Effects of the mycotoxin patulin at the level of nuclear receptor transcriptional activity and steroidogenesis in vitro

Patulin (PAT) is a mycotoxin produced by various species of fungi, with Penicillium expansum being the most commonly occurring. Apples and apple products are the main sources of PAT contamination. This mycotoxin has been shown to induce toxic effects in animals, a few of which include reproductive toxicity and interference with the endocrine system. Here the endocrine disrupting potential of PAT has been investigated in vitro to identify disruption at the level of oestrogen, androgen, progestagen and glucocorticoid nuclear receptor transcriptional activity, and to assess interferences in estradiol, testosterone and progesterone steroid hormone production. At the receptor level, 0.5-5000ng/ml (0.0032-32μM) PAT did not appear to induce any specific (ant) agonistic responses in reporter gene assays (RGAs); however, nuclear transcriptional activity was affected. A >6 fold increase in the glucocorticoid receptor transcriptional activity was observed following treatment with 5000ng/ml PAT in the presence of cortisol. At the hormone production level, despite cytotoxicity being observed after treatment with 5000ng/ml PAT, estradiol levels had increased >2 fold. At 500ng/ml PAT treatment, an increase in progesterone and a decrease in testosterone production were observed. The findings of this study could be considered in assessing the health risks following exposure to PAT.

In Vitro and In Vivo Anti-Schistosomal Activity of the Alkylphospholipid Analog Edelfosine

Background: Schistosomiasis is a parasitic disease caused by trematodes of the genus Schistosoma. Five species of Schistosoma are known to infect humans, out of which S. haematobium is the most prevalent, causing the chronic parasitic disease schistosomiasis that still represents a major problem of public health in many regions of the world and especially in tropical areas, leading to serious manifestations and mortality in developing countries. Since the 1970s, praziquantel (PZQ) is the drug of choice for the treatment of schistosomiasis, but concerns about relying on a single drug to treat millions of people, and the potential appearance of drug resistance, make identification of alternative schistosomiasis chemotherapies a high priority. Alkylphospholipid analogs (APLs), together with their prototypic molecule edelfosine (EDLF), are a family of synthetic antineoplastic compounds that show additional pharmacological actions, including antiparasitic activities against several protozoan parasites.

Methodology/Principal Findings: We found APLs ranked edelfosine> perifosine> erucylphosphocholine> miltefosine for their in vitro schistosomicidal activity against adult S. mansoni worms. Edelfosine accumulated mainly in the worm tegument, and led to tegumental alterations, membrane permeabilization, motility impairment, blockade of male-female pairing as well as induction of apoptosis-like processes in cells in the close vicinity to the tegument. Edelfosine oral treatment also showed in vivo schistosomicidal activity and decreased significantly the egg burden in the liver, a key event in schistosomiasis.

Conclusions/Significance: Our data show that edelfosine is the most potent APL in killing S. mansoni adult worms in vitro. Edelfosine schistosomicidal activity seems to depend on its action on the tegumental structure, leading to tegumental damage, membrane permeabilization and apoptosis-like cell death. Oral administration of edelfosine diminished worm and egg burdens in S. mansoni-infected CD1 mice. Here we report that edelfosine showed promising antischistosomal properties in vitro and in vivo.

Key performance indicators – A new approach for specifying concrete and assessing state of health of concrete structure

The focus of this paper is to outline a method for consolidating and implementing the work on performance-based specification and testing. First part of the paper will review the mathematical significance of the variables used in common service life models. The aim is to identify a set of significant variables that influence the ingress of chloride ions into concrete. These variables are termed as Key Performance Indicators (KPI’s). This will also help to reduce the complexity of some of the service life models and make them more appealing for practicing engineers. The second part of the paper presents a plan for developing a database based on these KPI’s so that relationships can then be drawn between common concrete mix parameters and KPI’s. This will assist designers in specifying a concrete with adequate performance for a particular environment. This, collectively, is referred to as the KPI based approach and the concluding remarks will outline how the authors envisage the KPI theory to relate to performance assessment and monitoring.

Use of the child health utility and strengths and difficulties outcome measures in economic evaluations of school-based interventions: data from a cluster-randomised controlled trial in Northern Ireland

Background There is growing evidence linking early social and emotional wellbeing to later academic performance and various health outcomes including mental health. An economic evaluation was designed alongside the Roots of Empathy cluster-randomised trial evaluation, which is a school-based intervention for improving pupils’ social and emotional wellbeing. Exploration of the relevance of the Strengths and Diffi culties Questionnaire (SDQ) and Child Health Utility 9D (CHU9D) in school-based health economic evaluations is warranted. The SDQ is a behavioural screening questionnaire for 4–17-year-old children, consisting of a total diffi culties score, and also prosocial behaviour,
which aims to identify positive aspects of behaviour. The CHU9D is a generic preference-based health-related quality of life instrument for 7–17-year-old children.

Validity of the Global Physical Activity Questionnaire (GPAQ) in assessing levels and change in moderate-vigorous physical activity and sedentary behaviour

Background

Feasible, cost-effective instruments are required for the surveillance of moderate-to-vigorous physical activity (MVPA) and sedentary behaviour (SB) and to assess the effects of interventions. However, the evidence base for the validity and reliability of the World Health Organisation-endorsed Global Physical Activity Questionnaire (GPAQ) is limited. We aimed to assess the validity of the GPAQ, compared to accelerometer data in measuring and assessing change in MVPA and SB.

Participants (n = 101) were selected randomly from an on-going research study, stratified by level of physical activity (low, moderate or highly active, based on the GPAQ) and sex. Participants wore an accelerometer (Actigraph GT3X) for seven days and completed a GPAQ on Day 7. This protocol was repeated for a random sub-sample at a second time point, 3–6 months later. Analysis involved Wilcoxon-signed rank tests for differences in measures, Bland-Altman analysis for the agreement between measures for median MVPA and SB mins/day, and Spearman’s rho coefficient for criterion validity and extent of change.

95 participants completed baseline measurements (44 females, 51 males; mean age 44 years, (SD 14); measurements of change were calculated for 41 (21 females, 20 males; mean age 46 years, (SD 14). There was moderate agreement between GPAQ and accelerometer for MVPA mins/day (r = 0.48) and poor agreement for SB (r = 0.19). The absolute mean difference (self-report minus accelerometer) for MVPA was −0.8 mins/day and 348.7 mins/day for SB; and negative bias was found to exist, with those people who were more physically active over-reporting their level of MVPA: those who were more sedentary were less likely to under-report their level of SB. Results for agreement in change over time showed moderate correlation (r = 0.52, p = 0.12) for MVPA and poor correlation for SB (r = −0.024, p = 0.916).

Levels of agreement with objective measurements indicate the GPAQ is a valid measure of MVPA and change in MVPA but is a less valid measure of current levels and change in SB. Thus, GPAQ appears to be an appropriate measure for assessing the effectiveness of interventions to promote MVPA.

Increase in the pharmacological management of Type 2 diabetes with pay-for-performance in primary care in the UK

Aims To determine whether the financial incentives for tight glycaemic control, introduced in the UK as part of a pay-for-performance scheme in 2004, increased the rate at which people with newly diagnosed Type 2 diabetes were started on anti-diabetic medication.

Methods A secondary analysis of data from the General Practice Research Database for the years 1999-2008 was performed using an interrupted time series analysis of the treatment patterns for people newly diagnosed with Type 2 diabetes (n=21 197).

Results Overall, the proportion of people with newly diagnosed diabetes managed without medication 12months after diagnosis was 47% and after 24months it was 40%. The annual rate of initiation of pharmacological treatment within 12months of diagnosis was decreasing before the introduction of the pay-for-performance scheme by 1.2% per year (95% CI -2.0, -0.5%) and increased after the introduction of the scheme by 1.9% per year (95% CI 1.1, 2.7%). The equivalent figures for treatment within 24months of diagnosis were -1.4% (95% CI -2.1, -0.8%) before the scheme was introduced and 1.6% (95% CI 0.8, 2.3%) after the scheme was introduced.

Conclusion The present study suggests that the introduction of financial incentives in 2004 has effected a change in the management of people newly diagnosed with diabetes. We conclude that a greater proportion of people with newly diagnosed diabetes are being initiated on medication within 1 and 2years of diagnosis as a result of the introduction of financial incentives for tight glycaemic control.

Sonification as Concurrent Augmented Feedback for Motor Skill Learning and the Importance of Mapping Design

In recent years, sonification of movement has emerged as a viable method for the provision of feedback in motor learning. Despite some experimental validation of its utility, controlled trials to test the usefulness of sonification in a motor learning context are still rare. As such, there are no accepted conventions for dealing with its implementation. This article addresses the question of how continuous movement information should be best presented as sound to be fed back to the learner. It is proposed that to establish effective approaches to using sonification in this context, consideration must be given to the processes that underlie motor learning, in particular the nature of the perceptual information available to the learner for performing the task at hand. Although sonification has much potential in movement performance enhancement, this potential is largely unrealised as of yet, in part due to the lack of a clear framework for sonification mapping: the relationship between movement and sound. By grounding mapping decisions in a firmer understanding of how perceptual information guides learning, and an embodied cognition stance in general, it is hoped that greater advances in use of sonification to enhance motor learning can be achieved.

Evaluation of the Retinal Vasculature in Hypertension and Chronic Kidney Disease in an elderly population of Irish nuns

Background: Chronic kidney disease (CKD) and hypertension are global public health problems associated with considerable morbidity, premature mortality and attendant healthcare costs. Previous studies have highlighted that non-invasive examination of the retinal microcirculation can detect microvascular pathology that is associated with systemic disorders of the circulatory system such as hypertension. We examined the associations between retinal vessel caliber (RVC) and fractal dimension (DF), with both hypertension and CKD in elderly Irish nuns.

Methods: Data from 1233 participants in the cross-sectional observational Irish Nun Eye Study (INES) were assessed from digital photographs with a standardized protocol using computer-assisted software. Multivariate regression analyses were used to assess associations with hypertension and CKD, with adjustment for age, body mass index (BMI), refraction, fellow eye RVC, smoking, alcohol consumption, ischemic heart disease (IHD), cerebrovascular accident (CVA), diabetes and medication use.

Results: In total, 1122 (91%) participants (mean age: 76.3 [range: 56-100] years) had gradable retinal images of sufficient quality for blood vessel assessment. Hypertension was significantly associated with a narrower central retinal arteriolar equivalent (CRAE) in a fully adjusted analysis (P = 0.002; effect size= -2.16 μm; 95% confidence intervals [CI]: -3.51, -0.81 μm). No significant associations between other retinal vascular parameters and hypertension or between any retinal vascular parameters and CKD were found.

Conclusions: Individuals with hypertension have significantly narrower retinal arterioles which may afford an earlier opportunity for tailored prevention and treatment options to optimize the structure and function of the microvasculature, providing additional clinical utility. No significant associations between retinal vascular parameters and CKD were detected.