Incidence of Primary Mitochondrial Disease in Children Younger Than 2 Years Presenting With Acute Liver Failure

Background: Mitochondrial liver disease (MLD), and in particular mitochondrial DNA (mtDNA) depletion syndrome (MDS) is an important cause of acute liver failure (ALF) in infancy. Early and accurate diagnosis is important because liver transplantation (LT) is often contraindicated. It is unclear which methods are the best to diagnose MLD in the setting of ALF. Objective: The aim of the study was to determine the incidence of MLD in children younger than 2 years with ALF and the utility of routine investigations to detect MLD. Methods: Thirty-nine consecutive infants with ALF were admitted to a single unit from 2009 to 2011. All were extensively investigated using an established protocol. Genes implicated in mitochondrial DNA depletion syndrome were sequenced in all cases and tissue mtDNA copy number measured where available. Results: Five infants (17%) had genetically proven MLD: DGUOK (n ¼ 2), POLG (n ¼ 2), and MPV17 (1). Four of these died, whereas 1 recovered. Two had normal muscle mtDNA copy number and 3 had normal muscle respiratory chain enzymes. An additional 8 children had low hepatic mtDNA copy number but pathogenic mutations were not detected. One of these developed fatal multisystemic disease after LT, whereas 5 who survived remain well without evidence of multisystemic disease up to 6 years later. Magnetic resonance spectroscopy did not distinguish between those with and without MLD. Conclusions: Low liver mtDNA copy number may be a secondary phenomenon in ALF. Screening for mtDNA maintenance gene mutations may be the most efficient way to confirm MLD in ALF in the first 2 years of life

Post coital aortic dissection: a case report

<p>Abstract</p> <p>Background</p> <p>Sudden onset peri- or post-coital cardiovascular disease is well documented in the literature including myocardial infarction, pulmonary embolus and subarachnoid haemorrhage. The occurrence of aortic dissection in this setting has been reported only once previously.</p> <p>Case presentation</p> <p>We report the case of a 47 year old man who developed sudden onset right leg pain during coitus. This was initially believed to be neurological due to nerve impingement but an MRI failed to identify a prolapse. On further review after 6 weeks, pulses were noted to be absent in the patient's right leg and an urgent vascular review with investigation identified a dissection of the aorta which was subsequently successfully treated.</p> <p>Conclusion</p> <p>This case illustrates a rare presentation of aortic dissection and demonstrates the importance of a thorough vascular assessment in the presence of sudden onset limb pain.</p

Quality assurance for HIV point-of-care testing and treatment monitoring assays

In 2015, UNAIDS launched the 90-90-90 targets aimed at increasing the number of people infected with HIV to become aware of their status, access antiretroviral therapies and ultimately be virally suppressed. To achieve these goals, countries may need to scale up point-of-care (POC) testing in addition to strengthening central laboratory services. While decentralising testing increases patient access to diagnostics, it presents many challenges with regard to training and assuring the quality of tests and testing. To ensure synergies, the London School of Hygiene & Tropical Medicine held a series of consultations with countries with an interest in quality assurance and their implementing partners, and agreed on an external quality assessment (EQA) programme to ensure reliable results so that the results lead to the best possible care for HIV patients. As a result of the consultations, EQA International was established, bringing together EQA providers and implementers to develop a strategic plan for countries to establish national POC EQA programmes and to estimate the cost of setting up and maintaining the programme. With the dramatic increase in the number of proficiency testing panels required for thousands of POC testing sites across Africa, it is important to facilitate technology transfer from global EQA providers to a network of regional EQA centres in Africa for regional proficiency testing panel production. EQA International will continue to identify robust and cost-effective EQA technologies for quality POC testing, integrating novel technologies to support sustainable country-owned EQA programmes in Africa

Social factors and obesity: an investigation of the role of health behaviours

OBJECTIVES: This study evaluated a behavioural model of the relation between social factors and obesity, in which differences in body mass index (BMI) across sociodemographic groups were hypothesized to be attributable to social group differences in health behaviours affecting energy expenditure (physical activity, diet and alcohol consumption and weight control). METHODS: A total of 8667 adults who participated in the 1995 Australian National Health and Nutrition Surveys provided data on a range of health factors including objectively measured height and weight, health behaviours, and social factors including family status, employment status, housing situation and migration status. RESULTS: Social factors remained significant predictors of BMI after controlling for all health behaviours. Neither social factors alone, nor health behaviours alone, adequately explained the variance in BMI. Gender-specific interactions were found between social factors and individual health behaviours. CONCLUSIONS: These results suggest that social factors moderate the relation between BMI and weight-related behaviours, and that the mechanisms underlying sociodemographic group differences in obesity may vary among men and women. Additional factors are likely to act in conjunction with current health behaviours to explain variation in obesity prevalence across sociodemographic groups.<br /

Root aphid (Aploneura lentisci) population size on perennial ryegrass is determined by drought and endophyte strain

Climate change is anticipated to lead to an increase in the occurrence and intensity of drought and fluctuations in insect cycles that will challenge modern pasture systems. Feeding by root aphids such as Aploneura lentisci Pass. can be a significant challenge to pastures. These below-ground living aphids are commonly found in New Zealand and Australia, feeding year-round on the roots of graminaceous plants such as perennial ryegrass (Lolium perenne L.). Some strains of the fungal endophyte Epichloë festucae var. lolii in perennial ryegrass can provide protection against root aphids and greater resilience under drought, contributing to higher persistency and growth than endophyte-free plants. However, the interaction between insect pressure and drought is not understood. This study examined the effect of drought on root aphid populations and plant performance in perennial ryegrass plants relative to endophyte status (±) and endophyte strain (AR37, NZCT) in a glasshouse experiment. Plants were cloned across the drought and well-watered treatments, and half of the plants were inoculated with root aphids, whilst half of the plants were treated with insecticide. Endophyte infection with strain NZCT and AR37 reduced root aphid numbers. Aphid populations were significantly higher in drought-stressed than in well-watered plants in both endophyte-infected and endophyte-free treatments. Under drought conditions, root aphid populations were increased 4-fold in NZCT and 8-fold in AR37 and endophyte-free plants in comparison with their well-watered counterparts. Root aphids reduced shoot dry weight by 16% in drought-exposed and 26% in well-watered plants in comparison with their insecticide-treated counterparts whilst reducing root biomass by 49%. Our results suggest that root aphids are likely able to exploit the higher availability of amino acids in the plant sap of drought-exposed plants. This study provides evidence that climate change-mediated impacts of root aphids could reduce production in perennial ryegrass-dominant pastures. However, field trials would be necessary to determine whether this effect is seen in situ, where numerous additional factors will be operating at the same time

SCAMP:standardised, concentrated, additional macronutrients, parenteral nutrition in very preterm infants: a phase IV randomised, controlled exploratory study of macronutrient intake, growth and other aspects of neonatal care

<p>Abstract</p> <p>Background</p> <p>Infants born <29 weeks gestation are at high risk of neurocognitive disability. Early postnatal growth failure, particularly head growth, is an important and potentially reversible risk factor for impaired neurodevelopmental outcome. Inadequate nutrition is a major factor in this postnatal growth failure, optimal protein and calorie (macronutrient) intakes are rarely achieved, especially in the first week. Infants <29 weeks are dependent on parenteral nutrition for the bulk of their nutrient needs for the first 2-3 weeks of life to allow gut adaptation to milk digestion. The prescription, formulation and administration of neonatal parenteral nutrition is critical to achieving optimal protein and calorie intake but has received little scientific evaluation. Current neonatal parenteral nutrition regimens often rely on individualised prescription to manage the labile, unpredictable biochemical and metabolic control characteristic of the early neonatal period. Individualised prescription frequently fails to translate into optimal macronutrient delivery. We have previously shown that a standardised, concentrated neonatal parenteral nutrition regimen can optimise macronutrient intake.</p> <p>Methods</p> <p>We propose a single centre, randomised controlled exploratory trial of two standardised, concentrated neonatal parenteral nutrition regimens comparing a standard macronutrient content (maximum protein 2.8 g/kg/day; lipid 2.8 g/kg/day, dextrose 10%) with a higher macronutrient content (maximum protein 3.8 g/kg/day; lipid 3.8 g/kg/day, dextrose 12%) over the first 28 days of life. 150 infants 24-28 completed weeks gestation and birthweight <1200 g will be recruited. The primary outcome will be head growth velocity in the first 28 days of life. Secondary outcomes will include a) auxological data between birth and 36 weeks corrected gestational age b) actual macronutrient intake in first 28 days c) biomarkers of biochemical and metabolic tolerance d) infection biomarkers and other intravascular line complications e) incidence of major complications of prematurity including mortality f) neurodevelopmental outcome at 2 years corrected gestational age</p> <p>Trial registration</p> <p>Current controlled trials: <a href="http://www.controlled-trials.com/ISRCTN76597892">ISRCTN76597892</a>; EudraCT Number: 2008-008899-14</p

Resilience to obesity among socioeconomically disadvantaged women : the READI study

Objective: This cross-sectional study aimed to identify sociodemographic and behavioural characteristics of &lsquo;overweight-resilient&rsquo; women, that is, women who were in a healthy body weight range, despite living in socioeconomically disadvantaged neighbourhoods that place them at increased risk of obesity. The study also aimed to test a comprehensive theoretically derived model of the associations between intrapersonal, social and environmental factors and obesity among this target group.Participants: A total of 3235 women aged 18&ndash;45 years from 80 urban and rural neighbourhoods throughout Victoria, Australia, participated in the Resilience for Eating and Activity Despite Inequality study.Measurements: Women reported height, weight, sociodemographic characteristics, leisure-time physical activity, dietary behaviours and a range of theoretically derived cognitive, social and neighbourhood environmental characteristics hypothesized to influence obesity risk. A theoretical model predicting body mass index (BMI) was tested using structural equation models.Results: Women classified as &lsquo;resilient&rsquo; to obesity tended to be younger, born overseas, more highly educated, unmarried and to have higher or undisclosed household incomes. They engaged in more leisure-time physical activity and consumed less fast foods and soft drinks than overweight/obese women. Neighbourhood characteristics, social characteristics and cognitive characteristics all contributed to explaining variation in BMI in the hypothesized directions.Conclusions: These results demonstrate several characteristics of women appearing &lsquo;resilient&rsquo; to obesity, despite their increased risk conferred by residing in socioeconomically disadvantaged neighbourhoods. Acknowledging the cross-sectional study design, the results advance theoretical frameworks aimed at investigating obesity risk by providing evidence in support of a comprehensive model of direct and indirect effects on obesity of neighbourhood, as well as social, cognitive and behavioural characteristics

IMP1 KH1 and KH2 domains create a structural platform with unique RNA recognition and re-modelling properties

IGF2 mRNA-binding protein 1 (IMP1) is a key regulator of messenger RNA (mRNA) metabolism and transport in organismal development and, in cancer, its mis-regulation is an important component of tumour metastasis. IMP1 function relies on the recognition of a diverse set of mRNA targets that is mediated by the combinatorial action of multiple RNA-binding domains. Here, we dissect the structure and RNA-binding properties of two key RNA-binding domains of IMP1, KH1 and KH2, and we build a kinetic model for the recognition of RNA targets. Our data and model explain how the two domains are organized as an intermolecular pseudo-dimer and that the important role they play in mRNA target recognition is underpinned by the high RNA-binding affinity and fast kinetics of this KH1KH2-RNA recognition unit. Importantly, the high-affinity RNA-binding by KH1KH2 is achieved by an inter-domain coupling 50-fold stronger than that existing in a second pseudo-dimer in the protein, KH3KH4. The presence of this strong coupling supports a role of RNA re-modelling in IMP1 recognition of known cancer targets

Association between fast food purchasing and the local food environment

Objective: In this study, an instrument was created to measure the healthy and unhealthy characteristics of food environments and investigate associations between the whole of the food environment and fast food consumption.Design and subjects: In consultation with other academic researchers in this field, food stores were categorised to either healthy or unhealthy and weighted (between +10 and &minus;10) by their likely contribution to healthy/unhealthy eating practices. A healthy and unhealthy food environment score (FES) was created using these weightings. Using a cross-sectional study design, multilevel multinomial regression was used to estimate the effects of the whole food environment on the fast food purchasing habits of 2547 individuals.Results: Respondents in areas with the highest tertile of the healthy FES had a lower likelihood of purchasing fast food both infrequently and frequently compared with respondents who never purchased, however only infrequent purchasing remained significant when simultaneously modelled with the unhealthy FES (odds ratio (OR) 0.52; 95% confidence interval (CI) 0.32&ndash;0.83). Although a lower likelihood of frequent fast food purchasing was also associated with living in the highest tertile of the unhealthy FES, no association remained once the healthy FES was included in the models. In our binary models, respondents living in areas with a higher unhealthy FES than healthy FES were more likely to purchase fast food infrequently (OR 1.35; 95% CI 1.00&ndash;1.82) however no association was found for frequent purchasing.Conclusion: Our study provides some evidence to suggest that healthier food environments may discourage fast food purchasing.<br /