6-thioguanine treatment in inflammatory bowel disease: A critical appraisal by a European 6-TG working party

Recently, the suggestion to use 6-thioguanine (6-TG) as an alternative thiopurine in patients with inflammatory bowel disease (IBD) has been discarded due to reports about possible (hepato) toxicity. During meetings arranged in Vienna and Prague in 2004, European experts applying 6-TG further on in IBD patients presented data on safety and efficacy of 6-TG. After thorough evaluation of its risk-benefit ratio, the group consented that 6-TG may still be considered as a rescue drug in stringently defined indications in IBD, albeit restricted to a clinical research setting. As a potential indication for administering 6-TG, we delineated the requirement for maintenance therapy as well as intolerance and/or resistance to aminosalicylates, azathioprine, 6-mercaptopurine, methotrexate and infliximab. Furthermore, indications are preferred in which surgery is thought to be inappropriate. The standard 6-TG dosage should not exceed 25 mg daily. Routine laboratory controls are mandatory in short intervals. Liver biopsies should be performed after 6-12 months, three years and then three-yearly accompanied by gastroduodenoscopy, to monitor for potential hepatotoxicity, including nodular regenerative hyperplasia (NRH) and veno-occlusive disease (VOD). Treatment with 6-TG must be discontinued in case of overt or histologically proven hepatotoxicity. Copyright (c) 2006 S. Karger AG, Basel

The role of honey in the ecology of the hive: Nutrition, detoxification, longevity, and protection against hive pathogens

Honey is the source of energy for the European honey bee, Apis mellifera. Beyond simple nutrition and a hedge against the seasonal, geographic, and chemical unpredictability of nectar, honey has properties that protect the hive against various stresses. Enzyme-mediated detoxification during honey ripening neutralizes potentially toxic phytochemicals, and bees that consume honey have enhanced tolerance to other ingested toxins. Catalase and antioxidant phenolics protect honey bees from oxidative damage caused by reactive oxygen species, promoting their longevity. Phytochemical components of honey and microRNAs have the potential to influence developmental pathways, with diet playing a large role in honey bee caste determination. Components of honey mediate stress response and promote cold tolerance during overwintering. Honey has a suite of antimicrobial mechanisms including osmotic pressure, low water activity, low pH, hydrogen peroxide, and plant-, honey bee-, and microbiota-derived compounds such as phytochemicals and antimicrobial peptides. Certain types of honey, particularly polyfloral honeys, have been shown to inhibit important honey bee pathogens including the bacteria responsible for American and European Foulbrood, the microsporidian Nosema ceranae, and the fungi responsible for Stonebrood. Understanding the diverse functional properties of honey has far-ranging implications for honey bee and hive health and management by beekeepers.</jats:p

Increased entropy of signal transduction in the cancer metastasis phenotype

Studies into the statistical properties of biological networks have led to important biological insights, such as the presence of hubs and hierarchical modularity. There is also a growing interest in studying the statistical properties of networks in the context of cancer genomics. However, relatively little is known as to what network features differ between the cancer and normal cell physiologies, or between different cancer cell phenotypes. Based on the observation that frequent genomic alterations underlie a more aggressive cancer phenotype, we asked if such an effect could be detectable as an increase in the randomness of local gene expression patterns. Using a breast cancer gene expression data set and a model network of protein interactions we derive constrained weighted networks defined by a stochastic information flux matrix reflecting expression correlations between interacting proteins. Based on this stochastic matrix we propose and compute an entropy measure that quantifies the degree of randomness in the local pattern of information flux around single genes. By comparing the local entropies in the non-metastatic versus metastatic breast cancer networks, we here show that breast cancers that metastasize are characterised by a small yet significant increase in the degree of randomness of local expression patterns. We validate this result in three additional breast cancer expression data sets and demonstrate that local entropy better characterises the metastatic phenotype than other non-entropy based measures. We show that increases in entropy can be used to identify genes and signalling pathways implicated in breast cancer metastasis. Further exploration of such integrated cancer expression and protein interaction networks will therefore be a fruitful endeavour.Comment: 5 figures, 2 Supplementary Figures and Table

Does Uptake of Pharmaceuticals Vary Across Earthworm Species?

This study compared the uptake and depuration of four commonly used pharmaceuticals (carbamazepine, diclofenac, fluoxetine and orlistat) in two earthworm species (Lumbricus terrestris and Eisenia fetida). L. terrestris are a larger species and often found in deep burrows whereas E. fetida prefer to reside near the soil surface. Species burrowing habits and sizes may alter uptake by earthworms. All four pharmaceuticals were taken up into both L. terrestris and E. fetida tissue after 21 days exposure to spiked soil. Bioconcentration factors (BCFs) ranged between 1.72 and 29.83 for L. terrestris and 1.14 and 63.03 for E. fetida. For carbamazepine and diclofenac, BCFs were similar whereas for fluoxetine and orlistat, BCFs in E. fetida were more than double those seen in L. terrestris. Results indicate that uptake into earthworms cannot be generalised between species and that the influence of species traits can vary depending on the nature of the study chemical

Imaging-guided chest biopsies: techniques and clinical results

Background This article aims to comprehensively describe indications, contraindications, technical aspects, diagnostic accuracy and complications of percutaneous lung biopsy. Methods Imaging-guided biopsy currently represents one of the predominant methods for obtaining tissue specimens in patients with lung nodules; in many cases treatment protocols are based on histological information; thus, biopsy is frequently performed, when technically feasible, or in case other techniques (such as bronchoscopy with lavage) are inconclusive. Results Although a coaxial system is suitable in any case, two categories of needles can be used: fine-needle aspiration biopsy (FNAB) and core-needle biopsy (CNB), with the latter demonstrated to have a slightly higher overall sensitivity, specificity and accuracy. Conclusion Percutaneous lung biopsy is a safe procedure even though a few complications are possible: pneumothorax, pulmonary haemorrhage and haemoptysis are common complications, while air embolism and seeding are rare, but potentially fatal complications

Transport in holographic superfluids

We construct a slowly varying space-time dependent holographic superfluid and compute its transport coefficients. Our solution is presented as a series expansion in inverse powers of the charge of the order parameter. We find that the shear viscosity associated with the motion of the condensate vanishes. The diffusion coefficient of the superfluid is continuous across the phase transition while its third bulk viscosity is found to diverge at the critical temperature. As was previously shown, the ratio of the shear viscosity of the normal component to the entropy density is 1/(4 pi). As a consequence of our analysis we obtain an analytic expression for the backreacted metric near the phase transition for a particular type of holographic superfluid.Comment: 45 pages + appendice

Suturing training in Augmented Reality: gaining proficiency in suturing skills faster

Background: Providing informative feedback and setting goals tends to motivate trainees to practice more extensively. Augmented Reality simulators retain the benefit of realistic haptic feedback and additionally generate objective assessment and informative feedback during the training. This study researched the performance curve of the adapted suturing module on the ProMIS Augmented Reality simulator. Methods: Eighteen novice participants were pretrained on the MIST-VR to become acquainted with laparoscopy. Subsequently, they practiced 16 knots on the suturing module, of which the assessment scores were recorded to evaluate the gain in laparoscopic suturing skills. The scoring of the assessment method was calculated from the “time spent in the correct area” during the knot tying and the quality of the knot. Both the baseline knot and the knot at the top of the performance curve were assessed by two independent objective observers, by means of a standardized evaluation form, to objectify the gain in suturing skills. Results: There was a statistically significant difference between the scores of the second knot (mean 72.59, standard deviation (SD) 16.28) and the top of the performance curve (mean 95.82, SD 3.05; p < 0.001, paired t-test). The scoring of the objective observers also differed significantly (mean 11.83 and 22.11, respectively; SD 3.37 and 3.89, respectively; p < 0.001) (interobserver reliability Cronbach’s alpha = 0.96). The median amount of repetitions to reach the top of the performance curve was eight, which also showed significant differences between both the assessment score (mean 88.14, SD 13.53, p < 0.001) and scoring of the objective observers of the second knot (mean 20.51, SD 4.14; p < 0.001). Conclusions: This adapted suturing module on the ProMIS Augmented Reality laparoscopic simulator is a potent tool for gaining laparoscopic suturing skills.Industrial DesignIndustrial Design Engineerin

Appointing Women to Boards: Is There a Cultural Bias?

Companies that are serious about corporate governance and business ethics are turning their attention to gender diversity at the most senior levels of business (Institute of Business Ethics, Business Ethics Briefing 21:1, 2011). Board gender diversity has been the subject of several studies carried out by international organizations such as Catalyst (Increasing gender diversity on boards: Current index of formal approaches, 2012), the World Economic Forum (Hausmann et al., The global gender gap report, 2010), and the European Board Diversity Analysis (Is it getting easier to find women on European boards? 2010). They all lead to reports confirming the overall relatively low proportion of women on boards and the slow pace at which more women are being appointed. Furthermore, the proportion of women on corporate boards varies much across countries. Based on institutional theory, this study hypothesizes and tests whether this variation can be attributed to differences in cultural settings across countries. Our analysis of the representation of women on boards for 32 countries during 2010 reveals that two cultural characteristics are indeed associated with the observed differences. We use the cultural dimensions proposed by Hofstede (Culture’s consequences: International differences in work-related values, 1980) to measure this construct. Results show that countries which have the greatest tolerance for inequalities in the distribution of power and those that tend to value the role of men generally exhibit lower representations of women on boards

Blood Lead Secular Trend in a Cohort of Children in Mexico City (1987–2002)

We determined the secular trend in blood lead levels in a cohort of 321 children born in Mexico City between 1987 and 1992. Blood lead level was measured every 6 months during a 10-year period. We modeled the effect of yearly air lead concentration nested within the calendar year in which the child was born, family use of lead-glazed pottery, socioeconomic status, year in which the child was born, age of the child at the time of blood lead measurement, place of residence, and an indicator variable for subjects with complete or incomplete blood lead values. The yearly mean of air lead of the Valley of Mexico decreased from its highest level of 2.80 μg/m(3) in 1987 to 0.07 μg/m(3) in 2002. The contribution of air lead to blood lead according to year of birth was strongest for subjects born in 1987 and fell to nearly zero for children born in 1992. The geometric mean of the entire cohort rose from 8.4 μg/dL in the first year of life to 10.1 μg/dL in the second and decreased thereafter until it reached 6.4 μg/dL at 10 years of age. Children of families who used lead-glazed ceramics had blood lead levels 18.5% higher than did children of nonusing families. Children who belonged to the lowest socioeconomic levels had blood lead levels 32.2% higher than did those of highest socioeconomic levels. Children who lived in the northeast part of the city had blood lead levels 10.9% higher compared with those who lived in the southwest

Summer and winter differences in zooplankton biomass, distribution and size composition in the KwaZulu-Natal Bight, South Africa

Zooplankton biomass and distribution in the KwaZulu-Natal Bight were investigated in relation to environmental parameters during summer (January–February 2010) and winter (July–August 2010). Mean zooplankton biomass was significantly higher in winter (17.1 mg dry weight [DW] m–3) than in summer (9.5 mg DW m−3). In summer, total biomass was evenly distributed within the central bight, low off the Thukela River mouth and peaked near Durban. In winter, highest biomass was found offshore between Richards Bay and Cape St Lucia. Zooplankton biomass in each size class was significantly, negatively related to sea surface temperature and integrated nitrate, but positively related to surface chlorophyll a and dissolved oxygen. Zooplankton biomass was significantly related to bottom depth, with greatest total biomass located inshore (<50 m). Distribution across the shelf varied with zooplankton size. Seasonal differences in copepod size composition suggest that a smaller, younger community occupied the cool, chlorophyll-rich waters offshore from the St Lucia upwelling cell in winter, and a larger, older community occurred within the relatively warm and chlorophyll-poor central bight in summer. Nutrient enrichment from quasi-permanent upwelling off Durban and Richards Bay appears to have a greater influence on zooplankton biomass and distribution in the bight than the strongly seasonal nutrient input from the Thukela River.DHE