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171.
Bruna Gigante Rona J. Strawbridge Ilais Moreno Velasquez Zahra Golabkesh Angela Silveira Anuj Goel Damiano Baldassarre Fabrizio Veglia Elena Tremoli Robert Clarke Hugh Watkins Anders Hamsten Steve E. Humphries Ulf de Faire 《PloS one》2015,10(3)
Variants at the interleukin 6 receptor (IL6R) gene regulate inflammation and are associated with risk of coronary heart disease (CHD). The aim of the present study was to investigate the effects of IL6R haplotypes on circulating levels of inflammatory biomarkers and risk of CHD. We performed a discovery analysis in SHEEP, a myocardial infarction (MI) case control study (n = 2,774) and replicated our results in two large, independent European populations, PROCARDIS, a CHD case control study (n = 7,998), and IMPROVE (n = 3,711) a prospective cardiovascular cohort study. Two major haplotype blocks (rs12083537A/G and rs4075015A/T—block 1; and rs8192282G/A, rs4553185T/C, rs8192284A/C, rs4240872T/C and rs7514452T/C—block 2) were identified in the IL6R gene. IL6R haplotype associations with C-reactive protein (CRP), fibrinogen, IL6, soluble IL6R (sIL6R), IL6, IL8 and TNF-α in SHEEP, CRP and fibrinogen in PROCARDIS and CRP in IMPROVE as well as association with risk of MI and CHD, were analyzed by THESIAS. Haplotypes in block 1 were associated neither with circulating inflammatory biomarkers nor with the MI/CHD risk. Haplotypes in block 2 were associated with circulating levels of CRP, in all three study populations, with fibrinogen in SHEEP and PROCARDIS, with IL8 and sIL6Rin SHEEP and with a modest, non significant, increase (7%) in MI/CHD risk in the three populations studied. Our results indicate that IL6R haplotypes regulate the circulating levels of inflammatory biomarkers. Lack of association with the risk of CHD may be explained by the combined effect of SNPs with opposite effect on the CHD risk, the sample size as well as by structural changes affecting sIL6R stability in the circulation. 相似文献
172.
Molecular Characterization of Subtype H11N9 Avian Influenza Virus Isolated from Shorebirds in Brazil
Renata Hurtado Thomas Fabrizio Ralph Eric Thijl Vanstreels Scott Krauss Richard J. Webby Robert G. Webster Edison Luiz Durigon 《PloS one》2015,10(12)
Migratory aquatic birds play an important role in the maintenance and spread of avian influenza viruses (AIV). Many species of aquatic migratory birds tend to use similar migration routes, also known as flyways, which serve as important circuits for the dissemination of AIV. In recent years there has been extensive surveillance of the virus in aquatic birds in the Northern Hemisphere; however in contrast only a few studies have been attempted to detect AIV in wild birds in South America. There are major flyways connecting South America to Central and North America, whereas avian migration routes between South America and the remaining continents are uncommon. As a result, it has been hypothesized that South American AIV strains would be most closely related to the strains from North America than to those from other regions in the world. We characterized the full genome of three AIV subtype H11N9 isolates obtained from ruddy turnstones (Arenaria interpres) on the Amazon coast of Brazil. For all gene segments, all three strains consistently clustered together within evolutionary lineages of AIV that had been previously described from aquatic birds in North America. In particular, the H11N9 isolates were remarkably closely related to AIV strains from shorebirds sampled at the Delaware Bay region, on the Northeastern coast of the USA, more than 5000 km away from where the isolates were retrieved. Additionally, there was also evidence of genetic similarity to AIV strains from ducks and teals from interior USA and Canada. These findings corroborate that migratory flyways of aquatic birds play an important role in determining the genetic structure of AIV in the Western hemisphere, with a strong epidemiological connectivity between North and South America. 相似文献
173.
In-Kyu Yoon Maria Theresa Alera Catherine B. Lago Ilya A. Tac-An Daisy Villa Stefan Fernandez Butsaya Thaisomboonsuk Chonticha Klungthong Jens W. Levy John Mark Velasco Vito G. Roque Jr. Henrik Salje Louis R. Macareo Laura L. Hermann Ananda Nisalak Anon Srikiatkhachorn 《PLoS neglected tropical diseases》2015,9(5)
Background
Chikungunya virus (CHIKV) is a globally re-emerging arbovirus for which previous studies have indicated the majority of infections result in symptomatic febrile illness. We sought to characterize the proportion of subclinical and symptomatic CHIKV infections in a prospective cohort study in a country with known CHIKV circulation.Methods/Findings
A prospective longitudinal cohort of subjects ≥6 months old underwent community-based active surveillance for acute febrile illness in Cebu City, Philippines from 2012-13. Subjects with fever history were clinically evaluated at acute, 2, 5, and 8 day visits, and at a 3-week convalescent visit. Blood was collected at the acute and 3-week convalescent visits. Symptomatic CHIKV infections were identified by positive CHIKV PCR in acute blood samples and/or CHIKV IgM/IgG ELISA seroconversion in paired acute/convalescent samples. Enrollment and 12-month blood samples underwent plaque reduction neutralization test (PRNT) using CHIKV attenuated strain 181/clone25. Subclinical CHIKV infections were identified by ≥8-fold rise from a baseline enrollment PRNT titer <10 without symptomatic infection detected during the intervening surveillance period. Selected CHIKV PCR-positive samples underwent viral isolation and envelope protein-1 gene sequencing. Of 853 subjects who completed all study procedures at 12 months, 19 symptomatic infections (2.19 per 100 person-years) and 87 subclinical infections (10.03 per 100 person-years) occurred. The ratio of subclinical-to-symptomatic infections was 4.6:1 varying with age from 2:1 in 6 month-5 year olds to 12:1 in those >50 years old. Baseline CHIKV PRNT titer ≥10 was associated with 100% (95%CI: 46.1, 100.0) protection from symptomatic CHIKV infection. Phylogenetic analysis demonstrated Asian genotype closely related to strains from Asia and the Caribbean.Conclusions
Subclinical infections accounted for a majority of total CHIKV infections. A positive baseline CHIKV PRNT titer was associated with protection from symptomatic CHIKV infection. These findings have implications for assessing disease burden, understanding virus transmission, and supporting vaccine development. 相似文献174.
Gianluigi Forloni Mauro Tettamanti Ugo Lucca Yasmin Albanese Elena Quaglio Roberto Chiesa Alessandra Erbetta Flavio Villani Veronica Redaelli Fabrizio Tagliavini Vladimiro Artuso Ignazio Roiter 《朊病毒》2015,9(2):75-79
The text describes a preventive clinical trial with drug treatment in a very rare neurodegenerative disease (Fatal familial Insomnia, FFI) designed with the help of individuals at genetic risk of developing the disease, asymptomatic carriers, who have agreed to be exposed over a 10-year period to doxycycline, an antibiotic with anti-prion activity. At least 10 carriers of the FFI mutation over 42 y old will be treated with doxycycline (100 mg/die) and the incidence of the disease will be compared to that of an historical dataset. For ethical reasons a randomized, double-blind, placebo-controlled trial was not feasible, however the study design and the statistical analysis ensure the scientific value of the results. This approach might represent an important breakthrough in terms of potential therapy and knowledge of rare diseases that could give some hopes to these neglected patients. 相似文献
175.
C. Simone Sutherland Joshua Yukich Ron Goeree Fabrizio Tediosi 《PLoS neglected tropical diseases》2015,9(2)
Human African trypanosomiasis (HAT) is a disease caused by infection with the parasite Trypanosoma brucei gambiense or T. b. rhodesiense. It is transmitted to humans via the tsetse fly. Approximately 70 million people worldwide were at risk of infection in 1995, and approximately 20,000 people across Africa are infected with HAT. The objective of this review was to identify existing economic evaluations in order to summarise cost-effective interventions to reduce, control, or eliminate the burden of HAT. The studies included in the review were compared and critically appraised in order to determine if there were existing standardised methods that could be used for economic evaluation of HAT interventions or if innovative methodological approaches are warranted. A search strategy was developed using keywords and was implemented in January 2014 in several databases. The search returned a total of 2,283 articles. After two levels of screening, a total of seven economic evaluations were included and underwent critical appraisal using the Scottish Intercollegiate Guidelines Network (SIGN) Methodology Checklist 6: Economic Evaluations. Results from the existing studies focused on the cost-effectiveness of interventions for the control and reduction of disease transmission. Modelling was a common method to forecast long-term results, and publications focused on interventions by category, such as case detection, diagnostics, drug treatments, and vector control. Most interventions were considered cost-effective based on the thresholds described; however, the current treatment, nifurtomix-eflornithine combination therapy (NECT), has not been evaluated for cost-effectiveness, and considerations for cost-effective strategies for elimination have yet to be completed. Overall, the current evidence highlights the main components that play a role in control; however, economic evaluations of HAT elimination strategies are needed to assist national decision makers, stakeholders, and key funders. These analyses would be of use, as HAT is currently being prioritized as a neglected tropical disease (NTD) to reach elimination by 2020. 相似文献
176.
177.
Daniel Pereira Maria Cristina Dreher Mansur Leandro D. S. Duarte Arthur Schramm de Oliveira Daniel Mansur Pimpão Cláudia Tasso Callil Cristián Ituarte Esperanza Parada Santiago Peredo Gustavo Darrigran Fabrizio Scarabino Cristhian Clavijo Gladys Lara Igor Christo Miyahira Maria Teresa Raya Rodriguez Carlos Lasso 《Hydrobiologia》2014,735(1):15-44
Based on literature review and malacological collections, 168 native freshwater bivalve and five invasive species have been recorded for 52 hydrographic regions in South America. The higher species richness has been detected in the South Atlantic, Uruguay, Paraguay, and Amazon Brazilian hydrographic regions. Presence or absence data were analysed by Principal Coordinate for Phylogeny-Weighted. The lineage Veneroida was more representative in hydrographic regions that are poorer in species and located West of South America. The Mycetopodidae and Hyriidae lineages were predominant in regions that are richest in species toward the East of the continent. The distribution of invasive species Limnoperna fortunei is not related to species richness in different hydrographic regions there. The species richness and its distribution patterns are closely associated with the geological history of the continent. The hydrographic regions present distinct phylogenetic and species composition regardless of the level of richness. Therefore, not only should the richness be considered to be a criterion for prioritizing areas for conservation, but also the phylogenetic diversity of communities engaged in services and functional aspects relevant to ecosystem maintenance. A plan to the management of this fauna according to particular ecological characteristics and human uses of hydrographic regions is needed. 相似文献
178.
Christine E. Brotherton-Pleiss Michael P. Dillon Anthony P.D.W. Ford Joel R. Gever David S. Carter Shelley K. Gleason Clara J. Lin Amy G. Moore Anthony W. Thompson Marzia Villa Yansheng Zhai 《Bioorganic & medicinal chemistry letters》2010,20(3):1031-1036
Despite the extensive literature describing the role of the ATP-gated P2X3 receptors in a variety of physiological processes the potential of antagonists as therapeutic agents has been limited by the lack of drug-like selective molecules. In this paper we report the discovery and optimization of RO-85, a novel drug-like, potent and selective P2X3 antagonist. High-throughput screening of the Roche compound collection identified a small hit series of heterocyclic amides from a large parallel synthesis library. Rapid optimization, facilitated by high-throughput synthesis, focusing on increasing potency and improving drug-likeness resulted in the discovery of RO-85. 相似文献
179.
Micheli F Antolini M Di Fabio R Pellacani A Pozzan A 《Bioorganic & medicinal chemistry letters》2010,20(22):6405-6407
A new class of selective orexin 2 antagonist was identified among commercial products. Initial SAR was obtained using commercial derivatives only prior to starting ad hoc medicinal chemistry activities. 相似文献
180.
Fabrizio Micheli Daniele Andreotti Simone Braggio Anna Checchia 《Bioorganic & medicinal chemistry letters》2010,20(15):4566-4568
A direct and specific comparison of a trifluoromethyl group with the corresponding pentafluorosulfanyl group is made in terms of primary affinity and pharmacokinetic properties. 相似文献