Genetic variation associated with hypersensitivity to mercury

OBJECTIVES: Very little is known about mechanisms of idiosyncratic sensitivity to the damaging effects of mercury (Hg); however, there is likely a genetic component. The aim of the present study was to search for genetic variation in genes thought to be involved in Hg metabolism and transport in a group of individuals identified as having elevated Hg sensitivity compared to a normal control group. MATERIALS AND METHODS: Survivors of pink disease (PD; infantile acrodynia) are a population of clinically identifiable individuals who are Hg sensitive. In the present study, single nucleotide polymorphisms in genes thought to be involved in Hg transport and metabolism were compared across two groups: (i) PD survivors (n = 25); and (ii) age- and sex-matched healthy controls (n = 25). RESULTS: Analyses revealed significant differences between groups in genotype frequencies for rs662 in the gene encoding paraoxanase 1 (PON1) and rs1801131 in the gene encoding methylenetetrahydrofolate reductase (MTHFR). CONCLUSIONS: We have identified two genetic polymorphisms associated with increased sensitivity to Hg. Genetic variation in MTHFR and PON1 significantly differentiated a group formerly diagnosed with PD (a condition of Hg hypersensitivity) with age- and gender-matched healthy controls

Galleria mellonella larvae exhibit a weight-dependent lethal median dose when infected with methicillin-resistant Staphylococcus aureus

ABSTRACT Galleria mellonella is a recognised model to study antimicrobial efficacy; however, standardisation across the scientific field and investigations of methodological components are needed. Here, we investigate the impact of weight on mortality following infection with Methicillin-resistant Staphylococcus aureus (MRSA). Larvae were separated into six weight groups (180–300 mg at 20 mg intervals) and infected with a range of doses of MRSA to determine the 50% lethal dose (LD50), and the ‘lipid weight’ of larvae post-infection was quantified. A model of LD50 values correlated with weight was developed. The LD50 values, as estimated by our model, were further tested in vivo to prove our model. We establish a weight-dependent LD50 in larvae against MRSA and demonstrate that G. mellonella is a stable model within 180–260 mg. We present multiple linear models correlating weight with: LD50, lipid weight, and larval length. We demonstrate that the lipid weight is reduced as a result of MRSA infection, identifying a potentially new measure in which to understand the immune response. Finally, we demonstrate that larval length can be a reasonable proxy for weight. Refining the methodologies in which to handle and design experiments involving G. mellonella, we can improve the reliability of this powerful model.</jats:p

UK Breastfeeding Helpline support: An investigation of influences upon satisfaction

Background Incentive or reward schemes are becoming increasingly popular to motivate healthy lifestyle behaviours. In this paper, insights from a qualitative and descriptive study to investigate the uptake, impact and meanings of a breastfeeding incentive intervention integrated into an existing peer support programme (Star Buddies) are reported. The Star Buddies service employs breastfeeding peer supporters to support women across the ante-natal, intra-partum and post-partum period. Methods In a disadvantaged area of North West England, women initiating breastfeeding were recruited by peer supporters on the postnatal ward or soon after hospital discharge to participate in an 8 week incentive (gifts and vouchers) and breastfeeding peer supporter intervention. In-depth interviews were conducted with 26 women participants who engaged with the incentive intervention, and a focus group was held with the 4 community peer supporters who delivered the intervention. Descriptive analysis of routinely collected data for peer supporter contacts and breastfeeding outcomes before and after the incentive intervention triangulated and retrospectively provided the context for the qualitative thematic analysis. Results A global theme emerged of 'incentives as connectors', with two sub-themes of 'facilitating connections' and 'facilitating relationships and wellbeing'. The incentives were linked to discussion themes and gift giving facilitated peer supporter access for proactive weekly home visits to support women. Regular face to face contacts enabled meaningful relationships and new connections within and between the women, families, peer supporters and care providers to be formed and sustained. Participants in the incentive scheme received more home visits and total contact time with peer supporters compared to women before the incentive intervention. Full participation levels and breastfeeding rates at 6-8 weeks were similar for women before and after the incentive intervention. Conclusion The findings suggest that whilst the provision of incentives might not influence women's intentions or motivations to breastfeed, the connections forged provided psycho-social benefits for both programme users and peer supporters

Are urinary porphyrins a valid diagnostic biomarker of autism spectrum disorder?

A fundamental challenge to the timely diagnosis of Autism Spectrum Disorder (ASD) is the reliance on the observation of a set of aberrant behavior. Consequently, the diagnostic process requires that the child reach an age where the behaviors would typically be exhibited. The identification of a reliable biological marker (biomarker) could be of considerable benefit to the diagnostic process. As a diagnostic biomarker, porphyrins present an attractive prospect as previous studies have reported consistent findings of children with ASD showing significant elevations in porphyrin levels in contrast to controls. Furthermore, there is some evidence that ASD severity may be associated with porphyrins, which would be a valuable characteristic of any ASD biomarker. Importantly, for practical use, porphyrins can be tested non-invasively via a sample of urine. The present study sought to investigate whether porphyrin profiles can reliably be used to (a) differentiate ASD cases from healthy controls; and (b) predict ASD severity. The study compared the porphyrin levels of three groups of children aged 2-6 years: Group 1-children diagnosed with ASD (n&thinsp;=&thinsp;70); Group 2-healthy, normally developing siblings of children diagnosed with ASD (n&thinsp;=&thinsp;36); and Group 3-healthy, normally developing children with no known blood relative diagnosed with ASD (n&thinsp;=&thinsp;54). The results of logistic regression analyses failed to find support for the hypotheses that porphyrin levels could be used as a valid tool to detect ASD cases or predict severity. Autism Res 2014, 7: 535-542. &copy; 2014 International Society for Autism Research, Wiley Periodicals, Inc

Effect of maternal glucocorticoid treatment on ovine fetal fluids at 0.6 gestation

This study examined the effects of maternal dexamethasone treatment on the volume and composition of fetal fluids, and on placental morphology at 0.6 gestation (80-90 days). Nine pregnant ewes were infused with dexamethasone (D, 0.76 mg h(-1) for 72 h) while an additional nine ewes received saline (S, 0.38 mL h(-1) for 72 h). Allantoic fluid (ALF) volume was significantly greater (P < 0.02) in the D group (737+/-116 mL) than in the S group (190+/-55 mL), but there was no difference in amniotic fluid (AMF) volume. The urine flow rate was 11 times higher in three D fetuses. The Cr-51-EDTA infused into the bladders of four fetuses during the final 4-5 h of the 72 infusions was detected in both AMF and ALE Dexamethasone treatment significantly altered the composition of the fetal fluids but had no affect on fetal body weight, organ weights and placental weight; however, there were fewer cotyledons under 5 g (P < 0.05). In the D group, 3% of cotyledons were of the 'bovine' type in morphology, whereas all cotyledons in the S group were of the 'ovine' type. These findings suggest that prolonged exposure to large doses of glucocorticoids during pregnancy would affect the volume and composition of the fetal fluids and placental morphology, with potentially detrimental effects on the fetus

Effect of maternal glucocorticoid treatment on ovine fetal fluids at 0.6 gestation

This study examined the effects of maternal dexamethasone treatment on the volume and composition of fetal fluids, and on placental morphology at 0.6 gestation (80-90 days). Nine pregnant ewes were infused with dexamethasone (D, 0.76 mg h(-1) for 72 h) while an additional nine ewes received saline (S, 0.38 mL h(-1) for 72 h). Allantoic fluid (ALF) volume was significantly greater (P < 0.02) in the D group (737+/-116 mL) than in the S group (190+/-55 mL), but there was no difference in amniotic fluid (AMF) volume. The urine flow rate was 11 times higher in three D fetuses. The Cr-51-EDTA infused into the bladders of four fetuses during the final 4-5 h of the 72 infusions was detected in both AMF and ALE Dexamethasone treatment significantly altered the composition of the fetal fluids but had no affect on fetal body weight, organ weights and placental weight; however, there were fewer cotyledons under 5 g (P < 0.05). In the D group, 3% of cotyledons were of the 'bovine' type in morphology, whereas all cotyledons in the S group were of the 'ovine' type. These findings suggest that prolonged exposure to large doses of glucocorticoids during pregnancy would affect the volume and composition of the fetal fluids and placental morphology, with potentially detrimental effects on the fetus

Ovine AQP1: cDNA cloning, ontogeny, and control of renal gene expression

10.1007/s004670050502Pediatric Nephrology127545-553PEDN

A Fully Automated Enzyme Immunoassay for the Measurement of Cortisol in Biological Fluids

Peer Reviewe