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Modelling the role of microbial p-cresol in colorectal genotoxicity
Get PDFBACKGROUND
A greater understanding of mechanisms explaining the interactions between diet and the gut microbiota in colorectal cancer is desirable. Genotoxic microbial metabolites present in the colon may be implicated in carcinogenesis and potentially influenced by diet.
AIMS
We hypothesised that microbial p-cresol is a colonic genotoxin and set out to model potential exposures in the colon and the effects of these exposures on colonic cells.
METHODS
Batch culture fermentations with human faecal inoculate were used to determine the synthesis of p-cresol and other metabolites in response to various substrates. The fermentation supernatants were evaluated for genotoxicity and the independent effects of p-cresol on colonic cells were studied in vitro.
RESULTS
In batch culture fermentation, supplementary protein increased the synthesis of phenols, indoles and p-cresol, whereas supplementary fructoligosaccharide (FOS) increased the synthesis of short chain fatty acids. The p-cresol was the greatest predictor of genotoxicity against colonocytes in the fermentation supernatants. Spiking fermentation supernatants with exogenous p-cresol further increased DNA damage, and independently p-cresol induced DNA damage in a dose-dependent manner against HT29 and Caco-2 cells and influenced cell cycle kinetics.
CONCLUSIONS
In the colon p-cresol may reach physiologically significant concentrations which contribute to genotoxic exposures in the intestinal lumen, p-cresol production may be attenuated by substrate, and therefore diet, making it a potential modifiable biomarker of genotoxicity in the colon
Evaluation of a specialist weight management service for patients with severe obesity in Liverpool
Get PDFObjective: To evaluate a specialist weight management treatment for patients with severe obesity and follow up at 3 months, monitoring changes in weight, BMI and clinical outcome variables. Changes in food intake, self esteem and health related quality of life (HRQL) were also compared to pre- and post- intervention. Design: Step by step is a new obesity servive which specifically targets obese patients at greater risk of further ill health. Only patients who are referred by their G.P. or health professional have been included in the evaluation. After an assessment appointment all patients choose one of two treatment options: group programme, individual dietetic care or both. The group programme offered weekly contact over twelve weeks and monthly follow up thereafter in a community setting. One-to-one care offered monthly appointments with the Dietician over a three month period. Subjects: A total of 50 patients with a BMI>30kg/m2, mean age 59 years, mean weight for males 113.5kg, BMI 39,3kg/m2 and females 92.7kg, BMI 36.5kg/m2. Main outcome measures: weight, BMI, total cholesterol, LDL, TG, HDL, FBG, HbA1C, blood pressure, food intake, self esteem and quality of life were measured pre and post intervention. Results: Patients who attended the group programme showed significant weight loss 1.99kg (P<0.05) and BMI 0.66kg/m2 at three months. Male patients lost more weight (3.9kg) during the three month period compared to females (1.4kg). Data was not available for individual dietetic care. Patients significantly reduced intake of negative marker foods (P<0.00). No changes were observed between self esteem pre and post programme however quality of life score increased considerably, 44.83 (S.D. 34.26) to 70.37 (S.D. 15.86) P<0.001. Conclusion: Patients attending a twelve week weight management programme run by community dietians and foodworkers achieve clinically worth while reducations in weight and BMI, improvements in food choice and choice and improved HRQL
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Metabolic targets of watercress and PEITC in MCF-7 and MCF-10A cells explain differential sensitisation responses to ionising radiation
No full textPurpose: Watercress is a rich source of phytochemicals with anticancer potential, including phenethyl isothiocyanate (PEITC). We examined the potential for watercress extracts and PEITC to increase the DNA damage caused by ionising radiation (IR) in breast cancer cells and to be protective against radiation-induced collateral damage in healthy breast cells. The metabolic events that mediate such responses were explored using metabolic profiling. Methods: 1H nuclear magnetic resonance spectroscopy-based metabolic profiling was coupled with DNA damage-related assays (cell cycle, Comet assay, viability assays) to profile the comparative effects of watercress and PEITC in MCF-7 breast cancer cells and MCF-10A non-tumorigenic breast cells with and without exposure to IR. Results: Both the watercress extract and PEITC-modulated biosynthetic pathways of lipid and protein synthesis and resulted in changes in cellular bioenergetics. Disruptions to the redox balance occurred with both treatments in the two cell lines, characterised by shifts in the abundance of glutathione. PEITC enhanced the sensitivity of the breast cancer cells to IR increasing the effectiveness of the cancer-killing process. In contrast, watercress-protected non-tumorigenic breast cells from radiation-induced damage. These effects were driven by changes in the cellular content of the antioxidant glutathione following exposure to PEITC and other phytochemicals in watercress. Conclusion: These findings support the potential prophylactic impact of watercress during radiotherapy. Extracted compounds from watercress and PEITC differentially modulate cellular metabolism collectively enhancing the therapeutic outcomes of radiotherapy.</p
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Telomere length analysis: A new tool for molecular photofitting
No full textThis thesis describes a new assay and analytical protocol to determine the telomere length of an individual, and its potential application in criminal investigations. The most commonly used existing assay is based on real-time qPCR. The Telomeric Multiplication Factor (TMF) assay described here instead uses end-point PCR and densitometry. Because most existing forensic DNA techniques already use end-point PCR, the TMF assay can be more easily integrated into the suite of tests available. Along with the TMF assay, a new procedure to use telomere length to determine age is presented. Previous attempts to do this rely on the calculation of a linear regression, and the interpolation of an age based on telomere length, which is not accurate enough for use in criminal investigations (with a covariance between known and predicted age of 0.2848, P=0.010564). Telomere Length Analysis (TLA) uses a database of known individuals. An unknown individual’s telomere length is compared to all telomere lengths on the database, and used to calculate the unknown individual’s age as a multiple of each age on the database. This increases exponentially the number of comparisons that can be made, and improves the accuracy of age predictions (with a covariance between known and predicted age of 0.4561, P=0.000021). The accuracy increases as the size of the database increases. TLA was developed using buccal epithelial cell samples. However, this thesis demonstrates that TLA also works on hair and blood samples, although to a lesser degree of accuracy. This makes TLA applicable in more forensic scenarios. TLA is intended to operate alongside the recent developments in molecular photofitting, to provide phenotypic and biographical information about an unknown offender to hasten his arrest and conviction, in the event that no matching DNA profile is recorded on investigating authorities’ databases. The new TMF assay and TLA analytical profile are more accurate and more applicable to a forensic scenario than other, previous, attempts to use telomere length to determine age
The effects of the Wigan Borough Healthy Business Award on the dietary attitudes and behaviours of awardees
Get PDFAim: The study aims to investigate whether the Wigan Borough Healthy Business Award (HBA) influences the dietary attitudes and behaviours of awardees. Objectives are to: investigate the dietary attitudes of awardees prior to the HBA intervention; investigate the dietary behaviours of awardees prior to the HBA intervention; investigate the dietary attitudes of awardees post intervention; investigate the dietary behaviours of awardees post intervention; assess whether the HBA intervention has influenced attitudes and/or behaviours - positively, negatively or no change; gain a basic overview of the links between dietary attitudes and behaviours; form a set of recommendations based on the findings from the above objectives to inform best practice. Methodology: Case - control study, using purposive sampling of businesses undertaking the HBA, conducted using a pre and post intervention questionnaire and short supplementary post intervention semi structured interview, which seeks to assess whether the HBA affects the dietary attitudes and behaviours of awardees. Main findings: 6 staff from HBA businesses were compared with 7 staff from none HBA businesses. From the interview data, most participants demonstrated positive dietary attitudes and behaviours though not always directly linked with the HBA. Key themes included appreciation of learning and support, enablement to promote healthier options, benefits to the business and customers, other influences on dietary attitudes and behaviours, such as weight, family, health, individual responsibility, practical barriers such as time and society and upbringing. Where participants indicated the HBA had no direct impact on them as individuals, they still showed positive attitudes towards the receipt and recognition of the award, wanted to promote healthier options for customers and were positive about the award. Statistical analysis of the baseline and follow up questionnaire data showed the results were not significant, however due to the small sample size the relevance of this analysis for making generalisations, and identification of trends is limited. Overall conclusions: Participants involved in the HBA demonstrated positive dietary attitudes and behaviours manifesting from a range of influencing factors. The factors that linked with the HBA highlighted some key insights into the impact of the HBA and the complex interrelationship between dietary attitudes and behaviours. Whether the HBA positively influenced individuals dietary attitudes and behaviours or not, overall participants found the intervention to be worthwhile
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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