Knowledge, attitudes and practices of medical staff towards obesity management in patients with spinal cord injuries: an International survey of four western European countries

Objective: To (1) examine the opinions of medical staff working in spinal cord injury (SCI) centres (SCICs); (2) evaluate their knowledge, attitudes and practices towards obesity prevention and management; (3) report the number of beds and dietitians available at each SCIC. Methods: A 37-item questionnaire was sent to 23 SCICs in the UK, the Netherlands, Belgium and the Republic of Ireland between September 2012 and January 2013. Results: Eighteen SCICs returned the questionnaires for analysis. All respondents stated that they had an interest in obesity treatment but only 2.3% of the respondents received training in obesity management. Sixty-one percent of staff did not consider body mass index (BMI) to be appropriate for use in SCI patients and subsequently less than half of the respondents use BMI routinely. The majority of respondents reported that they are confident in dealing with overweight (74.5%) and obese (66.1%) SCI adults, less than half (44.1%) are confident in treating overweight and obese SCI children. Respondents also indicated the need for nationally adopted guidelines and a lack of physical activity provision. There were 17.5 whole-time equivalent (WTE) dietitians recorded in 22 SCICs, equivalent to 47.8 beds per WTE dietitians (range 10–420). Non-UK SCIC dietitians are significantly better resourced than in UK SCICs (beds per WTE dietitian: 36 vs 124, P=0.035). Conclusion: Medical staff expressed the need to participate in obesity prevention and management. Appropriate training should be considered for all medical staff and the development of specific weight management guidelines and dietetic provision should be considered

Supporting the game construction process: development of artefacts in the context of a Toolkit to Game Design

The Gamers4Nature project aims to deliver a set of strategies to empower and en-courage youngsters (upper-secondary and undergraduate students) to actively participate in games creation while raising knowledge about environmental preservation and biodiversity conservation. To accomplish these goals, a Toolkit to Game Design is being created, containing a set of resources and tools aiming to help in the creation of mobile digital games, namely a Game Construction Cards Set. This paper presents the creation process of the project’s general identi-ty and its concept adaptation to the Game Construction Cards Set, which required a deep understanding of the target audience and the development of a strategy to engage the participants in its activities. A general identity was defined, where a specific “language” to reach this audience was designed and a brand to support it was created. This “language” was applied in all graphic materials developed since day one, namely to the Game Construction Cards Set – focus of this paper. The validation of the prototypes was made through focus groups, using an iterative design approach. The focus groups participants’ inputs were integrated in the de-sign and helped with the graphic elements’ evolution, allowing the project to maintain a coherent strategy in all its representations that exceeds its graphic lan-guage and a deeper identification with the developed artefacts.publishe

Use of probiotics in preventing antibiotic associated diarrhoea and Clostridium difficile associated diarrhoea in spinal injury centres: An international survey of four western European countries

Probiotics may prevent antibiotic-associatedand Clostridium difficile-associated- diarrhoea (AAD/CDAD). Many spinal cord injury centres (SCICs) practitioners consider probiotics generically and may not realise that efficacy can be strain-, dose-, and disease-specific. One to four SCICs per country (depending on population size) were contacted (UK:4; the Netherlands:3; Belgium: I; Republic of Ireland: 1) to (a) determine if they stocked probiotics; (b) determine whether the use of those probiotics was evidence-based; and (c) document their C. difficile infection (CDI) practices. All nine SCICs responded to the survey (7 physicians, 3 microbiologists, 1 nurse and 2 dietitians). Five (55.5%) stocked probiotics; five different probiotics were identified. Four probiotics were preferred choice prevention o f AAD/CDAD were Lactobacillus casei Shirota (44.4%), L. casei D N -114001 (22.2%), L. acidophilus (22.2%) and a mixed-strains probiotic (Ecologic Pro-AD) (11.1%). Only one evidence base study was identified supporting the use of probiotic for prevention of AAD in SCI patients. Mean CDI cases per 10,000 patient-days were 0.307 (s.d: 0.486, range 0.00 to 1.08). Definitions of diarrhoea and CDI varied among SCICs. Stocking probiotics for the prevention of AAD / CDAD is not common. There is only one single study showing efficiency of a particular strain in SCI populations. The study highlighted the importance of using a standardised definition o f diarrhoea when conducting AAD/CDAD research

Determination of the Hurst Exponent by Use of Wavelet Transforms

We propose a new method for (global) Hurst exponent determination based on wavelets. Using this method, we analyze synthetic data with predefined Hurst exponents, fracture surfaces and data from economy. The results are compared with those obtained from Fourier spectral analysis. When many samples are available, the wavelet and Fourier methods are comparable in accuracy. However, when one or only a few samples are available, the wavelet method outperforms the Fourier method by a large margin.Comment: 10 pages RevTeX, 13 Postscript figures. Some additional material compared to previous versio

Sterol 14α-Demethylase as a Potential Target for Antitrypanosomal Therapy: Enzyme Inhibition and Parasite Cell Growth

SummarySterol 14α-demethylases (CYP51) serve as primary targets for antifungal drugs, and specific inhibition of CYP51s in protozoan parasites Trypanosoma brucei (TB) and Trypanosoma cruzi (TC) might provide an effective treatment strategy for human trypanosomiases. Primary inhibitor selection is based initially on the cytochrome P450 spectral response to ligand binding. Ligands that demonstrate strongest binding parameters were examined as inhibitors of reconstituted TB and TC CYP51 activity in vitro. Direct correlation between potency of the compounds as CYP51 inhibitors and their antiparasitic effect in TB and TC cells implies essential requirements for endogenous sterol production in both trypanosomes and suggests a lead structure with a defined region most promising for further modifications. The approach developed here can be used for further large-scale search for new CYP51 inhibitors

Concerning P450 Evolution: Structural Analyses Support Bacterial Origin of Sterol 14α-Demethylases

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Lamb, D. C., Hargrove, T. Y., Zhao, B., Wawrzak, Z., Goldstone, J. V., Nes, W. D., Kelly, S. L., Waterman, M. R., Stegeman, J. J., & Lepesheva, G. I. Concerning P450 evolution: structural analyses support bacterial origin of sterol 14α-demethylases. Molecular Biology and Evolution, (2020): msaa260, doi:10.1093/molbev/msaa260.Sterol biosynthesis, primarily associated with eukaryotic kingdoms of life, occurs as an abbreviated pathway in the bacterium Methylococcus capsulatus. Sterol 14α-demethylation is an essential step in this pathway and is catalyzed by cytochrome P450 51 (CYP51). In M. capsulatus, the enzyme consists of the P450 domain naturally fused to a ferredoxin domain at the C-terminus (CYP51fx). The structure of M. capsulatus CYP51fx was solved to 2.7 Å resolution and is the first structure of a bacterial sterol biosynthetic enzyme. The structure contained one P450 molecule per asymmetric unit with no electron density seen for ferredoxin. We connect this with the requirement of P450 substrate binding in order to activate productive ferredoxin binding. Further, the structure of the P450 domain with bound detergent (which replaced the substrate upon crystallization) was solved to 2.4 Å resolution. Comparison of these two structures to the CYP51s from human, fungi, and protozoa reveals strict conservation of the overall protein architecture. However, the structure of an “orphan” P450 from nonsterol-producing Mycobacterium tuberculosis that also has CYP51 activity reveals marked differences, suggesting that loss of function in vivo might have led to alterations in the structural constraints. Our results are consistent with the idea that eukaryotic and bacterial CYP51s evolved from a common cenancestor and that early eukaryotes may have recruited CYP51 from a bacterial source. The idea is supported by bioinformatic analysis, revealing the presence of CYP51 genes in >1,000 bacteria from nine different phyla, >50 of them being natural CYP51fx fusion proteins.The study was supported by National Institutes of Health (Grant No. R01 GM067871 to G.I.L.) and by a UK-USA Fulbright Scholarship and the Royal Society (to D.C.L.)

The impact of loco-regional recurrences on metastatic progression in early-stage breast cancer: a multistate model

To study whether the effects of prognostic factors associated with the occurrence of distant metastases (DM) at primary diagnosis change after the incidence of loco-regional recurrences (LRR) among women treated for invasive stage I or II breast cancer. The study population consisted of 3,601 women, enrolled in EORTC trials 10801, 10854, or 10902 treated for early-stage breast cancer. Data were analysed in a multivariate, multistate model by using multivariate Cox regression models, including a state-dependent covariate. The presence of a LRR in itself is a significant prognostic risk factor (HR: 3.64; 95%-CI: 2.02-6.5) for the occurrence of DM. Main prognostic risk factors for a DM are young age at diagnosis (</=40: HR: 1.79; 95%-CI: 1.28-2.51), larger tumour size (HR: 1.58; 95%-CI: 1.35-1.84) and node positivity (HR: 2.00; 95%-CI: 1.74-2.30). Adjuvant chemotherapy is protective for a DM (HR: 0.66; 95%-CI: 0.55-0.80). After the occurrence of a LRR the latter protective effect has disappeared (P = 0.009). The presence of LRR in itself is a significant risk factor for DM. For patients who are at risk of developing LRR, effective local control should be the main target of therapy