Mouse maternal systemic inflammation at the zygote stage causes blunted cytokine responsiveness in lipopolysaccharide-challenged adult offspring

These results demonstrate for the first time that the preimplantation embryo in vivo is sensitive to maternal systemic inflammation, with effects on blastocyst cell lineage allocation and consequences for behaviour, adiposity and innate immune response in adult offspring. Critically, we identify a novel mechanism mediated through maternal-embryonic interactions that confers plasticity in the development of the innate immune system, which is potentially important in setting postnatal tolerance to environmental pathogens. Our study extends the concept of developmental programming of health and disease to include maternal health at the time of conceptio

Effects of Exogenous Yeast and Bacteria on the Microbial Population Dynamics and Outcomes of Olive Fermentations.

In this study, we examined Sicilian-style green olive fermentations upon the addition of Saccharomyces cerevisiae UCDFST 09-448 and/or Pichia kudriazevii UCDFST09-427 or the lactic acid bacteria (LAB) Lactobacillus plantarum AJ11R and Leuconostoc pseudomesenteroides BGM3R. Olives containing S. cerevisiae UCDFST 09-448, a strain able to hydrolyze pectin, but not P. kudriazevii UCDFST 09-427, a nonpectinolytic strain, exhibited excessive tissue damage within 4 weeks. DNA sequencing of fungal internal transcribed spacer (ITS) regions and comparisons to a yeast-specific ITS sequence database remarkably showed that neither S. cerevisiae UCDFST 09-448 nor P. kudriazevii UCDFST 09-427 resulted in significant changes to yeast species diversity. Instead, Candida boidinii constituted the majority (>90%) of the total yeast present, independent of whether S. cerevisiae or P. kudriazevii was added. By comparison, Lactobacillus species were enriched in olives inoculated with potential starter LAB L. plantarum AJ11R and L. pseudomesenteroides BGM3R according to community 16S rRNA gene sequence analysis. The bacterial diversity of those olives was significantly reduced and resembled control fermentations incubated for a longer period of time. Importantly, microbial populations were highly dynamic at the strain level, as indicated by the large variations in AJ11R and BGM3R cell numbers over time and reductions in the numbers of yeast isolates expressing polygalacturonase activity. These findings show the distinct effects of exogenous spoilage and starter microbes on indigenous communities in plant-based food fermentations that result in very different impacts on product quality. IMPORTANCE Food fermentations are subject to tremendous selective pressures resulting in the growth and persistence of a limited number of bacterial and fungal taxa. Although these foods are vulnerable to spoilage by unintended contamination of certain microorganisms, or alternatively, can be improved by the deliberate addition of starter culture microbes that accelerate or beneficially modify product outcomes, the impact of either of those microbial additions on community dynamics within the fermentations is not well understood at strain-specific or global scales. Herein, we show how exogenous spoilage yeast or starter lactic acid bacteria confer very different effects on microbial numbers and diversity in olive fermentations. Introduced microbes have long-lasting consequences and result in changes that are apparent even when levels of those inoculants and their major enzymatic activities decline. This work has direct implications for understanding bacterial and fungal invasions of microbial habitats resulting in pivotal changes to community structure and function

Waste not, want not: CO2 (re)cycling into block polymers

A new way to combine two different polymerisation reactions, using a single catalyst, results in efficient block polymer synthesis. The selective polymerisation of mixtures of L-lactide-O-carboxyanhydride and cyclohexene oxide, using a di-zinc catalyst in a one-pot procedure, allows the preparation of poly(L-lactide-b-cyclohexene carbonate). The catalysis near quantitatively recycles the carbon dioxide released during polyester formation into the subsequent polycarbonate block, with an atom economy of up to of 91%

Moving anticoagulation initiation and monitoring services into the community:Evaluation of the Brighton and hove community pharmacy service

Abstract Background As part of the NHS desire to move services closer to where people live, and provide greater accessibility and convenience to patients, Brighton and Hove Clinical Commissioning Group (CCG) underwent a review of their anticoagulation services during 2008. The outcome was to shift the initiation and monitoring service in secondary care for non-complex patients, including domiciliary patients, into the community. This was achieved via a procurement process in 2008 resulting in the Community Pharmacy Anticoagulation Management Service (CPAMs) managed by Boots UK (a large chain of community pharmacies across the United Kingdom). Methods This evaluation aims to review the outcomes (International Normalised Ratio [INR] readings) and experiences of those patients attending the anticoagulation monitoring service provided by community pharmacists in Brighton and Hove. All patients on warfarin are given a target INR range they need to achieve; dosing of and frequency of appointment are dependent on the INR result. Outcome measures for patients on the CPAM service included percentage INR readings that were within target range and the percentage time the patient was within therapeutic range. Data collected from 2009 to 2016 were analysed and results compared to the service targets. Patient experience of the service was evaluated via a locally developed questionnaire that was issued to patients annually in the pharmacy. Results The evaluation shows that community pharmacy managed anticoagulation services can achieve outcomes at a level consistently exceeding national and local targets for both percentage INR readings in therapeutic target range (65.4%) compared to the recommended minimum therapeutic target range of 60.0% and percentage time in therapeutic range (72.5%, CI 71.9–73.1%) compared to the national target of 70.0%. Patients also indicated they were satisfied with the service, with over 98.6% patients rating the service as good, very good or excellent. Conclusion The Brighton and Hove CPAM service achieved above average national target management of INR and positive patient feedback, demonstrating that community pharmacy is ideally placed to provide this service safely and deliver enhanced clinical outcomes and positive patient experience

Catalytic Synergy Using Al(III) and Group 1 Metals to Accelerate Epoxide and Anhydride Ring-Opening Copolymerizations

The controlled synthesis of polyesters via epoxide/anhydride ring-opening copolymerization is a versatile and generally applicable method to make many sustainable polymers, but catalyst activities are limited and the required catalyst loadings are typically high. Here, novel heterodinuclear complexes, featuring Al(III)/M(I) (M = Na, K, Rb, Cs), show exceptional activities for phthalic anhydride and cyclohexene oxide copolymerization (catalyst = Al(III)/K(I), turnover frequency = 1072 h–1, 0.25 mol % catalyst loading vs anhydride, 100 °C). The Al(III)/K(I) catalyst is also tolerant to low loadings, maintaining a good performance at 0.025 mol % catalyst vs anhydride loading and 0.005 mol % vs epoxide. It rapidly polymerizes other epoxide/anhydride combinations yielding various semi-aromatic, rigid, and/or functionalizable polyesters and also shows activity in carbon dioxide/epoxide copolymerizations. The results of structure–activity, X-ray crystallography, polymerization kinetics, and density functional theory investigations support a mechanism with chain growth alternation between the metals. The rate-limiting step is proposed to involve epoxide coordination at Al(III) with K(I) carboxylate attack. Future exploitation of abundant and inexpensive Group 1 metals to deliver synergic polymerization catalysts is recommended

Ultrarapid cerium(III)–NHC catalysts for high molar mass cyclic polylactide

The EPSRC are acknowledged for research funding through the Centre for Doctoral Training in Critical Resource Catalysis (CRITICAT, EP/ L016419/1, R. W. F. K., P. M. D. A. E.), EP/J018139/1, the UK Catalysis Hub (EP/K014714/1, P. L. A., C. K. W., S. K. R.), EP/M010554/1 (P. L. A.) and EP/S018603/1 (C. K. W.). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 740311, P.L.A.).Cyclic polyesters could improve the properties of degradable plastics, but routes to them that provide a product with faster rates, higher molar mass, and greater selectivity for cyclic vs linear polymer are needed. Here, homogeneous Ce(III)–N-heterocyclic carbene (NHC) catalysts show outstanding activities (turn-over-frequency (TOF) > 864 000 h–1), excellent control, and selectivity for cyclic polylactide (PLA) topology (>95%), yielding high molar mass PLA (60 < Mn < 250 kg mol–1). They efficiently produce cyclic PLA from rac-lactide or l-lactide and aliphatic cyclic polyesters from ε-caprolactone or β-butyrolactone. The enhanced performances are only achievable from combining cooperative Lewis acidic cerium(III) and hemilabile N-heterocyclic carbene functionalities.PostprintPostprintPeer reviewe

Systemic immunosuppression depletes peripheral blood regulatory B cells in patients with immune thrombocytopenia

Regulatory B (Breg) cells are potentially implicated in the pathogenesis of immune thrombocytopenia (ITP). We analysed a prospective cohort of newly diagnosed steroid naïve ITP patients enrolled in the multicentre FLIGHT trial and found that the numbers of Bregs in their peripheral blood were similar to healthy controls. In contrast, Breg numbers were significantly reduced in ITP patients treated with systemic immunosuppression (glucocorticoids or mycophenolate mofetil). We also demonstrate that glucocorticoid treatment impairs Breg interleukin-10 production via an indirect T-cell-mediated mechanism