Enhancement of the chemoprotective enzymes glucuronosyl transferase and glutathione transferase in specific organs of the rat by the coffee components kahweol and cafestol

The coffee components kahweol and cafestol (K/C) have been reported to protect the colon and other organs of the rat against the formation of DNA adducts by 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) and aflatoxin B1. PhIP is a cooked-food mutagen to which significant human exposure and a role in colon cancer etiology are attributed, and, interestingly, such cancers appear to develop at a lower rate in consumers of coffees with high amounts of K/C. Earlier studies in rodent liver have shown that a key role in the chemopreventive effect of K/C is likely to be due to the potential of these compounds to induce the detoxification of xenobiotics by glutathione transferase (GST) and to enhance the synthesis of the corresponding co-factor glutathione. However, mutagens like PhIP may also be detoxified by UDP-glucuronosyl transferase (UDPGT) for which data are lacking regarding a potential effect of K/C. Therefore, in the present study, we investigated the effect of K/C on UDPGT and, concomitantly, we studied overall GST and the pattern of individual GST classes, particularly GST-θ, which was not included in earlier experiments. In addition, we analyzed the organ-dependence of these potentially chemopreventive effects. K/C was fed to male F344 rats at 0.122% in the chow for 10 days. Enzyme activities in liver, kidney, lung, colon, salivary gland, pancreas, testis, heart and spleen were quantified using five characteristic substrates and the hepatic protein pattern of GST classes α, μ, and π was studied with affnity chromatography/HPLC. Our study showed that K/C is not only capable of increasing overall GST and GST classes α, μ, and π but also of enhancing UDGPT and GST-θ. All investigated K/C effects were strongest in liver and kidney, and some response was seen in lung and colon but none in the other organs. In summary, our results show that K/C treatment leads to a wide spectrum of increases in phase II detoxification enzymes. Notably, these effects occurred preferentially in the well perfused organs liver and kidney, which may thus not only contribute to local protection but also to anti-carcinogenesis in distant, less stimulated organs such as the colon.

Association of CYP1B1 codon 432 mutant allele in head and neck squamous cell cancer is reflected by somatic mutations of p53 in tumor tissue

Tobacco use is causally associated with head and neck squamous cell cancer (HNSCC). Here, we present the results of a case-control study that investigated the effects that the genetic variants of the cytochrome (CYP)1A1, CYP1B1, glutathione-S-transferase (GST)M1, GSTT1, and GSTP1 genes have on modifying the risk of smoking-related HNSCC. Allelisms of the CYP1A1, GSTT1, GSTM1, and GSTT1 genes alone were not associated with an increased risk. CYP1B1 codon 432 polymorphism was found to be a putative susceptibility factor in smoking-related HNSCC. The frequency of CYP1B1 polymorphism was significantly higher (P < 0.001) in the group of smoking cases when compared with smoking controls. Additionally, an odds ratio (OR) of 4.53 (2.62-7.98) was discovered when investigating smoking and nonsmoking cases for the susceptible genotype CYP1B1*2/*2, when compared with the presence of the genotype wild type. In combination with polymorphic variants of the GST genes, a synergistic-effect OR was observed. The calculated OR for the combined genotype CYP1B1*2/*2 and GSTM1*2/*2 was 12.8 (4.09-49.7). The calculated OR for the combined genotype was 13.4 (2.92-97.7) for CYP1B1*2/*2 and GSTT1*2/*2, and 24.1 (9.36-70.5) for the combination of CYP1B1*2/*2 and GSTT1-expressors. The impact of the polymorphic variants of the CYP1B1 gene on HNSCC risk is reflected by the strong association with the frequency of somatic mutations of the p53 gene. Smokers with susceptible genotype CYP1B1*2/*2 were 20 times more likely to show evidence of p53 mutations than were those with CYP1B1 wild type. Combined genotype analysis of CYP1B1 and GSTM1 or GSTT1 revealed interactive effects on the occurrence of p53 gene mutations. The results of the present study indicate that polymorphic variants of CYP1B1 relate significantly to the individual susceptibility of smokers to HNSCC.

The adhesion molecule L1 regulates transendothelial migration and trafficking of dendritic cells

The adhesion molecule L1, which is extensively characterized in the nervous system, is also expressed in dendritic cells (DCs), but its function there has remained elusive. To address this issue, we ablated L1 expression in DCs of conditional knockout mice. L1-deficient DCs were impaired in adhesion to and transmigration through monolayers of either lymphatic or blood vessel endothelial cells, implicating L1 in transendothelial migration of DCs. In agreement with these findings, L1 was expressed in cutaneous DCs that migrated to draining lymph nodes, and its ablation reduced DC trafficking in vivo. Within the skin, L1 was found in Langerhans cells but not in dermal DCs, and L1 deficiency impaired Langerhans cell migration. Under inflammatory conditions, L1 also became expressed in vascular endothelium and enhanced transmigration of DCs, likely through L1 homophilic interactions. Our results implicate L1 in the regulation of DC trafficking and shed light on novel mechanisms underlying transendothelial migration of DCs. These observations might offer novel therapeutic perspectives for the treatment of certain immunological disorders.

Privacy concerns and purchase of travel product online

The travel and tourism industry has come to rely heavily on information and communication technologies to facilitate relations with consumers. Compiling consumer data profiles has become easier and it is widely thought that consumers place great importance on how that data is handled by firms. Lack of trust may cause consumers to have privacy concerns and may, in turn, have an adverse impact on consumers’ willingness to purchase online. Three specific aspects of privacy that have received attention from researchers are unauthorized use of secondary data, invasion of privacy, and errors. A survey study was undertaken to examine the effects of these factors on both prior purchase of travel products via the Internet and future purchase probability. Surprisingly, no significant relationships were found to indicate that such privacy concerns affect online purchase behavior within the travel industry. Implications for managers are discussed.

On fundamental limitations for rudder roll stabilization of ships

The main purpose of the rudder in ships is course keeping. However, the rudder can also be used, in some cases, to reject undesirable wave produced rolling motions. From a fundamental point of view, the main issues associated with this problem are the presence of a nonminimum phase zero and the single input two output nature of the system. In this paper, the limitations imposed on the achievable closed loop performance due to these issues are analyzed. This gives a deeper understanding of the problem and leads to conclusions regarding the inherent design trade-offs which hold regardless of the control strategy used.

Measuring reliability and validity of the ActiGraph GT3X accelerometer for children with cerebral palsy : a feasibility study

PURPOSE The purposes of this study were to: 1) establish inter-instrument reliability between left and right hip accelerometer placement; 2) examine procedural reliability of a walking protocol used to measure physical activity (PA), and; 3) confirm concurrent validity of accelerometers in measuring PA intensity as compared to the gold standard of oxygen consumption measured by indirect calorimetry. METHODS Eight children (mean age: 11.9; SD: 3.2, 75% male) with CP (GMFCS levels I-III) wore ActiGraph GT3X accelerometers on each hip and the Cosmed K4b^{2} portable indirect calorimeter during two measurement sessions in which they performed the six minute walk test (6MWT) at three self-selected speeds (comfortable/slow, brisk, fast). Oxygen consumption (VO2) and accelerometer step and activity count data were recorded. RESULTS Inter-instrument reliability of ActiGraph GT3X accelerometers placed on left and right hips was excellent (ICC=0.96-0.99, CI_{95}: 0.81-0.99). Reproducibility of the protocol was good/excellent (ICC=0.75-0.95, CI_{95}: 0.75-0.98). Concurrent validity of accelerometer count data and VO2 was fair/good (rho=0.67, p< 0.001). The correlation between step count and VO2 was not significant (rho=0.29, p=0.2). CONCLUSION This preliminary research suggests that ActiGraph GT3X accelerometers are reliable and valid devices to monitor PA during walking in children with CP and may be appropriate in rehabilitation research and clinical practice. ActiGraph GTX3 step counts were not valid for this sample and further research is warranted.

Longitudinal performance of polycaprolactone-based scaffold plus recombinant human morphogenetic protein-2 (rhBMP-2) in large preclinical animal model : 6- versus 12 months

There is strong current interest in the use of biodegradable scaffolds in combination with bone growth factors as a valuable alternative to the current gold standard autograft in spinal fusion surgery Yong et al. (2013). Here we report on 6- vs 12- month data set evaluating the longitudinal performance of a CaP coated polycaprolactone (PCL) scaffold loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone graft substitute within a preclinical ovine thoracic spine. The results of this study demonstrate the efficacy of scaffold-based delivery of rhBMP-2 in promoting higher fusion grades at 6- and 12- months in comparison to the scaffold alone or autograft group within the same time frame. Fusion grades achieved at six months using PCL+rhBMP-2 are not significantly increased at twelve months post surgery.

Development of a new index of balance in adults with intellectual and developmental disabilities

Purposes: The first objective was to propose a new model representing the balance level of adults with intellectual and developmental disabilities (IDD) using Principal Components Analysis (PCA); and the second objective was to use the results from the PCA recorded by regression method to construct and validate summative scales of the standardized values of the index, which may be useful to facilitate a balance assessment in adults with IDD. Methods: A total of 801 individuals with IDD (509 males) mean 33.1±8.5 years old, were recruited from Special Olympic Games in Spain 2009 to 2012. The participants performed the following tests: the timed-stand test, the single leg stance test with open and closed eyes, the Functional Reach Test, the Expanded Timed-Get-up-and-Go Test. Data was analyzed using principal components analysis (PCA) with Oblimin rotation and Kaiser normalization. We examined the construct validity of our proposed two-factor model underlying balance for adults with IDD. The scores from PCA were recorded by regression method and were standardized. Results: The Component Plot and Rotated Space indicated that a two-factor solution (Dynamic and Static Balance components) was optimal. The PCA with direct Oblimin rotation revealed a satisfactory percentage of total variance explained by the two factors: 51.6 and 21.4%, respectively. The median score standardized for component dynamic and static of the balance index for adults with IDD is shown how references values. Conclusions: Our study may lead to improvements in the understanding and assessment of balance in adults with IDD. First, it confirms that a two-factor model may underlie the balance construct, and second, it provides an index that may be useful for identifying the balance level for adults with IDD.

Health consequences of exposure to e-waste : a systematic review

Background The population exposed to potentially hazardous substances through inappropriate and unsafe management practices related to disposal and recycling of end-of-life electrical and electronic equipment, collectively known as e-waste, is increasing. We aimed to summarise the evidence for the association between such exposures and adverse health outcomes. Methods We systematically searched five electronic databases (PubMed, Embase, Web of Science, PsycNET, and CINAHL) for studies assessing the association between exposure to e-waste and outcomes related to mental health and neurodevelopment, physical health, education, and violence and criminal behaviour, from Jan 1, 1965, to Dec 17, 2012, and yielded 2274 records. Of the 165 full-text articles assessed for eligibility, we excluded a further 142, resulting in the inclusion of 23 published epidemiological studies that met the predetermined criteria. All studies were from southeast China. We assessed evidence of a causal association between exposure to e-waste and health outcomes within the Bradford Hill framework. Findings We recorded plausible outcomes associated with exposure to e-waste including change in thyroid function, changes in cellular expression and function, adverse neonatal outcomes, changes in temperament and behaviour, and decreased lung function. Boys aged 8–9 years living in an e-waste recycling town had a lower forced vital capacity than did those living in a control town. Significant negative correlations between blood chromium concentrations and forced vital capacity in children aged 11 and 13 years were also reported. Findings from most studies showed increases in spontaneous abortions, stillbirths, and premature births, and reduced birthweights and birth lengths associated with exposure to e-waste. People living in e-waste recycling towns or working in e-waste recycling had evidence of greater DNA damage than did those living in control towns. Studies of the effects of exposure to e-waste on thyroid function were not consistent. One study related exposure to e-waste and waste electrical and electronic equipment to educational outcomes. Interpretation Although data suggest that exposure to e-waste is harmful to health, more well designed epidemiological investigations in vulnerable populations, especially pregnant women and children, are needed to confirm these associations. Funding Children's Health and Environment Program, Queensland Children's Medical Research Institute, The University of Queensland, Australia.

A critical evaluation of written discharge advice for people with mild traumatic brain injury : what should we be looking for?

Objective: To formally evaluate the written discharge advice for people with mild traumatic brain injury (mTBI). Methods: Eleven publications met the inclusion criteria: (1) intended for adults; (2) ≤two A4 pages; (3) published in English; (4) freely accessible; and (5) currently used (or suitable for use) in Australian hospital emergency departments or similar settings. Two independent raters evaluated the content and style of each publication against established standards. The readability of the publication, the diagnostic term(s) contained in it and a modified Patient Literature Usefulness Index (mPLUI) were also evaluated. Results: The mean content score was 19.18 ± 8.53 (maximum = 31) and the mean style score was 6.8 ± 1.34 (maximum = 8). The mean Flesch-Kincaid reading ease score was 66.42 ± 4.3. The mean mPLUI score was 65.86 ± 14.97 (maximum = 100). Higher scores on these metrics indicate more desirable properties. Over 80% of the publications used mixed diagnostic terminology. One publication scored optimally on two of the four metrics and highly on the others. Discussion: The content, style, readability and usefulness of written mTBI discharge advice was highly variable. The provision of written information to patients with mTBI is advised, but this variability in materials highlights the need for evaluation before distribution. Areas are identified to guide the improvement of written mTBI discharge advice.