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

A potent nonporphyrin class of photodynamic therapeutic agent: cellular localisation, cytotoxic potential and influence of hypoxia

We have developed a totally new class of nonporphyrin photodynamic therapeutic agents with a specific focus on two lead candidates azadipyrromethene (ADPM)01 and ADPM06. Confocal laser scanning microscopy imaging showed that these compounds are exclusively localised to the cytosolic compartment, with specific accumulation in the endoplasmic reticulum and to a lesser extent in the mitochondria. Light-induced toxicity assays, carried out over a broad range of human tumour cell lines, displayed EC50 values in the micro-molar range for ADPM01 and nano-molar range for ADPM06, with no discernable activity bias for a specific cell type. Strikingly, the more active agent, ADPM06, even retained significant activity under hypoxic conditions. Both photosensitisers showed low to nondeterminable dark toxicity. Flow cytometric analysis revealed that ADPM01 and ADPM06 were highly effective at inducing apoptosis as a mode of cell death. The photophysical and biological characteristics of these PDT agents suggest that they have potential for the development of new anticancer therapeutics

The origin of dust in galaxies revisited: the mechanism determining dust content

The origin of cosmic dust is a fundamental issue in planetary science. This paper revisits the origin of dust in galaxies, in particular, in the Milky Way, by using a chemical evolution model of a galaxy composed of stars, interstellar medium, metals (elements heavier than helium), and dust. We start from a review of time-evolutionary equations of the four components, and then, we present simple recipes for the stellar remnant mass and yields of metal and dust based on models of stellar nucleosynthesis and dust formation. After calibrating some model parameters with the data from the solar neighborhood, we have confirmed a shortage of the stellar dust production rate relative to the dust destruction rate by supernovae if the destruction efficiency suggested by theoretical works is correct. If the dust mass growth by material accretion in molecular clouds is active, the observed dust amount in the solar neighborhood is reproduced. We present a clear analytic explanation of the mechanism for determining dust content in galaxies after the activation of accretion growth: a balance between accretion growth and supernova destruction. Thus, the dust content is independent of the uncertainty of the stellar dust yield after the growth activation. The timing of the activation is determined by a critical metal mass fraction which depends on the growth and destruction efficiencies. The solar system formation seems to have occurred well after the activation and plenty of dust would have existed in the proto-solar nebula.Comment: 12 pages, 11 figure

Oral health promotion: the economic benefits to the NHS of increased use of sugarfree gum in the UK.

INTRODUCTION: The effect of sugarfree gum (SFG) on the prevention of dental caries has been established for some time. With increased constraints placed on healthcare budgets, the importance of economic considerations in decision-making about oral health interventions has increased. The aim of this study was to demonstrate the potential cost savings in dental care associated with increased levels of SFG usage. METHODS: The analysis examined the amount of money which would hypothetically be saved if the UK 12-year-old population chewed more SFG. The number of sticks chewed per year and the caries risk reduction were modelled to create a dose response curve. The costs of tooth restoration, tooth extraction in primary care settings and under general anaesthetic were considered, and the effects of caries reduction on these costs calculated. RESULTS: If all members of the UK 12-year-old population chewed SFG frequently (twice a day), the potential cost savings for the cohort over the course of one year were estimated to range from £1.2 to £3.3 million and if they chewed three times a day, £8.2 million could be saved each year. Sensitivity analyses of the key parameters demonstrated that cost savings would still be likely to be observed even in scenarios with less significant increases in SFG use. CONCLUSION: This study shows that if levels of SFG usage in the teenage population in the UK could be increased, substantial cost savings might be achieved

Phenotypic Variation and Bistable Switching in Bacteria

Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

Stability in Ecosystem Functioning across a Climatic Threshold and Contrasting Forest Regimes

Classical ecological theory predicts that changes in the availability of essential resources such as nitrogen should lead to changes in plant community composition due to differences in species-specific nutrient requirements. What remains unknown, however, is the extent to which climate change will alter the relationship between plant communities and the nitrogen cycle. During intervals of climate change, do changes in nitrogen cycling lead to vegetation change or do changes in community composition alter the nitrogen dynamics? We used long-term ecological data to determine the role of nitrogen availability in changes of forest species composition under a rapidly changing climate during the early Holocene (16k to 8k cal. yrs. BP). A statistical computational analysis of ecological data spanning 8,000 years showed that secondary succession from a coniferous to deciduous forest occurred independently of changes in the nitrogen cycle. As oak replaced pine under a warming climate, nitrogen cycling rates increased. Interestingly, the mechanism by which the species interacted with nitrogen remained stable across this threshold change in climate and in the dominant tree species. This suggests that changes in tree population density over successional time scales are not driven by nitrogen availability. Thus, current models of forest succession that incorporate the effects of available nitrogen may be over-estimating tree population responses to changes in this resource, which may result in biased predictions of future forest dynamics under climate warming

Participants’ perspectives on mindfulnessbased cognitive therapy for inflammatory bowel disease: a qualitative study nested within a pilot randomised controlled trial

Background: Mindfulness-based interventions have shown to improve depression and anxiety symptoms as well as quality of life in patients with inflammatory bowel disease (IBD). However, little is known about the experiences of this group of patients participating in mindfulness interventions. This paper sets out to explore the perspectives of patients with IBD recruited to a pilot randomised controlled trial (RCT) of mindfulness-based cognitive therapy (MBCT) about the intervention. Methods: In a qualitative study nested within a parallel two-arm pilot RCT of mindfulness-based cognitive therapy for patients with IBD, two focus group interviews (using the same schedule) and a free text postal survey were conducted. Data from both were analysed using thematic analysis. Data and investigator triangulation was performed to enhance confidence in the ensuing findings. Forty-four patients with IBD were recruited to the pilot RCT from gastroenterology outpatient clinics from two Scottish NHS boards. Eighteen of these patients (ten from mindfulness intervention and eight from control group) also completed a postal survey and participated in two focus groups after completing post intervention assessments. Results: The major themes that emerged from the data were the following: perceived benefits of MBCT for IBD, barriers to attending MBCT and expectations about MBCT. Participants identified MBCT as a therapeutic, educational and an inclusive process as key benefits of the intervention. Key barriers included time and travel constraints. Conclusions: This qualitative study has demonstrated the acceptability of MBCT in a group of patients with IBD. Participants saw MBCT as a therapeutic and educational initiative that transformed their relationship with the illness. The inclusive process and shared experience of MBCT alleviated the sense of social isolation commonly associated with IBD. However, time commitment and travel were recognised as a barrier to MBCT which could potentially influence the degree of therapeutic gain from MBCT for some participants. Keywords: Inflammatory bowel disease, Mindfulness, MBCT, Focus groups, Qualitative stud

Extracellular nucleotides inhibit growth of human oesophageal cancer cells via P2Y2-receptors

Extracellular ATP is known to inhibit growth of various tumours by activating specific purinergic receptors (P2-receptors). Since the therapy of advanced oesophageal cancer is unsatisfying, new therapeutic approaches are mandatory. Here, we investigated the functional expression and potential antiproliferative effects of P2-purinergic receptors in human oesophageal cancer cells. Prolonged incubation of primary cell cultures of human oesophageal cancers as well as of the squamous oesophageal cancer cell line Kyse-140 with ATP or its stable analogue ATPγS dose-dependently inhibited cell proliferation. This was due to both an induction of apoptosis and cell cycle arrest. The expression of P2-receptors was examined by RT-PCR, immunocytochemistry, and [Ca2+]i-imaging. Application of various extracellular nucleotides dose-dependently increased [Ca2+]i. The rank order of potency was ATP=UTP>ATPγS>ADP=UDP. 2-methylthio-ATP and α,β-methylene-ATP had no effects on [Ca2+]i. Complete cross-desensitization between ATP and UTP was observed. Moreover, the phospholipase C inhibitor U73122 dose-dependently reduced the ATP triggered [Ca2+]i signal. The pharmacological features strongly suggest the functional expression of G-protein coupled P2Y2-receptors in oesophageal squamous cancer cells. P2Y2-receptors are involved in the antiproliferative actions of extracellular nucleotides. Thus, P2Y2-receptors are promising target proteins for innovative approaches in oesophageal cancer therapy