The natural history of respiratory syncytial virus in a birth cohort: the influence of age and previous infection on reinfection and disease.

This study aimed to quantify the effect of age, time since last infection, and infection history on the rate of respiratory syncytial virus infection and the effect of age and infection history on the risk of respiratory syncytial virus disease. A birth cohort of 635 children in Kilifi, Kenya, was monitored for respiratory syncytial virus infections from January 31, 2002, to April 22, 2005. Predictors of infection were examined by Cox regression and disease risk by binomial regression. A total of 598 respiratory syncytial virus infections were identified (411 primary, 187 repeat), with 409 determined by antigen assay and 189 by antibody alone (using a "most pragmatic" serologic definition). The incidence decreased by 70% following a primary infection (adjusted hazard ratio = 0.30, 95% confidence interval: 0.21, 0.42; P < 0.001) and by 59% following a secondary infection (hazard ratio = 0.41, 95% confidence interval: 0.22, 0.73; P = 0.003), for a period lasting 6 months. Relative to the age group <6 months, all ages exhibited a higher incidence of infection. A lower risk of severe disease following infection was independently associated with increasing age (P < 0.001) but not reinfection. In conclusion, observed respiratory syncytial virus incidence was lowest in the first 6 months of life, immunity to reinfection was partial and short lived, and disease risk was age related

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Blood pressure patterns in rural, semi-urban and urban children in the Ashanti region of Ghana, West Africa

BACKGROUND: High blood pressure, once rare, is rapidly becoming a major public health burden in sub-Saharan/Africa. It is unclear whether this is reflected in children. The main purpose of this study was to assess blood pressure patterns among rural, semi-urban, and urban children and to determine the association of blood pressure with locality and body mass index (BMI) in this sub-Saharan Africa setting. METHODS: We conducted a cross-sectional survey among school children aged 8–16 years in the Ashanti region of Ghana (West-Africa). There were 1277 children in the study (616 boys and 661 females). Of these 214 were from rural, 296 from semi-urban and 767 from urban settings. RESULTS: Blood pressure increased with increasing age in rural, semi-urban and urban areas, and in both boys and girls. The rural boys had a lower systolic and diastolic blood pressure than semi-urban boys (104.7/62.3 vs. 109.2/66.5; p < 0.001) and lower systolic blood pressure than urban boys (104.7 vs. 107.6; p < 0.01). Girls had a higher blood pressure than boys (109.1/66.7 vs. 107.5/63.8; p < 0.01). With the exception of a lower diastolic blood pressure amongst rural girls, no differences were found between rural girls (107.4/64.4) and semi-urban girls (108.0/66.1) and urban girls (109.8/67.5). In multiple linear regression analysis, locality and BMI were independently associated with blood pressure in both boys and girls. CONCLUSION: These findings underscore the urgent need for public health measures to prevent increasing blood pressure and its sequelae from becoming another public health burden. More work on blood pressure in children in sub-Saharan African and other developing countries is needed to prevent high blood pressure from becoming a major burden in many of these countries

Airway response to respiratory syncytial virus has incidental antibacterial effects.

RSV infection is typically associated with secondary bacterial infection. We hypothesise that the local airway immune response to RSV has incidental antibacterial effects. Using coordinated proteomics and metagenomics analysis we simultaneously analysed the microbiota and proteomes of the upper airway and determined direct antibacterial activity in airway secretions of RSV-infected children. Here, we report that the airway abundance of Streptococcus was higher in samples collected at the time of RSV infection compared with samples collected one month later. RSV infection is associated with neutrophil influx into the airway and degranulation and is marked by overexpression of proteins with known antibacterial activity including BPI, EPX, MPO and AZU1. Airway secretions of children infected with RSV, have significantly greater antibacterial activity compared to RSV-negative controls. This RSV-associated, neutrophil-mediated antibacterial response in the airway appears to act as a regulatory mechanism that modulates bacterial growth in the airways of RSV-infected children

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Infectious disease management in primary care: perceptions of GPs

<p>Abstract</p> <p>Background</p> <p>It is important to keep the level of antibiotic prescribing low to contain the development of resistant bacteria. This study was conducted to reveal new knowledge about how GPs think in relation to the prescribing of antibiotics - knowledge that could be used in efforts toward rational treatment of infectious diseases in primary care. The aim was to explore and describe the variations in GPs' perceptions of infectious disease management, with special reference to antibiotic prescribing.</p> <p>Methods</p> <p>Twenty GPs working at primary care centres in a county in south-west Sweden were purposively selected based on the strategy of including GPs with different kinds of experience. The GPs were interviewed and perceptions among GPs were analysed by a phenomenographic approach.</p> <p>Results</p> <p>Five qualitatively different perceptions of infectious disease management were identified. They were: (A) the GP must help the patient to achieve health and well-being; (B) the management must meet the GP's perceived personal, professional and organisational demands; (C) restrictive antibiotic prescribing is time-consuming; (D) restrictive antibiotic prescribing can protect the effectiveness of antibiotics; and (E) patients benefit personally from restrictive antibiotic prescribing.</p> <p>Conclusions</p> <p>Restrictive antibiotic prescribing was considered important in two perceptions, was not an issue as such in two others, and was considered in one perception although the actual prescribing was greatly influenced by the interaction between patient and GP. Accordingly, to encourage restrictive antibiotic prescribing several aspects must be addressed. Furthermore, different GPs need various kinds of support. Infectious disease management in primary care is complex and time-consuming, which must be acknowledged in healthcare organisation and planning.</p

Different fatty acid metabolism effects of (−)-epigallocatechin-3-gallate and C75 in adenocarcinoma lung cancer

Background Fatty acid synthase (FASN) is overexpressed and hyperactivated in several human carcinomas, including lung cancer. We characterize and compare the anti-cancer effects of the FASN inhibitors C75 and (−)-epigallocatechin-3-gallate (EGCG) in a lung cancer model. Methods We evaluated in vitro the effects of C75 and EGCG on fatty acid metabolism (FASN and CPT enzymes), cellular proliferation, apoptosis and cell signaling (EGFR, ERK1/2, AKT and mTOR) in human A549 lung carcinoma cells. In vivo, we evaluated their anti-tumour activity and their effect on body weight in a mice model of human adenocarcinoma xenograft. Results C75 and EGCG had comparable effects in blocking FASN activity (96,9% and 89,3% of inhibition, respectively). In contrast, EGCG had either no significant effect in CPT activity, the rate-limiting enzyme of fatty acid β-oxidation, while C75 stimulated CPT up to 130%. Treating lung cancer cells with EGCG or C75 induced apoptosis and affected EGFR-signaling. While EGCG abolished p-EGFR, p-AKT, p-ERK1/2 and p-mTOR, C75 was less active in decreasing the levels of EGFR and p-AKT. In vivo, EGCG and C75 blocked the growth of lung cancer xenografts but C75 treatment, not EGCG, caused a marked animal weight loss. Conclusions In lung cancer, inhibition of FASN using EGCG can be achieved without parallel stimulation of fatty acid oxidation and this effect is related mainly to EGFR signaling pathway. EGCG reduce the growth of adenocarcinoma human lung cancer xenografts without inducing body weight loss. Taken together, EGCG may be a candidate for future pre-clinical development

Therapeutic Benefit of Radial Optic Neurotomy in a Rat Model of Glaucoma

Radial optic neurotomy (RON) has been proposed as a surgical treatment to alleviate the neurovascular compression and to improve the venous outflow in patients with central retinal vein occlusion. Glaucoma is characterized by specific visual field defects due to the loss of retinal ganglion cells and damage to the optic nerve head (ONH). One of the clinical hallmarks of glaucomatous neuropathy is the excavation of the ONH. The aim of this work was to analyze the effect of RON in an experimental model of glaucoma in rats induced by intracameral injections of chondroitin sulfate (CS). For this purpose, Wistar rats were bilaterally injected with vehicle or CS in the eye anterior chamber, once a week, for 10 weeks. At 3 or 6 weeks of a treatment with vehicle or CS, RON was performed by a single incision in the edge of the neuro-retinal ring at the nasal hemisphere of the optic disk in one eye, while the contralateral eye was submitted to a sham procedure. Electroretinograms (ERGs) were registered under scotopic conditions and visual evoked potentials (VEPs) were registered with skull-implanted electrodes. Retinal and optic nerve morphology was examined by optical microscopy. RON did not affect the ocular hypertension induced by CS. In eyes injected with CS, a significant decrease of retinal (ERG a- and b-wave amplitude) and visual pathway (VEP N2-P2 component amplitude) function was observed, whereas RON reduced these functional alterations in hypertensive eyes. Moreover, a significant loss of cells in the ganglion cell layer, and Thy-1-, NeuN- and Brn3a- positive cells was observed in eyes injected with CS, whereas RON significantly preserved these parameters. In addition, RON preserved the optic nerve structure in eyes with chronic ocular hypertension. These results indicate that RON reduces functional and histological alterations induced by experimental chronic ocular hypertension

Clinical trials to estimate the efficacy of preventive interventions against malaria in paediatric populations: a methodological review

BACKGROUND: Recent years have seen publication of a considerable number of clinical trials of preventive interventions against clinical malaria in children. There has been variability in the specification of end-points, case definitions, analysis methods and reporting and the relative lack of standardization complicates the ability to make comparative evaluations between trials. METHODS: To prepare for a WHO consultation on design issues in malaria vaccine trials, controlled trials of preventive interventions against malaria in children in endemic countries were identified in which clinical malaria, or death, had been one of the main end-points. Trials were included that evaluated the impact of vaccines, insecticide-treated bed nets (ITN), intermittent presumptive or preventive therapy in infants (IPTi) or, in one instance, vitamin A supplementation. Methods that had been used in these trials were summarized and compared in order to identify issues that were directly relevant to the design of malaria vaccine trials. RESULTS: 29 controlled trials of preventive malaria interventions were identified, of which eight were vaccine trials. Vaccine trials that were designed to detect an effect on clinical malaria all reported the incidence rate of first episodes of clinical malaria as their primary endpoint. Only one trial of a preventive intervention (of ITN) was identified that was designed to detect an effect on severe malaria. A group of larger trials were designed to detect an effect of impregnated bed nets or curtains on all-cause mortality as the primary end-point. Key methodological and reporting differences between trials are noted in the text. Two issues have been identified that are of some concern. Firstly, the choice of primary endpoint is not stated in the reports of a number of the trials and, secondly, the relationship between pre-specified analysis plans and trial reports is rarely made clear. CONCLUSION: This article reports an investigation into the ways in which trial design and reporting could be improved and standardized to enable comparative evaluation of the relative merits of malaria control measures, and specifically with respect to the design of malaria vaccine trials. The need for standardization of clinical trial design, conduct, analysis and reporting has been also affirmed as a priority area by the Malaria Vaccine Technology Roadmap