Structural outcomes in the Cleft Care UK study. Part 2:Dento-facial outcomes

OBJECTIVES: To compare facial appearance and dento-alveolar relationship outcomes from the CSAG (1998) and CCUK (2013) studies. SETTING AND SAMPLE POPULATION: Five-year-olds born with non-syndromic unilateral cleft lip and palate. Those in the original CSAG were treated in a dispersed model of care with low-volume operators. Those in CCUK were treated in a more centralized, high-volume operator model. MATERIALS AND METHODS: We compared facial appearance using frontal view photographs (252 CCUK, 239 CSAG) and dental relationships using study models (198 CCUK, 223 CSAG). Facial appearance was scored by a panel of six assessors using a standardized and validated outcome tool. Dento-alveolar relationships were scored by two assessors using the 5-Year-Olds’ Index. Ordinal regression was used to compare results between surveys. RESULTS: Excellent or good facial appearance was seen in 36.2% of CCUK compared with 31.9% in CSAG. In CCUK, 21.6% were rated as having poor or very poor facial appearance compared with 27.6% in CSAG. The percentage rated as having excellent or good dento-alveolar relationships was 53.0% in CCUK compared with 29.6% in CSAG. In CCUK, 19.2% were rated as having poor or very poor dento-alveolar relationships compared to 36.3% in CSAG. The odds ratios for improved outcome in CCUK compared to CSAG were 1.43 (95% CI 1.03, 1.97) for facial appearance and 2.29 (95% CI 1.47, 3.55) for dento-alveolar relationships. CONCLUSIONS: Facial and dento-alveolar outcomes were better in CCUK children compared to those in CSAG

Quantitative Proteomics of Intracellular Campylobacter jejuni Reveals Metabolic Reprogramming

Campylobacter jejuni is the major cause of bacterial food-borne illness in the USA and Europe. An important virulence attribute of this bacterial pathogen is its ability to enter and survive within host cells. Here we show through a quantitative proteomic analysis that upon entry into host cells, C. jejuni undergoes a significant metabolic downshift. Furthermore, our results indicate that intracellular C. jejuni reprograms its respiration, favoring the respiration of fumarate. These results explain the poor ability of C. jejuni obtained from infected cells to grow under standard laboratory conditions and provide the bases for the development of novel anti microbial strategies that would target relevant metabolic pathways

National BOS Orthognathic Audit 2017-2018

OBJECTIVE: To carry out a UK national clinical audit of orthognathic acceptance criteria and information provided to orthognathic patients before treatment. DESIGN: National clinical audit. SETTING: Data collected using Bristol Online Surveys. PARTICIPANTS: Sixty-nine UK hospital orthodontic departments submitted data. METHODS: Data were collected at two time points using Bristol Online Surveys over a period of 12 months. These were before treatment at the first multidisciplinary clinic (MDT) and immediately after surgery. The data collected included: Index of Orthognathic Functional Treatment Need (IOFTN); Index of Orthodontic Treatment Need (IOTN); age; previous orthodontic treatment; attendance at an MDT; treatment times; and information provision. RESULTS: Eighty-five units agreed to take part in the audit with 69 submitting data, giving a response rate of 81%. The data from 3404 patients were uploaded, 2263 before treatment and 1141 immediately after surgery. Of patients, 91.07% had an IOFTN score of 4 or 5 and 88.73% had an IOTN score of 4 or 5. The mean age at the first MDT was 22 years in the first cohort and 21 years and 4 months in the second immediate post-surgery cohort. Of patients, 37.93% had undergone some form of previous orthodontic treatment, but only 0.28% had undergone previous orthognathic treatment; 96.93% had an MDT confirm that orthodontic treatment by itself was insufficient to adequately correct their functional symptoms. The average treatment time from bond up to surgery was 2 years and 6 months. With respect to information provision, patients received information from a number of sources, principally the British Orthodontic Society (BOS) patient information leaflets and the BOS website Your Jaw Surgery. CONCLUSIONS: In the UK, the majority of orthognathic cases fulfil the criteria for acceptance for NHS-funded orthognathic treatment, as outlined by the Chief Dental Officer's interim guidance on orthognathic treatment. This suggests any prior approval process would not be a good use of NHS resources in the commissioning of orthognathic treatment

New engineering approach for the development and demonstration of a multi-purpose platform for the Blue Growth Economy

Aquaculture is currently the fastest growing food sector in the world and the open oceans are seen as one of the most likely areas for large scale expansion [1], [2], [3]. The global demand for seafood is continuing to rise sharply, driven by both population growth and increased per capita consumption, whilst wild capture fisheries are constrained in their potential to produce more seafood. A recently funded EC project, the Blue Growth Farm BGF (GA n. 774426, 1st June 2018 ÷ 30th September 2021) aims at contributing to this world need with an original solution. The Blue Growth Farm proposes an efficient, cost competitive and environmentally friendly multi purpose offshore farm concept based on a modular floating structure, moored to the seabed, meeting requirements of efficiency, cost-competitiveness and environmental friendless, where automated aquaculture and renewable energy production systems are integrated and engineered for profitable applications in the open sea. In the present paper, the overall engineering approach developed to carry out the research work is presented, described and justified. Different technical and scientific challenges are addressed through an integrated industrial engineering design approach, where all disciplines are tuned to achieve the Blue Growth Farm main targets, represented by: i) guaranteeing expected nominal fish production thanks to advanced automation and remote control capabilities; ii) minimizing the pollution introduced at marine ecosystem level when exploiting the marine natural resources, whilst increasing the social acceptance and users community agreement; iii) maximizing the electricity production in the Blue Growth Farm potential installation area ecosystem to provide energy supply to the on board electrical equipment and to dispatch the extra produced electric energy to the land network. Preliminary engineering design results are promising to demonstrate effective increase of safety and efficiency by reducing on board human effort and consequently risks at offshore, thus to make commercial scale open ocean farming a reality

Tyrosine 121 moves revealing a ligandable pocket that couples catalysis to ATP-binding in serine racemase

Human serine racemase (hSR) catalyses racemisation of L-serine to D-serine, the latter of which is a co-agonist of the NMDA subtype of glutamate receptors that are important in synaptic plasticity, learning and memory. In a ‘closed’ hSR structure containing the allosteric activator ATP, the inhibitor malonate is enclosed between the large and small domains while ATP is distal to the active site, residing at the dimer interface with the Tyr121 hydroxyl group contacting the α-phosphate of ATP. In contrast, in ‘open’ hSR structures, Tyr121 sits in the core of the small domain with its hydroxyl contacting the key catalytic residue Ser84. The ability to regulate SR activity by flipping Tyr121 from the core of the small domain to the dimer interface appears to have evolved in animals with a CNS. Multiple X-ray crystallographic enzyme-fragment structures show Tyr121 flipped out of its pocket in the core of the small domain. Data suggest that this ligandable pocket could be targeted by molecules that inhibit enzyme activity

African trypanosomiasis: Synthesis & SAR enabling novel drug discovery of ubiquinol mimics for trypanosome alternative oxidase

African trypanosomiasis is a parasitic disease affecting 5000 humans and millions of livestock animals in sub-Saharan Africa every year. Current treatments are limited, difficult to administer and often toxic causing long term injury or death in many patients. Trypanosome alternative oxidase is a parasite specific enzyme whose inhibition by the natural product ascofuranone (AF) has been shown to be curative in murine models. Until now synthetic methods to AF analogues have been limited, this has restricted both understanding of the key structural features required for binding and also how this chemotype could be developed to an effective therapeutic agent. The development of 3 amenable novel synthetic routes to ascofuranone-like compounds is described. The SAR generated around the AF chemotype is reported with correlation to the inhibition of T. b. brucei growth and corresponding selectivity in cytotoxic assessment in mammalian HepG2 cell lines. These methods allow access to greater synthetic diversification and have enabled the synthesis of compounds that have and will continue to facilitate further optimisation of the AF chemotype into a drug-like lead