported in the workplace. This study sought a definition of 'reasonable' and explored facilitators and barriers to employers making reasonable adjustments. 98 employers and employees across a UK city completed a survey; 15% identified as being autistic. Qualitative data were analysed using framework analysis. Reasonable adjustments were defined as having a positive impact on autistic employees' wellbeing and work outputs without being detrimental to non-autistic employees or the organisation; they were low cost and easily implemented. Recommendations were for autism awareness training, low-stimulus work spaces, clear instructions and flexible working hours. A definition of reasonable is added to the literature, with suggestions of where to invest support efforts. Recommendations mostly apply to the education sector., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Two α-aminoisobutyric acid (Aib) foldamers bearing Zn(II)-chelating N-termini have been synthesized and compared with a reported Aib foldamer that has a bis(quinolinyl)/mono(pyridyl) cap (BQPA group). Replacement of the quinolinyl arms of the BQPA-capped foldamer with pyridyl gave a BPPA-capped foldamer, then further replacement of the linking pyridyl with a 1,2,3-triazole gave a BPTA-capped foldamer. Their ability to relay chiral information from carboxylate bound to Zn(II) at the N-terminus to a glycinamide-based NMR reporter of conformational preference at the C-terminus was measured. The importance of the quinolinyl arms became readily apparent, as the foldamers with pyridyl arms were unable to report on the presence of chiral carboxylate in acetonitrile. Low solubility, X-ray crystallography and 1 H NMR spectroscopy suggested that interfoldamer interactions inhibited carboxylate binding. However changing solvent to methanol revealed that the end-to-end relay of chiral information could be observed for the Zn(II) complex of the BPTA-capped foldamer at low temperature., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

A crystallographically characterised zinc(ii)-capped foldamer can sense the enantiomeric excess of scalemic carboxylate solutions, including those produced by enantioselective organocatalysis, and can relay this input signal along the foldamer body to a remote glycinamide group, which then provides an NMR spectroscopic output.

Exploring the detailed structural features of synthetic molecules in the membrane phase requires sensitive probes of conformation. Here we describe the design, synthesis and characterization of bis(pyrene) probes that report conformational changes in membrane-active dynamic foldamers. The probes were designed to distinguish between left-handed ( M ) and right-handed ( P ) screw-sense conformers of 3 10 -helical α-aminoisobutyric acid (Aib) peptide foldamers, both in solution and in bilayer membranes. Several different bis(pyrene) probes were synthesized and ligated to the C-terminus of Aib tetramers that had different chiral residues at the N-terminus, residues that favored either an M or a P screw-sense in the 3 10 -helix. The readily synthesized and conveniently incorporated N -acetyl-1,2-bis(pyren-1'-yl)ethylenediamine probe proved to have the best properties. In solution, changes in foldamer screw-sense induced substantial changes in the ratio of excimer/monomer fluorescence emission ( E / M ) for this reporter of conformation, with X-ray crystallography revealing that opposite screw-senses produce very different interpyrene distances in the reporter. In bilayers, this convenient and sensitive fluorescent reporter allowed, for the first time, an investigation of how the chirality of natural phospholipids affects foldamer conformation.

Antagonism of αvβ6 is emerging as a potential treatment of idiopathic pulmonary fibrosis based on strong target validation. Starting from an αvβ3 antagonist lead and through simple variation in the nature and position of the aryl substituent, the discovery of compounds with improved αvβ6 activity is described. The compounds also have physicochemical properties commensurate with oral bioavailability and are high quality starting points for a drug discovery program. Compounds 33S and 43E1 are pan αv antagonists having ca. 100 nM potency against αvβ3, αvβ5, αvβ6, and αvβ8 in cell adhesion assays. Detailed structure activity relationships with these integrins are described which also reveal substituents providing partial selectivity (defined as at least a 0.7 log difference in pIC50 values between the integrins in question) for αvβ3 and αvβ5.

Phorbol esters and related compounds provide a promising source of potential anticancer agents. The mechanism of their toxicity, however, is unclear, and interpretation has been complicated by the conflicting responses exhibited by different transformed cell lines. Previously we showed that in primary thyroid follicular cells, expression of mutant p21ras conferred a striking sensitivity to the toxic effects of phorbol esters. We have now extended this work using a thyroid cell line with an inducible mutant ras gene to exclude the possibility that this result was a trivial consequence of the marked growth stimulation induced in these cells by mutant p21ras. Furthermore, by assessing the action of a panel of phorbol esters and a potential chemotherapeutic agent, bryostatin, we demonstrated that this phenomenon was only a function of biologically active phorbol esters. These results provide a molecular rationale for the development of phorbol ester analogues as chemotherapeutic agents.