Annex to Quirke et al. Quality assurance in pathology in colorectal cancer screening and diagnosis: annotations of colorectal lesions

Multidisciplinary, evidence-based European Guidelines for quality assurance in colorectal cancer screening and diagnosis have recently been developed by experts in a pan-European project coordinated by the International Agency for Research on Cancer. The full guideline document includes a chapter on pathology with pan-European recommendations which take into account the diversity and heterogeneity of health care systems across the EU. The present paper is based on the annex to the pathology chapter which attempts to describe in greater depth some of the issues raised in the chapter in greater depth, particularly details of special interest to pathologists. It is presented here to make the relevant discussion known to a wider scientific audience

Evolution of protein domain architectures

This chapter reviews current research on how protein domain architectures evolve. We begin by summarizing work on the phylogenetic distribution of proteins, as this will directly impact which domain architectures can be formed in different species. Studies relating domain family size to occurrence have shown that they generally follow power law distributions, both within genomes and larger evolutionary groups. These findings were subsequently extended to multi-domain architectures. Genome evolution models that have been suggested to explain the shape of these distributions are reviewed, as well as evidence for selective pressure to expand certain domain families more than others. Each domain has an intrinsic combinatorial propensity, and the effects of this have been studied using measures of domain versatility or promiscuity. Next, we study the principles of protein domain architecture evolution and how these have been inferred from distributions of extant domain arrangements. Following this, we review inferences of ancestral domain architecture and the conclusions concerning domain architecture evolution mechanisms that can be drawn from these. Finally, we examine whether all known cases of a given domain architecture can be assumed to have a single common origin (monophyly) or have evolved convergently (polyphyly). We end by a discussion of some available tools for computational analysis or exploitation of protein domain architectures and their evolution

Honey Bee PTEN – Description, Developmental Knockdown, and Tissue-Specific Expression of Splice-Variants Correlated with Alternative Social Phenotypes

Phosphatase and TENsin (PTEN) homolog is a negative regulator that takes part in IIS (insulin/insulin-like signaling) and Egfr (epidermal growth factor receptor) activation in Drosophila melanogaster. IIS and Egfr signaling events are also involved in the developmental process of queen and worker differentiation in honey bees (Apis mellifera). Here, we characterized the bee PTEN gene homologue for the first time and begin to explore its potential function during bee development and adult life.Honey bee PTEN is alternatively spliced, resulting in three splice variants. Next, we show that the expression of PTEN can be down-regulated by RNA interference (RNAi) in the larval stage, when female caste fate is determined. Relative to controls, we observed that RNAi efficacy is dependent on the amount of PTEN dsRNA that is delivered to larvae. For larvae fed queen or worker diets containing a high amount of PTEN dsRNA, PTEN knockdown was significant at a whole-body level but lethal. A lower dosage did not result in a significant gene down-regulation. Finally, we compared same-aged adult workers with different behavior: nursing vs. foraging. We show that between nurses and foragers, PTEN isoforms were differentially expressed within brain, ovary and fat body tissues. All isoforms were expressed at higher levels in the brain and ovaries of the foragers. In fat body, isoform B was expressed at higher level in the nurse bees.Our results suggest that PTEN plays a central role during growth and development in queen- and worker-destined honey bees. In adult workers, moreover, tissue-specific patterns of PTEN isoform expression are correlated with differences in complex division of labor between same-aged individuals. Therefore, we propose that knowledge on the roles of IIS and Egfr activity in developmental and behavioral control may increase through studies of how PTEN functions can impact bee social phenotypes

Honey Bee PTEN – Description, Developmental Knockdown, and Tissue-Specific Expression of Splice-Variants Correlated with Alternative Social Phenotypes

Phosphatase and TENsin (PTEN) homolog is a negative regulator that takes part in IIS (insulin/insulin-like signaling) and Egfr (epidermal growth factor receptor) activation in Drosophila melanogaster. IIS and Egfr signaling events are also involved in the developmental process of queen and worker differentiation in honey bees (Apis mellifera). Here, we characterized the bee PTEN gene homologue for the first time and begin to explore its potential function during bee development and adult life.Honey bee PTEN is alternatively spliced, resulting in three splice variants. Next, we show that the expression of PTEN can be down-regulated by RNA interference (RNAi) in the larval stage, when female caste fate is determined. Relative to controls, we observed that RNAi efficacy is dependent on the amount of PTEN dsRNA that is delivered to larvae. For larvae fed queen or worker diets containing a high amount of PTEN dsRNA, PTEN knockdown was significant at a whole-body level but lethal. A lower dosage did not result in a significant gene down-regulation. Finally, we compared same-aged adult workers with different behavior: nursing vs. foraging. We show that between nurses and foragers, PTEN isoforms were differentially expressed within brain, ovary and fat body tissues. All isoforms were expressed at higher levels in the brain and ovaries of the foragers. In fat body, isoform B was expressed at higher level in the nurse bees.Our results suggest that PTEN plays a central role during growth and development in queen- and worker-destined honey bees. In adult workers, moreover, tissue-specific patterns of PTEN isoform expression are correlated with differences in complex division of labor between same-aged individuals. Therefore, we propose that knowledge on the roles of IIS and Egfr activity in developmental and behavioral control may increase through studies of how PTEN functions can impact bee social phenotypes

Diabetes and the Risk of Multi-System Aging Phenotypes: A Systematic Review and Meta-Analysis

[[abstract]]Background: Observational studies suggested an association between diabetes and the risk of various geriatric conditions (i.e., cognitive impairment, dementia, depression, mobility impairment, disability, falls, and urinary incontinence). However, the magnitude and impact of diabetes on older adults have not been reviewed. Methodology/Principal Findings: MEDLINE and PSYCINFO databases were searched through November 2007 for published studies, supplemented by manual searches of bibliographies of key articles. Population-based, prospective cohort studies that reported risk of geriatric outcomes in relation to diabetes status at baseline were selected. Two authors independently extracted the data, including study population and follow-up duration, ascertainment of diabetes status at baseline, outcomes of interest and their ascertainment, adjusted covariates, measures of association, and brief results. Fifteen studies examined the association of DM with cognitive dysfunction. DM was associated with a faster decline in cognitive function among older adults. The pooled adjusted risk ratio (RR) for all dementia when persons with DM were compared to those without was 1.47 (95% CI, 1.25 to 1.73). Summary RRs for Alzheimer's disease and vascular dementia comparing persons with DM to those without were 1.39 (CI, 1.16 to 1.66) and 2.38 (CI, 1.79 to 3.18), respectively. Four of 5 studies found significant association of DM with faster mobility decline and incident disability. Two studies examined the association of diabetes with falls in older women. Both found statistically significant associations. Insulin users had higher RR for recurrent falls. One study for urinary incontinence in older women found statistically significant associations. Two studies for depression did not suggest that DM was an independent predictor of incident depression. Conclusions/Significance: Current evidence supports that DM is associated with increased risk for selected geriatric conditions. Clinicians should increase their awareness and provide appropriate care. Future research is required to elucidate the underlying pathological pathway. 2009 Lu et al

Developments in silicone technology for use in stoma care

YesSoft silicone's flexibility, adhesive capacity and non-toxic, non-odourous and hypoallergenic nature have made it an established material for adhesive and protective therapeutic devices. In wound care, silicone is a component of contact layer dressings for superficial wounds and silicone gel sheeting for reducing the risk of scarring, as well as of barriers for incontinence-associated dermatitis. Regarding stoma accessories, silicone is established in barrier films to prevent contact dermatitis, adhesive removers to prevent skin stripping and filler gels to prevent appliance leaks. Until recently, silicone has not been used in stoma appliances flanges, as its hydrophobic nature has not allowed for moisture management to permit trans-epidermal water loss and prevent maceration. Traditional hydrocolloid appliances manage moisture by absorbing water, but this can lead to saturation and moisture-associated skin damage (MASD), as well as increased adhesion and resultant skin tears on removal, known as medical adhesive-related skin injury (MARSI). However, novel silicone compounds have been developed with a distinct evaporation-based mechanism of moisture management. This uses colloidal separation to allow the passage of water vapour at a rate equivalent to normal trans-epidermal water loss. It has been shown to minimise MASD, increase wear time and permit atraumatic removal without the use of adhesive solvents. Trio Healthcare has introduced this technology with a range of silicone-based flange extenders and is working with the University of Bradford Centre for Skin Sciences on prototype silicone-based stoma appliance flanges designed to significantly reduce the incidence of peristomal skin complications, such as MARSI and MASD. It is hoped that this will also increase appliance wear time, reduce costs and improve patient quality of life

Gene Expression in Brain and Liver Produced by Three Different Regimens of Alcohol Consumption in Mice: Comparison with Immune Activation

Chronically available alcohol escalates drinking in mice and a single injection of the immune activator lipopolysaccharide can mimic this effect and result in a persistent increase in alcohol consumption. We hypothesized that chronic alcohol drinking and lipopolysaccharide injections will produce some similar molecular changes that play a role in regulation of alcohol intake. We investigated the molecular mechanisms of chronic alcohol consumption or lipopolysaccharide insult by gene expression profiling in prefrontal cortex and liver of C57BL/6J mice. We identified similar patterns of transcriptional changes among four groups of animals, three consuming alcohol (vs water) in different consumption tests and one injected with lipopolysaccharide (vs. vehicle). The three tests of alcohol consumption are the continuous chronic two bottle choice (Chronic), two bottle choice available every other day (Chronic Intermittent) and limited access to one bottle of ethanol (Drinking in the Dark). Gene expression changes were more numerous and marked in liver than in prefrontal cortex for the alcohol treatments and similar in the two tissues for lipopolysaccharide. Many of the changes were unique to each treatment, but there was significant overlap in prefrontal cortex for Chronic-Chronic Intermittent and for Chronic Intermittent-lipopolysaccharide and in liver all pairs showed overlap. In silico cell-type analysis indicated that lipopolysaccharide had strongest effects on brain microglia and liver Kupffer cells. Pathway analysis detected a prefrontal cortex-based dopamine-related (PPP1R1B, DRD1, DRD2, FOSB, PDNY) network that was highly over-represented in the Chronic Intermittent group, with several genes from the network being also regulated in the Chronic and lipopolysaccharide (but not Drinking in the Dark) groups. Liver showed a CYP and GST centered metabolic network shared in part by all four treatments. We demonstrate common consequences of chronic alcohol consumption and immune activation in both liver and brain and show distinct genomic consequences of different types of alcohol consumption.This work was supported by grants from the National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism (NIH/NIAAA) Integrated Neuroscience Initiative on Alcoholism (INIA-West, http://www.scripps.edu/california/resear​ch/inia/; AA13520), NIH K award to IP (AA017234), and NIH grant AA013518 to RAH (NIH, http://www.nih.gov/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.Pharmac