Cytomegalovirus: Educational outcomes and implications for newborn screening

The focus of this study was to review existing literature and analyze a survey of professional opinion regarding how children with hearing loss caused by congenital cytomegalovirus (CMV) function audiologically and educationally. This study proposes a benefit for adding CMV screening to the battery of tests included in the newborn screening protocol to improve educational outcomes of children deafened from CMV.

Inclusion, social networks and resilience: strategies, practices and outcomes for disabled children and their families

This paper explores the strategies of service providers and the benefits reported by disabled children and their parents/carers in three Children's Fund programmes in England. Based on National Evaluation of the Children's Fund research, we discuss how different understandings of ‘inclusion’ informed the diverse strategies and approaches service providers adopted. While disabled children and families perceived the benefits of services predominantly in terms of building individual children's resilience and social networks, the paper highlights the need for holistic approaches which have a broad view of inclusion, support children's networks and tackle disabling barriers within all the spheres of children's lives.

Effect of acute administration of recombinant human leptin during the neonatal period on body temperature and endocrine profile of the piglet

Background: Leptin is produced predominantly by white adipocytes; in adults it regulates appetite and energy expenditure but its role in the neonate remains to be fully established. Objectives: To examine the effects of acute administration of recombinant human leptin on the endocrine profile and thermoregulation of neonatal pigs. Methods: 24 pairs of siblings (n = 48) were administered with either a single dose (4 mu g ml(-1) kg(-1) body weight) of leptin (L: n = 24) or a placebo (P: n = 24) on day 6 of neonatal life. Rectal temperature was recorded, and tissue samples were taken at 1 (n = 12), 2 (n = 12), 4 (n = 12) or 6 (n = 12) hours post-administration. Plasma concentrations of hormones and metabolites were determined in conjunction with messenger RNA (mRNA) for leptin and uncoupling protein-2. Results: Plasma leptin increased following leptin administration, and differences in concentrations of insulin, thyroxine and non-esterified fatty acids were observed between the two groups. Initially, rectal temperature decreased in L pigs but returned to start values by 1.5 h. This decline in rectal temperature was delayed in placebo animals, resulting in differences between treatments at 1.5 and 2 h. Conclusions: Acute leptin administration alters the endocrine profile of pigs and influences the thermoregulatory ability of the neonate. Copyright (C) 2007 S. Karger AG, Basel.

Differential effects of thyroid hormone manipulation and ß adrenoceptor agonist administration on uncoupling protein mRNA abundance in adipose tissue and thermoregulation in neonatal pigs

We have shown that there is significant disparity in the expression of uncoupling proteins (UCP) 2 and 3 between modern-commercial and ancient-Meishan porcine genotypes, commercial pigs also have higher plasma triiodothyronine (T(3)) in on the first day of life. T(3) and the sympathetic nervous system are both known to regulate UCPs in rodents and humans; their role in regulating these proteins in the pig is unknown. This study examined whether thyroid hormone manipulation or administration of a selective beta3 adrenoceptor agonist (ZD) influenced plasma hormones, colonic temperature and UCP expression in adipose tissue of two breeds of pig. To mimic the differences observed in thyroid hormone status, piglets from Meishan and commercial litters were randomly assigned to control (1 ml/kg water), T(3) (10 mg/kg) (Meishan only), methimazole (a commonly used antithyroid drug) (50 mg/kg) (commercial only) or ZD (10 mg/kg) oral administration for the first 4 days of postnatal life. Adipose tissue UCP2/3 mRNA abundance was measured on day 4 using PCR. T(3) administration raised plasma T(3) concentrations and increased colonic temperature on day 4. UCP3 mRNA abundance was higher in Meishan, than commercial piglets (p = 0.042) and was downregulated following T(3) administration (p = 0.014). Irrespective of genotype, ZD increased UCP2 mRNA abundance (Meishan p = 0.05, commercial p = 0.03). Expression of neither UCP2 nor 3 was related to colonic temperature, regardless of treatment. In conclusion, we have demonstrated a dissociation between thyroid hormones and the sympathetic nervous system in the regulation of UCPs in porcine adipose tissue. We have also suggested that expression of adipose tissue UCP2 and 3 are not related to body temperature in piglets.

Developmental programming: Deficits in reproductive hormone dynamics and ovulatory outcomes in prenatal, testosterone-treated sheep

Prenatal testosterone excess leads to neuroendocrine, ovarian, and metabolic disruptions, culminating in reproductive phenotypes mimicking that of women with polycystic ovary syndrome (PCOS). The objective of this study was to determine the consequences of prenatal testosterone treatment on periovulatory hormonal dynamics and ovulatory outcomes. To generate prenatal testosterone-treated females, pregnant sheep were injected intramuscularly (days 30-90 of gestation, term = 147 days) with 100 mg of testosterone-propionate in cottonseed oil semi-weekly. Female offspring born to untreated control females and prenatal testosterone-treated females were then studied during their first two breeding seasons. Sheep were given two injections of prostaglandin F-2alpha 11 days apart, and blood samples were collected at 2-h intervals for 120 h, 10-min intervals for 8 h during the luteal phase (first breeding season only), and daily for an additional 15 days to characterize changes in reproductive hormonal dynamics. During the first breeding season, prenatal testosterone-treated females manifested disruptions in the timing and magnitude of primary gonadotropin surges, luteal defects, and reduced responsiveness to progesterone negative feedback. Disruptions in the periovulatory sequence of events during the second breeding season included: 1) delayed but increased preovulatory estradiol rise, 2) delayed and severely reduced primary gonadotropin surge in prenatal testosterone-treated females having an LH surge, 3) tendency for an amplified secondary FSH surge and a shift in the relative balance of FSH regulatory proteins, and 4) luteal responses that ranged from normal to anovulatory. These outcomes are likely to be of relevance to developmental origin of infertility disorders and suggest that differences in fetal exposure or fetal susceptibility to testosterone may account for the variability in reproductive phenotypes.

Bayesian design and conduct of phase II single-arm clinical trials with binary outcomes: a tutorial

The aim of phase II single-arm clinical trials of a new drug is to determine whether it has sufficient promising activity to warrant its further development. For the last several years Bayesian statistical methods have been proposed and used. Bayesian approaches are ideal for earlier phase trials as they take into account information that accrues during a trial. Predictive probabilities are then updated and so become more accurate as the trial progresses. Suitable priors can act as pseudo samples, which make small sample clinical trials more informative. Thus patients have better chances to receive better treatments. The goal of this paper is to provide a tutorial for statisticians who use Bayesian methods for the first time or investigators who have some statistical background. In addition, real data from three clinical trials are presented as examples to illustrate how to conduct a Bayesian approach for phase II single-arm clinical trials with binary outcomes.

Developmental expression of myostatin in cardiomyocytes and its effect on foetal and neonatal rat cardiomyocyte proliferation

Objectives: Myostatin, a member of the transforming growth factor-beta (TGF-beta) family, plays a key role in skeletal muscle myogenesis by limiting hyperplastic and hypertrophic muscle growth. In cardiac muscle, myostatin has been shown to limit agonist-induced cardiac hypertrophic growth. However, its role in cardiac hyperplastic growth remains undetermined. The aim of this study was to characterise the expression of myostatin in developing myocardium, determine its effect on cardiomyocyte proliferation, and explore the signalling mechanisms affected by myostatin in dividing cardiomyocytes. Methods: We used quantitative PCR and Western blotting to study the expression of myostatin in cardiomyocytes isolated from rat myocardium at different developmental ages. We. determined the effect of recombinant myostatin on proliferation and cell viability in dividing cardiomyocytes in culture. We analysed myostatin's effect on cardiomyocyte cell cycle progression by flow cytometry and used Western blotting to explore the signalling mechanisms involved. Results: Myostatin is expressed differentially in cardiomyocytes during cardiac development such that increasing expression correlated with a low cardiomyocyte proliferation index. Proliferating foetal cardiomyocytes, from embryos at 18 days of gestation, expressed low levels of myostatin mRNA and protein, whereas isolated cardiomyocytes from postnatal day 10 hearts, wherein the majority of cardiomyocytes have lost their ability to proliferate, displayed a 6-fold increase in myostatin expression. Our in vitro studies demonstrated that myostatin inhibited proliferation of dividing foetal and neonatal cardiomyocytes. Flow cytometric analysis showed that this inhibition occurs mainly via a block in the G1-S phase transition of the cardiomyocyte cell cycle. Western blot analysis showed that part of the mechanism underpinning the inhibition of cardiomyocyte proliferation by myostatin involves phosphorylation of SMAD2 and altered expressions of the cell cycle proteins p21 and CDK2. Conclusions: We conclude that myostatin is an inhibitor of cardiomyocyte proliferation with the potential to limit cardiomyocyte hyperplastic growth by altering cardiac cell cycle progression. (c) 2007 European Society of Cardiology. Published by Elsevier B.V. All fights reserved.

Educational and psychosocial programmes for adolescents with diabetes: approaches, outcomes and cost-effectiveness

Diabetes incurs heavy personal and health system costs. Self-management is required if complications are to be avoided. Adolescents face particular challenges as they learn to take responsibility for their diabetes. A systematic review of educational and psychosocial programmes for adolescents with diabetes was undertaken. This aimed to: identify and categorise the types of programmes that have been evaluated; assess the cost-effectiveness of interventions; identify areas where further research is required. Sixty-two papers were identified and Subjected to a narrative review. Generic programmes focus on knowledge/skills, psychosocial issues, and behaviour/self-management. They result in modest improvements across a range of outcomes but improvements are often not sustained, suggesting a need for continuous support, possibly integrated into normal care. In-hospital education at diagnosis confers few advantages over home treatment. The greatest returns may be obtained by targeting poorly controlled individuals. Few studies addressed resourcing issues and robust cost-effectiveness appraisals are required to identify interventions that generate the greatest returns on expenditure. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

Introducing assistive technology into the existing homes of older people: Feasibility, acceptability, costs and outcomes

We examined how far, and at what cost, the housing stock could be modified to accommodate the assistive technology (AT) necessary to enable older people to remain in their own homes. A multidisciplinary team devised seven hypothetical user profiles for 10 case study areas, with five local authorities and five housing associations in England and Wales. Each profile was considered at two times, five years apart, with the users' functional abilities deteriorating in between. In addition, in-depth interviews were carried out with a sample of 67 older people in the case study areas about their use and experience of a wide range of AT. The interviews showed the need to listen to older people and that they welcomed AT when it addressed a perceived need. The results showed that the extent of adaptation required of buildings to accommodate a user's needs varied greatly. It was also found that there was confusion about the terminology of AT, including the idea of the 'smart house'. The study shows that the adaptability of the housing depends on a range of factors and costs.

Educational participation post-16: a longitudinal analysis of intentions and outcomes

The issue of levels of participation in post-compulsory education has been emphasised by the current policy initiatives to increase the age to which some form of participation is compulsory. One of the acknowledged weaknesses of research in the field of children's intentions with regard to participation is the lack of longitudinal data. This paper offers a longitudinal analysis using the Youth Survey from the British Household Panel Survey. The results show that most children can express intentions with regard to future participation very early in their secondary school careers and that these intentions are good predictors of actual behaviour five years later. Intentions to stay on are more consistent than intentions to leave and most children who finally leave at 16 have at some point said they want to remain in education post-16. The strongest association with participation levels is attainment at GCSE. However, there are also influences of gender and parental background and these remain, even after attainment is held constant. The results show the value of focusing on intentions for participation at a very early stage of children's school careers and also the importance of current attempts to reform curriculum and assessment for the 14-19 age group.

Conjugated linoleic acid and human health-related outcomes

There has been increasing interest in health benefits of conjugated linoleic acid (CLA) based on findings with laboratory animals. Some human studies have also suggested health benefits of CLA, but because of the mixes used these could not be readily associated with a particular isomer of CLA. A recent study examined the separate effects of near-pure cis-9,trans-11 CLA (c9,t11 CLA) or trans-10,cis-12 CLA (t10,c12 CLA) on health-related outcomes in healthy young males. The CLA isomers were provided in capsules and at three doses (up to about 2.5 g/day) each for 8 weeks. Both c9,t11 and t10,c12 CLA were incorporated in a dose–response fashion into blood lipids and cells. At the doses and durations used, neither isomer of CLA affected bodyweight, body mass index or body composition, insulin sensitivity, immune function or markers of inflammation. However, at the doses and durations used, c9,t11 and t10,c12 CLA had opposing effects on blood lipid concentrations. Altered dairy cow-feeding practices were used to produce c9,t11 CLA-rich milk and, from this ultra heat-treated milk, cheese and butter were produced. The milk and the dairy products made from it had ninefold higher contents of c9,t11 CLA, higher contents of n-3 fatty acids and lower contents of total fat and of saturated fatty acids. They also contained much higher contents of trans-vaccenic acid (tVA). The modified dairy products were used in a 6-week controlled dietary intervention study in healthy middle-aged males. c9,t11 CLA and tVA were incorporated from dairy products into blood lipids and cells. Consumption of the CLA-rich (and tVA-rich) dairy products did not affect bodyweight or body mass index, insulin sensitivity or inflammatory markers. However, there were some detrimental effects on blood lipids. These effects may be due to tVA rather than to c9,t11 CLA, as they are consistent with the effects of trans fatty acids and not consistent with the effects of c9,t11 CLA identified in the earlier study with c9,t11 CLA in capsules.

Neonatal mortality in puppies due to bacteremia by Streptococcus dysgalactiae subsp dysgalactiae

We report a case of bacteremia in puppies caused by Streptococcus dysgalactiae subsp. dysgalactiae. Identification was achieved by phenotypic and molecular genetic methods. This is the first report of the recovery of S. dysgalactiae subsp. dysgalactiae from dogs.