849 research outputs found

    Physicochemical analysis of rotavirus segment 11 supports a 'modified panhandle' structure and not the predicted alternative tRNA-like structure (TRLS)

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    .Rotaviruses are a major cause of acute gastroenteritis, which is often fatal in infants. The viral genome consists of 11 double-stranded RNA segments, but little is known about their cis-acting sequences and structural elements. Covariation studies and phylogenetic analysis exploring the potential structure of RNA11 of rotaviruses suggested that, besides the previously predicted "modified panhandle" structure, the 5' and 3' termini of one of the isoforms of the bovine rotavirus UKtc strain may interact to form a tRNA-like structure (TRLS). Such TRLSs have been identified in RNAs of plant viruses, where they are important for enhancing replication and packaging. However, using tRNA mimicry assays (in vitro aminoacylation and 3'- adenylation), we found no biochemical evidence for tRNA-like functions of RNA11. Capping, synthetic 3' adenylation and manipulation of divalent cation concentrations did not change this finding. NMR studies on a 5'- and 3'-deletion construct of RNA11 containing the putative intra-strand complementary sequences supported a predominant panhandle structure and did not conform to a cloverleaf fold despite the strong evidence for a predicted structure in this conserved region of the viral RNA. Additional viral or cellular factors may be needed to stabilise it into a form with tRNA-like properties

    6Questionnaire-based approach to assess schoolchildren's physical fitness and its potential role in exploring the putative impact of helminth and Plasmodium spp. infections in Côte d'Ivoire

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    BACKGROUND: Disability weights (DWs) are important for estimating burden of disease in terms of disability-adjusted life years. The previous practice of eliciting DWs by expert opinion has been challenged. More recent approaches employed quality of life (QoL) questionnaires to establish patient-based DWs, but results are ambiguous. METHODS: In early 2010, we administered a questionnaire pertaining to physical fitness to 200 schoolchildren in Cote d'Ivoire. Helminth and Plasmodium spp. infections were determined and schoolchildren's physical fitness objectively measured in a maximal multistage 20 m shuttle run test. Associations between objectively measured and self-reported physical fitness and between self-reported physical fitness and infection status were determined. Spearman rank correlation coefficient, uni- and multivariable linear regression models adjusting for children's age and sex, ambient air temperature and humidity, Fisher's test, chi^2 and t-test statistics were used for statistical analysis. RESULTS: The prevalence of Schistosoma haematobium, Plasmodium spp., Schistosoma mansoni, hookworm and Ascaris lumbricoides in 167 children with complete parasitological results was 84.4%, 74.9%, 54.5%, 14.4% and 1.2%, respectively. High infection intensities and multiple species parasite infections were common. In the 137 children with complete data also from the shuttle run test, we found statistically significant correlations between objectively measured and self-reported physical fitness. However, no statistically significant correlation between the children's parasitic infection status and self-reported physical fitness was identified. An attrition analysis revealed considerably lower self-reported physical fitness scores of parasitized children who were excluded from shuttle run testing due to medical concerns in comparison to parasitized children who were able to successfully complete the shuttle run test. CONCLUSIONS: Our QoL questionnaire proofed valid to assess children's physical fitness in the current study area. Reasons why no differences in self-reported physical fitness in children with different parasitic infections were found are manifold, but do not preclude the use of QoL questionnaires in the elicitation of DWs. Indeed, the questionnaire was particularly useful in assessing physical fitness of those children, who were - supposedly due to parasitic infections - unable to complete the shuttle run test. Hence, we encourage others to use QoL questionnaires to determine not only physical fitness, but also more subtle morbidities

    The impact of albendazole treatment on the incidence of viral- and bacterial-induced diarrhea in school children in southern Vietnam: study protocol for a randomized controlled trial

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    Anthelmintics are one of the more commonly available classes of drugs to treat infections by parasitic helminths (especially nematodes) in the human intestinal tract. As a result of their cost-effectiveness, mass school-based deworming programs are becoming routine practice in developing countries. However, experimental and clinical evidence suggests that anthelmintic treatments may increase susceptibility to other gastrointestinal infections caused by bacteria, viruses, or protozoa. Hypothesizing that anthelmintics may increase diarrheal infections in treated children, we aim to evaluate the impact of anthelmintics on the incidence of diarrheal disease caused by viral and bacterial pathogens in school children in southern Vietnam.This is a randomized, double-blinded, placebo-controlled trial to investigate the effects of albendazole treatment versus placebo on the incidence of viral- and bacterial-induced diarrhea in 350 helminth-infected and 350 helminth-uninfected Vietnamese school children aged 6-15 years. Four hundred milligrams of albendazole, or placebo treatment will be administered once every 3 months for 12 months. At the end of 12 months, all participants will receive albendazole treatment. The primary endpoint of this study is the incidence of diarrheal disease assessed by 12 months of weekly active and passive case surveillance. Secondary endpoints include the prevalence and intensities of helminth, viral, and bacterial infections, alterations in host immunity and the gut microbiota with helminth and pathogen clearance, changes in mean z scores of body weight indices over time, and the number and severity of adverse events.In order to reduce helminth burdens, anthelmintics are being routinely administered to children in developing countries. However, the effects of anthelmintic treatment on susceptibility to other diseases, including diarrheal pathogens, remain unknown. It is important to monitor for unintended consequences of drug treatments in co-infected populations. In this trial, we will examine how anthelmintic treatment impacts host susceptibility to diarrheal infections, with the aim of informing deworming programs of any indirect effects of mass anthelmintic administrations on co-infecting enteric pathogens.ClinicalTrials.gov: NCT02597556 . Registered on 3 November 2015

    Smoking and health-related quality of life in English general population: Implications for economic evaluations

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    Copyright @ 2012 Vogl et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.Background: Little is known as to how health-related quality of life (HRQoL) when measured by generic instruments such as EQ-5D differ across smokers, ex-smokers and never-smokers in the general population; whether the overall pattern of this difference remain consistent in each domain of HRQoL; and what implications this variation, if any, would have for economic evaluations of tobacco control interventions. Methods: Using the 2006 round of Health Survey for England data (n = 13,241), this paper aims to examine the impact of smoking status on health-related quality of life in English population. Depending upon the nature of the EQ-5D data (i.e. tariff or domains), linear or logistic regression models were fitted to control for biology, clinical conditions, socio-economic background and lifestyle factors that an individual may have regardless of their smoking status. Age- and gender-specific predicted values according to smoking status are offered as the potential 'utility' values to be used in future economic evaluation models. Results: The observed difference of 0.1100 in EQ-5D scores between never-smokers (0.8839) and heavy-smokers (0.7739) reduced to 0.0516 after adjusting for biological, clinical, lifestyle and socioeconomic conditions. Heavy-smokers, when compared with never-smokers, were significantly more likely to report some/severe problems in all five domains - mobility (67%), self-care (70%), usual activity (42%), pain/discomfort (46%) and anxiety/depression (86%) -. 'Utility' values by age and gender for each category of smoking are provided to be used in the future economic evaluations. Conclusion: Smoking is significantly and negatively associated with health-related quality of life in English general population and the magnitude of this association is determined by the number of cigarettes smoked. The varying degree of this association, captured through instruments such as EQ-5D, may need to be fed into the design of future economic evaluations where the intervention being evaluated affects (e.g. tobacco control) or is affected (e.g. treatment for lung cancer) by individual's (or patients') smoking status

    A review of physical supply and EROI of fossil fuels in China

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    This paper reviews China’s future fossil fuel supply from the perspectives of physical output and net energy output. Comprehensive analyses of physical output of fossil fuels suggest that China’s total oil production will likely reach its peak, at about 230 Mt/year (or 9.6 EJ/year), in 2018; its total gas production will peak at around 350 Bcm/year (or 13.6 EJ/year) in 2040, while coal production will peak at about 4400 Mt/year (or 91.9 EJ/year) around 2020 or so. In terms of the forecast production of these fuels, there are significant differences among current studies. These differences can be mainly explained by different ultimately recoverable resources assumptions, the nature of the models used, and differences in the historical production data. Due to the future constraints on fossil fuels production, a large gap is projected to grow between domestic supply and demand, which will need to be met by increasing imports. Net energy analyses show that both coal and oil and gas production show a steady declining trend of EROI (energy return on investment) due to the depletion of shallow-buried coal resources and conventional oil and gas resources, which is generally consistent with the approaching peaks of physical production of fossil fuels. The peaks of fossil fuels production, coupled with the decline in EROI ratios, are likely to challenge the sustainable development of Chinese society unless new abundant energy resources with high EROI values can be found

    Multi-parallel qPCR provides increased sensitivity and diagnostic breadth for gastrointestinal parasites of humans: field-based inferences on the impact of mass deworming

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    BACKGROUND: Although chronic morbidity in humans from soil transmitted helminth (STH) infections can be reduced by anthelmintic treatment, inconsistent diagnostic tools make it difficult to reliably measure the impact of deworming programs and often miss light helminth infections. METHODS: Cryopreserved stool samples from 796 people (aged 2-81 years) in four villages in Bungoma County, western Kenya, were assessed using multi-parallel qPCR for 8 parasites and compared to point-of-contact assessments of the same stools by the 2-stool 2-slide Kato-Katz (KK) method. All subjects were treated with albendazole and all Ascaris lumbricoides expelled post-treatment were collected. Three months later, samples from 633 of these people were re-assessed by both qPCR and KK, re-treated with albendazole and the expelled worms collected. RESULTS: Baseline prevalence by qPCR (n = 796) was 17 % for A. lumbricoides, 18 % for Necator americanus, 41 % for Giardia lamblia and 15% for Entamoeba histolytica. The prevalence was <1% for Trichuris trichiura, Ancylostoma duodenale, Strongyloides stercoralis and Cryptosporidium parvum. The sensitivity of qPCR was 98% for A. lumbricoides and N. americanus, whereas KK sensitivity was 70% and 32%, respectively. Furthermore, qPCR detected infections with T. trichiura and S. stercoralis that were missed by KK, and infections with G. lamblia and E. histolytica that cannot be detected by KK. Infection intensities measured by qPCR and by KK were correlated for A. lumbricoides (r = 0.83, p < 0.0001) and N. americanus (r = 0.55, p < 0.0001). The number of A. lumbricoides worms expelled was correlated (p < 0.0001) with both the KK (r = 0.63) and qPCR intensity measurements (r = 0.60). CONCLUSIONS: KK may be an inadequate tool for stool-based surveillance in areas where hookworm or Strongyloides are common or where intensity of helminth infection is low after repeated rounds of chemotherapy. Because deworming programs need to distinguish between populations where parasitic infection is controlled and those where further treatment is required, multi-parallel qPCR (or similar high throughput molecular diagnostics) may provide new and important diagnostic information

    New approaches to measuring anthelminthic drug efficacy: parasitological responses of childhood schistosome infections to treatment with praziquantel

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    By 2020, the global health community aims to control and eliminate human helminthiases, including schistosomiasis in selected African countries, principally by preventive chemotherapy (PCT) through mass drug administration (MDA) of anthelminthics. Quantitative monitoring of anthelminthic responses is crucial for promptly detecting changes in efficacy, potentially indicative of emerging drug resistance. Statistical models offer a powerful means to delineate and compare efficacy among individuals, among groups of individuals and among populations.; We illustrate a variety of statistical frameworks that offer different levels of inference by analysing data from nine previous studies on egg counts collected from African children before and after administration of praziquantel.; We quantify responses to praziquantel as egg reduction rates (ERRs), using different frameworks to estimate ERRs among population strata, as average responses, and within strata, as individual responses. We compare our model-based average ERRs to corresponding model-free estimates, using as reference the World Health Organization (WHO) 90 % threshold of optimal efficacy. We estimate distributions of individual responses and summarize the variation among these responses as the fraction of ERRs falling below the WHO threshold.; Generic models for evaluating responses to anthelminthics deepen our understanding of variation among populations, sub-populations and individuals. We discuss the future application of statistical modelling approaches for monitoring and evaluation of PCT programmes targeting human helminthiases in the context of the WHO 2020 control and elimination goals
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