Nucleotide supplementation: a randomised double-blind placebo controlled trial of IntestAidIB in people with Irritable Bowel Syndrome [ISRCTN67764449]

BACKGROUND: Dietary nucleotide supplementation has been shown to have important effects on the growth and development of cells which have a rapid turnover such as those in the immune system and the gastrointestinal tract. Work with infants has shown that the incidence and duration of diarrhoea is lower when nucleotide supplementation is given, and animal work shows that villi height and crypt depth in the intestine is increased as a result of dietary nucleotides. Dietary nucleotides may be semi-essential under conditions of ill-health, poor diet or stress. Since people with Irritable Bowel Syndrome tend to fulfil these conditions, we tested the hypothesis that symptoms would be improved with dietary nucleotide supplementation. METHODS: Thirty-seven people with a diagnosis of Irritable Bowel gave daily symptom severity ratings for abdominal pain, diarrhoea, urgency to have a bowel movement, incomplete feeling of evacuation after a bowel movement, bloating, flatulence and constipation for 28 days (baseline). They were then assigned to either placebo (56 days) followed by experimental (56 days) or the reverse. There was a four week washout period before crossover. During the placebo and experimental conditions participants took one 500 mg capsule three times a day; in the experimental condition the capsule contained the nutroceutical substances. Symptom severity ratings and psychological measures (anxiety, depression, illness intrusiveness and general health) were obtained and analysed by repeated measures ANOVAs. RESULTS: Symptom severity for all symptoms (except constipation) were in the expected direction of baseline>placebo>experimental condition. Symptom improvement was in the range 4 – 6%. A feeling of incomplete evacuation and abdominal pain showed the most improvement. The differences between conditions for diarrhoea, bloating and flatulence were not significant at the p < .05 level. There were no significant differences between the conditions for any of the psychological measures. CONCLUSION: Dietary nucleotide supplementation improves some of the symptoms of irritable bowel above baseline and placebo level. As expected, placebo effects were high. Apart from abdominal pain and urgency to have a bowel movement, the improvements, while consistent, are modest, and were not accompanied by improvements in any of the psychological measures. We suggest that the percentage improvement over and above the placebo effect is a physiological effect of the nucleotide supplement on the gut. The mechanisms by which these effects might improve symptoms are discussed

Combination of RAD001 (everolimus) and docetaxel reduces prostate and breast cancer cell VEGF production and tumour vascularisation independently of sphingosine-kinase-1

Resistance to docetaxel is a key problem in current prostate and breast cancer management. We have recently discovered a new molecular mechanism of prostate cancer docetaxel chemoresistance mediated by the mammalian target of rapamycin (mTOR)/sphingosine-kinase-1 (SK1) pathway. Here we investigated the influence of this pathway on vascular endothelial growth factor (VEGF) production and tumour vascularisation in hormone resistant prostate and breast cancer models. Immunofluorescent staining of tumour sections from human oestrogen receptor (ER)-negative breast cancer patients showed a strong correlation between phosphorylated P70S6 kinase (mTOR downstream target), VEGF and SK1 protein expression. In hormone-insensitive prostate (PC3) and breast (MDA-MB-231 and BT-549) cancer cell lines the mTOR inhibitor RAD001 (everolimus) has significantly inhibited SK1 and VEGF expression, while low dose (5 nM) docetaxel had no significant effect. In these cell lines, SK1 overexpression slightly increased the basal levels of VEGF, but did not block the inhibitory effect of RAD001 on VEGF. In a human prostate xenograft model established in nude mice, RAD001 alone or in combination with docetaxel has suppressed tumour growth, VEGF expression and decreased tumour vasculature. Overall, our data demonstrate a new mechanism of an independent regulation of SK1 and VEGF by mTOR in hormone-insensitive prostate and breast cancers

A systematic review on the relationship between self-esteem and interrogative suggestibility

Some factors, such as age, learning disability and mental health difficulties, have been identified as making police suspects more vulnerable to suggestibility and false confessions during interview. However, there has been no systematic review on the association between self-esteem and suggestibility. Seven electronic bibliographic databases and reference lists of previous literature reviews of suggestibility in children were searched. Selected studies were quality assessed using pre-defined criteria before data were extracted. Electronic searches yielded 1914 hits. Of these, 685 duplicates, 1181 irrelevant references and 39 references that did not meet the inclusion criteria were removed. Nine publications were included in the review. Significant correlations between self-esteem and suggestibility, most notably on the Yield 1 subscale of the GSS, were found but four of the nine studies found no significant correlation. The prevalent use of self-report measures and lack of clarity in defining self-esteem limit the validity of those studies

Using guided individualised feedback to review self-reported quality of life in health and its importance

© 2014 Taylor & Francis. This pilot study investigated the effects of providing guided, individualised feedback on subjective quality of life (QoL), using results from the multidimensional WHOQOL-BREF profile. Participants (n=129; 85 chronically ill) were recruited in the community, and primary care. They were randomised to receive written or verbal guidance on interpreting a new graphical summary profile, which simultaneously presented (a) their individual self-ratings of QoL and (b) the importance attributed to each QoL dimension. Before and after feedback, participants completed health status, subjective QoL, QoL Importance, goal-oriented QoL and mood measures. Receiving individualised feedback was associated with increased psychological QoL, with modest effect size. No effects were found for physical, social or environmental QoL or QoL importance, health status, mood or goal-oriented QoL. There were no differences between modes of delivering guidance, indicating equal effectiveness. Chronic illness participants reported poorer QoL, moved more slowly towards their QoL goals, and had larger differences between core QoL and QoL Importance than healthy participants. Guided individualised empirical feedback about QoL judgements could be used to promote psychological well-being. Although professional interpretation of feedback is unnecessary, if shared, patients’ profiled WHOQOL information could support self-monitoring, self-management and clinical decision-making

Shared mental models and intra-team psychophysiological patterns: A test of the juggling paradigm

We explored implicit coordination mechanisms underlying the conceptual notion of "shared mental models" (SMM) through physiological (i.e., breathing and heart rates) and affective-cognitive (i.e., arousal, pleasantness, attention, self-efficacy, other's efficacy) monitoring of two professional jugglers performing a real-time interactive task of increasing difficulty. There were two experimental conditions: "individual" (i.e., solo task) and "interactive" (i.e., two jugglers established a cooperative interaction by juggling sets of balls with each other). In both conditions, there were two task difficulties: “easy” and “hard”. Descriptive analyses revealed that engaging in a dyadic cooperative motor task (interactive condition) required greater physiological effort (Median Cohen’s d = 2.13) than performing a solo motor task (individual condition) of similar difficulty. Our results indicated a strong positive correlation between the jugglers’ heart rate for the easy (r = .87) and hard tasks (r = .77). The relationship between the jugglers’ breathing rate was significant for the easy task (r = .73) but non-significant for the hard task. The findings are interpreted based on research on SMM and Theory of Mind. Practitioners should advance the notion of “shared-regulation” in the context of team coordination through the use of biofeedback training

Porosity estimation of (Moso bamboo) by computed tomography and backscattered electron imaging

This study aims to investigate and quantify the porosity in the cross section of Phyllostachys edulis (Moso bamboo) culm wall. The porosity results are expected to be utilised in numerical study of heat and moisture transfer. Computed tomography (CT) and backscattered electron (BSE) imaging methods are utilised in this study because these two methods allow measurements of the anisotropic features of bamboo specimens. The results of these two methods can be represented as the function of the real dimension rather than the pore size distribution of the specimen. The specimens are obtained from eight different locations along the Moso bamboo culms. Both internodes and nodes specimens are measured in this study. The average porosity, standard deviation (SD) and coefficient of variation (COV) are calculated for BSE and CT results. Pearson product-moment correlation coefficient (PPMCC) is also calculated in this study to analyse the correlation between the BSE results and CT results. Typical porosity results from 400 sampling points and 10 portions average porosity are analysed in this study. The CT scanning results show similar trend with BSE results. The correlation relationship between BSE and CT results approaches moderate correlation level to strong correlation level. The average porosity of internode specimens is from 43.9 to 58.8 % by BSE measurement and from 44.9 to 63.4 % by CT measurement. The average porosity of node specimens is from 37.4 to 56.6 % by BSE measurement and from 32.1 to 62.2 % by CT measurement

Porosity estimation of Phyllostachys edulis (Moso bamboo) by computed tomography and backscattered electron imaging

This study aims to investigate and quantify the porosity in the cross section of Phyllostachys edulis (Moso bamboo) culm wall. The porosity results are expected to be utilised in numerical study of heat and moisture transfer. Computed tomography (CT) and backscattered electron (BSE) imaging methods are utilised in this study because these two methods allow measurements of the anisotropic features of bamboo specimens. The results of these two methods can be represented as the function of the real dimension rather than the pore size distribution of the specimen. The specimens are obtained from eight different locations along the Moso bamboo culms. Both internodes and nodes specimens are measured in this study. The average porosity, standard deviation (SD) and coefficient of variation (COV) are calculated for BSE and CT results. Pearson product-moment correlation coefficient (PPMCC) is also calculated in this study to analyse the correlation between the BSE results and CT results. Typical porosity results from 400 sampling points and 10 portions average porosity are analysed in this study. The CT scanning results show similar trend with BSE results. The correlation relationship between BSE and CT results approaches moderate correlation level to strong correlation level. The average porosity of internode specimens is from 43.9 to 58.8 % by BSE measurement and from 44.9 to 63.4 % by CT measurement. The average porosity of node specimens is from 37.4 to 56.6 % by BSE measurement and from 32.1 to 62.2 % by CT measurement

Activation of PI3K/mTOR pathway occurs in most adult low-grade gliomas and predicts patient survival

Recent evidence suggests the Akt-mTOR pathway may play a role in development of low-grade gliomas (LGG). We sought to evaluate whether activation of this pathway correlates with survival in LGG by examining expression patterns of proteins within this pathway. Forty-five LGG tumor specimens from newly diagnosed patients were analyzed for methylation of the putative 5′-promoter region of PTEN using methylation-specific PCR as well as phosphorylation of S6 and PRAS40 and expression of PTEN protein using immunohistochemistry. Relationships between molecular markers and overall survival (OS) were assessed using Kaplan-Meier methods and exact log-rank test. Correlation between molecular markers was determined using the Mann-Whitney U and Spearman Rank Correlation tests. Eight of the 26 patients with methylated PTEN died, as compared to 1 of 19 without methylation. There was a trend towards statistical significance, with PTEN methylated patients having decreased survival (P = 0.128). Eight of 29 patients that expressed phospho-S6 died, whereas all 9 patients lacking p-S6 expression were alive at last follow-up. There was an inverse relationship between expression of phospho-S6 and survival (P = 0.029). There was a trend towards decreased survival in patients expressing phospho-PRAS40 (P = 0.077). Analyses of relationships between molecular markers demonstrated a statistically significant positive correlation between expression of p-S6(235) and p-PRAS40 (P = 0.04); expression of p-S6(240) correlated positively with PTEN methylation (P = 0.04) and negatively with PTEN expression (P = 0.03). Survival of LGG patients correlates with phosphorylation of S6 protein. This relationship supports the use of selective mTOR inhibitors in the treatment of low grade glioma