Inhibition of triclabendazole metabolism in vitro by ketoconazole increases disruption to the tegument of a triclabendazole-resistant isolate of Fasciola hepatica

A study has been carried out to investigate whether the action of triclabendazole (TCBZ) against Fasciola hepatica is altered by inhibition of drug metabolism. The cytochrome P450 (CYP 450) enzyme pathway was inhibited using ketoconazole (KTZ) to see whether a TCBZ-resistant isolate could be made more sensitive to TCBZ action. The Oberon TCBZ-resistant and Cullompton TCBZ-susceptible isolates were used for these experiments. The CYP 450 system was inhibited by a 2-h pre-incubation in ketoconazole (40 mu M), then incubated for a further 22 h in NCTC medium containing either KTZ, KTZ+nicotinamide adenine dinucleotide phosphate (NADPH) (1 nM), KTZ+NADPH+TCBZ (15 mu g/ml), or KTZ+NADPH+triclabendazole sulphoxide (TCBZ. SO; 15 mu g/ml). Changes to fluke ultrastructure following drug treatment and metabolic inhibition were assessed using transmission electron microscopy. After treatment with either TCBZ or TCBZ. SO on their own, there was greater disruption to the TCBZ-susceptible than TCBZ-resistant isolate. However, co-incubation with KTZ+TCBZ, but more particularly KTZ+TCBZ. SO, led to more severe changes to the TCBZ-resistant isolate than with each drug on its own: in the syncytium, for example, there was severe swelling of the basal infolds and their associated mucopolysaccharide masses, accompanied by an accumulation of secretory bodies just below the apex. Golgi complexes were greatly reduced or absent in the tegumental cells and the synthesis, production, and transport of secretory bodies were badly disrupted. With the TCBZ-susceptible Cullompton isolate, there was limited potentiation of drug action. The results support the concept of altered drug metabolism in TCBZ-resistant flukes and this process may play a role in the development of drug resistance.

Translating policy into practice: A case study in the secondary prevention of coronary heart disease

Background: This paper focuses on the relationships between health ‘policy’ as it is embodied in official documentation, and health ‘practice’ as reported and reflected on in the talk of policy makers, health professionals and patients. The specific context for the study involves a comparison of policies relating to the secondary prevention of coronary heart disease (CHD) in the two jurisdictions of Ireland – involving as they do a predominantly state funded (National Health Service) system in the north and a mixed healthcare economy in the south. The key question is to determine how the rhetoric of health policy as contained in policy documents connects to, and gets translated into practice and action.

Methods: The data sources for the study include relevant healthcare policy documents (N=5) and progress reports (N=6) in the two Irish jurisdictions, and semi-structured interviews with a range of policy-makers (N=28), practice nurses (14), general practitioners (12) and patients (13) to explore their awareness of the documents’ contents and how they saw the impact of ‘policy’ on primary care practice.

Results: The findings suggest that although strategic policy documents can be useful for highlighting and channelling attention to health issues that require concerted action, they have little impact on what either professionals or lay people do.

Conclusion: To influence the latter and to encourage a systematic approach to the delivery of health care it seems likely that contractual arrangements – specifying tasks to be undertaken and methods for monitoring and reporting on activity - are required.

Novel Analysis of Oceanic Surface Water Metagenomes Suggests Importance of Polyphosphate Metabolism in Oligotrophic Environments

Polyphosphate is a ubiquitous linear homopolymer of phosphate residues linked by high-energy bonds similar to those found in ATP. It has been associated with many processes including pathogenicity, DNA uptake and multiple stress responses across all domains. Bacteria have also been shown to use polyphosphate as a way to store phosphate when transferred from phosphate-limited to phosphate-rich media - a process exploited in wastewater treatment and other environmental contaminant remediation. Despite this, there has, to date, been little research into the role of polyphosphate in the survival of marine bacterioplankton in oligotrophic environments. The three main proteins involved in polyphosphate metabolism, Ppk1, Ppk2 and Ppx are multi-domain and have differential inter-domain and inter-gene conservation, making unbiased analysis of relative abundance in metagenomic datasets difficult. This paper describes the development of a novel Isofunctional Homolog Annotation Tool (IHAT) to detect homologs of genes with a broad range of conservation without bias of traditional expect-value cutoffs. IHAT analysis of the Global Ocean Sampling (GOS) dataset revealed that genes associated with polyphosphate metabolism are more abundant in environments where available phosphate is limited, suggesting an important role for polyphosphate metabolism in marine oligotrophs.

The effect of month of birth on the attainments of primary and secondary school pupils

Background: Previous research has produced conflicting results regarding the effects of season of birth and age-position on cognitive attainments. In Northern Ireland the school year divides the summer season into two providing an opportunity to evaluate the relative contribution of season of birth and age-position effects. Aims: To investigate the relationship between attainment in literacy skills and month of birth for primary and secondary school pupils and to determine the relationship between motor skills and month of birth in primary school pupils. Sample: One thousand one hundred and twenty four primary school pupils participated, and results for key stage 3 (KS3) English and GCSE English Language, for 3,493 Year 10 and 3,697 Year 12 secondary school pupils, respectively, were obtained. Method: Primary school pupils were individually assessed using standardised reading and spelling tests, as well as tests of motor skill. They were also assessed using a standardised group reading test in their class groups. For the secondary school pupils, the results for two year cohorts, in KS3 English and GCSE English language, respectively, were analysed. Results: For the primary school pupils there was evidence of both a season of birth and an age-position effect on all of the cognitive measures, particularly in the early years of schooling. There was, also, evidence of a significant age-position effect at both KS3 and GCSE in favour of the older pupils. For the younger primary school pupils there was evidence of significant age-position effects on both motor measures. Conclusions: The findings from the present study suggest that month of birth may be related to both season of birth and age-position effects. These effects may be compounded, particularly in the early years of primary school, when summer born children are youngest in their year, as in England. In Northern Ireland, age-position effects are also evident in secondary school public examination results, which may have implications for long-term life choices. © 2009 The British Psychological Society.

Gender differences in the role of emotional intelligence during the primary-secondary school transition

The relationship between components of emotional intelligence (EI) (interpersonal
ability, intrapersonal ability, adaptability and stress management) and academic
performance in English, maths and science was examined in a sample of 86 children
(49 males and 37 females) aged 11–12 years during the primary–secondary school
transition period. Results indicated that for both males and females, intrapersonal
ability had little relationship with academic achievement, while adaptability had the
strongest relationship with achievement in all subjects. Gender differences were particularly
pronounced for science, for which stronger relationships were observed with all
EI components for males. In addition, apparent only for males was a negative
relationship between stress management and science. These findings offer support for
the current inclusion of a personal and emotional element in the primary school curriculum,
and indicate that such training is likely to help males more than females to make
a successful transition from primary to secondary school.

Predator diversity enhances secondary production and decreases the likelihood of trophic cascades

We manipulated the diversity of top predators in a three trophic level marine food web. The food web included four top benthic marine fish predators (black goby, rock goby, sea scorpion and shore rockling), an intermediate trophic level of small fish, and a lower trophic level of benthic invertebrates. We kept predator density constant and monitored the response of the lower trophic levels. As top predator diversity increased, secondary production increased. We also observed that in the presence of the manipulated fish predators, the density of small gobiid fish (intermediate consumers) was suppressed, releasing certain groups of benthic invertebrates (caprellid amphipods, copepods, nematodes and spirorbid worms) from heavy intermediate predation pressure. We attribute the mechanism responsible for this trophic cascade to a trait-mediated indirect interaction, with the small gobiid fish changing their use of space in response to altered predator diversity. In the absence of top fish predators, a full-blown trophic cascade occurs. Therefore the diversity of predators reduces the likelihood of trophic cascades occurring and hence provides insurance against the loss of an important ecosystem function (i.e. secondary production).

Interbirth interval is associated with childhood type 1 diabetes risk

Short interbirth interval has been associated with maternal complications and childhood autism and leukemia, possibly due to deficiencies in maternal micronutrients at conception or increased exposure to sibling infections. A possible association between interbirth interval and subsequent risk of childhood type 1 diabetes has not been investigated. A secondary analysis of 14 published observational studies of perinatal risk factors for type 1 diabetes was conducted. Risk estimates of diabetes by category of interbirth interval were calculated for each study. Random effects models were used to calculate pooled odds ratios (ORs) and investigate heterogeneity between studies. Overall, 2,787 children with type 1 diabetes were included. There was a reduction in the risk of childhood type 1 diabetes in children born to mothers after interbirth intervals <3 years compared with longer interbirth intervals (OR 0.82 [95% CI 0.72-0.93]). Adjustments for various potential confounders little altered this estimate. In conclusion, there was evidence of a 20% reduction in the risk of childhood diabetes in children born to mothers after interbirth intervals <3 years.