1,370 research outputs found

    CMV in the gut: a critical review of CMV detection in the immunocompetent host with colitis.

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    As scientific techniques for the detection of cytomegalovirus (CMV) improve, we are able to detect small amounts of CMV in the mucosal wall. As clinicians, we are unsure how to interpret the results of this novel test. There is controversy in the literature as to the significance of the detection of CMV in the gut. Whilst the importance of CMV and reactivation of the virus is clear in those patients such as allograft recipients with established immune compromise, the role is less clear in patients with less damaged immune systems. We explore whether the detection of CMV in such cases influences outcome and how it should be optimally managed. We discuss the optimal management of such cases, according to current guidelines, with a review of the literature

    An integrated general practice and pharmacy-based intervention to promote the use of appropriate preventive medications among individuals at high cardiovascular disease risk: protocol for a cluster randomized controlled trial

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    Background: Cardiovascular diseases (CVD) are responsible for significant morbidity, premature mortality, and economic burden. Despite established evidence that supports the use of preventive medications among patients at high CVD risk, treatment gaps remain. Building on prior evidence and a theoretical framework, a complex intervention has been designed to address these gaps among high-risk, under-treated patients in the Australian primary care setting. This intervention comprises a general practice quality improvement tool incorporating clinical decision support and audit/feedback capabilities; availability of a range of CVD polypills (fixed-dose combinations of two blood pressure lowering agents, a statin ± aspirin) for prescription when appropriate; and access to a pharmacy-based program to support long-term medication adherence and lifestyle modification. Methods: Following a systematic development process, the intervention will be evaluated in a pragmatic cluster randomized controlled trial including 70 general practices for a median period of 18 months. The 35 general practices in the intervention group will work with a nominated partner pharmacy, whereas those in the control group will provide usual care without access to the intervention tools. The primary outcome is the proportion of patients at high CVD risk who were inadequately treated at baseline who achieve target blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) levels at the study end. The outcomes will be analyzed using data from electronic medical records, utilizing a validated extraction tool. Detailed process and economic evaluations will also be performed. Discussion: The study intends to establish evidence about an intervention that combines technological innovation with team collaboration between patients, pharmacists, and general practitioners (GPs) for CVD prevention. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN1261600023342

    Sustained Effects of Incredible Years as a Preventive Intervention in Preschool Children with Conduct Problems

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    The present study evaluated preventive effects of the Incredible Years program for parents of preschool children who were at risk for a chronic pattern of conduct problems, in the Netherlands. In a matched control design, 72 parents of children with conduct problems received the Incredible Years program. These families (intervention group) were compared with 72 families who received care as usual (control group). Two years after termination of the intervention, it appeared that observed and selfrated parenting skills were significantly improved in the intervention group. Likewise, in this group, observed child conduct problems showed sustained intervention effects. The decrease in observed critical parenting mediated the decrease in observed child conduct problems over time. In addition, it appeared that parental influence increased over time

    A single residue substitution in the receptor-binding domain of H5N1 hemagglutinin is critical for packaging into pseudotyped lentiviral particles

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    © 2012 Tang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Serological studies for influenza infection and vaccine response often involve microneutralization and hemagglutination inhibition assays to evaluate neutralizing antibodies against human and avian influenza viruses, including H5N1. We have previously characterized lentiviral particles pseudotyped with H5-HA (H5pp) and validated an H5pp-based assay as a safe alternative for high-throughput serological studies in BSL-2 facilities. Here we show that H5-HAs from different clades do not always give rise to efficient production of H5pp and the underlying mechanisms are addressed. Methodology/Findings: We have carried out mutational analysis to delineate the molecular determinants responsible for efficient packaging of HA from A/Cambodia/40808/2005 (H5Cam) and A/Anhui/1/2005 (H5Anh) into H5pp. Our results demonstrate that a single A134V mutation in the 130-loop of the receptor binding domain is sufficient to render H5Anh the ability to generate H5Anh-pp efficiently, whereas the reverse V134A mutation greatly hampers production of H5Cam-pp. Although protein expression in total cell lysates is similar for H5Anh and H5Cam, cell surface expression of H5Cam is detected at a significantly higher level than that of H5Anh. We further demonstrate by several independent lines of evidence that the behaviour of H5Anh can be explained by a stronger binding to sialic acid receptors implicating residue 134. Conclusions: We have identified a single A134V mutation as the molecular determinant in H5-HA for efficient incorporation into H5pp envelope and delineated the underlying mechanism. The reduced binding to sialic acid receptors as a result of the A134V mutation not only exerts a critical influence in pseudotyping efficiency of H5-HA, but has also an impact at the whole virus level. Because A134V substitution has been reported as a naturally occurring mutation in human host, our results may have implications for the understanding of human host adaptation of avian influenza H5N1 virusesThis work was supported by grants from the Research Fund for the Control of Infectious Diseases of Hong Kong (RFCID#08070972), the Area of Excellence Scheme of the University Grants Committee (grant AoE/M-12/-06 of the Hong Kong Special Administrative Region, China), the French Ministry of Health, and the RESPARI project of the Institut Pasteur International Network

    Extended Follow-Up Following a Phase 2b Randomized Trial of the Candidate Malaria Vaccines FP9 ME-TRAP and MVA ME-TRAP among Children in Kenya

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    Background. "FFM ME-TRAP'' is sequential immunisation with two attenuated poxvirus vectors (FP9 and modified vaccinia virus Ankara) delivering the pre-erythrocytic malaria antigen ME-TRAP. Over nine months follow-up in our original study, there was no evidence that FFM ME-TRAP provided protection against malaria. The incidence of malaria was slightly higher in children who received FFM ME-TRAP, but this was not statistically significant (hazard ratio 1.5, 95% CI 1.0-2.3). Although the study was unblinded, another nine months follow-up was planned to monitor the incidence of malaria and other serious adverse events. Methods and Findings. 405 children aged 1-6 yrs were initially randomized to vaccination with either FFM ME-TRAP or control (rabies vaccine). 380 children were still available for follow-up after the first nine months. Children were seen weekly and whenever they were unwell for nine months monitoring. The axillary temperature was measured, and blood films taken when febrile. The primary analysis was time to parasitaemia >2,500/mu l. During the second nine months monitoring, 49 events met the primary endpoint (febrile malaria with parasites >2,500/mu l) in the Intention To Treat (ITT) group. 23 events occurred among the 189 children in the FFM ME-TRAP group, and 26 among the 194 children in the control group. In the full 18 months of monitoring, there were 63 events in the FFM ME-TRAP group and 60 in the control group (HR = 1.2, CI 0.84-1.73, p = 0.35). There was no evidence that the HR changed over the 18 months (test for interaction between time and vaccination p = 0.11). Conclusions. Vaccination with FFM ME-TRAP was not protective against malaria in this study. Malaria incidence during 18 months of surveillance was similar in both vaccine groups. Trial Registration. Controlled-Trials. com ISRCTN88335123

    Nitrogen and sulphur management: challenges for organic sources in temperate agricultural systems

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    A current global trend towards intensification or specialization of agricultural enterprises has been accompanied by increasing public awareness of associated environmental consequences. Air and water pollution from losses of nutrients, such as nitrogen (N) and sulphur (S), are a major concern. Governments have initiated extensive regulatory frameworks, including various land use policies, in an attempt to control or reduce the losses. This paper presents an overview of critical input and loss processes affecting N and S for temperate climates, and provides some background to the discussion in subsequent papers evaluating specific farming systems. Management effects on potential gaseous and leaching losses, the lack of synchrony between supply of nutrients and plant demand, and options for optimizing the efficiency of N and S use are reviewed. Integration of inorganic and organic fertilizer inputs and the equitable re-distribution of nutrients from manure are discussed. The paper concludes by highlighting a need for innovative research that is also targeted to practical approaches for reducing N and S losses, and improving the overall synchrony between supply and demand

    A bibliometric analysis of research productivity in Parasitology by different world regions during a 9-year period (1995–2003)

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    BACKGROUND: The objective of this study was to estimate the research productivity of different world regions in the field of Parasitology. METHODS: Using the PubMed database we retrieved articles from journals included in the "Parasitology" category of the "Journal Citation Reports" database of the Institute for Scientific Information for the period 1995–2003. Research productivity was evaluated based on a methodology we developed and used in other bibliometric studies by analysing: (1) the total number of publications, (2) the mean impact factor of all papers, and (3) the product of the above two parameters, (4) the research productivity in relation to gross domestic product of each region, and (5) the research productivity in relation to gross national income per capita and population of each region. RESULTS: Data on the country of origin of the research was available for 18,110 out of 18,377 articles (98.6% of all articles from the included journals). Western Europe exceeds all world regions in research production for the period studied (34.8% of total articles), with USA ranking second (19.9%), and Latin America & the Caribbean ranking third (17.2%). The mean impact factor in articles published in Parasitology journals was highest for the USA (1.88). Oceania ranked first in research productivity when adjustments for both the gross national income per capita (GNIPC) and population were made. Eastern Europe almost tripled the production of articles from only 1.9% of total production in 1995 to 4.3% in 2003. Similarly, Latin America and the Caribbean and Asia doubled their production. However, the absolute and relative production by some developing areas, including Africa, is still very low, despite the fact that parasitic diseases are major public health problems in these areas. CONCLUSION: Our data suggest that more help should be provided by the developed nations to developing areas for improvement of the infrastructure of research

    Who attends antenatal care and expanded programme on immunization services in Chad, Mali and Niger? the implications for insecticide-treated net delivery

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    UNLABELLED: ABSTRACT: BACKGROUND: Malaria remains one of the largest public health problems facing the developing world. Insecticide-treated nets (ITNs) are an effective intervention against malaria. ITN delivery through routine health services, such as antenatal care (ANC) and childhood vaccination (EPI), is a promising channel of delivery to reach individuals with the highest risk (pregnant women and children under five years old). Decisions on whether to deliver ITNs through both channels depends upon the reach of each of these systems, whether these are independent and the effectiveness and cost effectiveness of each. Predictors of women attending ANC and EPI separately have been studied, but the predictors of those who attend neither service have not been identified. METHODS: Data from Chad, Mali and Niger demographic and health surveys (DHS) were analyzed to determine risk factors for attending neither service. A conceptual framework for preventative health care-seeking behaviour was created to illustrate the hierarchical relationships between the potential risk factors. The independence of attending both ANC and EPI was investigated. A multivariate model of predictors for non-attendance was developed using logistic regression. RESULTS: ANC and EPI attendance were found to be strongly associated in all three countries. However, 47% of mothers in Chad, 12% in Mali and 36% in Niger did not attend either ANC or EPI. Region, mother's education and partner's education were predictors of non-attendance in all three countries. Wealth index, ethnicity, and occupation were associated with non-attendance in Mali and Niger. Other predictors included religion, healthcare autonomy, household size and number of children under five. CONCLUSIONS: Attendance of ANC and EPI are not independent and therefore the majority of pregnant women in these countries will have the opportunity to receive ITNs through both services. Although attendance at ANC and EPI are not independent, delivery through both systems may still add incrementally to delivery through one alone. Therefore, there is potential to increase the proportion of women and children receiving ITNs by delivering through both of these channels. However, modelling is required to determine the level of attendance and incremental potential at which it's cost effective to deliver through both services
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