Prognostic DNA methylation markers for sporadic colorectal cancer: a systematic review

Background Biomarkers that can predict the prognosis of colorectal cancer (CRC) patients and that can stratify high-risk early stage patients from low-risk early stage patients are urgently needed for better management of CRC. During the last decades, a large variety of prognostic DNA methylation markers has been published in the literature. However, to date, none of these markers are used in clinical practice. Methods To obtain an overview of the number of published prognostic methylation markers for CRC, the number of markers that was validated independently, and the current level of evidence (LoE), we conducted a systematic review of PubMed, EMBASE, and MEDLINE. In addition, we scored studies based on the REMARK guidelines that were established in order to attain more transparency and complete reporting of prognostic biomarker studies. Eighty-three studies reporting on 123 methylation markers fulfilled the study entry criteria and were scored according to REMARK. Results Sixty-three studies investigated single methylation markers, whereas 20 studies reported combinations of methylation markers. We observed substantial variation regarding the reporting of sample sizes and patient characteristics, statistical analyses, and methodology. The median (range) REMARK score for the studies was 10.7 points (4.5 to 17.5) out of a maximum of 20 possible points. The median REMARK score was lower in studies, which reported a p value below 0.05 versus those, which did not (p = 0.005). A borderline statistically significant association was observed between the reported p value of the survival analysis and the size of the study population (p = 0.051). Only 23 out of 123 markers (17%) were investigated in two or more study series. For 12 markers, and two multimarker panels, consistent results were reported in two or more study series. For four markers, the current LoE is level II, for all other markers, the LoE is lower. Conclusion This systematic review reflects that adequate reporting according to REMARK and validation of prognostic methylation markers is absent in the majority of CRC methylation marker studies. However, this systematic review provides a comprehensive overview of published prognostic methylation markers for CRC and highlights the most promising markers that have been published in the last two decades

Evolution of educational inequalities in site-specific cancer mortality among Belgian men between the 1990s and 2000s using a “fundamental cause” perspective

Background: According to the "fundamental cause" theory, emerging knowledge on health-enhancing behaviours and technologies results in health disparities. This study aims to assess (trends in) educational inequalities in site-specific cancer mortality in Belgian men in the 1990s and the 2000s using this framework. Methods: Data were derived from record linkage between the Belgian censuses of 1991 and 2001 and register data on mortality. The study population comprised all Belgian men aged 50-79 years during follow-up. Both absolute and relative inequality measures have been calculated. Results: Despite an overall downward trend in cancer mortality, educational differences are observed for the majority of cancer sites in the 2000s. Generally, inequalities are largest for mortality from preventable cancers. Trends over time in inequalities are rather stable compared with the 1990s. Conclusions: Educational differences in site-specific cancer mortality persist in the 2000s in Belgium, mainly for cancers related to behavioural change and medical interventions. Policy efforts focussing on behavioural change and healthcare utilization remain crucial in order to tackle these increasing inequalities.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Levels of alpha-toxin correlate with distinct phenotypic response profiles of blood mononuclear cells and with agr background of community-associated Staphylococcus aureus isolates

Epidemiological studies of Staphylococcus aureus have shown a relation between certain clones and the presence of specific virulence genes, but how this translates into virulence-associated functional responses is not fully elucidated. Here we addressed this issue by analyses of community-acquired S. aureus strains characterized with respect to antibiotic resistance, ST types, agr types, and virulence gene profiles. Supernatants containing exotoxins were prepared from overnight bacterial cultures, and tested in proliferation assays using human peripheral blood mononuclear cells (PBMC). The strains displayed stable phenotypic response profiles, defined by either a proliferative or cytotoxic response. Although, virtually all strains elicited superantigen-mediated proliferative responses, the strains with a cytotoxic profile induced proliferation only in cultures with the most diluted supernatants. This indicated that the superantigen-response was masked by a cytotoxic effect which was also confirmed by flow cytometry analysis. The cytotoxic supernatants contained significantly higher levels of α-toxin than did the proliferative supernatants. Addition of α-toxin to supernatants characterized as proliferative switched the response into cytotoxic profiles. In contrast, no effect of Panton Valentine Leukocidin, δ-toxin or phenol soluble modulin α-3 was noted in the proliferative assay. Furthermore, a significant association between agr type and phenotypic profile was found, where agrII and agrIII strains had predominantly a proliferative profile whereas agrI and IV strains had a predominantly cytotoxic profile. The differential response profiles associated with specific S. aureus strains with varying toxin production could possibly have an impact on disease manifestations, and as such may reflect specific pathotypes

Biophysical interactions in tropical agroforestry systems

sequential systems, simultaneous systems Abstract. The rate and extent to which biophysical resources are captured and utilized by the components of an agroforestry system are determined by the nature and intensity of interac-tions between the components. The net effect of these interactions is often determined by the influence of the tree component on the other component(s) and/or on the overall system, and is expressed in terms of such quantifiable responses as soil fertility changes, microclimate modification, resource (water, nutrients, and light) availability and utilization, pest and disease incidence, and allelopathy. The paper reviews such manifestations of biophysical interactions in major simultaneous (e.g., hedgerow intercropping and trees on croplands) and sequential (e.g., planted tree fallows) agroforestry systems. In hedgerow intercropping (HI), the hedge/crop interactions are dominated by soil fertility improvement and competition for growth resources. Higher crop yields in HI than in sole cropping are noted mostly in inherently fertile soils in humid and subhumid tropics, and are caused by large fertility improvement relative to the effects of competition. But, yield increases are rare in semiarid tropics and infertile acid soils because fertility improvement does not offse

What is the available evidence concerning relative performance of different designs of mixed-species plantings for smallholder and community forestry in the tropics? A systematic map protocol

Background There has been growing interest in mixed species plantation systems because of their potential to provide a range of socio-economic and bio-physical benefits which can be matched to the diverse needs of smallholders and communities. Potential benefits include the production of a range of forest products for home and commercial use; improved soil fertility especially when nitrogen fixing species are included; improved survival rates and greater productivity of species; a reduction in the amount of damage from pests or disease; and improved biodiversity and wildlife habitats. Despite these documented services and growing interest in mixed species plantation systems, the actual planting areas in the tropics are low, and monocultures are still preferred for industrial plantings and many reforestation programs because of perceived higher economic returns and readily available information about the species and their silviculture. In contrast, there are few guidelines for the design and management of mixed-species systems, including the social and ecological factors of successful mixed species plantings. Methods This protocol explains the methodology used to investigate the following question: What is the available evidence for the relative performance of different designs of mixed-species plantings for smallholder and community forestry in the tropics? This study will systematically search, identify and describe studies related to mixed species plantings across tropical and temperate zones to identify the social and ecological factors that affect polyculture systems. The objectives of this study are first to identify the evidence of biophysical or socio-economic factors that have been considered when designing mixed species systems for community and smallholder forestry in the tropics; and second, to identify gaps in research of mixed species plantations. Results of the study will help create guidelines that can assist practitioners, scientists and farmers to better design mixed species plantation systems for smallholders in the tropics