7,526 research outputs found

    Predicting the safety and efficacy of butter therapy to raise tumour pHe: an integrative modelling study

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    Background: Clinical positron emission tomography imaging has demonstrated the vast majority of human cancers exhibit significantly increased glucose metabolism when compared with adjacent normal tissue, resulting in an acidic tumour microenvironment. Recent studies demonstrated reducing this acidity through systemic buffers significantly inhibits development and growth of metastases in mouse xenografts.\ud \ud Methods: We apply and extend a previously developed mathematical model of blood and tumour buffering to examine the impact of oral administration of bicarbonate buffer in mice, and the potential impact in humans. We recapitulate the experimentally observed tumour pHe effect of buffer therapy, testing a model prediction in vivo in mice. We parameterise the model to humans to determine the translational safety and efficacy, and predict patient subgroups who could have enhanced treatment response, and the most promising combination or alternative buffer therapies.\ud \ud Results: The model predicts a previously unseen potentially dangerous elevation in blood pHe resulting from bicarbonate therapy in mice, which is confirmed by our in vivo experiments. Simulations predict limited efficacy of bicarbonate, especially in humans with more aggressive cancers. We predict buffer therapy would be most effectual: in elderly patients or individuals with renal impairments; in combination with proton production inhibitors (such as dichloroacetate), renal glomular filtration rate inhibitors (such as non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors), or with an alternative buffer reagent possessing an optimal pK of 7.1–7.2.\ud \ud Conclusion: Our mathematical model confirms bicarbonate acts as an effective agent to raise tumour pHe, but potentially induces metabolic alkalosis at the high doses necessary for tumour pHe normalisation. We predict use in elderly patients or in combination with proton production inhibitors or buffers with a pK of 7.1–7.2 is most promising

    Different cell disruption methods for astaxanthin recovery by Phaffia rhodozyma

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    Astaxanthin (3,3'-dihydroxy-b,b'-carotene-4,4'-dione) is carotenoid of high market value whose demand has increased in such fields as aquaculture, pharmaceutical supplements and natural coloring. Cell disruption is the first step for isolating intracellular materials and it depends on the cell wall permeability. In order to maximize the  recovery of astaxanthin from Phaffia rhodozyma NRRL-Y17268, drying and freeze pretreatments were tested by different cell disruption methods: abrasion with celite, glass pearls in vortex agitator, ultrasonic waves, sodium  carbonate (Na2CO3) and dimethyl sulfoxide (DMSO). The method with Na2CO3 was not effective; meanwhile, the agitator with glass pearls, the abrasion with celite and the ultrasonic waves were found as promising for future  studies. As a result, the DMSO in freeze-dried biomass with 4 process cycles and biomass/DMSO relation of 0.025 g/ml was found to be the most efficient for analytical determination, increasing about up to 25 times the astaxanthin recovery.Key words: Carotenoids, yeast, chemical disruption, dimethyl sulfoxide

    Computer simulation of simultaneous evolution of individual texture components During recrystallization of an IF steel

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    Computer simulation of simultaneous evolution of individual texture components during recrystallization of an IF steel is carried out. A new methodology has been developed that takes as its starting point experimental data of each texture component evolving during recrystallization. In particular, Magnusson et al. data on IF steel was analyzed in a previous work with the help of the exact analytical tools developed by Rios and Villa for simultaneous transformations. From this analysis parameters such as number of nuclei of each texture component per unit of volume could be obtained and were employed as input for the present computer simulation. From this input 3-d microstructures could then be generated. The methodology proposed here combines experimental data, exact analytical methods and computer simulation and may be employed to extract the maximum information from the experimental data

    Consumption patterns of sweet drinks in a population of Australian children and adolescents (2003–2008)

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    <p>Abstract</p> <p>Background</p> <p>Intake of sweet drinks has previously been associated with the development of overweight and obesity among children and adolescents. The present study aimed to assess the consumption pattern of sweet drinks in a population of children and adolescents in Victoria, Australia.</p> <p>Methods</p> <p>Data on 1,604 children and adolescents (4–18 years) from the comparison groups of two quasi-experimental intervention studies from Victoria, Australia were analysed<it>.</it> Sweet drink consumption (soft drink and fruit juice/cordial) was assessed as one day’s intake and typical intake over the last week or month at two time points between 2003 and 2008 (mean time between measurement: 2.2 years).</p> <p>Results</p> <p>Assessed using dietary recalls, more than 70% of the children and adolescents consumed sweet drinks, with no difference between age groups (p = 0.28). The median intake among consumers was 500 ml and almost a third consumed more than 750 ml per day. More children and adolescents consumed fruit juice/cordial (69%) than soft drink (33%) (p < 0.0001) and in larger volumes (median intake fruit juice/cordial: 500 ml and soft drink: 375 ml). Secular changes in sweet drink consumption were observed with a lower proportion of children and adolescents consuming sweet drinks at time 2 compared to time 1 (significant for age group 8 to <10 years, p = 0.001).</p> <p>Conclusion</p> <p>The proportion of Australian children and adolescents from the state of Victoria consuming sweet drinks has been stable or decreasing, although a high proportion of this sample consumed sweet drinks, especially fruit juice/cordial at both time points.</p

    Adverse psychosocial working conditions and minor psychiatric disorders among bank workers

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    <p>Abstract</p> <p>Background</p> <p>In most countries, the financial service sector has undergone great organizational changes in the past decades, with potential negative impact on bank workers' mental health. The aim of this paper is to estimate the prevalence of minor psychiatric disorders (MPD) among Brazilian bank workers and to investigate whether they are associated with an adverse psychosocial working environment.</p> <p>Methods</p> <p>A cross-sectional study of a random sample of 2,500 workers in a Brazilian state bank in 2008. The presence of MPD was determined by the General Health Questionnaire.(GHQ). Psychosocial work conditions were assessed by means of the Effort-Reward Imbalance (ERI) and Job Content Questionnaire (JCQ). The presence and magnitude of the independent associations between MPD and adverse psychosocial working conditions were determined by Prevalence Ratios, obtained by Poisson regression.</p> <p>Results</p> <p>From 2,337 eligible workers, 88% participated. The prevalence of MPD was greater among women (45% vs. 41%; p > 0.05). In the multivariate analysis, the prevalence of MPD was twice as high among bank workers exposed to high psychological demand and low control at work and under high effort and low reward working conditions. The lack of social support at work and the presence of over-commitment were also associated with higher prevalence of MPD. A negative interaction effect was found between over-commitment and effort-reward imbalance.</p> <p>Conclusion</p> <p>The prevalence of MPD is high among bank workers. The results reinforce the association between MPD and adverse psychosocial working conditions, assessed by the JCQ and ERI models. The direction of the interaction observed between over-commitment and ERI was contrary to what was expected.</p
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